bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease
Authors: Gayed Matthew M. , Jung Seung-Hye , Huggins Erin , Rodriguez-Rassi Eleanor , DeArmey Stephanie , Kishnani Priya Sunil , Stiles Ashlee R.
Published: November 2022

Historically, disease burden and treatment responses in patients with Gaucher disease (GD) was assessed by monitoring clinical data, laboratory, imaging, chitotriosidase (CHITO), and other biomarkers; however, these biomarkers lack specificity and CHITO is uninformative in patients heterozygous or homozygous for the CHIT1 c.1049_1072dup24 variant. Recently, glucosylsphingosine (lyso-Gb1), a sensitive and specific GD biomarker, has been recommended for patient monitoring. Furthermore, studies measuring lyso-Gb1 and CHITO in patients on long-term treatment with enzyme replacement therapy (ERT) and/or substrate reduction therapy (SRT) reported as group data show a reduction in both analytes, yet individualized patient data are generally unavailable. We describe seven patients on long-term treatment with longitudinal clinical data with monitoring based on current treatment guidelines. We present four patients who exhibit stable disease with normalized CHITO despite elevated lyso-Gb1. We present one patient who transitioned from ERT to SRT due to lack of a clinical response with life-threatening thrombocytopenia who responded with marked improvement in platelets, and normalized levels of both CHITO and lyso-Gb1. Finally, we present two ERT to SRT switch patients with stable disease on ERT who exhibited non-compliance on SRT, one with mirrored marked elevations of CHITO and lyso-Gb1; and another with normal CHITO and platelets, but increasing lyso-Gb1 levels and enlarged spleen. These clinical vignettes highlight the role of lyso-Gb1 as a sensitive biomarker in management of patients with GD, and its further value when CHITO is normal and thus uninformative. We highlight the personalized medicine approach needed to optimize treatment outcomes and recommendations for these patients.
Gene Therapy in Combination with Nitrogen Scavenger Pretreatment Corrects Biochemical and Behavioral Abnormalities of Infant Citrullinemia Type 1 Mice
Authors: Bazo Andrea , Lantero Aquilino , Mauleón Itsaso , Neri Leire , Poms Martin , Häberle Johannes , Ricobaraza Ana , Bénichou Bernard , Combal Jean-Philippe , Gonzalez-Aseguinolaza Gloria , Aldabe Rafael
Published: November 2022

Citrullinemia type I (CTLN1) is a rare autosomal recessive disorder caused by mutations in the gene encoding argininosuccinate synthetase 1 (ASS1) that catalyzes the third step of the urea cycle. CTLN1 patients suffer from impaired elimination of nitrogen, which leads to neurotoxic levels of circulating ammonia and urea cycle byproducts that may cause severe metabolic encephalopathy, death or irreversible brain damage. Standard of care (SOC) of CTLN1 consists of daily nitrogen-scavenger administration, but patients remain at risk of life-threatening decompensations. We evaluated the therapeutic efficacy of a recombinant adeno-associated viral vector carrying the ASS1 gene under the control of a liver-specific promoter (VTX-804). When administered to three-week-old CTLN1 mice, all the animals receiving VTX-804 in combination with SOC gained body weight normally, presented with a normalization of ammonia and reduction of citrulline levels in circulation, and 100% survived for 7 months. Similar to what has been observed in CTLN1 patients, CTLN1 mice showed several behavioral abnormalities such as anxiety, reduced welfare and impairment of innate behavior. Importantly, all clinical alterations were notably improved after treatment with VTX-804. This study demonstrates the potential of VTX-804 gene therapy for future clinical translation to CTLN1 patients.
Coordination of the AMPK, Akt, mTOR, and p53 Pathways under Glucose Starvation
Authors: Zhou Yifan , Liu Feng
Published: November 2022

Glucose is a direct energy source for eukaryotic cells, and its deficiency elicits complex stress responses and diverse cellular outcomes. Although several signaling pathways involved have been identified, how they coordinately dictate the cell fate remains obscure. We propose a minimal network model for the cellular response to glucose restriction, characterizing the glucose uptake and signaling of the AMPK, Akt, mTOR, and p53 pathways. We demonstrate that in the presence of sufficient growth factors and amino acids, cells may undergo proliferation, senescence, or apoptosis, depending on the extracellular glucose level. AMPK is first activated upon glucose limitation, activating p53 to induce cell-cycle arrest; possibly, cells resume proliferation after timely glucose restoration. For long-term energy stress, cell senescence is maintained by low/intermediate levels of p53 and persistent activation of mTOR and Akt, or cells commit apoptosis when the proteins undergo biphasic dynamics, e.g., p53 switches from intermediate levels to high levels while mTOR and Akt become inactivated in the later phase. The biphasic dynamics of p53 are associated with flipping of two bistable switches. Appropriate mTOR levels are required for optimal cell-fate decision. This work suggests that senescence and apoptosis occur sequentially in glucose-depleted cells, and a theoretical framework is provided for exploring the cellular response to energy stress.
Nitric Oxide in Seed Biology
Authors: Ciacka Katarzyna , Staszek Pawel , Sobczynska Katarzyna , Krasuska Urszula , Gniazdowska Agnieszka
Published: November 2022

