bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacodynamic evaluation of dihydroxyflavone derivate chrysin in a guinea pig model of allergic asthma
Authors: Franova Sona , Molitorisova Miroslava , Kazimierova Ivana , Joskova Marta , Forsberg Christina Imnoy Noss , Novakova Elena , Sutovska Martina
Published: January 2021

Objective

This experimental study evaluated the anti-asthmatic capacity of the dihydroxyflavone chrysin in the settings of ovalbumin (OVA)-induced allergic inflammation.

Methods

The parameters that were used to assess the anti-asthmatic activity of chrysin included the specific airway resistance to histamine, the sensitivity to a chemically induced cough and the activity of chrysin on the ciliary beat frequency (CBF) of the respiratory epithelium. The anti-inflammatory potential was confirmed by the measurement of cytokine concentrations Th2 (IL-4, IL-5 and IL-13), Th1 (Granulocyte-macrophage colony-stimulating factor [GM-CSF], INF-γ and IL-12), leucocyte count in the bronchoalveolar lavage fluid (BALF) and growth factor TBF-β1 in lung homogenate.

Key findings

Chronic administration of chrysin (30 mg/kg/day for 21 days) to OVA-sensitised guinea pigs showed bronchodilatory activity comparable to that of long-acting β 2 receptors agonist (LABA) salmeterol. Chrysin revealed antitussive efficiency but was not able to abolish the negative effect of OVA on CBF. Chrysin managed to ameliorate the progression of chronic airway inflammation by decreasing the count of eosinophils, lymphocytes and basophils, IL-5, L-13, GM-CSF, INF-γ in BALF, and TGF-β1 in lung homogenate.

Conclusions

The acquired results support the complex anti-asthmatic profile of chrysin. The flavone may represent an attractive compound for further studies concerning the prevention or treatment of asthma.
Icarrin prevents cardiomyocyte apoptosis in spontaneously hypertensive rats by inhibiting endoplasmic reticulum stress pathways
Authors: Qian Zhiqiang , Zhu Ling , Li Yeli , Li Yiqi , Wu Yuting , Fu Shu , Yang Danli
Published: January 2021

Objectives

This study aimed to explore whether icarrin (ICA) can protect cardiomyocytes from hypertension-induced damage by inhibiting endoplasmic reticulum stress (ERS).

Methods

Spontaneously hypertensive rats (SHRs) were orally administered water or ICA at 10, 20 and 40 mg/kg once daily for 12 weeks, and Wistar–Kyoto (WKY) rats were used as control. Changes in the growth and blood pressure of rats were assessed. Cardiac function was determined by ultrasound and the left ventricle mass was calculated. Myocardial tissue structure was assessed by haematoxylin and eosin staining, cardiomyocyte apoptosis was observed by TUNEL staining and the expression of ERS-related proteins was determined by western blotting.

Results

In the SHR group, blood pressure was significantly high, left ventricular function decreased and left ventricular mass index increased. Additionally, left ventricular cardiomyocyte hypertrophy, disordered myofilament arrangement and increased cardiomyocyte apoptosis were observed by histological staining. ERS-induced proteins associated with apoptosis, including GRP78, PERK, ATF-6, ATF-4, CHOP, DR5, Caspase 12, c-JUN and ASK-1 were found to be highly expressed. ICA treatment reduced blood pressure and regulated the expression of proteins induced by ERS. Cardiomyocyte apoptosis decreased and left ventricular function improved.

Conclusions

ICA can inhibit ERS-induced apoptosis of cardiomyocytes and protect ventricular function in SHR.
Sildenafil improves right ventricular remodelling in monocrotaline-induced rats by decreasing myocardial apoptosis and activating peroxisome proliferator-activated receptors
Authors: Li Ye-li , Li Yi-qi , Zeng Fan-qun , Lin Xiao-ying , Li Xiao-tong , Ren Xing-qiao , Yang Dan-li
Published: January 2021

Objectives

To assess the effect of sildenafil on monocrotaline-induced right ventricular (RV) remodeling and investigate the possible mechanism.

Methods

Rats were subcutaneously injected with monocrotaline to establish an RV remodeling model and then administered sildenafil (25 mg/kg) from days 1 to 28. After 28 days of administration, the RV systolic pressure and the RV hypertrophy index (RVHI) were measured. The morphology of the right ventricle was observed by H&E staining. The ultrastructure of the right ventricle was observed using a transmission electron microscope. The myocardial apoptosis of the right ventricle was evaluated by TUNEL staining. The protein expression of apoptosis-related proteins and PPARs were examined by western blotting.

Key findings

The results indicated that sildenafil decreased the RV systolic pressure and RVHI, and improved the microstructure and ultrastructure of the right ventricle in monocrotaline-induced rats. In addition, sildenafil suppressed myocardial apoptosis and promoted the protein expression of PPARs of the right ventricle in monocrotaline-induced rats.

Conclusion

Sildenafil inhibits RV remodeling in monocrotaline-induced rats, which might be partially mediated by reducing myocardial apoptosis and activating PPARs.
Antimalarial primaquine for skin infiltration analgesia in rats
Authors: Chang Ying-Jen , Liu Kuo-Sheng , Wang Jhi-Joung , Chen Yu-Wen , Hung Ching-Hsia
Published: January 2021

Objectives

The purpose of this study was to estimate the ability of antimalarial medications to induce local infiltration analgesia.

Methods

Using a rat model of skin infiltration anaesthesia, the effects of antimalarial medications (primaquine, chloroquine, hydroxychloroquine and amodiaquine) were compared with the application of lidocaine.

