Current Issues in Molecular Biology

13 pages, 3742 KiB

Open AccessArticle

Parkin, as a Regulator, Participates in Arsenic Trioxide-Triggered Mitophagy in HeLa Cells

by Zhewen Zhang, Juan Yi, Bei Xie, Jing Chen, Xueyan Zhang, Li Wang, Jingyu Wang, Jinxia Hou and Hulai Wei

Curr. Issues Mol. Biol. 2022, 44(6), 2759-2771; https://doi.org/10.3390/cimb44060189 - 20 Jun 2022

Cited by 4 | Viewed by 2499 | Correction

Abstract

Parkin is a well-established synergistic mediator of mitophagy in dysfunctional mitochondria. Mitochondria are the main target of arsenic trioxide (ATO) cytotoxicity, and the effect of mitophagy on ATO action remains unclear. In this study, we used stable Parkin-expressing (YFP-Parkin) and Parkin loss-of-function mutant [...] Read more.

Parkin is a well-established synergistic mediator of mitophagy in dysfunctional mitochondria. Mitochondria are the main target of arsenic trioxide (ATO) cytotoxicity, and the effect of mitophagy on ATO action remains unclear. In this study, we used stable Parkin-expressing (YFP-Parkin) and Parkin loss-of-function mutant (Parkin C431S) HeLa cell models to ascertain whether Parkin-mediated mitophagy participates in ATO-induced apoptosis/cell death. Our data showed that the overexpression of Parkin significantly sensitized HeLa cells to ATO-initiated proliferation inhibition and apoptosis; however, the mutation of Parkin C431S significantly weakened this Parkin-mediated responsiveness. Our further investigation found that ATO significantly downregulated two fusion proteins (Mfn1/2) and upregulated fission-related protein (Drp1). Autophagy was also activated as evidenced by the formation of autophagic vacuoles and mitophagosomes, increased expression of PINK1, and recruitment of Parkin to impaired mitochondria followed by their degradation, accompanied by the increased transformation of LC3-I to LC3-II, increased expression of Beclin1 and decreased expression of P62 in YFP-Parkin HeLa cells. Enhanced mitochondrial fragmentation and autophagy indicated that mitophagy was activated. Furthermore, during the process of mitophagy, the overproduction of ROS implied that ROS might represent a key factor that initiates mitophagy following Parkin recruitment to mitochondria. In conclusion, our findings indicate that Parkin is critically involved in ATO-triggered mitophagy and functions as a potential antiproliferative target in cancer cells. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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14 pages, 1728 KiB

Open AccessArticle

Effect of Aqueous Extract of Phenolic Compounds Obtained from Red Wine in Experimental Model of Colitis in Mice

by Vanessa Mateus, João Estarreja, Inês Silva, Fernando Gonçalves, Edite Teixeira-Lemos and Rui Pinto

Curr. Issues Mol. Biol. 2022, 44(6), 2745-2758; https://doi.org/10.3390/cimb44060188 - 18 Jun 2022

Cited by 6 | Viewed by 2359

Abstract

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder represented by Crohn’s disease and ulcerative colitis. Currently, there is no cure and pharmacological treatment aims to induce and maintain remission on patients. Because the therapy reveals a relatively high toxicity, during [...] Read more.

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder represented by Crohn’s disease and ulcerative colitis. Currently, there is no cure and pharmacological treatment aims to induce and maintain remission on patients. Because the therapy reveals a relatively high toxicity, during a long-term utilization, it is essential to investigate new pharmacological approaches. Polyphenols, commonly present on red wine, have shown health-beneficial effects related to their antioxidant and anti-inflammatory effects through the inhibition of NF-kB activation, COX-2 and iNOS induction. In this sense, it would be interesting to study their effects in an IBD context. Therefore, this study aims to evaluate the effects of an aqueous extract of phenolic compounds in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced model of colitis. Method: Experimental colitis was induced in mice through an intrarectal administration of TNBS and then the mice were treated with an aqueous extract of phenolic compounds intraperitoneally for four days. Results and Discussion: The extract demonstrated an anti-inflammatory effect, reducing TNF-α levels in the colon, and had a beneficial effect on the extraintestinal manifestations related to IBD, without any significant side effects. The extract of phenolic compounds demonstrated to be a valuable object of study for the management of IBD in the future. Full article

(This article belongs to the Special Issue Polyphenols as Cellular Metabolic Regulators)

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15 pages, 1806 KiB

Open AccessArticle

Inflammatory Breast Cancer: The Cytokinome of Post-Mastectomy Wound Fluid Augments Proliferation, Invasion, and Stem Cell Markers

by Alshaimaa Tarek, Shrouk Khalaf El-Sayed, Wendy A. Woodward, Mohamed El-Shinawi, Jon Mark Hirshon and Mona Mostafa Mohamed

Curr. Issues Mol. Biol. 2022, 44(6), 2730-2744; https://doi.org/10.3390/cimb44060187 - 17 Jun 2022

Cited by 1 | Viewed by 2478

Abstract

Inflammatory breast cancer (IBC) is an aggressive phenotype with a high recurrence and low survival rate. Approximately 90% of local breast cancer recurrences occur adjacent to the same quadrant as the initial cancer, implying that tumor recurrence may be caused by residual cancer [...] Read more.

Inflammatory breast cancer (IBC) is an aggressive phenotype with a high recurrence and low survival rate. Approximately 90% of local breast cancer recurrences occur adjacent to the same quadrant as the initial cancer, implying that tumor recurrence may be caused by residual cancer cells and/or quiescent cancer stem cells (CSCs) in the tumor. We hypothesized that wound fluid (WF) collected after modified radical mastectomy (MRM) may activate cancer cells and CSCs, promoting epithelial mesenchymal transition (EMT) and invasion. Therefore, we characterized the cytokinome of WF drained from post-MRM cavities of non-IBC and IBC patients. The WF of IBC patients showed a significantly higher expression of various cytokines than in non-IBC patients. In vitro cell culture models of non-IBC and IBC cell lines were grown in media conditioned with and/without WF for 48 h. Afterwards, we assessed cell viability, the expression of CSCs and EMT-specific genes, and tumor invasion. Genes associated with CSCs properties and EMT markers were regulated in cells seeded in media conditioned by WF. IBC-WF exhibited a greater potential for inducing IBC cell invasion than non-IBC cells. The present study demonstrates the role of the post-surgical tumor cavity in IBC recurrence and metastasis. Full article

(This article belongs to the Special Issue Advances in Molecular Pathogenesis Regulation in Cancer)

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13 pages, 3100 KiB

Open AccessArticle

Expression, Purification, and Characterisation of South African Cassava Mosaic Virus Cell-to-Cell Movement Protein

by Nikita Nankoo, Ikechukwu Anthony Achilonu and Marie Emma Christine Rey

Curr. Issues Mol. Biol. 2022, 44(6), 2717-2729; https://doi.org/10.3390/cimb44060186 - 15 Jun 2022

Cited by 2 | Viewed by 2203

Abstract

South African cassava mosaic virus (SACMV) is a circular ssDNA bipartite begomovirus, whose genome comprises DNA-A (encodes six genes) and DNA-B (encodes BC1 cell-to-cell movement and BV1 nuclear shuttle proteins) components. A few secondary and tertiary structural and physicochemical characteristics of partial but [...] Read more.