Nitric oxide (NO) has been recognized as a gasotransmitter in the mainstream of plant research since the beginning of the 21st century. It is produced in plant tissue and the environment. It influences plant physiology during every ontogenetic stage from seed germination to plant senescence. In this review, we demonstrate the increased interest in NO as a regulatory molecule in combination with other signalling molecules and phytohormones in the information network of plant cells. This work is a summary of the current knowledge on NO action in seeds, starting from seed pretreatment techniques applied to increase seed quality. We describe mode of action of NO in the regulation of seed dormancy, germination, and aging. During each stage of seed physiology, NO appears to act as a key agent with a predominantly beneficial effect.
New Perspectives on the Sustainable Employment of Chestnut Shells as Active Ingredient against Oral Mucositis: A First Screening
Authors: Ferreira Ana Sofia , Silva Ana Margarida , Pinto Diana , Moreira Manuela M. , Ferraz Ricardo , Švarc-Gajić Jaroslava , Costa Paulo C. , Delerue-Matos Cristina , Rodrigues Francisca
Published: November 2022

Oral mucositis (OM), a common side effect of oncological treatment, is an oral mucosal disorder characterized by painful ulcerations and increased risk of infection. The use of natural antioxidants to suppress the redox imbalance responsible for the OM condition has emerged as an interesting approach to prevent/treat OM. This study aims to explore the chestnut (Castana sativa) shells as potential active ingredient against OM. Therefore, chestnut shells were extracted at different temperatures (110–180 °C) by Subcritical Water Extraction (SWE), aiming to recover antioxidants. The extracts were also evaluated against microorganisms present in the oral cavity as well as on human oral cell lines (TR146 and HSC3). The highest phenolic content was obtained with the extraction temperature of 110 °C, exhibiting the best antioxidant/antiradical activities and scavenging efficiencies against HOCl (IC50 = 4.47 μg/mL) and ROO• (0.73 μmol TE/mg DW). High concentrations of phenolic acids (e.g., gallic and protocatechuic acids) and flavanoids (catechin, epicatechin and rutin) characterized the phenolic profile. The antimicrobial activity against several oral microorganisms present in the oral cavity during OM, such as Streptococcus, Staphylococcus, Enterococcus, and Escherichia, was demonstrated. Finally, the effects on HSC3 and TR146 cell lines revealed that the extract prepared at 110 °C had the lowest IC50 (1325.03 and 468.15 µg/mL, respectively). This study highlights the potential effects of chestnut shells on OM.
Evidence for Multilevel Chemopreventive Activities of Natural Phenols from Functional Genomic Studies of Curcumin, Resveratrol, Genistein, Quercetin, and Luteolin
Authors: Huminiecki Lukasz
Published: November 2022

Herein, I present an updated and contextualized literature review of functional genomic studies of natural phenols in the context of cancer. I suggest multilevel chemopreventive and anticancer mechanisms of action, which are shared by multiple dietary natural phenols. Specifically, I cite evidence that curcumin and resveratrol have multilevel anti-cancer effects through: (1) inducing either p53-dependent or p53-independent apoptosis in cancer cell lines, (2) acting as potent regulators of expression of oncogenic and anti-oncogenic microRNAs, and (3) inducing complex epigenetic changes that can switch off oncogenes/switch on anti-oncogenes. There is no simple reductionist explanation for anti-cancer effects of curcumin and resveratrol. More generally, multilevel models of chemoprevention are suggested for related natural phenols and flavonoids such as genistein, quercetin, or luteolin.
TRPV3 and Itch: The Role of TRPV3 in Chronic Pruritus according to Clinical and Experimental Evidence
Authors: Um Ji Young , Kim Han Bi , Kim Jin Cheol , Park Jin Seo , Lee So Yeon , Chung Bo Young , Park Chun Wook , Kim Hye One
Published: November 2022

Itching is a sensory phenomenon characterized by an unpleasant sensation that makes you want to scratch the skin, and chronic itching diminishes the quality of life. In recent studies, multiple transient receptor potential (TRP) channels present in keratinocytes or nerve endings have been shown to engage in the propagation of itch signals in chronic dermatological or pruritic conditions, such as atopic dermatitis (AD) and psoriasis (PS). TRPV3, a member of the TRP family, is highly expressed in the epidermal keratinocytes. Normal TRPV3 signaling is essential for maintaining epidermal barrier homeostasis. In recent decades, many studies have suggested that TRPV3 contributes to detecting pruritus signals. Gain-of-function mutations in TRPV3 in mice and humans are characterized by severe itching, hyperkeratosis, and elevated total IgE levels. These studies suggest that TRPV3 is an important channel for skin itching. Preclinical studies have provided evidence to support the development of TRPV3 antagonists for treating inflammatory skin conditions, itchiness, and pain. This review explores the role of TRPV3 in chronic pruritus, collating clinical and experimental evidence. We also discuss underlying cellular and molecular mechanisms and explore the potential of TRPV3 antagonists as therapeutic agents.
Therapeutic Effects of Acer palmatum Thumb. Leaf Extract (KIOM-2015E) on Benzalkonium Chloride-Induced Dry Eye in a Mouse Model
Authors: Yim Nam-Hui , Park Eunhee , Cho Won-Kyung , Kim Yeoun-Hee , Ma Jin Yeul
Published: November 2022

We determined the effects of two extracts from Acer palmatum Thumb. leaves (hot water extract KIOM-2015EW and 25% ethanol extract KIOM-2015EE) in a benzalkonium chloride (BAC)-induced dry eye mouse model. Dry eye was induced by 0.2% BAC for 2 weeks, followed by treatment three times (eye drop) or once (oral administration) daily with KIOM-2015E for 2 weeks. Treatment with both KIOM-2015EE and KIOM-2015EW resulted in a marked increase in tear volume production for the 4 days of treatment. The Lissamine Green staining score, TUNEL-positive cells, and inflammatory index were significantly decreased after 2 weeks. Topical KIOM-2015EE administration exhibited a greater improvement in decreasing the ocular surface staining scores, inflammation, dead cells, and increasing tear production in a dose-dependent manner compared with the other groups. Furthermore, KIOM-2015E significantly reduced the phosphorylation of NF-κB, which was activated in the BAC-treated cornea. Topical administration was much more effective than oral administration for KIOM-2015E and KIOM-2015EE was more effective than KIOM-2015EW. Application of KIOM-2015E resulted in clinical improvement, inhibited the inflammatory response, and alleviated signs of dry eye. These results indicate that KIOM-2015E has potential as a therapeutic agent for the clinical treatment of dry eye.
Identifying the Active Sites of Heteroatom Graphene as a Conductive Membrane for the Electrochemical Filtration of Organic Contaminants
Authors: Pan Meilan , Li Junjian , Pan Bingjun
Published: November 2022

