Specification of the embryonic limb primordium by graded activity of Decapentaplegic

Development ◽  
1997 ◽  
Vol 124 (1) ◽  
pp. 125-132 ◽  
Author(s):  
S. Goto ◽  
S. Hayashi
Keyword(s):  
Imaginal Disc ◽  
Egf Receptor ◽  
Lateral Position ◽  
Negative Control ◽  
Dependent Manner ◽  
Additional Cell ◽  
Embryonic Limb ◽  
Graded Activity ◽  
Limb Pattern ◽  
Late Function

Two thoracic limbs of Drosophila, the leg and the wing, originate from a common cluster of cells that include the source of two secreted signaling molecules, Decapentaplegic and Wingless. We show that Wingless, but not Decapentaplegic, is responsible for initial specification of the limb primordia with a distal identity. Limb formation is restricted to the lateral position of the embryo by negative control of the early function of Decapentaplegic and the EGF receptor homolog that determine the global dorsoventral pattern. Late function of Decapentaplegic locally determines two additional cell identities in a dosage dependent manner. Loss of Decapentaplegic activity results in a deletion of the proximal structures of the limb, which is in contrast to the consequence of decapentaplegic mutations in the imaginal disc, which cause a deletion of distal structures. The results indicate that the limb pattern elements are added in a distal to proximal direction in the embryo, which is opposite to what is happening in the growing imaginal disc. We propose that Wingless and Decapentaplegic act sequentially to initiate the proximodistal axis.

In Vivo Anti-Anemic Effect of an Aqueous Root Extract of Phyllanthus Muellerianus (Kuntze) Exell in Model Rats.

2021 ◽  
Author(s):  
James Nyirenda ◽  
Gershom B. Lwanga ◽  
Kaampwe M. Muzandu ◽  
David K. Chuba ◽  
Gibson M. Sijumbila
Keyword(s):  
Plant Extract ◽  
Hematological Parameters ◽  
Negative Control ◽  
Control Group ◽  
Albino Rats ◽  
Root Extract ◽  
Dependent Manner ◽  
Phytochemical Screening ◽  
Aqueous Root Extract

Abstract Ethnopharmacological relevanceAnemia is a very serious condition in Zambia. One of the plants that has been used traditionally is Phyllanthus muellerianus where different parts of shrub are used to treat a number of diseases in Zambian folklore medicine. Earlier studies have investigated medicinal properties of its aqueous root extracts. This study evaluated the effect of P. muellerianus roots on the hematological indices of albino rats and determined its phytochemical profile. Aim of the studyTo carry out phytochemical screening of the root extract and assess the ant-anemic effect of the aqueous extract on laboratory rats with tail-bled induced anemia Materials and MethodsThirty-six male albino rats placed in six groups were used for the study. The groups comprised the 100, 200, and 400 mg/kg plant extract, Ranferon (200 mg/kg) positive control, anemic non treated control and a normal (non-anemic) control. Anemia, induced through bleeding of the rats, was defined as hemoglobin (Hb) levels less than 12 g/dL. The anti-anemic potential of the plant was determined by comparing its effect on the hematological parameters of rats on treatment to that of the control group.ResultsAfter treatment, rats on the 400 mg/kg plant extract dose showed the greatest increase in the mean values for Hb, Packed cell volume (PCV) and RBC count were 43.3±1.2%, 15.4±0.3 g/dL and 6.3±0.3 x106 /mL respectively, when compared to the negative control group (P < 0.05). Phytochemical screening revealed positive results for alkaloids, flavonoids, saponins, glycosides, steroids, triterpenoids and tannins with varying amounts.Conclusions. The aqueous root extract of P. muellerianus was efficacious against anemia in a dose-dependent manner. The phytochemical compositions seem to be responsible for its hematopoietic properties. Thus, the root decoction of P. muellerianus is useful in alleviating anemia and the results lend credence to its use in traditional medicine in the management of anemia.