South African cassava mosaic virus (SACMV) is a circular ssDNA bipartite begomovirus, whose genome comprises DNA-A (encodes six genes) and DNA-B (encodes BC1 cell-to-cell movement and BV1 nuclear shuttle proteins) components. A few secondary and tertiary structural and physicochemical characteristics of partial but not full-length begomovirus proteins have been elucidated to date. The full-length codon-optimised SACMV BC1 gene was cloned into a pET-28a (+) expression vector and transformed into expression host cells E. coli BL21 (DE3). The optimal expression of the full-length BC1-encoded movement protein (MP) was obtained via induction with 0.25 mM IPTG at an OD₆₀₀ of ~0.45 at 37 °C for four hours. Denatured protein fractions (dialysed in 4 M urea), passed through an IMAC column, successfully bound to the nickel resin, and eluted using 250 mM imidazole. The protein was refolded using stepwise dialysis. The molecular weight of MP was confirmed to be 35 kDa using SDS–PAGE. The secondary structure of SACMV MP presented as predominantly β-strands. An ANS (1-anilino-8-naphthalene sulphonate)-binding assay confirmed that MP possesses hydrophobic pockets with the ability to bind ligands such as ANS (8-anilino-1-naphthalenesulphonic acid). A 2′ (3′)-N-methylanthraniloyl-ATP (mant-ATP) assay showed binding of mant-ATP to MP and indicated that, while hydrophobic pockets are present, MP also exhibits hydrophilic regions. Intrinsic tryptophan fluorescence indicated a significant conformational change in the denatured form of BC1 in the presence of ATP. In addition, a phosphatase assay showed that MP possessed ATPase activity. Full article

(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)

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7 pages, 658 KiB

Open AccessBrief Report

Procoagulant Activity in Amniotic Fluid Is Associated with Fetal-Derived Extracellular Vesicles

by Kirill R. Butov, Natalia A. Karetnikova, Dmitry Y. Pershin, Dmitry Y. Trofimov and Mikhail A. Panteleev

Curr. Issues Mol. Biol. 2022, 44(6), 2710-2716; https://doi.org/10.3390/cimb44060185 - 13 Jun 2022

Cited by 1 | Viewed by 2074

Abstract

Procoagulant activity in amniotic fluid (AF) is positively correlated with phosphatidylserine (PS) and tissue factor (TF)-expressing(+) extracellular vesicles (EVs). However, it is unknown if pathological fetal conditions may affect the composition, phenotype, and procoagulant potency of EVs in AF. We sought to evaluate [...] Read more.

Procoagulant activity in amniotic fluid (AF) is positively correlated with phosphatidylserine (PS) and tissue factor (TF)-expressing(+) extracellular vesicles (EVs). However, it is unknown if pathological fetal conditions may affect the composition, phenotype, and procoagulant potency of EVs in AF. We sought to evaluate EV-dependent procoagulant activity in AF from pregnant people with fetuses with or without diagnosed chromosomal mutations. AF samples were collected by transabdominal amniocentesis and assessed for common karyotype defects (total n = 11, 7 healthy and 4 abnormal karyotypes). The procoagulant activity of AF was tested using a fibrin generation assay with normal pooled plasma and plasmas deficient in factors XII, XI, IX, X, V, and VII. EV number and phenotype were determined by flow cytometry with anti-CD24 and anti-TF antibodies. We report that factor-VII-, X-, or V-deficient plasmas did not form fibrin clots in the presence of AF. Clotting time was significantly attenuated in AF samples with chromosomal mutations. In addition, CD24+, TF+, and CD24+ TF+ EV counts were significantly lower in this group. Finally, we found a significant correlation between EV counts and the clotting time induced by AF. In conclusion, we show that AF samples with chromosomal mutations had fewer fetal-derived CD24-bearing and TF-bearing EVs, which resulted in diminished procoagulant potency. This suggests that fetal-derived EVs are the predominant source of procoagulant activity in AF. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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15 pages, 1223 KiB

Open AccessReview

Current and Future Perspectives of Cell-Free DNA in Liquid Biopsy

by Shicai Liu and Jinke Wang

Curr. Issues Mol. Biol. 2022, 44(6), 2695-2709; https://doi.org/10.3390/cimb44060184 - 10 Jun 2022

Cited by 15 | Viewed by 5191

Abstract

A liquid biopsy is a minimally invasive or non-invasive method to analyze a range of tumor material in blood or other body fluids, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), messenger RNA (mRNA), microRNA (miRNA), and exosomes, which is a very promising [...] Read more.

A liquid biopsy is a minimally invasive or non-invasive method to analyze a range of tumor material in blood or other body fluids, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), messenger RNA (mRNA), microRNA (miRNA), and exosomes, which is a very promising technology. Among these cancer biomarkers, plasma cfDNA is the most widely used in clinical practice. Compared with a tissue biopsy of traditional cancer diagnosis, in assessing tumor heterogeneity, a liquid biopsy is more reliable because all tumor sites release cfDNA into the blood. Therefore, a cfDNA liquid biopsy is less invasive and comprehensive. Moreover, the development of next-generation sequencing technology makes cfDNA sequencing more sensitive than a tissue biopsy, with higher clinical applicability and wider application. In this publication, we aim to review the latest perspectives of cfDNA liquid biopsy clinical significance and application in cancer diagnosis, treatment, and prognosis. We introduce the sequencing techniques and challenges of cfDNA detection, analysis, and clinical applications, and discuss future research directions. Full article

(This article belongs to the Special Issue Linking Genomic Changes with Cancer in the NGS Era)

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12 pages, 2505 KiB

Open AccessArticle

Hemin with Peroxidase Activity Can Inhibit the Oxidative Damage Induced by Ultraviolet A

by Wenli Hui, Zhipeng Yang, Ke Fang, Mengdi Wu, Wenhua Mu, Cong Zhao, Dan Xue, Tengteng Zhu, Xiao Li, Ming Gao, Yunhua Lu and Kunping Yan

Curr. Issues Mol. Biol. 2022, 44(6), 2683-2694; https://doi.org/10.3390/cimb44060183 - 10 Jun 2022

Cited by 2 | Viewed by 2209

Abstract

Excessive reactive oxygen species (ROS), a highly reactive substance that contains oxygen, induced by ultraviolet A (UVA) cause oxidative damage to skin. We confirmed that hemin can catalyze the reaction of tyrosine (Tyr) and hydrogen peroxide (H₂O₂). Catalysis was [...] Read more.