The dopants of sulfur, nitrogen, or both, serving as the active sites, into the graphitic framework of graphene is an efficient strategy to improve the electrochemical performance of electrochemical membrane filtration. However, the covalent bonds between the doped atoms and the substrate that form different functional groups have a significant role in the specific activity for pollutant degradation. Herein, we found that the singly doped heteroatom graphene (NG and SG) achieved superior removal efficiency of pollutants as compared with that of the double doped heteroatom graphene (SNG). Mechanism studies showed that the doped N of NG presented as graphitic N and substantially increased electron transfer, whereas the doped S of SG posed as -C-SOx-C- provided more adsorption sites to improve electrochemical performance. However, in the case of SNG, the co-doped S and N cannot form the efficient graphitic N and -C-SOx-C- for electrochemical degradation, resulting in a low degradation efficiency. Through the fundamental insights into the bonding of the doped heteroatom on graphene, this work furnishes further directives for the design of desirable heteroatom graphene for membrane filtration.
Thermophilic Nucleic Acid Polymerases and Their Application in Xenobiology
Authors: Wang Guangyuan , Du Yuhui , Ma Xingyun , Ye Fangkai , Qin Yanjia , Wang Yangming , Xiang Yuming , Tao Rui , Chen Tingjian
Published: November 2022

Thermophilic nucleic acid polymerases, isolated from organisms that thrive in extremely hot environments, possess great DNA/RNA synthesis activities under high temperatures. These enzymes play indispensable roles in central life activities involved in DNA replication and repair, as well as RNA transcription, and have already been widely used in bioengineering, biotechnology, and biomedicine. Xeno nucleic acids (XNAs), which are analogs of DNA/RNA with unnatural moieties, have been developed as new carriers of genetic information in the past decades, which contributed to the fast development of a field called xenobiology. The broad application of these XNA molecules in the production of novel drugs, materials, and catalysts greatly relies on the capability of enzymatic synthesis, reverse transcription, and amplification of them, which have been partially achieved with natural or artificially tailored thermophilic nucleic acid polymerases. In this review, we first systematically summarize representative thermophilic and hyperthermophilic polymerases that have been extensively studied and utilized, followed by the introduction of methods and approaches in the engineering of these polymerases for the efficient synthesis, reverse transcription, and amplification of XNAs. The application of XNAs facilitated by these polymerases and their mutants is then discussed. In the end, a perspective for the future direction of further development and application of unnatural nucleic acid polymerases is provided.
Multi-Faceted Roles of DNAJB Protein in Cancer Metastasis and Clinical Implications
Authors: Kim Hye-Youn , Hong Suntaek
Published: November 2022

Heat shock proteins (HSPs) are highly conserved molecular chaperones with diverse cellular activities, including protein folding, assembly or disassembly of protein complexes, and maturation process under diverse stress conditions. HSPs also play essential roles in tumorigenesis, metastasis, and therapeutic resistance across cancers. Among them, HSP40s are widely accepted as regulators of HSP70/HSP90 chaperones and an accumulating number of biological functions as molecular chaperones dependent or independent of either of these chaperones. Despite large numbers of HSP40s, little is known about their physiologic roles, specifically in cancer progression. This article summarizes the multi-faceted role of DNAJB proteins as one subclass of the HSP40 family in cancer development and metastasis. Regulation and deregulation of DNAJB proteins at transcriptional, post-transcriptional, and post-translational levels contribute to tumor progression, particularly cancer metastasis. Furthermore, understanding differences in function and regulating mechanism between DNAJB proteins offers a new perspective on tumorigenesis and metastasis to improve therapeutic opportunities for malignant diseases.
Genetic Spectrum of Familial Hypercholesterolaemia in the Malaysian Community: Identification of Pathogenic Gene Variants Using Targeted Next-Generation Sequencing
Authors: Razman Aimi Zafira , Chua Yung-An , Mohd Kasim Noor Alicezah , Al-Khateeb Alyaa , Sheikh Abdul Kadir Siti Hamimah , Jusoh Siti Azma , Nawawi Hapizah
Published: November 2022

