Recombinant pebulin protein, a type 2 ribosome-inactivating protein isolated from dwarf elder (Sambucus ebulus L.) shows anticancer and antifungal activities in vitro

Type-2 ribosome-inactivating proteins, composed of a toxic A-chain and lectin-like B-chain, display various biological functions, including cytotoxicity and immunomodulation. We here cloned the lectin-like B-chain encoding fragment of a newly identified type-2 RIP gene,articulatingene, fromViscum articulatum, into a bacterial expression vector to obtain nonglycosylated recombinant protein expressed in inclusion bodies. After purification and protein refolding, soluble refolded recombinant articulatin B-chain (rATB) showed lectin activity specific toward galactoside moiety and was stably maintained while stored in low ionic strength solution. Despite lacking glycosylation, rATB actively bound leukocytes with preferential binding to monocytes andin vitrostimulated PBMCs to release cytokines without obvious cytotoxicity. These results implicated such a B-chain fragment as a potential immunomodulator.

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Formulation and Evaluation of Bilayer Sustained Release Tablets of Salbutamol and Theophylline

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2009.2.3.7 ◽

2009 ◽

Vol 2 (3) ◽

pp. 638-646

Author(s):

R. Nagaraju ◽

Rajesh Kaza

Keyword(s):

Ethyl Cellulose ◽

Xanthan Gum ◽

Dosage Forms ◽

In Vitro Dissolution ◽

Dissolution Studies ◽

Sustained Release Tablets ◽

Dissolution Apparatus ◽

Single Dosage

Salbutamol and theophylline are available in conventional dosage forms, administered four times a day, leading to saw tooth kinetics and resulting in ineffective therapy. The combination of these two drugs in a single dosage form will enhance the patient compliance and prolong bronchodilation. Various polymers, such as hydroxy propyl methylcellulose K4M (HPMC- K4M), hydroxy propyl methylcellulose K100M (HPMC- K100M), xanthan gum, ethyl cellulose and hydroxy propyl methylcellulose phthalate (HPMC-P) were studied. HPMC-P and HPMC- K4M were found to be best in controlling the release. In-vitro dissolution studies were carried out for all the bi-layered tablets developed using USP dissolution apparatus type 2 (paddle). It was found that the tablet FB15-FW3 showed 50% release of salbutamol in first hour and the remaining was released for eight hours. However, theophylline was found to be released as per the USP specifications. The IR spectrum was taken for FB15-FW3 formulation and it revealed that there is no disturbance in the principal peaks of pure drugs salbutamol and theophylline. This further confirms the integrity of pure drugs and no incompatibility of them with excipients. Also, formulation of FB15-FW3 has shown required release pattern and complies with all the evaluated parameters and comparable to the marketed formulation.

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Efﬁcacy of Catharanthus roseus Extract against Dengue Virus Type 2 Infection in Vitro

Indian Journal of Public Health Research & Development ◽

10.37506/v11/i2/2020/ijphrd/195051 ◽

2020 ◽

Vol 11 (2) ◽

pp. 1583

Author(s):

Noor Zarina Abd Wahab ◽

NorefrinaShafinaz Md. Nor ◽

Nazlina Ibrahim

Keyword(s):

Dengue Virus ◽

Virus Type ◽

Catharanthus Roseus ◽

Dengue Virus Type 2

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Novel coumarin containing dithiocarbamate derivatives as potent α-glucosidase inhibitors for management of type 2 diabetes

Medicinal Chemistry ◽

10.2174/1573406416666200826101205 ◽

2020 ◽

Vol 16 ◽

Author(s):

Marjan Mollazadeh ◽

Maryam Mohammadi-Khanaposhtani ◽

Yousef Valizadeh ◽

Afsaneh Zonouzi ◽

Mohammad Ali Faramarzi ◽

...

Keyword(s):

Type 2 Diabetes ◽

Kinetic Study ◽

Active Site ◽

Docking Study ◽

Secondary Amines ◽

Molecular Docking Study ◽

Glucosidase Inhibitors ◽

Dithiocarbamate Derivatives

Background: α-Glucosidase is a hydrolyze enzyme that plays a crucial role in degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in the carbohydrate mediated diseases such as diabetes mellitus. Objective: In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated against α-glucosidase in vitro and in silico. Methods: These compounds were obtained of reaction between 4-(bromomethyl)-7-methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, docking study of the most potent compounds was also performed by Auto Dock Tools (version 1.5.6). Results: Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0 ± 4.0-566.6 ± 8.6 μM) in comparison to acarbose as standard inhibitor (IC50 = 750.0 ± 9.0 µM). Among them, secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound compete with substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Also, molecular docking study predicted that this compound as well interacted with α-glucosidase active site pocket. Conclusion: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for design potent α-glucosidase inhibitors for treatment of type 2 diabetes.