Key findings

At a dose of 3 μmol, primaquine and chloroquine displayed better potency (all P < 0.05) and greater duration (all P < 0.01) of cutaneous analgesia than lidocaine, whereas the other antimalarial medications showed a similar potency and duration of cutaneous analgesia when compared with lidocaine. When a dose of 3 μmol antimalarial medication was used, primaquine was the most potent and had the longest duration of action among four antimalarial medications. The relative potency ranking (ED50, 50% effective dose) has been found to be primaquine [2.10 (1.87 – 2.37) μmol] > lidocaine [6.27 (5.32 –7.39) μmol] (P < 0.01). Infiltration analgesia of skin with primaquine had a greater duration of action than did lidocaine on the equipotent (ED25, ED50, ED75) basis (P < 0.01).

Conclusions

Primaquine and chloroquine have greater potency and longer lasting skin analgesia when compared with lidocaine, while the other antimalarials display a similar potency in comparison with lidocaine.
Propolis from southeastern Brazil produced by Apis mellifera affects innate immunity by modulating cell marker expression, cytokine production and intracellular pathways in human monocytes
Authors: Conte Fernanda Lopes , Santiago Karina Basso , Conti Bruno José , Cardoso Eliza de Oliveira , Oliveira Lucas Pires Garcia , Feltran Geórgia da Silva , Zambuzzi Willian Fernando , Golim Marjorie de Assis , Cruz Maria Teresa , Sforcin José Maurício
Published: January 2021

Objectives

Propolis is a bee-made product used for centuries due to its diverse biological properties, including its immunomodulatory action. This work aimed at investigating whether propolis may affect monocyte functions challenged with retinoic acid (RA), B subunit of Escherichia coli heat-labile enterotoxin (EtxB), human melanoma-associated antigen-1 (MAGE-1) and lipopolysaccharide (LPS).

Methods

Monocytes from healthy donors were treated with the stimuli separately or in the presence of propolis. Cell viability was evaluated by MTT assay, cell marker expression was assessed by flow cytometry, cytokine production by ELISA, gene expression by RT-qPCR.

Key findings

Propolis alone maintained TLR-2, TLR-4, HLA-DR, CD40 and CD80 expression in the monocytes; however, its combination with either MAGE-1 or LPS decreased CD40 expression triggered by the stimuli. Propolis maintained RA action on cell marker expression. Propolis inhibited TNF-α (with either EtxB or MAGE-1) and IL-6 (with either RA or MAGE-1), and increased IL-10 (with MAGE-1) production. Propolis downmodulated LC3 expression induced by LPS. It also induced a lower NF-kB expression than control cells and its combination with RA induced a higher expression than the stimulus alone.

Conclusions

Propolis potentially affected innate immunity by downmodulating the monocytes pro-inflammatory activity.
Ruscogenin attenuates sepsis-induced acute lung injury and pulmonary endothelial barrier dysfunction via TLR4/Src/p120-catenin/VE-cadherin signalling pathway
Authors: Wang Yuwei , Xue Lixuan , Wu Yunhao , Zhang Jiazhi , Dai Yujie , Li Fang , Kou Junping , Zhang Yuanyuan
Published: January 2021

Objectives

Sepsis-associated acute lung injury (ALI) occurs with the highest morbidity and carries the highest mortality rates among the pathogenies of ALI. Ruscogenin (RUS) has been found to exhibit anti-inflammation property and rescue lipopolysaccharide-induced ALI, but little is known about its role in sepsis-triggered ALI. The aim of this study was to investigate the potential role of RUS in sepsis-induced ALI and the probable mechanism.

Methods

Mice model of cecal ligation and puncture (CLP) was replicated, and three doses of RUS (0.01, 0.03 and 0.1 mg/kg) were administrated 1 h before CLP surgeries.

Key findings

RUS significantly extended the survival time and attenuated the lung pathological injury, oedema and vascular leakage in sepsis-induced ALI mice. RUS efficiently decreased the level of MPO in lung tissue and the WBC, NEU counts in BALF. In addition, RUS rescued the expression of VE-cadherin and p120-catenin and suppressed the TLR4/Src signalling in lung tissue.

Conclusions

RUS attenuated sepsis-induced ALI via protecting pulmonary endothelial barrier and regulating TLR4/Src/p120-catenin/VE-cadherin signalling pathway.
Zinc oxide nanoparticles synthesized from Aspergillus terreus induces oxidative stress-mediated apoptosis through modulating apoptotic proteins in human cervical cancer HeLa cells
Authors: Chen Hua , Luo Liping , Fan Sisi , Xiong Yuanhuan , Ling Yan , Peng Shiwei
Published: January 2021

Objectives

This study was aimed to analyze the cytotoxicity of biogenic zinc oxide nanoparticles (ZnO NPs) in human cervical epithelial cancer HeLa.

Methods

The ZnO NPs was synthesized from the culture filtrated of Aspergillus terreus, and examined by UV-spectroscopy, X-ray diffraction (XRD), transmission electron microscope (TEM), energy-dispersive X-ray (EDX) and Fourier transform infrared (FTIR) analysis. The cytotoxicity of synthesized ZnO NPs was analyzed by the MTT assay, and the expression of apoptotic proteins was examined by Western blot analyses.

Key findings

The ZnO NPs exhibited concentration-dependent cytotoxicity on HeLa cells and induced the apoptosis as evidenced by reduced superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) levels, and increased reactive oxygen species (ROS) and diminished mitochondrial membrane potential (MMP) was noticed in ZnO NPs treated HeLa cells. Western blot analyses explored that the Bcl-2 expression was significantly downregulated, whereas, the expression of p53, Bax, Caspase-3, Caspase-9 and Cytochrome-c were significantly upregulated in ZnO NPs treated cells.