EGF receptor signaling induces pointed P1 transcription and inactivates Yan protein in the Drosophila embryonic ventral ectoderm

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3355-3362 ◽  
Author(s):  
L. Gabay ◽  
H. Scholz ◽  
M. Golembo ◽  
A. Klaes ◽  
B.Z. Shilo ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Egf Receptor ◽  
Protein A ◽  
Drosophila Embryo ◽  
Cell Fates ◽  
Secondary Target ◽  
Graded Activity ◽  
Definition Of

The induction of different cell fates along the dorsoventral axis of the Drosophila embryo requires a graded activity of the EGF receptor tyrosine kinase (DER). Here we have identified primary and secondary target genes of DER, which mediate the determination of discrete ventral cell fates. High levels of DER activation in the ventralmost cells trigger expression of the transcription factors encoded by ventral nervous system defective (vnd) and pointed P1 (pntPl). Concomitant with the induction of pntP1, high levels of DER activity lead to inactivation of the Yan protein, a transcriptional repressor of Pointed-target genes. These two antagonizing transcription factors subsequently control the expression of secondary target genes such as otd, argos and tartan. The simultaneous effects of the DER pathway on pntP1 induction and Yan inactivation may contribute to the definition of the border of the ventralmost cell fates.

scholarly journals Sequestration of erythrocytes infected with Plasmodium berghei ANKA in BALB/c mice treated with goat bile

2020 ◽  
Vol 4 (2) ◽  
pp. 179
Author(s):  
Kartika Arum Wardani ◽  
Kholida Nur Aini ◽  
Heny Arwati ◽  
Willy Sandhika
Keyword(s):  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Negative Control ◽  
Control Group ◽  
Dependent Manner ◽  
Plasmodium Berghei Anka ◽  
Concentration Dependent Manner ◽  
Control Group Design ◽  
Bile Concentration

Abstract Sequestration of Plasmodium berghei ANKA-infected erythrocytes occurs in BALB/c mice as characteristic of  Plasmodium falciparum infection in humans. Animals’ bile has been widely used for centuries in Traditional Chinese Medicine. Goat bile has been used in healing infectious and non-infectious diseases; however, no report on the use of goat bile against malaria infection and sequestration. The purpose of this study was to analyze the correlation between parasitemia and sequestration in the liver of P.berghei ANKA-infected BALB/c mice treated with goat bile. This research was an in vivo experimental study using the post-test control group design. The male BALB/c mice aged ± 6 weeks, body weight 20-25 g were used. The mice were divided into five groups where Group 1-3 were mice treated with goat bile 25%, 50%, and 100%, respectively. Group 4-5 were negative (sterile water) and positive controls (DHP). Parasitemia was observed daily from each mouse and the number of sequestered infected erythrocytes on the endothelium of sinusoids. The data were analyzed using t independent test. Antimalarial activity of goat bile was shown by the lower parasitemia in goat bile-treated mice compared with the negative control. The average number of sequestration was goat bile concentration-dependent manner. The higher the concentration, the lower the number of sequestration. Sequestration was correlated with parasitemia (p=0,0001). Sequestration of P.berghei ANKA-infected erythrocytes correlated with parasitemia, and was goat bile concentration-dependent manner. Keywords: Malaria, parasitemia, sequestration, goat bileCorrespondence: [email protected]

scholarly journals Relaxant effect of quercetin on rabbit isolated bladder smooth muscles contractions

2020 ◽  
Vol 10 (1) ◽  
pp. 61-67
Author(s):  
Hassan Sadraei ◽  
Sabihe Tabesh
Keyword(s):  
Smooth Muscles ◽  
Electrical Field Stimulation ◽  
Negative Control ◽  
Flavonoid Compound ◽  
Drug Candidate ◽  
Control Group ◽  
Organ Bath ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Relaxant Effect

Introduction: Quercetin is a flavonoid compound found in many medicinal plants. Antispasmodic effect of quercetin has been reported in ileum and uterus smooth muscles but not in bladder. Therefore, the objective of this research was to investigate relaxant effect of quercetin in rabbit isolated bladder. Methods: Male rabbit was asphyxiated with carbon dioxide and then sacrificed. The whole bladder was dissected out and placed in oxygenated Tyrode’s solution. Isolated bladder was cut into longitudinal strips and placed in an organ bath for contraction studies. Contractions were induced with KCl (20mM), acetylcholine (5μM) and electrical field stimulation (EFS). Full inhibitory concentration–response curve was constructed for quercetin following addition of above spasmogens. Quercetin was added into the organ bath with 2 fold increments in concentration until maximum response was achieved. Nifedipine was used as positive control group and equivalent volume of quercetin vehicle (water + DMSO) was used as negative control group.Results: Quercetin (4 μg/mL to 640 μg/mL) in a concentration dependent manner inhibited isolated bladder strips contracted by KCl (IC50=159±25 μg/mL), acetylcholine (IC50=43±9.1 μg/mL) and EFS (IC50=38±9.3 μg/mL). In the highest used concentration, quercetin completely removed contractile responses to KCl, acetylcholine and electrical filed stimulation (EFS). Nifedipine totally inhibited KCl response (IC50=115±36 ng/mL) but only partially inhibited acetylcholine and EFS responses. Conclusion: These results confirm the relaxant effect of quercetin on rabbit bladder and if similar effects are seen in human studies, then quercetin would be a suitable drug candidate to be investigated for bladder incontinence.