Excessive reactive oxygen species (ROS), a highly reactive substance that contains oxygen, induced by ultraviolet A (UVA) cause oxidative damage to skin. We confirmed that hemin can catalyze the reaction of tyrosine (Tyr) and hydrogen peroxide (H₂O₂). Catalysis was found to effectively reduce or eliminate oxidative damage to cells induced by H₂O₂ or UVA. The scavenging effects of hemin for other free-radical ROS were also evaluated through pyrogallol autoxidation, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·)-scavenging assays, and phenanthroline–Fe²⁺ assays. The results show that a mixture of hemin and tyrosine exhibits strong scavenging activities for H₂O₂, superoxide anion (O₂⁻·), DPPH·, and the hydroxyl radical (·OH). Furthermore, the inhibition of oxidative damage to human skin keratinocyte (HaCaT) cells induced by H₂O₂ or UVA was evaluated. The results show that catalysis can significantly reduce the ratio of cell apoptosis and death and inhibit the release of lactate dehydrogenase (LDH), as well as accumulation of malondialdehyde (MDA). Furthermore, the resistance to apoptosis was found to be enhanced. These results show that the mixture of hemin and tyrosine has a significantly protective effect against oxidative damage to HaCaT cells caused by UVA, suggesting it as a protective agent for combating UVA damage. Full article

(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)

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19 pages, 669 KiB

Open AccessReview

CRISPR/Cas9 Technique for Temperature, Drought, and Salinity Stress Responses

by Xiaohan Li, Siyan Xu, Martina Bianca Fuhrmann-Aoyagi, Shaoze Yuan, Takeru Iwama, Misaki Kobayashi and Kenji Miura

Curr. Issues Mol. Biol. 2022, 44(6), 2664-2682; https://doi.org/10.3390/cimb44060182 - 8 Jun 2022

Cited by 32 | Viewed by 7531

Abstract

Global warming and climate change have severely affected plant growth and food production. Therefore, minimizing these effects is required for sustainable crop yields. Understanding the molecular mechanisms in response to abiotic stresses and improving agricultural traits to make crops tolerant to abiotic stresses [...] Read more.

Global warming and climate change have severely affected plant growth and food production. Therefore, minimizing these effects is required for sustainable crop yields. Understanding the molecular mechanisms in response to abiotic stresses and improving agricultural traits to make crops tolerant to abiotic stresses have been going on unceasingly. To generate desirable varieties of crops, traditional and molecular breeding techniques have been tried, but both approaches are time-consuming. Clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) and transcription activator-like effector nucleases (TALENs) are genome-editing technologies that have recently attracted the attention of plant breeders for genetic modification. These technologies are powerful tools in the basic and applied sciences for understanding gene function, as well as in the field of crop breeding. In this review, we focus on the application of genome-editing systems in plants to understand gene function in response to abiotic stresses and to improve tolerance to abiotic stresses, such as temperature, drought, and salinity stresses. Full article

(This article belongs to the Special Issue Advanced Research in Plant Metabolomics)

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18 pages, 972 KiB

Open AccessReview

The Pathological Links between Adiposity and the Carpal Tunnel Syndrome

by Marina Ruxandra Otelea, Roxana Nartea, Florina Georgeta Popescu, Anatoli Covaleov, Brindusa Ilinca Mitoiu and Adriana Sarah Nica

Curr. Issues Mol. Biol. 2022, 44(6), 2646-2663; https://doi.org/10.3390/cimb44060181 - 8 Jun 2022

Cited by 11 | Viewed by 4143

Abstract

An association between obesity and carpal tunnel syndrome is found in many epidemiological studies. Therefore, there is a need to evaluate the physiopathological links that could explain the association between these two entities. Ectopic adipose tissue is responsible for metabolic syndrome and inflammation, [...] Read more.

An association between obesity and carpal tunnel syndrome is found in many epidemiological studies. Therefore, there is a need to evaluate the physiopathological links that could explain the association between these two entities. Ectopic adipose tissue is responsible for metabolic syndrome and inflammation, and is a major risk factor for diabetes and cardiovascular diseases. Taking these elements into consideration, we conducted an extensive literature revision of the subject, considering as ectopic fat-related mechanisms the following: (a) the direct compression and the association with the metabolic syndrome of the fat deposition around the wrist, (b) the insulin resistance, dyslipidemia, inflammatory, and oxidative mechanisms related to the central deposition of the fat, (c) the impaired muscle contraction and metabolism related to myosteatosis. Each section presents the cellular pathways which are modified by the ectopic deposition of the adipose tissue and the impact in the pathogeny of the carpal tunnel syndrome. In conclusion, the experimental and clinical data support the epidemiological findings. Efforts to reduce the obesity epidemics will improve not only cardio-metabolic health but will reduce the burden of the disability-free life expectancy due to the carpal tunnel syndrome. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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11 pages, 3967 KiB

Open AccessArticle

Apigetrin Abrogates Lipopolysaccharide-Induced Inflammation in L6 Skeletal Muscle Cells through NF-κB/MAPK Signaling Pathways

by Sang-Eun Ha, Pritam Bhagwan Bhosale, Hun-Hwan Kim, Min-Yeong Park, Abuyaseer Abusaliya, Gon-Sup Kim and Jin-A Kim

Curr. Issues Mol. Biol. 2022, 44(6), 2635-2645; https://doi.org/10.3390/cimb44060180 - 8 Jun 2022

Cited by 8 | Viewed by 2412

Abstract

Apigetrin is a glycosidic flavonoid derived from Teucrium gnaphalodes that has a wide range of biological activities, including antioxidant, anti-inflammatory, and anticancer. Inflammation is a kind of defense mechanism in the body. Flavonoids are natural phytochemicals that exert anti-inflammatory effects in numerous cells. [...] Read more.