Conclusion

Consequently, the mycosynthesized ZnO NPs induces apoptosis in HeLa cells by persuading oxidative damage and modulating the apoptotic proteins. Therefore, A. terreus synthesized ZnO NPs could be used as an effective chemotherapeutic agent for cervical cancer treatment.
Glochidion ellipticum Wight extracts ameliorate dextran sulfate sodium-induced colitis in mice by modulating nuclear factor kappa-light-chain-enhancer of activated B cells signalling pathway
Authors: Hossen Imam , Hua Wu , Mehmood Arshad , Raka Rifat Nowshin , Jingyi Song , Jian-Ming Jin , Min Xu , Shakoor Ashbala , Yanping Cao , Wang Chengtao , Junsong Xiao
Published: January 2021

Objectives

Glochidion ellipticum Wight is a medicinal plant, rich in polyphenols, frequently used by the indigenous communities of Bangladesh and possess with multiple health benefits. It exerts anti-inflammatory and antidiarrheal properties, but the detailed chemical constituents are yet to be elucidated.

Methods

Glochidion ellipticum extracts were analyzed using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry and then tested by both lipopolysaccharide (LPS) induced inflammation of Raw 264.7 macrophage cells and dextran sulfate sodium (DSS) induced acute colitis model. Blood serum was taken for fluorescein isothiocyanate–dextran (FITC-dextran) measurement and tissue samples were used to perform histology, RT-PCR and Western blotting.

Key findings

The extracts could lower the levels of nitric oxide (NO), reactive oxygen species (ROS) and pro-inflammatory cytokines significantly in LPS induced macrophage cells. The extracts could also reduce disease activity index (DAI) score, restore antioxidants and pro-oxidants and improve macroscopic and microscopic features of colonic tissues in DSS induced mice. Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in protein level was markedly diminished (up to 51.21% and 71.11%, respectively) in the treatment groups compared to the model group of colitic mice.

Conclusions

Our findings suggested that G. ellipticum extracts ameliorate DSS colitis via blocking nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, which make them to be potential candidates for further research against inflammation and colitis.
The methanol extract of red algae, Dichotomaria obtusata, from Persian Gulf promotes in vitro osteogenic differentiation of bone marrow mesenchymal stem cells; a biological and phytochemical study
Authors: Nekooei Maryam , Shafiee Sayed Mohammad , Zahiri Maria , Maryamabadi Ammar , Nabipour Iraj
Published: January 2021

Objectives

Osteoporosis is a major public health problem that is appeared with increasing age. This study evaluated the effect of the algae Dichotomaria obtusata methanol extract on osteogenic differentiation of the cultured bone marrow mesenchymal stem cells (BMMSCs) in vitro and analyzed the algae methanol extract to find out the potent beneficial components.

Methods

Dichotomaria obtusata were collected from the coastal area of Bushehr City in the Persian Gulf, Iran. The expression of osteogenesis-related genes was examined using real-time PCR. The formation of calcium deposits in differentiated MSCs was examined by Alizarin R staining. Analyses of algae extract ingredients were performed by gas chromatography–mass spectrometry (GC–MS).

Key findings

Methanol extract of the algae caused the up-regulation of osteogenic genes that were significant for Osteopontin and Osteocalcin (P < 0.05) and also led to an increase in calcium deposits and matrix mineralization in BMMSCs. The GC–MS analyses of the algae extracts resulted in the identification of steroids and essential fatty acids.

Conclusion

The results of the study indicated that the methanol extract of D. obtusata may possess significant potentials for the prevention of osteoporosis in vitro.
Gallic acid attenuates isoniazid and rifampicin-induced liver injury by improving hepatic redox homeostasis through influence on Nrf2 and NF-κB signalling cascades in Wistar Rats
Authors: Sanjay Sukumaran , Girish Chandrashekaran , Toi Pampa Ch , Bobby Zachariah
Published: January 2021

Objectives

Anti-TB drugs-isoniazid and rifampicin induced hepatotoxicity present a significant clinical problem. We aimed to evaluate the beneficial effect of gallic acid in anti-TB drug-induced liver injury in vivo and for the mechanism of action, we explored the influence of gallic acid on Nrf2 and NF-κB pathways.

Methods

We assessed serum liver function tests and histopathological analysis for the preventive effect of gallic acid on liver injury. For exploring the beneficial mechanism, we studied Nrf2 and NF-κB signalling pathways using molecular assays. Subsequently, we conducted in vitro cytotoxicity assays with Nrf2(ML385) and NF-κB(BAY 11–7085) antagonists.

Key findings

Gallic acid co-administration attenuated the elevation of liver function enzymes, hepatic necrosis and inflammation compared to the anti-TB drug treatment alone. Mechanistic investigations reveal that gallic acid increased Nrf2 activation and induction of its downstream targets, preventing cytotoxicity by isoniazid and rifampicin. The protective effect of gallic acid diminished in the presence of Nrf2 antagonists in vitro. Furthermore, we found that gallic acid treatment inhibited NF-κB/TLR-4 axis upregulated by the anti-TB drugs.

Conclusions

Gallic acid is effective in preventing isoniazid and rifampicin induced hepatotoxicity in vivo by improving the redox homeostasis by activating Nrf2 and inhibiting NF-κB signalling pathways.
Epigallocatechin gallate alters leukotoxin secretion and Aggregatibacter actinomycetemcomitans virulence
Authors: Chang En Hyung , Brown Angela C
Published: January 2021

Objectives

We and others have previously shown that epigallocatechin gallate (EGCg) inhibits the activity of an important virulence factor, leukotoxin (LtxA), produced by the oral bacterium Aggregatibacter actinomycetemcomitans, suggesting the potential use of this molecule as an anti-virulence strategy to treat periodontal infections. Here, we sought to better understand the effects of EGCg on toxin secretion and A. actinomycetemcomitans pathogenicity in a co-culture model.

