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  • MDPI AG  (152)
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  • MDPI AG  (152)
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  • 1
    Online-Ressource
    Online-Ressource
    The Arabidopsis J-Protein AtDjC5 Facilitates Thermotolerance Likely by Aiding in the ER Stress Response
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 21 ( 2022-10-28), p. 13134-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 21 ( 2022-10-28), p. 13134-
    Kurzfassung: AtDjC5 belongs to the J-protein family in Arabidopsis thaliana. Its biological functions remain unclear. In this study, we examined the roles of AtDjC5 in resisting heat stress using reverse genetic analysis. After the seedlings were exposed directly to 44 °C for 90 min, AtDjC5 knockout seedlings displayed decreases in the survival rate, membrane system stability, and cell vitality compared to WT seedlings, indicating that AtDjC5 is involved in plant basal thermotolerance. The AtDjC5 knockout seedlings pre-exposed to 37 °C for 30 min exhibited decreases in the survival rate and total chlorophyll contents and increased cell death when they were subsequently exposed to 45 °C compared to the WT seedlings, indicating that AtDjC5 plays an important role in plant acquired thermotolerance. AtDjC5 was found to localize to the endoplasmic reticulum. The expression of the AtDjC5 gene was induced by heat and TM (an ER stress inducer) treatment. Furthermore, we found that the knockout of AtDjC5 inhibited ER stress-induced autophagy and the expression of ER stress-related genes. Taken together, these results suggest that AtDjC5 facilitates thermotolerance, likely by aiding in the ER stress response.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232113134
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2019364-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    GRP75 Modulates Endoplasmic Reticulum–Mitochondria Coupling and Accelerates Ca2+-Dependent Endothelial Cell Apoptosis in Diabetic Retinopathy
    MDPI AG ; 2022
    In:  Biomolecules Vol. 12, No. 12 ( 2022-11-29), p. 1778-
    Details
    In: Biomolecules, MDPI AG, Vol. 12, No. 12 ( 2022-11-29), p. 1778-
    Kurzfassung: Endoplasmic reticulum (ER) and mitochondrial dysfunction play fundamental roles in the pathogenesis of diabetic retinopathy (DR). However, the interrelationship between the ER and mitochondria are poorly understood in DR. Here, we established high glucose (HG) or advanced glycosylation end products (AGE)-induced human retinal vascular endothelial cell (RMEC) models in vitro, as well as a streptozotocin (STZ)-induced DR rat model in vivo. Our data demonstrated that there was increased ER–mitochondria coupling in the RMECs, which was accompanied by elevated mitochondrial calcium ions (Ca2+) and mitochondrial dysfunction under HG or AGE incubation. Mechanistically, ER–mitochondria coupling was increased through activation of the IP3R1–GRP75–VDAC1 axis, which transferred Ca2+ from the ER to the mitochondria. Elevated mitochondrial Ca2+ led to an increase in mitochondrial ROS and a decline in mitochondrial membrane potential. These events resulted in the elevation of mitochondrial permeability and induced the release of cytochrome c from the mitochondria into the cytoplasm, which further activated caspase-3 and promoted apoptosis. The above phenomenon was also observed in tunicamycin (TUN, ER stress inducer)-treated cells. Meanwhile, BAPTA-AM (calcium chelator) rescued mitochondrial dysfunction and apoptosis in DR, which further confirmed of our suspicions. In addition, 4-phenylbutyric acid (4-PBA), an ER stress inhibitor, was shown to reverse retinal dysfunction in STZ-induced DR rats in vivo. Taken together, our findings demonstrated that DR fueled the formation of ER–mitochondria coupling via the IP3R1–GRP75–VDAC1 axis and accelerated Ca2+-dependent cell apoptosis. Our results demonstrated that inhibition of ER–mitochondrial coupling, including inhibition of GRP75 or Ca2+ overload, may be a potential therapeutic target in DR.