Familial hypercholesterolaemia (FH) is caused by mutations in lipid metabolism genes, predominantly in low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin-type 9 (PCSK9) and LDL receptor adaptor protein 1 (LDLRAP1). The prevalence of genetically confirmed FH and the detection rate of pathogenic variants (PV) amongst clinically diagnosed patients is not well established. Targeted next-generation sequencing of LDLR, APOB, PCSK9 and LDLRAP1 was performed on 372 clinically diagnosed Malaysian FH subjects. Out of 361 variants identified, 40 of them were PV (18 = LDLR, 15 = APOB, 5 = PCSK9 and 2 = LDLRAP1). The majority of the PV were LDLR and APOB, where the frequency of both PV were almost similar. About 39% of clinically diagnosed FH have PV in PCSK9 alone and two novel variants of PCSK9 were identified in this study, which have not been described in Malaysia and globally. The prevalence of genetically confirmed potential FH in the community was 1:427, with a detection rate of PV at 0.2% (12/5130). About one-fourth of clinically diagnosed FH in the Malaysian community can be genetically confirmed. The detection rate of genetic confirmation is similar between potential and possible FH groups, suggesting a need for genetic confirmation in index cases from both groups. Clinical and genetic confirmation of FH index cases in the community may enhance the early detection of affected family members through family cascade screening.
Robust Supramolecular Dimers Derived from Benzylic-Substituted 1,2,4-Selenodiazolium Salts Featuring Selenium⋯π Chalcogen Bonding
Authors: Sapronov Alexander A. , Artemjev Alexey A. , Burkin Gleb M. , Khrustalev Victor N. , Kubasov Alexey S. , Nenajdenko Valentine G. , Gomila Rosa M. , Frontera Antonio , Kritchenkov Andreii S. , Tskhovrebov Alexander G.
Published: November 2022

The series of benzylic-substituted 1,2,4-selenodiazolium salts were prepared via cyclization reaction between 2-pyridylselenyl chlorides and nitriles and fully characterized. Substitution of the Cl anion by weakly binding anions promoted the formation supramolecular dimers featuring four center Se2N2 chalcogen bonding and two antiparallel selenium⋯π interactions. Chalcogen bonding interactions were studied using density functional theory calculations, molecular electrostatic potential (MEP) surfaces, the quantum theory of atoms-in-molecules (QTAIM), and the noncovalent interaction (NCI) plot. The investigations revealed fundamental role of the selenium⋯π contacts that are stronger than the Se⋯N interactions in supramolecular dimers. Importantly, described herein, the benzylic substitution approach can be utilized for reliable supramolecular dimerization of selenodiazolium cations in the solid state, which can be employed in supramolecular engineering.
Synthetic Melanin Acts as Efficient Peptide Carrier in Cancer Vaccine Strategy
Authors: Cuzzubbo Stefania , Roch Benoit , Darrasse-Jèze Guillaume , Hosten Benoit , Leclercq Manon , Vignal Nicolas , Banissi Claire , Tartour Eric , Carpentier Antoine F.
Published: November 2022

We previously reported that a novel peptide vaccine platform, based on synthetic melanin nanoaggregates, triggers strong cytotoxic immune responses and significantly suppresses tumor growth in mice. However, the mechanisms underlying such an efficacy remained poorly described. Herein, we investigated the role of dendritic cells (DCs) in presenting the antigen embedded in the vaccine formulation, as well as the potential stimulatory effect of melanin upon these cells, in vitro by coculture experiments and ELISA/flow cytometry analysis. The vaccine efficiency was evaluated in FLT3-L−/− mice constitutively deficient in DC1, DC2, and pDCs, in Zbtb46DTR chimera mice deficient in DC1 and DC2, and in LangerinDTR mice deficient in dermal DC1 and Langerhans cells. We concluded that DCs, and especially migratory conventional type 1 dendritic cells, seem crucial for mounting the immune response after melanin-based vaccination. We also assessed the protective effect of L-DOPA melanin on peptides from enzymatic digestion, as well as the biodistribution of melanin–peptide nanoaggregates, after subcutaneous injection using [18F]MEL050 PET imaging in mice. L-DOPA melanin proved to act as an efficient carrier for peptides by fully protecting them from enzymatic degradation. L-DOPA melanin did not display any direct stimulatory effects on dendritic cells in vitro. Using PET imaging, we detected melanin–peptide nanoaggregates up to three weeks after subcutaneous injections within the secondary lymphoid tissues, which could explain the sustained immune response observed (up to 4 months) with this vaccine technology.
Monodisperse Porous Silica/Polymer Nanocomposite Microspheres with Tunable Silica Loading, Morphology and Porosity
Authors: Steinbach Julia C. , Fait Fabio , Mayer Hermann A. , Kandelbauer Andreas
Published: November 2022

Hybrid organic/inorganic nanocomposites combine the distinct properties of the organic polymer and the inorganic filler, resulting in overall improved system properties. Monodisperse porous hybrid beads consisting of tetraethylene pentamine functionalized poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) particles and silica nanoparticles (SNPs) were synthesized under Stoeber sol-gel process conditions. A wide range of hybrid organic/silica nanocomposite materials with different material properties was generated. The effects of n(H2O)/n(TEOS) and c(NH3) on the hybrid bead properties particle size, SiO2 content, median pore size, specific surface area, pore volume and size of the SNPs were studied. Quantitative models with a high robustness and predictive power were established using a statistical and systematic approach based on response surface methodology. It was shown that the material properties depend in a complex way on the process factor settings and exhibit non-linear behaviors as well as partly synergistic interactions between the process factors. Thus, the silica content, median pore size, specific surface area, pore volume and size of the SNPs are non-linearly dependent on the water-to-precursor ratio. This is attributed to the effect of the water-to-precursor ratio on the hydrolysis and condensation rates of TEOS. A possible mechanism of SNP incorporation into the porous polymer network is discussed.
Multi-Omics Immune Interaction Networks in Lung Cancer Tumorigenesis, Proliferation, and Survival
Authors: Ye Qing , Hickey Justin , Summers Kathleen , Falatovich Brianne , Gencheva Marieta , Eubank Timothy D. , Ivanov Alexey V. , Guo Nancy Lan
Published: November 2022