Methods

We used a quantitative immunoblot assay to determine the concentrations of LtxA in the bacterial supernatant and on the bacterial cell surface. Using a co-culture model, consisting of A. actinomycetemcomitans and THP-1 cells, we studied the impact of EGCg-mediated changes in LtxA secretion on the toxicity of A. actinomycetemcomitans.

Key findings

EGCg increased production of LtxA and changed the localization of secreted LtxA from the supernatant to the surface of the bacterial cells. In the co-culture model, a single low dose of EGCg did not protect host THP-1 cells from A. actinomycetemcomitans-mediated cytotoxicity, but a multiple dosing strategy had improved effects.

Conclusions

Together, these results demonstrate that EGCg has important, but complicated, effects on toxin secretion and activity; new dosing strategies and comprehensive model systems may be required to properly develop these anti-virulence activities.
Effect of Hibiscus sabdariffa and Zingiber officinale on pharmacokinetics and pharmacodynamics of amlodipine
Authors: Alam Mohd Aftab , Bin Jardan Yousef A , Alzenaidy Bader , Raish Mohammad , Al-Mohizea Abdullah M , Ahad Abdul , Al-Jenoobi Fahad Ibrahim
Published: January 2021

Objectives

To study the effect of Zingiber officinale and Hibiscus sabdariffa on pharmacokinetics and pharmacodynamics of amlodipine.

Methods

Hypertension was induced in rats (SBP 173.2 ± 1.7 mmHg, mean, 1–24 h). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR) of group-I (amlodipine treated), group-II (Z. officinale, and Z. officinale + amlodipine) and group-III (H. sabdariffa, and H. sabdariffa + amlodipine) animals were measured by “tail-cuff system”. Pharmacokinetics of amlodipine with and without herbs (Z. officinale or H. sabdariffa) was also investigated.

Results

Z. officinale as well as H. sabdariffa decreased the SBP, DBP and MBP. Concurrent treatment with Z. officinale + amlodipine (SBP 129.4 ± 4.5) or H. sabdariffa + amlodipine (SBP 130.4 ± 3.9) showed higher decrease in BP (mean, 1–24h), than individually administered amlodipine (SBP 149.5 ± 2.4) or Z. officinale (SBP 150.2 ± 3.1) or H. sabdariffa (SBP 139.1 ± 1.2). These herbs also influenced the Cmax, AUC0-t, and Tmax of amlodipine. H. sabdariffa increased AUC0-t of amlodipine from 81.8 ± 14.7 to 125.0 ± 10.6 (ng h/mL).

Conclusion

Simultaneous administration of Z. officinale or H. sabdariffa with amlodipine, improves its pharmacodynamic response.
Jatrorrhizine: a review of its pharmacological effects
Authors: Rolle Janiqua , Asante Dorothy O , Kok-Fong Linsey L , Boucetta Hamza , Seidu Theodora A , Tai Lesieli L K , Alolga Raphael N
Published: January 2021

Objectives

Jatrorrhizine is an isoquinoline alkaloid found in medicinal plants. It is the main bioactive compound of the Chinese herbs, Coptis chinensis, Rhizoma coptidis, and Phellodendron chinense Schneid, plants that are predominantly used in traditional Chinese medicine (TCM) for the treatment of metabolic disorders, gastritis, stomachache among a host of others. This manuscript aims to provide a comprehensive review of the pharmacological effects of jatrorrhizine, proffer suggestions on research areas that need redress and potentially serve as a reference for future studies.

Key findings

Published scientific literature was therefore retrieved from all credible sources including Pubmed, Elsevier, Research Gate, Web of Science, Google Scholar, Science Direct, Europe PMC and Wiley Online library using key words such as ‘jatrorrhizine’, ‘botanical sources’, ‘pharmacology’, ‘toxicology’, ‘pharmacokinetics’ or their combinations. A cursory examination of relevant scientific literature using the aforementioned key words produced more than 400 publications.

Conclusions

Using an inclusion/exclusion criteria the subject matter of this review was adequately addressed. It is our hope that this review will provide a good platform for further research on fully harnessing the potential of this bioactive compound.
Propolis antiviral and immunomodulatory activity: a review and perspectives for COVID-19 treatment
Authors: Ripari Nicolas , Sartori Arthur Alves , da Silva Honorio Mariana , Conte Fernanda Lopes , Tasca Karen Ingrid , Santiago Karina Basso , Sforcin José Maurício
Published: January 2021

Objectives

Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a bee-made product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords “propolis”, “virus”, “antiviral”, “antimicrobial” and “coronavirus”.

Key findings

Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines.

Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals’ immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19.
Anti-Aβ-scFv-loaded polymeric nano-micelles with enhanced plasma stability
Authors: Sotoudegan Farnaz , Sotoudegan Farzaneh , Talebkhan Garoosi Yeganeh , Afshar Sahar H , Barkhordari Farzaneh , Davami Fatemeh
Published: January 2021

Objectives

Immunotherapy using recombinant monoclonal antibodies specifically Anti-amyloid-beta (Anti-Aβ) scFv is envisaged as an appropriate therapeutic for Alzheimer through reduction of amyloid-beta aggregation. The solubilization of therapeutics using polymeric micelles facilitates an improved bioavailability and extended blood half-life. In this study, the optimum production condition for Anti-amyloid-beta (Anti-Aβ) scFv was obtained. To increase the stability of plasma, Anti-Aβ-loaded polymeric micelles were synthesized.