Apigetrin is a glycosidic flavonoid derived from Teucrium gnaphalodes that has a wide range of biological activities, including antioxidant, anti-inflammatory, and anticancer. Inflammation is a kind of defense mechanism in the body. Flavonoids are natural phytochemicals that exert anti-inflammatory effects in numerous cells. In the present study, we investigated the anti-inflammatory effect of apigetrin and its underlying mechanism of activity in skeletal muscle cells (L6). The determination of cytotoxicity was performed by MTT assay. We treated L6 cells with apigetrin, and nontoxic concentrations were chosen to perform further experimentation. Apigetrin inhibited the expression of iNOS and COX-2 induced by LPS in a dose-dependent manner. iNOS and COX-2 are inflammatory markers responsible for enhancing the inflammatory response. Apigetrin also inhibited the LPS-induced phosphorylation of p65 and IκB-α. NF-κB signaling regulates the inflammatory process by mediating various proinflammatory genes. Similarly, the MAPK signaling pathway consists of ERK, JNK, and p38, which plays a critical role in the production of cytokines and downstream signaling events leading to inflammation. Apigetrin significantly downregulated the phosphorylation of JNK and p38, but did not affect the phosphorylation of ERK in the LPS-stimulated cells. These findings indicate the correlation between the anti-inflammatory activity of NF-κB and the MAPK signaling pathway. Thus, our overall finding suggests that apigetrin has anti-inflammatory effects and it can be considered for further drug design on L6 skeletal muscle cells. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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13 pages, 778 KiB

Open AccessReview

cAMP Signalling Pathway in Biocontrol Fungi

by Zhan-Bin Sun, Shu-Fan Yu, Chu-Lun Wang and Ling Wang

Curr. Issues Mol. Biol. 2022, 44(6), 2622-2634; https://doi.org/10.3390/cimb44060179 - 4 Jun 2022

Cited by 9 | Viewed by 3346

Abstract

Biocontrol is a complex process, in which a variety of physiological and biochemical characteristics are altered. The cAMP signalling pathway is an important signal transduction pathway in biocontrol fungi and consists of several key components. The G-protein system contains G-protein coupled receptors (GPCRs), [...] Read more.

Biocontrol is a complex process, in which a variety of physiological and biochemical characteristics are altered. The cAMP signalling pathway is an important signal transduction pathway in biocontrol fungi and consists of several key components. The G-protein system contains G-protein coupled receptors (GPCRs), heterotrimeric G-proteins, adenylate cyclase (AC), cAMP-dependent protein kinase (PKA), and downstream transcription factors (TFs). The cAMP signalling pathway can regulate fungal growth, development, differentiation, sporulation, morphology, secondary metabolite production, environmental stress tolerance, and the biocontrol of pathogens. However, few reviews of the cAMP signalling pathway in comprehensive biocontrol processes have been reported. This work reviews and discusses the functions and applications of genes encoding each component in the cAMP signalling pathway from biocontrol fungi, including the G-protein system components, AC, PKA, and TFs, in biocontrol behaviour. Finally, future suggestions are provided for constructing a complete cAMP signalling pathway in biocontrol fungi containing all the components and downstream effectors involved in biocontrol behavior. This review provides useful information for the understanding the biocontrol mechanism of biocontrol fungi by utilising the cAMP signalling pathway. Full article

(This article belongs to the Section Molecular Microbiology)

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8 pages, 1619 KiB

Open AccessArticle

The Annotation of Zebrafish Enhancer Trap Lines Generated with PB Transposon

by Wenzhu Jia, Zhongxia Guan, Shasha Shi, Kuilin Xiang, Peihong Chen, Fen Tan, Numan Ullah, Mohamed Diaby, Mengke Guo, Chengyi Song and Bo Gao

Curr. Issues Mol. Biol. 2022, 44(6), 2614-2621; https://doi.org/10.3390/cimb44060178 - 2 Jun 2022

Viewed by 1909

Abstract

An enhancer trap (ET) mediated by a transposon is an effective method for functional gene research. Here, an ET system based on a PB transposon that carries a mini Krt4 promoter (the keratin4 minimal promoter from zebrafish) and the green fluorescent protein gene [...] Read more.

An enhancer trap (ET) mediated by a transposon is an effective method for functional gene research. Here, an ET system based on a PB transposon that carries a mini Krt4 promoter (the keratin4 minimal promoter from zebrafish) and the green fluorescent protein gene (GFP) has been used to produce zebrafish ET lines. One enhancer trap line with eye-specific expression GFP named EYE was used to identify the trapped enhancers and genes. Firstly, GFP showed a temporal and spatial expression pattern with whole-embryo expression at 6, 12, and 24 hpf stages and eye-specific expression from 2 to 7 dpf. Then, the genome insertion sites were detected by splinkerette PCR (spPCR). The Krt4-GFP was inserted into the fourth intron of the gene itgav (integrin, alpha V) in chromosome 9 of the zebrafish genome, with the GFP direction the same as that of the itgav gene. By the alignment of homologous gene sequences in different species, three predicted endogenous enhancers were obtained. The trapped endogenous gene itgav, whose overexpression is related to hepatocellular carcinoma, showed a similar expression pattern as GFP detected by in situ hybridization, which suggested that GFP and itgav were possibly regulated by the same enhancers. In short, the zebrafish enhancer trap lines generated by the PB transposon-mediated enhancer trap technology in this study were valuable resources as visual markers to study the regulators and genes. This work provides an efficient method to identify and isolate tissue-specific enhancer sequences. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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21 pages, 5735 KiB

Open AccessArticle

Comparative Transcriptome Analysis of Softening and Ripening-Related Genes in Kiwifruit Cultivars Treated with Ethylene

by Han Ryul Choi, Min Woo Baek, Cheon Soon Jeong and Shimeles Tilahun

Curr. Issues Mol. Biol. 2022, 44(6), 2593-2613; https://doi.org/10.3390/cimb44060177 - 2 Jun 2022

Cited by 7 | Viewed by 2585

Abstract

This work presents the transcriptome analysis of green ‘Hayward’ (Actinidia deliciosa) and gold ‘Haegeum’ (Actinidia chinensis) kiwifruit cultivars after treatment with ethylene for three days at 25 °C. Illumina high-throughput sequencing platform was used to sequence total mRNAs and [...] Read more.