There are currently no effective biomarkers for prognosis and optimal treatment selection to improve non-small cell lung cancer (NSCLC) survival outcomes. This study further validated a seven-gene panel for diagnosis and prognosis of NSCLC using RNA sequencing and proteomic profiles of patient tumors. Within the seven-gene panel, ZNF71 expression combined with dendritic cell activities defined NSCLC patient subgroups (n = 966) with distinct survival outcomes (p = 0.04, Kaplan–Meier analysis). ZNF71 expression was significantly associated with the activities of natural killer cells (p = 0.014) and natural killer T cells (p = 0.003) in NSCLC patient tumors (n = 1016) using Chi-squared tests. Overexpression of ZNF71 resulted in decreased expression of multiple components of the intracellular intrinsic and innate immune systems, including dsRNA and dsDNA sensors. Multi-omics networks of ZNF71 and the intracellular intrinsic and innate immune systems were computed as relevant to NSCLC tumorigenesis, proliferation, and survival using patient clinical information and in-vitro CRISPR-Cas9/RNAi screening data. From these networks, pan-sensitive and pan-resistant genes to 21 NCCN-recommended drugs for treating NSCLC were selected. Based on the gene associations with patient survival and in-vitro CRISPR-Cas9, RNAi, and drug screening data, MEK1/2 inhibitors PD-198306 and U-0126, VEGFR inhibitor ZM-306416, and IGF-1R inhibitor PQ-401 were discovered as potential targeted therapy that may also induce an immune response for treating NSCLC.
The Role of Adipokines in Inflammatory Mechanisms of Obesity
Authors: Kirichenko Tatiana V. , Markina Yuliya V. , Bogatyreva Anastasia I. , Tolstik Taisiya V. , Varaeva Yurgita R. , Starodubova Antonina V.
Published: November 2022

Adipokines are currently widely studied cellular signaling proteins produced by adipose tissue and involved in various processes, including inflammation; energy and appetite modulation; lipid and glucose metabolism; insulin sensitivity; endothelial cell functioning; angiogenesis; the regulation of blood pressure; and hemostasis. The current review attempted to highlight the key functions of adipokines in the inflammatory mechanisms of obesity, its complications, and its associated diseases. An extensive search for materials on the role of adipokines in the pathogenesis of obesity was conducted online using the PubMed and Scopus databases until October 2022.
Barrier Membranes for Guided Bone Regeneration (GBR): A Focus on Recent Advances in Collagen Membranes
Authors: Ren Yanru , Fan Lu , Alkildani Said , Liu Luo , Emmert Steffen , Najman Stevo , Rimashevskiy Denis , Schnettler Reinhard , Jung Ole , Xiong Xin , Barbeck Mike
Published: November 2022

Guided bone regeneration (GBR) has become a clinically standard modality for the treatment of localized jawbone defects. Barrier membranes play an important role in this process by preventing soft tissue invasion outgoing from the mucosa and creating an underlying space to support bone growth. Different membrane types provide different biological mechanisms due to their different origins, preparation methods and structures. Among them, collagen membranes have attracted great interest due to their excellent biological properties and desired bone regeneration results to non-absorbable membranes even without a second surgery for removal. This work provides a comparative summary of common barrier membranes used in GBR, focusing on recent advances in collagen membranes and their biological mechanisms. In conclusion, the review article highlights the biological and regenerative properties of currently available barrier membranes with a particular focus on bioresorbable collagen-based materials. In addition, the advantages and disadvantages of these biomaterials are highlighted, and possible improvements for future material developments are summarized.
Identification and Characterization of AP2/ERF Transcription Factors in Yellow Horn
Authors: Hu Fang , Zhang Yunxiang , Guo Jinping
Published: November 2022

The AP2/ERF gene family involves numerous plant processes, including growth, development, metabolism, and various plant stress responses. However, several studies have been conducted on the AP2/ERF gene family in yellow horn, a new type of oil woody crop and an essential oil crop in China. According to sequence alignment and phylogenetic analyses, one hundred and forty-five AP2/ERF genes were detected from the yellow horn genome. They were divided into four relatively conserved subfamilies, including 21 AP2 genes, 119 ERBP genes, 4 RAV genes, and 1 Soloist gene. Gene analysis of XsAP2/ERF TFs showed 87 XsAP2/ERF TFs lacked introns. There were 75 pairs of collinearity relationships between X. sorbifolium and Arabidopsis, indicating a close similarity. In addition, the expression patterns of XsAP2/ERF TFs under cold treatments confirmed that the XsAP2/ERF TFs play essential roles in abiotic stress response. The expression of eight XsAP2/ERF transcription factors was verified in different tissues and under various stress treatments using RT-qPCR. This study establishes a starting point for further research to explore the potential mechanisms of identifying candidate AP2/ERF TFs that could respond to the abiotic stress of yellow horn.
Transdermal Delivery of 2-PAM as a Tool to Increase the Effectiveness of Traditional Treatment of Organophosphate Poisoning
Authors: Vasileva Leysan , Gaynanova Gulnara , Zueva Irina , Lyubina Anna , Amerhanova Syumbelya , Buzyurova Daina , Babaev Vasily , Voloshina Alexandra , Petrov Konstantin , Zakharova Lucia
Published: November 2022