scholarly journals Effect of Black Seed (Nigella sativa) and Uziza (Piper guineense) Leaf on the Histology of the Liver of Wistar Albino Rats

2019 ◽  
pp. 1-11
Author(s):  
Okoye Ngozi Franca ◽  
Ikiriko, Favour Ibiwari
Keyword(s):  
Aqueous Extract ◽  
Nigella Sativa ◽  
Positive Control ◽  
Negative Control ◽  
Positive Control Group ◽  
Control Group ◽  
Dependent Manner ◽  
Piper Guineense ◽  
The Third ◽  
Black Seed

Aim: This study was aimed at investigating the effects of aqueous extracts of both Nigella sativa and Piper guineense on the liver enzymes; alanine amino transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP). Also the effect of Nigella sativa and Piper guineense extracts on the histology of the liver of Wistar rat was also studied. Materials and Methods: A total of twenty five Wistar rats were used for the study. The animals were grouped into five groups, each having five animals. They were induced with sucrose and margarine to cause high sugar levels and hyperlipidemia respectively except the positive control group which was fed normal feed. The groups were: the positive control group, the negative control group which were induced without treatment, the uziza leaf group which were induced and were treated with 2 ml of aqueous extract of uziza leaf, the black seed group which were induced and were treated with 2 ml of aqueous extract of black seed, and the black seed and uziza group which were induced and were treated with 2ml of aqueous extract of black seed and 2 ml of aqueous extract of uziza leaf.  Results: The result showed that the extracts decreased the ALT and AST and ALP activities in the rats in a time dependent manner with highest decrease obtained on the third week of treatment with the extracts.  The ALT activity (U/L) on the third week of treatment showed for the, negative control (64.48 ± 0.22), uziza leaf (28.82 ± 0.12), black seed (32.65 ± 0.02), black seed and uziza leaf (16.04 ± 0.02) (p≤0.05). The decrease in activity for AST levels (U/L) on the third week of treatment, showed for the negative control (58.00 ± 0.02), uziza leaf (11.00 ± 0.01), black seed (12.00 ± 0.02), black seed and uziza leaf (8.00 ± 0.02). Conclusion: It can be concluded that both uziza leaf and black seed have hepatoprotective effect on the liver.

In vitro antihemolytic effect, in vivo anti inflammatory and In vitro antioxidant activity of Anchusa azurea Mill

2021 ◽  
Vol 20 ◽  
Author(s):  
Boussoualim Naouel ◽  
Trabsa Hayat ◽  
Krache Imane ◽  
Ouhida Soraya ◽  
Arrar Lekhmissi ◽  
...  
Keyword(s):  
Methanolic Extract ◽  
Folk Medicine ◽  
Oxidative Degradation ◽  
Negative Control ◽  
Dependent Manner ◽  
Anti Inflammatory ◽  
Β Carotene ◽  
Inflammatory Effect