This work presents the transcriptome analysis of green ‘Hayward’ (Actinidia deliciosa) and gold ‘Haegeum’ (Actinidia chinensis) kiwifruit cultivars after treatment with ethylene for three days at 25 °C. Illumina high-throughput sequencing platform was used to sequence total mRNAs and the transcriptome gene set was constructed by de novo assembly. A total of 1287 and 1724 unigenes were differentially expressed during the comparison of ethylene treatment with control in green ‘Hayward’ and gold ‘Haegeum’, respectively. From the differentially expressed unigenes, 594 and 906 were upregulated, and 693 and 818 were downregulated in the green and gold kiwifruit cultivars, respectively, when treated with ethylene. We also identified a list of genes that were expressed commonly and exclusively in the green and gold kiwifruit cultivars treated with ethylene. Several genes were expressed differentially during the ripening of kiwifruits, and their cumulative effect brought about the softening- and ripening-related changes. This work also identified and categorized genes related to softening and other changes during ripening. Furthermore, the transcript levels of 12 selected representative genes from the differentially expressed genes (DEGs) identified in the transcriptome analysis were confirmed via quantitative real-time PCR (qRT-PCR) to validate the reliability of the expression profiles obtained from RNA-Seq. The data obtained from the present study will add to the information available on the molecular mechanisms of the effects of ethylene during the ripening of kiwifruits. This study will also provide resources for further studies of the genes related to ripening, helping kiwifruit breeders and postharvest technologists to improve ripening quality. Full article

(This article belongs to the Special Issue Genetic Sight: Plant Traits during Postharvest)

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10 pages, 9857 KiB

Open AccessArticle

A Study on the Safety and Effects of Amorpha fruticosa Fruit Extract on Spontaneously Hypertensive Rats with Induced Type 2 Diabetes

by Rumyana Simeonova, Aleksandar Shkondrov, Ekaterina Kozuharova, Iliana Ionkova and Ilina Krasteva

Curr. Issues Mol. Biol. 2022, 44(6), 2583-2592; https://doi.org/10.3390/cimb44060176 - 2 Jun 2022

Cited by 5 | Viewed by 2421

Abstract

Metabolic syndrome is characterized by a variety of diagnostic criteria: obesity, dyslipidemia, type 2 diabetes, and arterial hypertension. They contribute to the elevated risk of cardiovascular morbidity and mortality. The potential for Amorpha fruticosa L. (Fabaceae) to improve diabetes and metabolic disease is [...] Read more.

Metabolic syndrome is characterized by a variety of diagnostic criteria: obesity, dyslipidemia, type 2 diabetes, and arterial hypertension. They contribute to the elevated risk of cardiovascular morbidity and mortality. The potential for Amorpha fruticosa L. (Fabaceae) to improve diabetes and metabolic disease is promising, based on in vitro tests. This is why a further investigation of the species is needed. Additionally, a toxicity review in relation to safety revealed that to date, there are no published data regarding the toxicity of A. fruticosa towards humans. This species could provide abundant and cheap resources because it is an aggressive invasive plant that grows almost unrestrictedly. The objective of this study was to evaluate the acute toxicity of a purified extract of A. fruticosa (EAF), and to assess its antioxidant, antihypertensive, and antihyperglycemic activity in streptozotocin-induced diabetic spontaneously hypertensive rats (SHRs). The EAF was slightly toxic (LD₅₀ = 2121 mg/kg, b.w.) when administered orally, and moderately toxic (LD₅₀ = 316 mg/kg, b.w.) at intraperitoneal administration, both in mice. The oral administration of EAF (100 mg/kg) for 35 days to SHRs caused significant decreases in the systolic pressure, blood glucose levels, and MDA quantity. It also increased the hepatic level of the endogenous antioxidant GSH, not only in diabetic SHRs, but also in the control group. An additional potential benefit to human health might be conferred through the environmental management of A. fruticosa based on its large-scale use for medicinal purposes, as this aggressive invasive species brings problems to natural habitats in many European countries. Full article

(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)

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14 pages, 1421 KiB

Open AccessArticle

Molecular Determination of Vascular Endothelial Growth Factor, miRNA-423 Gene Abnormalities by Utilizing ARMS-PCR and Their Association with Fetal Hemoglobin Expression in the Patients with Sickle Cell Disease

by Abdullah Hamadi, Rashid Mir, Ali Mahzari, Abdulrahim Hakami, Reema Almotairi, Gasim Dobie, Fawaz Hamdi, Mohammed Hassan Nahari, Razan Alhefzi, Mohammed Alasseiri, Nora Y. Hakami, Hadeel Al Sadoun, Osama M. Al-Amer, Jameel Barnawi and Hassan A. Madkhali

Curr. Issues Mol. Biol. 2022, 44(6), 2569-2582; https://doi.org/10.3390/cimb44060175 - 1 Jun 2022

Cited by 1 | Viewed by 2839

Abstract

Recent studies have indicated that microRNA and VEGF are considered to be genetic modifiers and are associated with elevated levels of fetal haemoglobin HbF, and thus they reduce the clinical impact of sickle haemoglobin (HbS) patients. This cross-sectional study was performed on clinical [...] Read more.

Recent studies have indicated that microRNA and VEGF are considered to be genetic modifiers and are associated with elevated levels of fetal haemoglobin HbF, and thus they reduce the clinical impact of sickle haemoglobin (HbS) patients. This cross-sectional study was performed on clinical confirmed subjects of SCD cases. miR-423-rs6505162 C>T and VEGF-2578 C>A genotyping was conducted by ARMS-PCR in SCD and healthy controls. A strong clinical significance was reported while comparing the association of miR-423 C>T genotypes between SCD patients and controls (p = 0.031). The microRNA-423 AA genotype was associated with an increased severity of SCD in codominant model with odd ratio (OR = 2.36, 95% CI, (1.15–4.84), p = 0.018) and similarly a significant association was observed in recessive inheritance model for microRNA-423 AA vs (CC+CA) genotypes (OR = 2.19, 95% CI, (1.32–3.62), p < 0.002). The A allele was associated with SCD severity (OR = 1.57, 95% CI, (1.13–2.19), p < 0.007). The distribution of VEGF-2578 C>A genotypes between SCD patients and healthy controls was significant (p < 0.013). Our results indicated that in the codominant model, the VEGF-2578-CA genotype was strongly associated with increased SCD severity with OR = 2.56, 95% CI, (1.36–4.82), p < 0.003. The higher expression of HbA1 (65.9%), HbA2 (4.40%), was reported in SCD patients carrying miR-423-AA genotype than miR-423 CA genotype in SCD patients carrying miR-423 CA genotype HbA1 (59.98%), HbA2 (3.74%) whereas SCD patients carrying miR-423 CA genotype has higher expression of HbF (0.98%) and HbS (38.1%) than in the patients carrying AA genotype HbF (0.60%), HbS (36.1%). ARMS-PCR has been proven to be rapid, inexpensive and is highly applicable to gene mutation screening in laboratories and clinical practices. This research highlights the significance of elucidating genetic determinants that play roles in the amelioration of the HbF levels that is used as an indicator of severity of clinical complications of the monogenic disease. Further well-designed studies with larger sample sizes are necessary to confirm our findings. Full article

(This article belongs to the Section Molecular Medicine)

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15 pages, 3588 KiB

Open AccessArticle

Construction and Characterization of T7 Bacteriophages Harboring Apidaecin-Derived Sequences

by Tobias Ludwig, Ralf Hoffmann and Andor Krizsan

Curr. Issues Mol. Biol. 2022, 44(6), 2554-2568; https://doi.org/10.3390/cimb44060174 - 1 Jun 2022

Viewed by 3094

Abstract

The global spread of multi- and pan-resistant bacteria has triggered research to identify novel strategies to fight these pathogens, such as antimicrobial peptides and, more recently, bacteriophages. In a proof-of-concept study, we have genetically modified lytic T7Select phages targeting Escherichia coli Rosetta by [...] Read more.