Methods

Escherichia coli SHuffle expression strain was used and purified by Ni-NTA. Pluronics P85 and F127 micelles were used for the Anti-Aβ delivery and were characterized in terms of morphology, drug loading and drug release in phosphate buffer and artificial cerebrospinal fluid. The stability profile was quantified at 4°C over a 30 days storage period. The stability in human plasma was also evaluated.

Key findings

Proteins expressed in SHuffle resulted in increased levels of protein expression and solubility. Low critical micelle concentration value and high micelle encapsulation efficiency (<200 nm) achieved via direct dissolution method. Anti-Aβ-loaded micelles were around 2.2-fold more stable than Anti-Aβ in plasma solution. A sustained in-vitro release of Anti-Aβ from micelles was observed.

Conclusions

Results confirmed that Pluronic-micelles pose benefits as a nano-carrier to increase the stability of Anti-Aβ scFvin in the plasma.
Sodium hydrogen sulfide upregulates cystathionine β-synthase and protects striatum against 3-nitropropionic acid-induced neurotoxicity in rats
Authors: Mohammed Reham A , Mansour Suzan M
Published: January 2021

Objectives

Hydrogen sulfide (H2S) is a neuromodulator that plays a protective role in multiple neurodegenerative diseases including Alzheimer’s (AD) and Parkinson’s (PD). However, the precise mechanisms underlying its effects against Huntington’s disease (HD) are still questioned.

This study aimed to examine the neuroprotective effects of sodium hydrogen sulfide (NaHS; H2S donor) against 3-nitropropionic acid (3NP)-induced HD like pathology in rats. Methods: Male Wistar rats were randomly allocated into four groups; (1) normal control receiving saline; (2) NaHS control receiving (0.5 mg/kg/day, i.p.) for 14 days; (3,4) receiving 3NP (10 mg/kg/day, i.p.) for 14 days, with NaHS 30 min later in group 4.

Key findings

NaHS improved cognitive and locomotor deficits induced by 3NP as confirmed by the striatal histopathological findings. These former events were biochemically supported by the increment in cystathionine β-synthase (CBS) gene expression, reduction of glutamate (Glu), dopamine (DA), malondialdehyde (MDA), tumour necrosis factor-alpha (TNF-α), cytochrome-c, cleaved caspase-3 and pc-FOS indicating antioxidant, anti-inflammatory as well as anti-apoptotic effects. Furthermore, NaHS pretreatment improved cholinergic dysfunction and increased brain-derived neurotropic factor (BDNF) and nuclear factor erythroid-2-related factor 2 (Nrf2).

Conclusions

These findings suggest that appropriate protection with H2S donors might represent a novel approach to slow down HD-like symptoms.
Balloon bursting: transurethral puncture of a Foley catheter balloon
Authors: Smith Stephanie F , Sengupta Anup
Published: January 2021

We describe the case of a 76-year-old male who presented with a retained Foley catheter. On the initial attempt to deflate the Foley catheter with a syringe attached to the inflation port, no fluid was aspirated. Using a flexible cystoscope passed alongside the catheter, the balloon was punctured under direct vision with an intravesical needle passed through the cystoscope working channel. We discuss this innovative and safe method for balloon puncture via the transurethral route that can be achieved in the urology outpatient or endoscopy suite.
SN 2014C: VLBI image shows a shell structure and decelerated expansion
Authors: Bietenholz Michael F , Bartel Norbert , Kamble Atish , Margutti Raffaella , Matthews David Jacob , Milisavljevic Danny
Published: January 2021

We report on new Very Long Baseline Interferometry radio measurements of supernova (SN) 2014C in the spiral galaxy NGC 7331, made with the European VLBI Network ∼5 yr after the explosion, as well as on flux density measurements made with the Jansky Very Large Array (VLA). SN 2014C was an unusual SN, initially of Type Ib, but over the course of ∼1 yr, it developed strong H α lines, implying the onset of strong interaction with some H-rich circumstellar medium (CSM). The expanding shock-front interacted with a dense shell of circumstellar material during the first year, but has now emerged from the dense shell and is expanding into the lower density CSM beyond. Our new VLBI observations show a relatively clear shell structure and continued expansion with some deceleration, with a suggestion that the deceleration is increasing at the latest times. Our multifrequency VLA observations show a relatively flat power-law spectrum with Sν ∝ ν−0.56 ± 0.03, and show no decline in the radio luminosity since t ∼ 1 yr.
KINESIN-12E regulates metaphase spindle flux and helps control spindle size in Arabidopsis
Authors: Herrmann Arvid , Livanos Pantelis , Zimmermann Steffi , Berendzen Kenneth , Rohr Leander , Lipka Elisabeth , Müller Sabine
Published: January 2021

The bipolar mitotic spindle is a highly conserved structure among eukaryotes that mediates chromosome alignment and segregation. Spindle assembly and size control are facilitated by force-generating microtubule-dependent motor proteins known as kinesins. In animals, kinesin-12 cooperates with kinesin-5 to produce outward-directed forces necessary for spindle assembly. In plants, the relevant molecular mechanisms for spindle formation are poorly defined. While an Arabidopsis thaliana kinesin-5 ortholog has been identified, the kinesin-12 ortholog in plants remains elusive. In this study, we provide experimental evidence for the function of Arabidopsis KINESIN-12E in spindle assembly. In kinesin-12e mutants, a delay in spindle assembly is accompanied by the reduction of spindle size, demonstrating that KINESIN-12E contributes to mitotic spindle architecture. Kinesin-12E localization is mitosis-stage specific, beginning with its perinuclear accumulation during prophase. Upon nuclear envelope breakdown, KINESIN-12E decorates subpopulations of microtubules in the spindle and becomes progressively enriched in the spindle midzone. Furthermore, during cytokinesis, KINESIN-12E shares its localization at the phragmoplast midzone with several functionally diversified Arabidopsis KINESIN-12 members. Changes in the kinetochore and in prophase and metaphase spindle dynamics occur in the absence of KINESIN-12E, suggest it might play an evolutionarily conserved role during spindle formation similar to its spindle-localized animal kinesin-12 orthologs.
Mutation of the imprinted geneOsEMF2ainduces autonomous endosperm development and delayed cellularization in rice
Authors: Tonosaki Kaoru , Ono Akemi , Kunisada Megumi , Nishino Megumi , Nagata Hiroki , Sakamoto Shingo , Kijima Saku T , Furuumi Hiroyasu , Nonomura Ken-Ichi , Sato Yutaka , Ohme-Takagi Masaru , Endo Masaki , Comai Luca , Hatakeyama Katsunori , Kawakatsu Taiji , Kinoshita Tetsu
Published: January 2021