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Molecular and Cellular Mechanisms of Metformin in Cervical Cancer

Cancers ◽

10.3390/cancers13112545 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2545

Author(s):

Ya-Hui Chen ◽

Po-Hui Wang ◽

Pei-Ni Chen ◽

Shun-Fa Yang ◽

Yi-Hsuan Hsiao

Keyword(s):

Cervical Cancer ◽

Potential Role ◽

Treatment Options ◽

Cellular Mechanisms ◽

Anticancer Effects ◽

Clinical Benefits ◽

Underlying Mechanisms

Cervical cancer is one of the major gynecologic malignancies worldwide. Treatment options include chemotherapy, surgical resection, radiotherapy, or a combination of these treatments; however, relapse and recurrence may occur, and the outcome may not be favorable. Metformin is an established, safe, well-tolerated drug used in the treatment of type 2 diabetes; it can be safely combined with other antidiabetic agents. Diabetes, possibly associated with an increased site-specific cancer risk, may relate to the progression or initiation of specific types of cancer. The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. The most frequently proposed mechanism underlying the diabetes–cancer association is insulin resistance, which leads to secondary hyperinsulinemia; furthermore, insulin may exert mitogenic effects through the insulin-like growth factor 1 (IGF-1) receptor, and hyperglycemia may worsen carcinogenesis through the induction of oxidative stress. Evidence has suggested clinical benefits of metformin in the treatment of gynecologic cancers. Combining current anticancer drugs with metformin may increase their efficacy and diminish adverse drug reactions. Accumulating evidence is indicating that metformin exerts anticancer effects alone or in combination with other agents in cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Here, we reviewed the potential anticancer effects of metformin against cervical cancer and discussed possible underlying mechanisms.

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Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽

10.3390/cells10020268 ◽

2021 ◽

Vol 10 (2) ◽

pp. 268

Author(s):

Jonathan Ribot ◽

Cyprien Denoeud ◽

Guilhem Frescaline ◽

Rebecca Landon ◽

Hervé Petite ◽

...

Keyword(s):

Type 2 Diabetes ◽

Bone Marrow ◽

Stromal Cells ◽

Adipogenic Differentiation ◽

Therapeutic Modality ◽

Multipotent Stromal Cells ◽

Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

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Effect of Different Fermentation Condition on Estimated Glycemic Index, In Vitro Starch Digestibility, and Textural and Sensory Properties of Sourdough Bread

Foods ◽

10.3390/foods10030514 ◽

2021 ◽

Vol 10 (3) ◽

pp. 514

Author(s):

Hilal Demirkesen-Bicak ◽

Muhammet Arici ◽

Mustafa Yaman ◽

Salih Karasu ◽

Osman Sagdic

Keyword(s):

Glycemic Index ◽

Sensory Properties ◽

Starch Digestibility ◽

In Vitro Starch Digestibility ◽

Whole Wheat ◽

Sourdough Bread ◽

Estimated Glycemic Index

This study aimed to evaluate the influence of sourdough fermentation on the estimated glycemic index (eGI), in vitro starch digestibility, and textural and sensory properties of eight experimentally prepared sourdough breads. Wheat and whole wheat flour bread samples were produced under different fermentation conditions (25 °C and 30 °C) and fermentation methods (type-1 and type-2). In type-1 fermentation, sourdough was obtained via spontaneous fermentation. Indigenous strains (Lactobacillus brevis ELB99, Lactiplantibacillus plantarum ELB75, and Saccharomyces cerevisiae TGM55) were used for type-2 fermentation. Fermentation type and temperature significantly affected eGI, the hydrolysis index (HI), the starch fraction, and the textural properties of the samples (p < 0.05). The resistant starch (RS) content increased after fermentation, while rapidly digestible starch (RDS), HI, and eGI decreased. RS values were significantly higher in type-2 than in type-1 at the same temperature for both flour types (p < 0.05). At 25 °C, RS values were higher in both fermentation types. In the white flour samples, eGI values were in the range of 60.8–78.94 and 62.10–78.94 for type-1 and type-2, respectively. The effect of fermentation type on eGI was insignificant (p < 0.05). In the whole flour samples, fermentation type and temperature significantly affected eGI (p < 0.05). The greatest eGI decreases were in whole wheat sourdough bread at 30 °C using type-2 (29.74%). The 30 °C and type-2 samples showed lower hardness and higher specific volume. This study suggests that fermentation type and temperature could affect the eGI and the textural and sensory properties of sourdough bread, and these factors should be considered during bread production. The findings also support the consumption of wheat and whole wheat breads produced by type-2 fermentation due to higher RS and slowly digestible starch (SDS) and lower RDS and eGI values.

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In vitro functional genetic modification of canine adenovirus type 2 genome by CRISPR/Cas9

Laboratory Investigation ◽

10.1038/s41374-021-00654-x ◽

2021 ◽

Author(s):

Abdul Mohin Sajib ◽

Payal Agarwal ◽

Daniel J. Patton ◽

Rebecca L. Nance ◽

Natalie A. Stahr ◽

...

Keyword(s):

Genetic Modification ◽

Adenovirus Type ◽

Adenovirus Type 2

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