For the first time, the efficacy of post-exposure treatment of organophosphate (OP) poisoning was increased by transdermal delivery of acetylcholinesterase (AChE) reactivator pyridine-2-aldoxime methochloride (2-PAM) as a preventive countermeasure. By selecting the optimal ratio of components, classical transfersomes (based on soybean phosphatidylcholine and Tween 20) and modified transfersomes (based on soybean phosphatidylcholine, Tween 20 and pyrrolidinium cationic surfactants with different hydrocarbon tail lengths) were obtained for 2-PAM encapsulation. Transfersomes modified with tetradecylpyrrolidinium bromide showed the best results in encapsulation efficiency and sustained release of 2-PAM from vesicles. Using Franz cells, it was found that the incorporation of surfactants into PC liposomes results in a more prolonged release of 2-PAM through the rat skin. Transfersomes containing 2-PAM, after exhaustive physical and chemical characterization, were embedded in a gel based on Carbopol® 940. A significantly high degree of erythrocyte AChE reactivation (23 ± 7%) was shown for 2-PAM in unmodified transfersomes in vivo. Preliminary transdermal administration of 2-PAM 24 h before emergency post-exposure treatment of OP poisoning leads to an increase in the survival rate of rats from 55% to 90%.
Neuroinflammation and Autophagy in Parkinson’s Disease—Novel Perspectives
Authors: Minchev Danail , Kazakova Maria , Sarafian Victoria
Published: November 2022

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. It is characterized by the accumulation of α-Synuclein aggregates and the degeneration of dopaminergic neurons in substantia nigra in the midbrain. Although the exact mechanisms of neuronal degeneration in PD remain largely elusive, various pathogenic factors, such as α-Synuclein cytotoxicity, mitochondrial dysfunction, oxidative stress, and pro-inflammatory factors, may significantly impair normal neuronal function and promote apoptosis. In this context, neuroinflammation and autophagy have emerged as crucial processes in PD that contribute to neuronal loss and disease development. They are regulated in a complex interconnected manner involving most of the known PD-associated genes. This review summarizes evidence of the implication of neuroinflammation and autophagy in PD and delineates the role of inflammatory factors and autophagy-related proteins in this complex condition. It also illustrates the particular significance of plasma and serum immune markers in PD and their potential to provide a personalized approach to diagnosis and treatment.
Correction: Hung et al. Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells. Int. J. Mol. Sci. 2021, 22, 9262
Authors: Hung Huey-Shan , Chang Kai-Bo , Tang Cheng-Ming , Ku Tian-Ren , Kung Mei-Lang , Yu Alex Yang-Hao , Shen Chiung-Chyi , Yang Yi-Chin , Hsieh Hsien-Hsu , Hsu Shan-hui
Published: November 2022

The authors wish to make the following correction to this paper [...]
A Central Contribution of TG2 Activity to the Antiproliferative and Pro-Apoptotic Effects of Caffeic Acid in K562 Cells of Human Chronic Myeloid Leukemia
Authors: Feriotto Giordana , Tagliati Federico , Brunello Arianna , Beninati Simone , Tabolacci Claudio , Mischiati Carlo
Published: November 2022

Caffeic acid (CA) has shown antitumor activity in numerous solid and blood cancers. We have recently reported that CA is active in reducing proliferation and triggering apoptosis in both Imatinib-sensitive and resistant Chronic Myeloid Leukemia (CML) cells. Tissue transglutaminase type 2 (TG2) enzyme is involved in cell proliferation and apoptosis of numerous types of cancer. However, its activity has different effects depending on the type of tumor. This work investigated the possible involvement of TG2 activation in the triggering of CA-dependent anticancer effects on the K562 cell line, which was studied as a model of CML. CA-dependent changes in TG2 activity were compared with the effects on cell proliferation and apoptosis. The use of N-acetylcysteine (NAC), an antioxidant molecule, suggested that the antiproliferative effect of CA was due to the increase in reactive oxygen species (ROS). The use of a TG2 inhibitor showed that TG2 activity was responsible for the increase in ROS generated by CA and reduced both caspase activation and triggering of CA-dependent apoptosis. The knocking-down of TGM2 transcripts confirmed the crucial involvement of TG2 activation in CML cell death. In conclusion, the data reported, in addition to ascertaining the important role of TG2 activation in the antiproliferative and pro-apoptotic mechanism of CA allowed us to hypothesize a possible therapeutic utility of the molecules capable of triggering the activation pathways of TG2 in the treatment of CML.
Ultrasonic-Assisted Method for the Preparation of Carbon Nanotube-Graphene/Polydimethylsiloxane Composites with Integrated Thermal Conductivity, Electromagnetic Interference Shielding, and Mechanical Performances
Authors: Li Chenglin , Yang Zhenzhou , Zhang Xiaowen , Ru Yue , Gao Dali , Wu Daming , Sun Jingyao
Published: November 2022

Due to the rapid development of the miniaturization and portability of electronic devices, the demand for polymer composites with high thermal conductivity and mechanical flexibility has significantly increased. A carbon nanotube (CNT)-graphene (Gr)/polydimethylsiloxane (PDMS) composite with excellent thermal conductivity and mechanical flexibility is prepared by ultrasonic-assisted forced infiltration (UAFI). When the mass ratio of CNT and Gr reaches 3:1, the thermal conductivity of the CNT-Gr(3:1)/PDMS composite is 4.641 W/(m·K), which is 1619% higher than that of a pure PDMS matrix. In addition, the CNT-Gr(3:1)/PDMS composite also has excellent mechanical properties. The tensile strength and elongation at break of CNT-Gr(3:1)/PDMS composites are 3.29 MPa and 29.40%, respectively. The CNT-Gr/PDMS composite also shows good performance in terms of electromagnetic shielding and thermal stability. The PDMS composites have great potential in the thermal management of electronic devices.
CRISPR/Cas9-Mediated Editing of AGAMOUS-like Genes Results in a Late-Bolting Phenotype in Chinese Cabbage (Brassica rapa ssp. pekinensis)
Authors: Shin Yun-Hee , Lee Hyun-Min , Park Young-Doo
Published: November 2022