In angiosperms, endosperm development comprises a series of developmental transitions controlled by genetic and epigenetic mechanisms that are initiated after double fertilization. Polycomb repressive complex 2 (PRC2) is a key component of these mechanisms that mediate histone H3 lysine 27 trimethylation (H3K27me3); the action of PRC2 is well described in Arabidopsis thaliana but remains uncertain in cereals. In this study, we demonstrate that mutation of the rice (Oryza sativa) gene EMBRYONIC FLOWER2a (OsEMF2a), encoding a zinc-finger containing component of PRC2, causes an autonomous endosperm phenotype involving proliferation of the central cell nuclei with separate cytoplasmic domains, even in the absence of fertilization. Detailed cytological and transcriptomic analyses revealed that the autonomous endosperm can produce storage compounds, starch granules, and protein bodies specific to the endosperm. These events have not been reported in Arabidopsis. After fertilization, we observed an abnormally delayed developmental transition in the endosperm. Transcriptome and H3K27me3 ChIP-seq analyses using endosperm from the emf2a mutant identified downstream targets of PRC2. These included >100 transcription factor genes such as type-I MADS-box genes, which are likely required for endosperm development. Our results demonstrate that OsEMF2a-containing PRC2 controls endosperm developmental programs before and after fertilization.
A systems genetics approach to deciphering the effect of dosage variation on leaf morphology inPopulus
Authors: Bastiaanse Héloïse , Henry Isabelle M , Tsai Helen , Lieberman Meric , Canning Courtney , Comai Luca , Groover Andrew
Published: January 2021

Gene copy number variation is frequent in plant genomes of various species, but the impact of such gene dosage variation on morphological traits is poorly understood. We used a large population of Populus carrying genomically characterized insertions and deletions across the genome to systematically assay the effect of gene dosage variation on a suite of leaf morphology traits. A systems genetics approach was used to integrate insertion and deletion locations, leaf morphology phenotypes, gene expression, and transcriptional network data, to provide an overview of how gene dosage influences morphology. Dosage-sensitive genomic regions were identified that influenced individual or pleiotropic morphological traits. We also identified cis-expression quantitative trait loci (QTL) within these dosage QTL regions, a subset of which modulated trans-expression QTL as well. Integration of data types within a gene co-expression framework identified co-expressed gene modules that are dosage sensitive, enriched for dosage expression QTL, and associated with morphological traits. Functional description of these modules linked dosage-sensitive morphological variation to specific cellular processes, as well as candidate regulatory genes. Together, these results show that gene dosage variation can influence morphological variation through complex changes in gene expression, and suggest that frequently occurring gene dosage variation has the potential to likewise influence quantitative traits in nature.
Enhanced nucleotide analysis enables the quantification of deoxynucleotides in plants and algae revealing connections between nucleoside and deoxynucleoside metabolism
Authors: Straube Henryk , Niehaus Markus , Zwittian Sarah , Witte Claus-Peter , Herde Marco
Published: January 2021

Detecting and quantifying low-abundance (deoxy)ribonucleotides and (deoxy)ribonucleosides in plants remains difficult; this is a major roadblock for the investigation of plant nucleotide (NT) metabolism. Here, we present a method that overcomes this limitation, allowing the detection of all deoxy- and ribonucleotides as well as the corresponding nucleosides from the same plant sample. The method is characterized by high sensitivity and robustness enabling the reproducible detection and absolute quantification of these metabolites even if they are of low abundance. Employing the new method, we analyzed Arabidopsis thaliana null mutants of CYTIDINE DEAMINASE, GUANOSINE DEAMINASE, and NUCLEOSIDE HYDROLASE 1, demonstrating that the deoxyribonucleotide (dNT) metabolism is intricately interwoven with the catabolism of ribonucleosides (rNs). In addition, we discovered a function of rN catabolic enzymes in the degradation of deoxyribonucleosides in vivo. We also determined the concentrations of dNTs in several mono- and dicotyledonous plants, a bryophyte, and three algae, revealing a correlation of GC to AT dNT ratios with genomic GC contents. This suggests a link between the genome and the metabolome previously discussed but not experimentally addressed. Together, these findings demonstrate the potential of this new method to provide insight into plant NT metabolism.
Anno genominis XX: 20 years of Arabidopsis genomics
Authors: Provart Nicholas J , Brady Siobhan M , Parry Geraint , Schmitz Robert J , Queitsch Christine , Bonetta Dario , Waese Jamie , Schneeberger Korbinian , Loraine Ann E
Published: January 2021