    Materialart: Online-Ressource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom12121778
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2701262-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Online-Ressource
    Online-Ressource
    Discovery of Novel Allopurinol Derivatives with Anticancer Activity and Attenuated Xanthine Oxidase Inhibition
    MDPI AG ; 2016
    In:  Molecules Vol. 21, No. 6 ( 2016-06-20), p. 771-
    Details
    In: Molecules, MDPI AG, Vol. 21, No. 6 ( 2016-06-20), p. 771-
    Materialart: Online-Ressource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules21060771
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2016
    ZDB Id: 2008644-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Online-Ressource
    Online-Ressource
    Olfactory Gene Families in Scopula subpunctaria and Candidates for Type-II Sex Pheromone Detection
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 24 ( 2022-12-12), p. 15775-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 24 ( 2022-12-12), p. 15775-
    Kurzfassung: Scopula subpunctaria, an abundant pest in tea gardens, produce type-II sex pheromone components, which are critical for its communicative and reproductive abilities; however, genes encoding the proteins involved in the detection of type-II sex pheromone components have rarely been documented in moths. In the present study, we sequenced the transcriptomes of the male and female S. subpunctaria antennae. A total of 150 candidate olfaction genes, comprising 58 odorant receptors (SsubORs), 26 ionotropic receptors (SsubIRs), 24 chemosensory proteins (SsubCSPs), 40 odorant-binding proteins (SsubOBPs), and 2 sensory neuron membrane proteins (SsubSNMPs) were identified in S. subpunctaria. Phylogenetic analysis, qPCR, and mRNA abundance analysis results suggested that SsubOR46 may be the Orco (non-traditional odorant receptor, a subfamily of ORs) of S. subpunctaria. SsubOR9, SsubOR53, and SsubOR55 belonged to the pheromone receptor (PR) clades which have a higher expression in male antennae. Interestingly, SsubOR44 was uniquely expressed in the antennae, with a higher expression in males than in females. SsubOBP25, SsubOBP27, and SsubOBP28 were clustered into the moth pheromone-binding protein (PBP) sub-family, and they were uniquely expressed in the antennae, with a higher expression in males than in females. SsubOBP19, a member of the GOBP2 group, was the most abundant OBP in the antennae. These findings indicate that these olfactory genes, comprising five candidate PRs, three candidate PBPs, and one candidate GOBP2, may be involved in type II sex pheromone detection. As well as these genes, most of the remaining SsubORs, and all of the SsubIRs, showed a considerably higher expression in the female antennae than in the male antennae. Many of these, including SsubOR40, SsubOR42, SsubOR43, and SsubIR26, were more abundant in female antennae. These olfactory and ionotropic receptors may be related to the detection of host plant volatiles. The results of this present study provide a basis for exploring the olfaction mechanisms in S. subpunctaria, with a focus on the genes involved in type II sex pheromones. The evolutionary analyses in our study provide new insights into the differentiation and evolution of lepidopteran PRs.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232415775
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2019364-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Online-Ressource
    Online-Ressource
    Total Synthesis and Anti-Inflammatory Bioactivity of (−)-Majusculoic Acid and Its Derivatives
    MDPI AG ; 2021
    In:  Marine Drugs Vol. 19, No. 6 ( 2021-05-21), p. 288-
    Details
    In: Marine Drugs, MDPI AG, Vol. 19, No. 6 ( 2021-05-21), p. 288-
    Kurzfassung: The first total synthesis of marine natural product, (−)-majusculoic acid (1) and its seven analogs (9–15), was accomplished in three to ten steps with a yield of 3% to 28%. The strategy featured the application of the conformational controlled establishment of the trans-cyclopropane and stereochemical controlled bromo-olefination or olefination by Horner–Wadsworth–Emmons (HWE) reaction. The potential anti-inflammatory activity of the eight compounds (1 and 9–15) was evaluated by determining the nitric oxide (NO) production in the lipopolysaccharide (LPS)-induced mouse macrophages RAW264.7. (−)-Majusculoic acid (1), methyl majusculoate (9), and (1R,2R)-2-((3E,5Z)-6-bromonona-3,5-dien-1-yl)cyclopropane-1-carboxylic acid (12) showed significant effect with inhibition rates of 33.68%, 35.75%, and 43.01%, respectively. Moreover, they did not show cytotoxicity against RAW264.7 cells, indicating that they might be potential anti-inflammatory agents.