Due to the sudden change in temperature in spring, Chinese cabbage, a leafy vegetable cultivated for consumption, loses its commercial value due to the onset of bolting—the phenomenon of switching from vegetative to reproductive growth. In this study, we applied clustered regularly interspaced short palindromic repeats/(CRISPR)-associated system 9 (CRISPR/Cas9) technology to analyze AGAMOUS-like genes. We performed functional analysis of AGL19 and AGL24 genes related to bolting and flowering using CRISPR/Cas9-mediated Chinese cabbage transformation. Single-guide RNA (sgRNA) sequences were created with a low off-targeting probability to construct gene-editing vectors. Agrobacterium-mediated transformation was conducted, and tentative E0 AGL-edited lines were analyzed using molecular biotechnological methods. Two AGL19-edited lines with nucleotide sequence mutations in the target sequence of the AGL19 genes and four AGL24-edited lines with nucleotide sequence mutations in the target sequence of the AGL24 genes showed particularly late bolting compared to the inbred line ‘CT001.’ Generational progression using bud pollination obtained T-DNA-free E1 AGL-edited lines, which also showed late bolting. The loss of function of the AGL protein was caused by the occurrence of an indel mutation in the AGL19 and AGL24 genes, which results in an early stop codon. Furthermore, frameshift mutations led to structural changes and the introduction of an early stop codon in the AGL19 and AGL24 proteins. Our results indicate that CRISPR/Cas9-mediated editing of AGAMOUS-like genes results in a late-bolting phenotype and that CRISPR/Cas9 is a useful technology for analyzing gene function in Chinese cabbage (Brassica rapa ssp. pekinensis).
Bio-Pulsed Stimulation Effectively Improves the Production of Avian Mesenchymal Stem Cell-Derived Extracellular Vesicles That Enhance the Bioactivity of Skin Fibroblasts and Hair Follicle Cells
Authors: Shieh Ju-Sheng , Chin Yu-Tang , Chiu Hsien-Chung , Hsieh Ya-Yu , Cheng Hui-Rong , Gu Hai , Chang Fung-Wei
Published: November 2022

Mesenchymal stem cell (MSC)-derived extracellular vesicles (exosomes) possess regeneration, cell proliferation, wound healing, and anti-senescence capabilities. The functions of exosomes can be modified by preconditioning MSCs through treatment with bio-pulsed reagents (Polygonum multiflorum Thunb extract). However, the beneficial effects of bio-pulsed small extracellular vesicles (sEVs) on the skin or hair remain unknown. This study investigated the in vitro mechanistic basis through which bio-pulsed sEVs enhance the bioactivity of the skin fibroblasts and hair follicle cells. Avian-derived MSCs (AMSCs) were isolated, characterized, and bio-pulsed to produce AMSC-sEVs, which were isolated, lyophilized, characterized, and analyzed. The effects of bio-pulsed AMSC-sEVs on cell proliferation, wound healing, and gene expression associated with skin and hair bioactivity were examined using human skin fibroblasts (HSFs) and follicle dermal papilla cells (HFDPCs). Bio-pulsed treatment significantly enhanced sEVs production by possibly upregulating RAB27A expression in AMSCs. Bio-pulsed AMSC-sEVs contained more exosomal proteins and RNAs than the control. Bio-pulsed AMSC-sEVs significantly augmented cell proliferation, wound healing, and gene expression in HSFs and HFDPCs. The present study investigated the role of bio-pulsed AMSC-sEVs in the bioactivity of the skin fibroblasts and hair follicle cells as mediators to offer potential health benefits for skin and hair.
Crosstalk between microRNA and Oxidative Stress in Heart Failure: A Systematic Review
Authors: Klimczak-Tomaniak Dominika , Haponiuk-Skwarlińska Julia , Kuch Marek , Pączek Leszek
Published: November 2022

Heart failure is defined as a clinical syndrome consisting of key symptoms and is due to a structural and/or functional alteration of the heart that results in increased intracardiac pressures and/or inadequate cardiac output at rest and/or during exercise. One of the key mechanisms determining myocardial dysfunction in heart failure is oxidative stress. MicroRNAs (miRNAs, miRs) are short, endogenous, conserved, single-stranded non-coding RNAs of around 21–25 nucleotides in length that act as regulators of multiple processes. A systematic review following the PRISMA guidelines was performed on the evidence on the interplay between microRNA and oxidative stress in heart failure. A search of Pubmed, Embase, Scopus, and Scopus direct databases using the following search terms: ‘heart failure’ AND ‘oxidative stress’ AND ‘microRNA’ or ‘heart failure’ AND ‘oxidative stress’ AND ‘miRNA’ was conducted and resulted in 464 articles. Out of them, 15 full text articles were eligible for inclusion in the qualitative analysis. Multiple microRNAs are involved in the processes associated with oxidative stress leading to heart failure development including mitochondrial integrity and function, antioxidant defense, iron overload, ferroptosis, and survival pathways.
Assessing How Residual Errors of Scoring Functions Correlate to Ligand Structural Features
Authors: Shulga Dmitry A. , Shaimardanov Arslan R. , Ivanov Nikita N. , Palyulin Vladimir A.
Published: November 2022