Twenty years ago, the Arabidopsis thaliana genome sequence was published. This was an important moment as it was the first sequenced plant genome and explicitly brought plant science into the genomics era. At the time, this was not only an outstanding technological achievement, but it was characterized by a superb global collaboration. The Arabidopsis genome was the seed for plant genomic research. Here, we review the development of numerous resources based on the genome that have enabled discoveries across plant species, which has enhanced our understanding of how plants function and interact with their environments.
Photoperiod-responsive changes in chromatin accessibility in phloem companion and epidermis cells of Arabidopsis leaves
Authors: Tian Hao , Li Yuru , Wang Ce , Xu Xingwen , Zhang Yajie , Zeb Qudsia , Zicola Johan , Fu Yongfu , Turck Franziska , Li Legong , Lu Zefu , Liu Liangyu
Published: January 2021

Photoperiod plays a key role in controlling the phase transition from vegetative to reproductive growth in flowering plants. Leaves are the major organs perceiving day-length signals, but how specific leaf cell types respond to photoperiod remains unknown. We integrated photoperiod-responsive chromatin accessibility and transcriptome data in leaf epidermis and vascular companion cells of Arabidopsis thaliana by combining isolation of nuclei tagged in specific cell/tissue types with assay for transposase-accessible chromatin using sequencing and RNA-sequencing. Despite a large overlap, vasculature and epidermis cells responded differently. Long-day predominantly induced accessible chromatin regions (ACRs); in the vasculature, more ACRs were induced and these were located at more distal gene regions, compared with the epidermis. Vascular ACRs induced by long days were highly enriched in binding sites for flowering-related transcription factors. Among the highly ranked genes (based on chromatin and expression signatures in the vasculature), we identified TREHALOSE-PHOSPHATASE/SYNTHASE 9 (TPS9) as a flowering activator, as shown by the late flowering phenotypes of T-DNA insertion mutants and transgenic lines with phloem-specific knockdown of TPS9. Our cell-type-specific analysis sheds light on how the long-day photoperiod stimulus impacts chromatin accessibility in a tissue-specific manner to regulate plant development.
Exportin-4 coordinates nuclear shuttling of TOPLESS family transcription corepressors to regulate plant immunity
Authors: Xu Feifei , Jia Min , Li Xin , Tang Yu , Jiang Keni , Bao Jinsong , Gu Yangnan
Published: January 2021

The regulated nucleocytoplasmic exchange of macromolecules is essential for the eukaryotic cell. However, nuclear transport pathways defined by different nuclear transport receptors (NTRs), including importins and exportins, and their significance in activating distinct stress responses are poorly understood in plants. Here, we exploited a CRISPR/Cas9-based genetic screen to search for modifiers of CONSTITUTIVE EXPRESSION OF PATHOGENESIS-RELATED GENE 5 (cpr5), an Arabidopsis thaliana nucleoporin mutant that activates autoimmune responses that partially mimic effector-triggered immunity (ETI). We identified an NTR gene, Exportin-4 (XPO4), as a genetic interactor of CPR5. The xpo4 cpr5 double mutant activates catastrophic immune responses, which leads to seedling lethality. By leveraging the newly developed proximity-labeling proteomics, we profiled XPO4 substrates and identified TOPLESS (TPL) and TPL-related (TPR) transcription corepressors as XPO4-specific cargo. TPL/TPRs target negative regulators of immunity and are redundantly required for ETI induction. We found that loss-of-XPO4 promotes the nuclear accumulation of TPL/TPRs in the presence of elevated salicylic acid (SA), which contributes to the SA-mediated defense amplification and potentiates immune induction in the cpr5 mutant. We showed that TPL and TPRs are required for the enhanced immune activation observed in xpo4 cpr5 but not for the cpr5 single-mutant phenotype, underscoring the functional interplay between XPO4 and TPL/TPRs and its importance in cpr5-dependent immune induction. We propose that XPO4 coordinates the nuclear accumulation of TPL/TPRs, which plays a role in regulating SA-mediated defense feedback to modulate immune strength downstream of CPR5 during ETI induction.
Full-length annotation with multistrategy RNA-seq uncovers transcriptional regulation of lncRNAs in cotton
Authors: Zheng Xiaomin , Chen Yanjun , Zhou Yifan , Shi Keke , Hu Xiao , Li Danyang , Ye Hanzhe , Zhou Yu , Wang Kun
Published: January 2021

Long noncoding RNAs (lncRNAs) are crucial factors during plant development and environmental responses. To build an accurate atlas of lncRNAs in the diploid cotton Gossypium arboreum, we combined Isoform-sequencing, strand-specific RNA-seq (ssRNA-seq), and cap analysis gene expression (CAGE-seq) with PolyA-seq and compiled a pipeline named plant full-length lncRNA to integrate multi-strategy RNA-seq data. In total, 9,240 lncRNAs from 21 tissue samples were identified. 4,405 and 4,805 lncRNA transcripts were supported by CAGE-seq and PolyA-seq, respectively, among which 6.7% and 7.2% had multiple transcription start sites (TSSs) and transcription termination sites (TTSs). We revealed that alternative usage of TSS and TTS of lncRNAs occurs pervasively during plant growth. Besides, we uncovered that many lncRNAs act in cis to regulate adjacent protein-coding genes (PCGs). It was especially interesting to observe 64 cases wherein the lncRNAs were involved in the TSS alternative usage of PCGs. We identified lncRNAs that are coexpressed with ovule- and fiber development–associated PCGs, or linked to GWAS single-nucleotide polymorphisms. We mapped the genome-wide binding sites of two lncRNAs with chromatin isolation by RNA purification sequencing. We also validated the transcriptional regulatory role of lnc-Ga13g0352 via virus-induced gene suppression assay, indicating that this lncRNA might act as a dual-functional regulator that either activates or inhibits the transcription of target genes.
Parasite dodder enables transfer of bidirectional systemic nitrogen signals between host plants
Authors: Zhang Jingxiong , Xu Yuxing , Xie Jing , Zhuang Huifu , Liu Hui , Shen Guojing , Wu Jianqiang
Published: January 2021