The global spread of multi- and pan-resistant bacteria has triggered research to identify novel strategies to fight these pathogens, such as antimicrobial peptides and, more recently, bacteriophages. In a proof-of-concept study, we have genetically modified lytic T7Select phages targeting Escherichia coli Rosetta by integrating DNA sequences derived from the proline-rich antimicrobial peptide, apidaecin. This allowed testing of our hypothesis that apidaecins and bacteriophages can synergistically act on phage-sensitive and phage-resistant E. coli cells and overcome the excessive cost of peptide drugs by using infected cells to express apidaecins before cell lysis. Indeed, the addition of the highly active synthetic apidaecin analogs, Api802 and Api806, to T7Select phage-infected E. coli Rosetta cultures prevented or delayed the growth of potentially phage-resistant E. coli Rosetta strains. However, high concentrations of Api802 also reduced the T7Select phage fitness. Additionally, plasmids encoding Api802, Api806, and Api810 sequences transformed into E. coli Rosetta allowed the production of satisfactory peptide quantities. When these sequences were integrated into the T7Select phage genome carrying an N-terminal green fluorescent protein (GFP-) tag to monitor the expression in infected E. coli Rosetta cells, the GFP–apidaecin analogs were produced in reasonable quantities. However, when Api802, Api806 and Api810 sequences were integrated into the T7Select phage genome, expression was below detection limits and an effect on the growth of potentially phage-resistant E. coli Rosetta strains was not observed for Api802 and Api806. In conclusion, we were able to show that apidaecins can be integrated into the T7Select phage genome to induce their expression in host cells, but further research is required to optimize the engineered T7Select phages for higher expression levels of apidaecins to achieve the expected synergistic effects that were visible when the T7Select phages and synthetic Api802 and Api806 were added to E. coli Rosetta cultures. Full article

(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)

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12 pages, 1252 KiB

Open AccessBrief Report

Cholecystokinin Outcome on Markers of Intestinal IgA Antibody Response

by Juan Morales-Magaña, Ivonne Maciel Arciniega-Martínez, Maria Elisa Drago-Serrano, Aldo Arturo Reséndiz-Albor, Rosa Adriana Jarillo-Luna, Andrea Cruz-Baquero, Modesto Gómez-López, Fabiola Guzmán-Mejía and Judith Pacheco-Yépez

Curr. Issues Mol. Biol. 2022, 44(6), 2542-2553; https://doi.org/10.3390/cimb44060173 - 1 Jun 2022

Cited by 1 | Viewed by 2339

Abstract

Cholecystokinin 8 (CCK8) is an entero-octapeptide that participates in crosstalk with components of intestinal immunity via the CCK receptor (CCKR), but its role in modulation of the IgA response is not fully known under physiological conditions. Male eight-week-old BALB/c mice each were intraperitoneally [...] Read more.

Cholecystokinin 8 (CCK8) is an entero-octapeptide that participates in crosstalk with components of intestinal immunity via the CCK receptor (CCKR), but its role in modulation of the IgA response is not fully known under physiological conditions. Male eight-week-old BALB/c mice each were intraperitoneally injected once during 7 days with CCK8, devazapide (CCKR1 antagonist), L365,260 (CCKR2 antagonist) or vehicle (sham group). In intestinal lavages, total and secretory IgA (SIgA) were determined by ELISA; in lamina propria, IgA⁺ B lymphocytes and IgA⁺ plasma cells were analyzed by flow cytometry; mRNA levels of polymeric immunoglobulin receptor (pIgR) in epithelial cells and α chain, interleukins (ILs) in lamina propria cells were assessed by qRTPCR. Regarding the sham conditions, IgA⁺ plasma-cell percentage and IL-2, IL-5, IL-10 and transforming growth factor-β (TGF-β) mRNA levels were either increased by CCK8 or decreased by both CCKR antagonists. For IgA/SIgA responses, IL-4/IL-6 mRNA levels were decreased by all drugs and pIgR mRNA was increased by CCK8 and reduced by L365,260. IgA⁺ B cell percentage and α chain mRNA levels were elicited by CCK8 and L365,260. Data suggested a presumable differential role of CCK/CCKR on the IgA-response; outcome of L365,260 on the elicitation of IgA⁺ B cells and α chain mRNA needs further examination. Full article

(This article belongs to the Section Molecular Medicine)

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13 pages, 3384 KiB

Open AccessArticle

Ascorbic Acid Ameliorates Cardiac and Hepatic Toxicity Induced by Azithromycin-Etoricoxib Drug Interaction

by Reham Z. Hamza, Fatima S. Alaryani, Fatma Omara, Mahmoud A. A. Said, Sayed A. Abd El-Aziz and Sawsan M. El-Sheikh

Curr. Issues Mol. Biol. 2022, 44(6), 2529-2541; https://doi.org/10.3390/cimb44060172 - 31 May 2022

Cited by 7 | Viewed by 3615

Abstract

The complexity of prescribing safe and effective drug therapy is still challenging. Due to the increased number of medications taken by patients, the potential for drug-drug interactions has clinically important consequences. This study focuses on the potential drug-drug interaction between azithromycin and etoricoxib [...] Read more.

The complexity of prescribing safe and effective drug therapy is still challenging. Due to the increased number of medications taken by patients, the potential for drug-drug interactions has clinically important consequences. This study focuses on the potential drug-drug interaction between azithromycin and etoricoxib and the possibility of counteracting this adverse reaction by giving ascorbic acid intraperitoneally to male albino rats. Sixty adult male albino rats weighing 150–180 g were used. The rats were allocated into six equal groups. One group was a control, and the others were given azithromycin, etoricoxib, either alone or combination, with one group treated with ascorbic acid and the last group treated with the drug combination and ascorbic acid. Blood samples were collected for measuring AST, ALT, LDH, CK-MB, and troponin alongside antioxidant enzymes and histopathological examination for both liver and heart tissue. The results showed both hepatic and cardiac damage in azithromycin and etoricoxib groups represented by increasing levels of heaptoc enzymes (ALT, AST, LDH, CK-MB, and troponin) with declining antioxidant enzymes and elevation of malondialdehyde and the appearance of hepatic and cardiac toxicities. Upon administration, ascorbic acid ameliorated all the mentioned biochemical parameters. In conclusion, ascorbic acid has great antioxidant capacities and hepatic and cardiac ameliorative effects and can alleviate drug interaction toxicity. Full article