    Materialart: Online-Ressource
    ISSN: 1660-3397
    URL: Article
    DOI: 10.3390/md19060288
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2175190-0
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    4′-O-methylpyridoxine: Preparation from Ginkgo biloba Seeds and Cytotoxicity in GES-1 Cells
    MDPI AG ; 2021
    In:  Toxins Vol. 13, No. 2 ( 2021-01-26), p. 95-
    Details
    In: Toxins, MDPI AG, Vol. 13, No. 2 ( 2021-01-26), p. 95-
    Kurzfassung: Ginkgo biloba seeds are wildly used in the food and medicine industry. It has been found that 4′-O-methylpyridoxine (MPN) is responsible for the poisoning caused by G. biloba seeds. The objective of this study was to explore and optimize the extraction method of MPN from G. biloba seeds, and investigate its toxic effect on human gastric epithelial cells (GES-1) and the potential related mechanisms. The results showed that the extraction amount of MPN was 1.933 μg/mg, when extracted at 40 °C for 100 min, with the solid–liquid ratio at 1:10. MPN inhibited the proliferation of GES-1 cells, for which the inhibition rate was 38.27% when the concentration of MPN was 100 μM, and the IC50 value was 127.80 μM; meanwhile, the cell cycle was arrested in G2 phase. High concentration of MPN (100 μM) had significant effects on the nucleus of GES-1 cells, and the proportion of apoptotic cells reached 43.80%. Furthermore, the Western blotting analysis showed that MPN could reduce mitochondrial membrane potential by increasing the expression levels of apoptotic proteins Caspase 8 and Bax in GES-1 cells. In conclusion, MPN may induce apoptosis in GES-1 cells, which leads to toxicity in the human body.
    Materialart: Online-Ressource
    ISSN: 2072-6651
    URL: Article
    DOI: 10.3390/toxins13020095
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2518395-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    New Monoterpenoid Indoles with Osteoclast Activities from Gelsemium elegans
    MDPI AG ; 2021
    In:  Molecules Vol. 26, No. 24 ( 2021-12-09), p. 7457-
    Details
    In: Molecules, MDPI AG, Vol. 26, No. 24 ( 2021-12-09), p. 7457-
    Kurzfassung: The well-known toxic medicine Gelsemium elegans is widely and historically used to treat bone fracture and skin ulcers by the folk people of China. Two new monoterpenoid indole alkaloids, gelselegandines D and E, together with the known analogue gelegamine A were isolated from G. elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. All isolated compounds were tested for the effects on RANKL-induced osteoclast formation. Interestingly, gelselegandine E and gelegamine A, respectively, showed significant promoting and inhibitory activities on osteoclastogenesis, while gelselegandine D had no activity under the same concentration. This work suggested the different configurations for the carbons near the C-19/20 oxygen rings of the isolated compounds may be the key active groups on osteoclast formation and provided the evidence for the rationality as the traditional treatment for bone-related diseases of G. elegans.
    Materialart: Online-Ressource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules26247457
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2008644-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    The Effect of Family Fertility Support Policies on Fertility, Their Contribution, and Policy Pathways to Fertility Improvement in OECD Countries
    MDPI AG ; 2023
    In:  International Journal of Environmental Research and Public Health Vol. 20, No. 6 ( 2023-03-08), p. 4790-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 20, No. 6 ( 2023-03-08), p. 4790-
    Kurzfassung: The cost of childbirth has been confirmed as a vital factor in families’ fertility decision-making, and family welfare policies are capable of compensating for the increase in household living expenses regarding childbirth, such that the country’s fertility situation can be optimized. In this study, the fertility promotion effects of family welfare policies in OECD(Organization for Economic Co-operation and Development) countries are investigated through regression analysis, grey correlation (GRA), and the fuzzy set qualitative comparative analysis fsQCA method. As indicated by the results: (1) Family welfare policies notably boost fertility, and the boosting effect is long-lasting. However, this boost will be weakened in countries where fertility rates remain below 1.5. (2) The contribution of welfare policy measures to the fertility-promotion effect varies by country. The contribution of cash benefits is highest in over half of the countries worldwide, the contribution of relevant services and in-kind expenditure is highest in 29% of the countries, and that of tax incentive expenditure is highest in 14% of the countries. (3) The policy mix to boost fertility also varies according to the social context, with three policy groups derived using the fsQCA method. To be specific, the core antecedent conditions comprise cash benefits, relevant services, and in-kind expenditure. On that basis, China should pay attention to the following three points when formulating family welfare policies to tackle their demographic challenges. First, a system of family welfare policies should be developed as early as possible in the context of increasingly severe demographic issues since the incentive effect of family welfare policies will be weakened in countries with chronically low fertility rates. Second, the effects of improvements vary by country, and China should comprehensively consider its national circumstances when formulating and dynamically adjusting the mix of government fertility support policies in accordance with its social development. Third, employment is the main means of securing family income and takes on critical significance to sustaining families. Unemployment exerts a significant disincentive effect, such that it is imperative to reduce youth unemployment and enhance the quality of youth employment. On that basis, the disincentive effect of unemployment on fertility can be reduced.