Dodder (Cuscuta spp., Convolvulaceae) is a genus of parasitic plants with worldwide distribution. Dodders are able to simultaneously parasitize two or more adjacent hosts, forming dodder-connected plant clusters. Nitrogen (N) deficiency is a common challenge to plants. To date, it has been unclear whether dodder transfers N-systemic signals between hosts grown in N-heterogeneous soil. Transcriptome and methylome analyses were carried out to investigate whether dodder (Cuscuta campestris) transfers N-systemic signals between N-replete and N-depleted cucumber (Cucumis sativus) hosts, and it was found that N-systemic signals from the N-deficient cucumber plants were rapidly translocated through C. campestris to the N-replete cucumber plants. Unexpectedly, certain systemic signals were also transferred from the N-replete to N-depleted cucumber hosts. We demonstrate that these systemic signals are able to regulate large transcriptome and DNA methylome changes in the recipient hosts. Importantly, N stress also induced many long-distance mobile mRNA transfers between C. campestris and hosts, and the bilateral N-systemic signaling between N-replete and N-depleted hosts had a strong impact on the inter-plant mobile mRNAs. Our 15N labeling experiment indicated that under N-heterogeneous conditions, N-systemic signals from the N-deficient cucumber hosts did not obviously change the N-uptake activity of the N-replete cucumber hosts; however, in plant clusters comprising C. campestris-connected cucumber and soybean (Glycine max) plants, if the soybean plants were N-starved, the cucumber plants exhibited increased N-uptake activity. This study reveals that C. campestris facilitates plant–plant communications under N-stress conditions by enabling extensive bilateral N-systemic signaling between different hosts.
HOMEODOMAIN GLABROUS2 regulates cellulose biosynthesis in seed coat mucilage by activating CELLULOSE SYNTHASE5
Authors: Kong Yingzhen , Pei Shengqiang , Wang Yiping , Xu Yan , Wang Xiaoyu , Zhou Gongke , Hu Ruibo
Published: January 2021

Numerous proteins involved in cellulose biosynthesis and assembly have been functionally characterized. Nevertheless, we have a limited understanding of the mechanisms underlying the transcriptional regulation of the genes that encode these proteins. Here, we report that HOMEODOMAIN GLABROUS2 (HDG2), a Homeobox-Leucine Zipper IV transcription factor, regulates cellulose biosynthesis in Arabidopsis (Arabidopsis thaliana) seed coat mucilage. HDG2 is a transcriptional activator with the transactivation domain located within its Leucine-Zipper domain. Transcripts of HDG2 were detected specifically in seed coat epidermal cells with peak expression at 10 d postanthesis. Disruptions of HDG2 led to seed coat mucilage with aberrant morphology due to a reduction in its crystalline cellulose content. Electrophoretic mobility shift and yeast one-hybrid assays, together with chromatin immunoprecipitation and quantitative PCR, provided evidence that HDG2 directly activates CELLULOSE SYNTHASE5 (CESA5) expression by binding to the L1-box cis-acting element in its promoter. Overexpression of CESA5 partially rescued the mucilage defects of hdg2-3. Together, our data suggest that HDG2 directly activates CESA5 expression and thus is a positive regulator of cellulose biosynthesis in seed coat mucilage.
deepEA: a containerized web server for interactive analysis of epitranscriptome sequencing data
Authors: Zhai Jingjing , Song Jie , Zhang Ting , Xie Shang , Ma Chuang
Published: January 2021

The containerized web server deepEA allows interactive, reproducible, and collaborative analysis of epitranscriptome sequencing data.
ConnecTF: A platform to integrate transcription factor–gene interactions and validate regulatory networks
Authors: Brooks Matthew D , Juang Che-Lun , Katari Manpreet Singh , Alvarez José M , Pasquino Angelo , Shih Hung-Jui , Huang Ji , Shanks Carly , Cirrone Jacopo , Coruzzi Gloria M
Published: January 2021

Deciphering gene regulatory networks (GRNs) is both a promise and challenge of systems biology. The promise lies in identifying key transcription factors (TFs) that enable an organism to react to changes in its environment. The challenge lies in validating GRNs that involve hundreds of TFs with hundreds of thousands of interactions with their genome-wide targets experimentally determined by high-throughput sequencing. To address this challenge, we developed ConnecTF, a species-independent, web-based platform that integrates genome-wide studies of TF–target binding, TF–target regulation, and other TF-centric omic datasets and uses these to build and refine validated or inferred GRNs. We demonstrate the functionality of ConnecTF by showing how integration within and across TF–target datasets uncovers biological insights. Case study 1 uses integration of TF–target gene regulation and binding datasets to uncover TF mode-of-action and identify potential TF partners for 14 TFs in abscisic acid signaling. Case study 2 demonstrates how genome-wide TF–target data and automated functions in ConnecTF are used in precision/recall analysis and pruning of an inferred GRN for nitrogen signaling. Case study 3 uses ConnecTF to chart a network path from NLP7, a master TF in nitrogen signaling, to direct secondary TF2s and to its indirect targets in a Network Walking approach. The public version of ConnecTF (https://ConnecTF.org) contains 3,738,278 TF–target interactions for 423 TFs in Arabidopsis, 839,210 TF–target interactions for 139 TFs in maize (Zea mays), and 293,094 TF–target interactions for 26 TFs in rice (Oryza sativa). The database and tools in ConnecTF will advance the exploration of GRNs in plant systems biology applications for model and crop species.