(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)

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24 pages, 11244 KiB

Open AccessArticle

A Possible Novel Protective Effect of Piceatannol against Isoproterenol (ISO)-Induced Histopathological, Histochemical, and Immunohistochemical Changes in Male Wistar Rats

by Samar A. Alghamdi, Maryam H. Mugri, Nahid M. H. Elamin, Mona Awad Kamil, Hind Osman, Basma G. Eid, Rasheed A. Shaik, Soad S. Shaker and Aziza Alrafiah

Curr. Issues Mol. Biol. 2022, 44(6), 2505-2528; https://doi.org/10.3390/cimb44060171 - 27 May 2022

Cited by 2 | Viewed by 4086

Abstract

Dry mouth is characterized by lower saliva production and changes in saliva composition. In patients with some salivary gland function remaining, pharmaceutical treatments are not recommended; therefore, new, more effective methods of promoting saliva production are needed. Hence, this study aimed to provide [...] Read more.

Dry mouth is characterized by lower saliva production and changes in saliva composition. In patients with some salivary gland function remaining, pharmaceutical treatments are not recommended; therefore, new, more effective methods of promoting saliva production are needed. Hence, this study aimed to provide an overview of the histological changes in the salivary gland in the model of isoproterenol (ISO)-induced degenerative changes in male Wistar rats and to evaluate the protective effect of piceatannol. Thirty-two male Wistar rats were randomly divided into four groups: the control group, the ISO group, and the piceatannol (PIC)-1, and -2 groups. After the third day of the experiment, Iso (0.8 mg/100 g) was injected intraperitoneally (IP) twice daily into the animals. PIC was given IP in different daily doses (20 and 40 mg/kg) for three days before ISO and seven days with ISO injection. The salivary glands were rapidly dissected and processed for histological, histochemical, immunohistochemical (Ki-67), and morphometric analysis. Upon seven days of treatment with ISO, marked hypertrophy was observed, along with an increased number of positive Ki-67 cells. Proliferation was increased in some endothelial cells as well as in ducts themselves. Despite the significant decrease in proliferation activity, the control group did not return to the usual activity level after treatment with low-dose PIC. Treatment with a high dose of PIC reduced proliferative activity to the point where it was substantially identical to the results seen in the control group. An ISO-driven xerostomia model showed a novel protective effect of piceatannol. A new era of regenerative medicine is dawning around PIC’s promising role. Full article

(This article belongs to the Section Molecular Medicine)

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15 pages, 3591 KiB

Open AccessArticle

Characterization of Insulin-like Peptide (ILP) and Its Potential Role in Ovarian Development of the Cuttlefish Sepiella japonica

by Zhenming Lü, Chenghao Yao, Shijie Zhao, Yao Zhang, Li Gong, Bingjian Liu and Liqin Liu

Curr. Issues Mol. Biol. 2022, 44(6), 2490-2504; https://doi.org/10.3390/cimb44060170 - 27 May 2022

Cited by 6 | Viewed by 2258

Abstract

The insulin-like peptide (ILP) family is well known for regulating reproduction in invertebrates, while its role in mollusks remains largely unknown. In this study, we first isolated and characterized the ILP gene in the cuttlefish Sepiella japonica. The full-length SjILP cDNA [...] Read more.

The insulin-like peptide (ILP) family is well known for regulating reproduction in invertebrates, while its role in mollusks remains largely unknown. In this study, we first isolated and characterized the ILP gene in the cuttlefish Sepiella japonica. The full-length SjILP cDNA obtained was 926 bp and encoded a precursor protein of 161 amino acids. The precursor protein consisted of a signal peptide, a B chain, a C-peptide, and an A chain. It possessed the typical features of ILP proteins, including two cleavage sites (KR) and eight conserved cysteines. To define the function of SjILP, the expression of SjILP in different tissues and ovarian development stages were analyzed using qRT-PCR. SjILP was mainly expressed in the ovary, and its gene expression correlated with ovarian development. Furthermore, silencing SjILP using RNA interference (RNAi) dramatically decreased the expression levels of four ovarian-development-related genes (vitellogenin1, vitellogenin2, cathepsin L1-like, and follistatin). These data suggest the critical role of SjILP in the regulation of ovarian development in S. japonica. Full article

(This article belongs to the Special Issue Multipotent and Multisystem Biomolecules—Associated Interlinking Networks and Crossing Organ Differentiation)

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18 pages, 10928 KiB

Open AccessArticle

Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma

by Wallax Augusto Silva Ferreira and Edivaldo Herculano Correa de Oliveira

Curr. Issues Mol. Biol. 2022, 44(6), 2472-2489; https://doi.org/10.3390/cimb44060169 - 25 May 2022

Cited by 7 | Viewed by 2871

Abstract

Clear cell renal cell carcinoma (KIRC) is the most common and highly malignant pathological type of kidney cancer, characterized by a profound metabolism dysregulation. As part of aspartate biosynthesis, mitochondrial GOT2 (glutamic-oxaloacetic transaminase 2) is essential for regulating cellular energy production and biosynthesis, [...] Read more.

Clear cell renal cell carcinoma (KIRC) is the most common and highly malignant pathological type of kidney cancer, characterized by a profound metabolism dysregulation. As part of aspartate biosynthesis, mitochondrial GOT2 (glutamic-oxaloacetic transaminase 2) is essential for regulating cellular energy production and biosynthesis, linking multiple pathways. Nevertheless, the expression profile and prognostic significance of GOT2 in KIRC remain unclear. This study comprehensively analyzed the transcriptional levels, epigenetic regulation, correlation with immune infiltration, and prognosis of GOT2 in KIRC using rigorous bioinformatics analysis. We discovered that the expression levels of both mRNA and protein of GOT2 were remarkably decreased in KIRC tissues in comparison with normal tissues and were also significantly related to the clinical features and prognosis of KIRC. Remarkably, low GOT2 expression was positively associated with poorer overall survival (OS) and disease-free survival (DFS). Further analysis revealed that GOT2 downregulation is driven by DNA methylation in the promoter-related CpG islands. Finally, we also shed light on the influence of GOT2 expression in immune cell infiltration, suggesting that GOT2 may be a potential prognostic marker and therapeutic target for KIRC patients. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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19 pages, 38466 KiB

Open AccessArticle

Exogenous Zeaxanthin Alleviates Low Temperature Combined with Low Light Induced Photosynthesis Inhibition and Oxidative Stress in Pepper (Capsicum annuum L.) Plants

by Dongxia Ding, Jing Li, Jianming Xie, Nenghui Li, Emily Patience Bakpa, Kangning Han, Yan Yang and Cheng Wang

Curr. Issues Mol. Biol. 2022, 44(6), 2453-2471; https://doi.org/10.3390/cimb44060168 - 25 May 2022

Cited by 12 | Viewed by 2424

Abstract

Low temperature combined with low light (LL) affects crop production, especially the yield and quality of peppers, in northwest China during the winter and spring seasons. Zeaxanthin (Z) is a known lipid protectant and active oxygen scavenger. However, whether exogenous Z can mitigate [...] Read more.