    Materialart: Online-Ressource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph20064790
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2175195-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
    Online-Ressource
    Transcriptome Sequencing Reveal That Rno-Rsf1_0012 Participates in Levodopa-Induced Dyskinesia in Parkinson’s Disease Rats via Binding to Rno-mir-298-5p
    MDPI AG ; 2022
    In:  Brain Sciences Vol. 12, No. 9 ( 2022-09-07), p. 1206-
    Details
    In: Brain Sciences, MDPI AG, Vol. 12, No. 9 ( 2022-09-07), p. 1206-
    Kurzfassung: Levodopa-induced dyskinesia (LID) is a common complication of chronic dopamine replacement therapy in the treatment of Parkinson’s disease (PD), and a noble cause of disability in advanced PD patients. Circular RNA (circRNA) is a novel type of non-coding RNA with a covalently closed-loop structure, which can regulate gene expression and participate in many biological processes. However, the biological roles of circRNAs in LID are not completely known. In the present study, we established typical LID rat models by unilateral lesions of the medial forebrain bundle and repeated levodopa therapy. High-throughput next-generation sequencing was used to screen circRNAs differentially expressed in the brain of LID and non-LID (NLID) rats, and key circRNAs were selected according to bioinformatics analyses. Regarding fold change ≥2 and p 〈 0.05 as the cutoff value, there were a total of 99 differential circRNAs, including 39 up-regulated and 60 down-regulated circRNAs between the NLID and LID groups. The expression of rno-Rsf1_0012 was significantly increased in the striatum of LID rats and competitively bound rno-mir-298-5p. The high expression of target genes PCP and TBP in LID rats also supports the conclusion that rno-Rsf1_0012 may be related to the occurrence of LID.
    Materialart: Online-Ressource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci12091206
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2651993-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    Effects of a Dulaglutide plus Calorie-Restricted Diet versus a Calorie-Restricted Diet on Visceral Fat and Metabolic Profiles in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial
    MDPI AG ; 2023
    In:  Nutrients Vol. 15, No. 3 ( 2023-01-20), p. 556-
    Details
    In: Nutrients, MDPI AG, Vol. 15, No. 3 ( 2023-01-20), p. 556-
    Kurzfassung: The effects of dulaglutide and a calorie-restricted diet (CRD) on visceral adipose tissue (VAT) and metabolic profiles in polycystic ovary syndrome (PCOS) have not been extensively investigated. In this study, we investigated whether dulaglutide combined with CRD could further reduce VAT and promote clinical benefits as compared with a CRD regimen alone in overweight or obese PCOS-affected women. Between May 2021 and May 2022, this single-center, randomized, controlled, open-label clinical trial was conducted. Overall, 243 participants with PCOS were screened, of which 68 overweight or obese individuals were randomly randomized to undergo dulaglutide combined with CRD treatment (n = 35) or CRD treatment alone (n = 33). The duration of intervention was set as the time taken to achieve a 7% weight loss goal from baseline body weight, which was restricted to 6 months. The primary endpoint was the difference in the change in VAT area reduction between the groups. The secondary endpoints contained changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition. As compared with the CRD group, the dulaglutide + CRD group had a considerably shorter median time to achieve 7% weight loss. There was no significant between-group difference in area change of VAT reduction (−0.97 cm2, 95% confidence interval from −14.36 to 12.42, p = 0.884). As compared with CRD alone, dulaglutide + CRD had significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels. The results of the analyses showed different changes in menstruation frequency, additional metabolic profiles, hormonal markers, liver fat, and body composition between the two groups did not differ significantly. Nausea, vomiting, constipation, and loss of appetite were the main adverse events of dulaglutide. These results emphasize the value of dietary intervention as the first line of treatment for PCOS-affected women, while glucagon-like peptide 1 receptor agonist therapy provides an efficient and typically well tolerated adjuvant therapy to aid in reaching weight targets based on dietary therapy in the population of overweight/obese PCOS-affected women.
    Materialart: Online-Ressource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu15030556
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2518386-2
    Standort Signatur Einschränkungen Verfügbarkeit
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