Scoring functions (SFs) are ubiquitous tools for early stage drug discovery. However, their accuracy currently remains quite moderate. Despite a number of successful target-specific SFs appearing recently, up until now, no ideas on how to systematically improve the general scope of SFs have been formulated. In this work, we hypothesized that the specific features of ligands, corresponding to interactions well appreciated by medicinal chemists (e.g., hydrogen bonds, hydrophobic and aromatic interactions), might be responsible, in part, for the remaining SF errors. The latter provides direction to efforts aimed at the rational and systematic improvement of SF accuracy. In this proof-of-concept work, we took a CASF-2016 coreset of 285 ligands as a basis for comparison and calculated the values of scores for a representative panel of SFs (including AutoDock 4.2, AutoDock Vina, X-Score, NNScore2.0, ΔVina RF20, and DSX). The residual error of linear correlation of each SF value, with the experimental values of affinity and activity, was then analyzed in terms of its correlation with the presence of the fragments responsible for certain medicinal chemistry defined interactions. We showed that, despite the fact that SFs generally perform reasonably, there is room for improvement in terms of better parameterization of interactions involving certain fragments in ligands. Thus, this approach opens a potential way for the systematic improvement of SFs without their significant complication. However, the straightforward application of the proposed approach is limited by the scarcity of reliable available data for ligand–receptor complexes, which is a common problem in the field.
Cell Wall Matrix Polysaccharides Contribute to Salt–Alkali Tolerance in Rice
Authors: Liu Zhijian , Hu Yongzhi , Du Anping , Yu Lan , Fu Xingyue , Wu Cuili , Lu Longxiang , Liu Yangxuan , Wang Songhu , Huang Weizao , Tu Shengbin , Ma Xinrong , Li Hui
Published: November 2022

Salt–alkali stress threatens the resilience to variable environments and thus the grain yield of rice. However, how rice responds to salt–alkali stress at the molecular level is poorly understood. Here, we report isolation of a novel salt–alkali-tolerant rice (SATR) by screening more than 700 germplasm accessions. Using 93-11, a widely grown cultivar, as a control, we characterized SATR in response to strong salt–alkali stress (SSAS). SATR exhibited SSAS tolerance higher than 93-11, as indicated by a higher survival rate, associated with higher peroxidase activity and total soluble sugar content but lower malonaldehyde accumulation. A transcriptome study showed that cell wall biogenesis-related pathways were most significantly enriched in SATR relative to 93-11 upon SSAS. Furthermore, higher induction of gene expression in the cell wall matrix polysaccharide biosynthesis pathway, coupled with higher accumulations of hemicellulose and pectin as well as measurable physio-biochemical adaptive responses, may explain the strong SSAS tolerance in SATR. We mapped SSAS tolerance to five genomic regions in which 35 genes were candidates potentially governing SSAS tolerance. The 1,4-β-D-xylan synthase gene OsCSLD4 in hemicellulose biosynthesis pathway was investigated in details. The OsCSLD4 function-disrupted mutant displayed reduced SSAS tolerance, biomass and grain yield, whereas the OsCSLD4 overexpression lines exhibited increased SSAS tolerance. Collectively, this study not only reveals the potential role of cell wall matrix polysaccharides in mediating SSAS tolerance, but also highlights applicable value of OsCSLD4 and the large-scale screening system in developing SSAS-tolerant rice.
Snapshot into the Type-2-Diabetes-Associated Microbiome of a Romanian Cohort
Authors: Gradisteanu Pircalabioru Gratiela , Chifiriuc Mariana-Carmen , Picu Ariana , Petcu Laura Madalina , Trandafir Maria , Savu Octavian
Published: November 2022

The prevalence of type 2 diabetes mellitus (T2D) is alarmingly increasing worldwide, urgently calling for a better understanding of the underlying mechanisms in order to step up prevention and improve therapeutic approaches. It is becoming evident that the gut microbiota seem to have an endless capacity to impact T2D. In this study, we profile the gut microbiome patterns in T2D patients from Romania, by using quantitative Real-Time PCR and next generation sequencing. We enrolled a total of 150 individuals (105 T2D patients, 50 of them without metformin treatment and 45 healthy volunteers). The levels of potentially beneficial butyrate-producing bacteria were significantly reduced, while potentially pathogenic microorganisms such as Enterobacteriaceae and Fusobacterium were enriched in T2D patients. We evaluated the correlation between clinical parameters and gut microbiota and identified the genera Bacteroides, Alistipes, Dialister, Bilophila and Sutterella as possible detrimental factors in T2D. Our findings suggest that the gut microbiota may be a potential target in novel approaches to halt the development of T2D-associated complications.
Camel (Camelus spp.) Urine Bioactivity and Metabolome: A Systematic Review of Knowledge Gaps, Advances, and Directions for Future Research
Authors: Iglesias Pastrana Carlos , Delgado Bermejo Juan Vicente , Sgobba Maria Noemi , Navas González Francisco Javier , Guerra Lorenzo , Pinto Diana C. G. A. , Gil Ana M. , Duarte Iola F. , Lentini Giovanni , Ciani Elena
Published: November 2022

Up to the present day, studies on the therapeutic properties of camel (Camelus spp.) urine and the detailed characterization of its metabolomic profile are scarce and often unrelated. Information on inter individual variability is noticeably limited, and there is a wide divergence across studies regarding the methods for sample storage, pre-processing, and extract derivatization for metabolomic analysis. Additionally, medium osmolarity is not experimentally adjusted prior to bioactivity assays. In this scenario, the methodological standardization and interdisciplinary approach of such processes will strengthen the interpretation, repeatability, and replicability of the empirical results on the compounds with bioactive properties present in camel urine. Furthermore, sample enlargement would also permit the evaluation of camel urine’s intra- and interindividual variability in terms of chemical composition, bioactive effects, and efficacy, while it may also permit researchers to discriminate potential animal-intrinsic and extrinsic conditioning factors. Altogether, the results would help to evaluate the role of camel urine as a natural source for the identification and extraction of specific novel bioactive substances that may deserve isolated chemical and pharmacognostic investigations through preclinical tests to determine their biological activity and the suitability of their safety profile for their potential inclusion in therapeutic formulas for improving human and animal health.