Background: Anchusa azurea Mill. (AA) is a medicinal plant largely used traditionally in folk medicine in Algeria, it is locally named: hamham. It is effective in the treatment of various diseases. Objectives: The aim of the present study is to determine the antioxidant, anti-inflammatory and anti-hemolytic effects of phenolic fractions from Anchusa azurea Mill. Methods: In this study, various extracts from Anchusa azurea Mill. (AA) using solvents with increasing polarity were prepared. The quantification of polyphenols and flavonoids was determined. The anti-radical activity of the different extracts was evaluated using DPPH and by measuring the inhibition of the oxidative degradation of β-carotene. The In vitro antihemolytic effect of the plant extracts is determined (CrE, ChE, AcE and AqE). For each extract, four concentrations were tested: 10.59, 21.18, 42.37, 84.74 µg/ml. Vitamin C is used as a standard. Free-radical attack was measured by measuring the HT50 (Half-Hemolysis Time). The anti-inflammatory effect using PMA on mice of the methanolic extract (CrE) was evaluated. Results: The quantification of polyphenols and flavonoids showed that ethyl acetate extract (AcE) contains a higher amount of polyphenols. However, chloroform extract (ChE) presents a higher amount of flavonoids. AcE showed an important scavenging activity using the DPPH radical (IC50= 68.35 µg/ml). The results showed that AcE also exhibited very great inhibition on the oxidation of β-carotene/linoleic acid (84.33%). All extracts increased the HT50 values (Half-Hemolysis Time) in a dose-dependent manner. The three highest concentrations (21.18, 42.37 and 84.74 µg / ml) of ChE caused a very significant delay (p ≤ 0.001) of hemolysis compared to the negative control and the positive control "VIT C". The anti-inflammatory effect using PMA on mice showed that the methanolic extract (CrE) of AA reduced the weight of the ear edema. Conclusions: This plant has a strong pharmacological power, which supports its traditional medicinal use.

Anti-tumor activity of SKLB-0322, a novel EZH2 covalent inhibitor, in ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15052-e15052
Author(s):  
Yongxia Zhu ◽  
Xinyi Chen ◽  
Qiangsheng Zhang ◽  
Lihong Shi ◽  
Luoting Yu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Target Genes ◽  
Competitive Inhibitor ◽  
Negative Control ◽  
Phase Cell ◽  
Dependent Manner ◽  
Independent Manner ◽  
Western Blot Assay ◽  
Concentration Dependent Manner ◽  
Covalent Inhibitor

e15052 Background: Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) that regulate downstream target genes expression, and then promotes tumor cell proliferation, metastasis and drug resistance. EZH2 also performs some functions in a PRC2-independent manner. Most of reported EZH2 inhibitors are S-adenosyle-methionine (SAM)-competitive inhibitor, and are less selective for EZH2 close homolog EZH1, which resulted in safety concerns and insufficient efficacy. To obtain irreversible EZH2 inhibitor, a novel covalent inhibitor was developed and characterized. Methods: SKLB-0322 and its derivatives were designed, synthesized and confirmed as EZH2 covalent inhibitor by us. The anti-tumor activities of SKLB-0322 were investigated by MTT assay, flow cytometry, and western blot assay. The reversible analog of SKLB-0322 (SKLB-0322’) was used as negative control. Results: SKLB-0322 inhibited EZH2 methyltransferase activity with nanomolar potency, while the inhibitory activities of SKLB-0322’ was reduced. The mass spectrometry (MS) analyses revealed that SKLB-0322 could efficiently forms a single modified covalent adduct. SKLB-0322 displayed noteworthy potency against ovarian cancer cell lines at low micromolar level and reduced the expression level of H3K27me3 in a concentration-dependent manner, which was about 5-fold more active than the reversible negative control SKLB-0322’. Besides, SKLB-0322 caused G2/M phase cell cycle arrest in A2780 and PA-1 cells. Furthermore, SKLB-0322 induced A2780 and PA-1 cell apoptosis in a time- and concentration- dependent manner. Conclusions: Our data clarified that SKLB-0322 is an EZH2 covalent inhibitor for ovarian cancer therapy which is worthy of further evaluation.

scholarly journals MicroRNA-518-3p suppresses cell proliferation, invasiveness, and migration in colorectal cancer via targeting TRIP4

2020 ◽  
Vol 98 (5) ◽  
pp. 575-582
Author(s):  
Heng Yang ◽  
Jia Ren ◽  
Yu Bai ◽  
Jielin Jiang ◽  
Shiyao Xiao
Keyword(s):  
Colorectal Cancer ◽  
Cell Viability ◽  
Colony Formation ◽  
Thyroid Hormone Receptor ◽  
Formation Rate ◽  
Negative Control ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Closure Rate ◽  
Normal Tissues