Low temperature combined with low light (LL) affects crop production, especially the yield and quality of peppers, in northwest China during the winter and spring seasons. Zeaxanthin (Z) is a known lipid protectant and active oxygen scavenger. However, whether exogenous Z can mitigate LL-induced inhibition of photosynthesis and oxidative stress in peppers remains unclear. In this study, we investigated the effects of exogenous Z on photosynthesis and the antioxidant machinery of pepper seedlings subject to LL stress. The results showed that the growth and photosynthesis of pepper seedlings were significantly inhibited by LL stress. In addition, the antioxidant machinery was disturbed by the uneven production and elimination of reactive oxygen species (ROS), which resulted in damage to the pepper. For example, membrane lipid peroxidation increased ROS content, and so on. However, exogenous application of Z before LL stress significantly increased the plant height, stem diameter, net photosynthetic rate (Pn), and stomata, which were obviously closed at LL. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), mono de-hydroascorbate reductase (MDHAR), de-hydroascorbate reductase (DHAR), ascorbate peroxidase (APX), and ascorbate oxidase (AAO) improved significantly due to the increased expression of CaSOD, CaCAT, CaAPX, CaMDHAR, and CaDHAR. The ascorbic (AsA) and glutathione (GSH) contents and ascorbic/dehydroascorbate (AsA/DHA) and glutathione/oxidized glutathione (GSH/GSSG) ratios also increased significantly, resulting in the effective removal of hydrogen peroxide (H₂O₂) and superoxide anions (O₂^•−) caused by LL stress. Thus, pre-treatment with Z significantly reduced ROS accumulation in pepper seedlings under LL stress by enhancing the activity of antioxidant enzymes and accumulation of components of the ascorbate–glutathione (AsA–GSH) cycle and upregulated key genes in the AsA–GSH cycle. Full article

(This article belongs to the Special Issue Advanced Research in Plant Metabolomics)

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10 pages, 2205 KiB

Open AccessArticle

Characterization of Gastric Tissue-Resident T Cells in Autoimmune and Helicobacter pylori-Associated Gastritis

by Daisuke Kametaka, Masaya Iwamuro, Takahide Takahashi, Araki Hirabata, Kenta Hamada, Yoshiyasu Kono, Hiromitsu Kanzaki, Seiji Kawano, Takehiro Tanaka, Fumio Otsuka, Yoshiro Kawahara and Hiroyuki Okada

Curr. Issues Mol. Biol. 2022, 44(6), 2443-2452; https://doi.org/10.3390/cimb44060167 - 25 May 2022

Cited by 6 | Viewed by 3702

Abstract

Data regarding the in-depth surface marker profiles of gastric tissue-resident lymphocytes in autoimmune and Helicobacter pylori-associated gastritis are lacking. In this study, we investigated potential differences in lymphocyte composition between these profiles. We enrolled patients with autoimmune (n = 14), active [...] Read more.

Data regarding the in-depth surface marker profiles of gastric tissue-resident lymphocytes in autoimmune and Helicobacter pylori-associated gastritis are lacking. In this study, we investigated potential differences in lymphocyte composition between these profiles. We enrolled patients with autoimmune (n = 14), active (current infection of H. pylori in the stomach; n = 10), and inactive gastritis (post-eradication of H. pylori; n = 20). Lymphocytes were isolated from the greater curvature of the stomach and lesser curvature of the body and analyzed using flow cytometry. The CD8⁺/CD3⁺ and CD4⁺/CD3⁺ ratios differed between the samples. Body CD4⁺/antrum CD4⁺, which is calculated by dividing the CD4⁺/CD3⁺ ratio in the body by that in the antrum, was significantly higher in autoimmune gastritis (3.54 ± 3.13) than in active (1.47 ± 0.41) and inactive gastritis (1.42 ± 0.77). Antrum CD8⁺/CD4⁺ in autoimmune gastritis (7.86 ± 7.23) was also higher than that in active (1.49 ± 0.58) and inactive gastritis (2.84 ± 2.17). The area under the receiver operating characteristic curve of antrum CD8⁺/CD4⁺ was 0.842, and the corresponding optimal cutoff point was 4.0, with a sensitivity of 71.4% and a specificity of 93.3%. We propose that an antrum CD8⁺/CD4⁺ ratio > 4.0 is a potential diagnostic marker for autoimmune gastritis. Full article

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12 pages, 4387 KiB

Open AccessArticle

miR-92a-2-5p Regulates the Proliferation and Differentiation of ASD-Derived Neural Progenitor Cells

by Wenting Zhuang, Hui Liu, Zhize He, Jielan Ju, Qiuxia Gao, Zhiyan Shan and Lei Lei

Curr. Issues Mol. Biol. 2022, 44(6), 2431-2442; https://doi.org/10.3390/cimb44060166 - 24 May 2022

Cited by 3 | Viewed by 2413

Abstract

Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders with abnormal behavior. However, the pathogenesis of ASD remains to be clarified. It has been demonstrated that miRNAs are essential regulators of ASD. However, it is still unclear how miR-92a-2-5p acts on [...] Read more.

Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders with abnormal behavior. However, the pathogenesis of ASD remains to be clarified. It has been demonstrated that miRNAs are essential regulators of ASD. However, it is still unclear how miR-92a-2-5p acts on the developing brain and the cell types directly. In this study, we used neural progenitor cells (NPCs) derived from ASD-hiPSCs as well as from neurotypical controls to examine the effects of miR-92a-2-5p on ASD-NPCs proliferation and neuronal differentiation, and whether miR-92a-2-5p could interact with genetic risk factor, DLG3 for ASD. We observed that miR-92a-2-5p upregulated in ASD-NPCs results in decreased proliferation and neuronal differentiation. Inhibition of miR-92a-2-5p could promote proliferation and neuronal differentiation of ASD-NPCs. DLG3 was negatively regulated by miR-92a-2-5p in NPCs. Our results suggest that miR-92a-2-5p is a strong risk factor for ASD and potentially contributes to neuropsychiatric disorders. Full article

(This article belongs to the Special Issue Signaling Pathways, Development, and Biomarkers in Neuropathy)

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Curr. Issues Mol. Biol., Volume 44, Issue 6 (June 2022) – 24 articles

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