MicroRNA (miR)-518-3p has been shown to function as a tumor suppressor. This study was conducted to investigate the effects of miR-518-3p in colorectal cancer (CRC). The miR-518-3p mimic, mimic negative control (NC), miR-518-3p inhibitor, inhibitor-NC, ShRNA-TRIP4, and ShRNA-NC vectors were transfected into SW480 cells using Lipofectamine 2000. Cell viability was detected using CCK-8. Colony formation, cell invasiveness, and cell migration were assessed by plate colony formation, Transwell assays, and wound healing assays, respectively. Relative mRNA and protein levels were detected using RT–qPCR and Western blot, respectively. The target gene thyroid hormone receptor interactor 4 (TRIP4) of miR-518-3p was identified and further verified using dual-luciferase reporter assay. Compared with normal tissues, levels of miR-518-3p were decreased and TRIP4 was significantly increased in the tissues from patients with CRC. Following transfection with a miR-518-3p mimic or ShRNA-TRIP4, cell viability decreased in a time-dependent manner, and colony formation rate, wound closure rate, and the number of invasive cells were much lower for the transfected cells than in the corresponding NC and control groups. miR-518-3p overexpression or silencing of TRIP4 significantly down-regulated the expression of MMP-2 and MMP-9. Knockdown of miR-518-3p had the opposite effects, and TRIP4 was identified as a target of miR-518-3p. The inhibitory effects of miR-518-3p on the progressions of CRC are associated with TRIP4.

scholarly journals Anti-inflammatory Potential of Silk Sericin

2013 ◽  
Vol 8 (4) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Pornanong Aramwit ◽  
Pasarapa Towiwat ◽  
Teerapol Srichana
Keyword(s):  
Negative Control ◽  
Dependent Manner ◽  
Silk Sericin ◽  
Plantar Surface ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
The Right ◽  
Dose Dependent ◽  
Control Water

Silk sericin was found to suppress the production of pro-inflammatory cytokines, which are related to the inflammatory reaction. The objectives of this study were to investigate the anti-inflammatory effect of sericin in vivo using the carrageenan-induced rat edema model and changes in the histology of tissues. The effects of sericin on the expression of COX-2 and iNOS were also evaluated. Sericin solutions at 0.004-0.080 mg/mL were applied topically to the top of the hind paw and carrageenan (1.0 mg) was injected subcutaneously to the plantar surface of the right hind paw. Our results indicated that sericin significantly reduced the inflammation in rats’ paw compared with the negative control (water and acetone) and its effect at 0.080 mg/mL was only slightly lower than that of 1.0% w/v indomethacin. Similar numbers of polymorphonuclear and macrophage cells were found in rats’ tissue treated with indomethacin and sericin solution, while the numbers were significantly higher in their absence. The gene expression results by RT-PCR showed that the COX-2 and iNOS genes were down-regulated in samples treated with sericin in a dose dependent manner. These data indicated that the anti-inflammatory properties of sericin may be partly attributable to the suppression of the COX-2 enzyme and nitric oxide production.

scholarly journals Five enzymes of the glycolytic pathway serve as substrates for purified epidermal-growth-factor-receptor kinase

1986 ◽  
Vol 239 (3) ◽  
pp. 691-697 ◽  
Author(s):  
N Reiss ◽  
H Kanety ◽  
J Schlessinger
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Glycolytic Pathway ◽  
Dependent Manner ◽  
Receptor Kinase ◽  
Epidermal Growth

Several enzymes of the glycolytic pathway are phosphorylated in vitro and in vivo by retroviral transforming protein kinases. These substrates include the enzymes phosphoglycerate mutase (PGM), enolase and lactate dehydrogenase (LDH). Here we show that purified EGF (epidermal growth factor)-receptor kinase phosphorylates the enzymes PGM and enolase and also the key regulatory enzymes of the glycolytic pathway, phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in an EGF-dependent manner. Stoichiometry of phosphate incorporation into GAPDH (calculated from native Mr) is the highest, reaching approximately 1. LDH and other enzymes of the glycolytic pathway are not phosphorylated by the purified EGF-receptor kinase. These enzymes are phosphorylated under native conditions, and the Km values of EGF-receptor kinase for their phosphorylation are close to the physiological concentrations of these enzymes in the cell. EGF stimulates the reaction by 2-5-fold by increasing the Vmax. without affecting the Km of this process. Phosphorylation is rapid at 22 degrees C and at higher temperatures. However, unlike the self-phosphorylation of EGF-receptor, which occurs at 4 degrees C, the glycolytic enzymes are poorly phosphorylated at this temperature. Some enzymes, in particular enolase, increase the receptor Km for ATP in the autophosphorylation process and thus may act as competitive inhibitors of EGF-receptor self-phosphorylation. On the basis of the Km values of EGF receptor for the substrate enzymes and for ATP in the phosphorylation reaction, these enzymes may also be substrates in vivo for the EGF-receptor kinase.

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