SEARCH FOR NOVEL ANTI-FERTILITY AGENT BY MONITORING IN VITRO METABOLIC INHIBITION, CELL MOTILITY AND CELLULAR INTERACTIONS OF NIFEDIPINE ANALOGUES

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (01) ◽  
pp. 32-39
Author(s):  
K. Malbari ◽  
M. Joshi ◽  
M. Kanyalkar ◽  
Keyword(s):  
Channel Blocker ◽  
Molecular Level ◽  
Cellular Interactions ◽  
Membrane Interaction ◽  
Male Contraceptive ◽  
Fertility Effect ◽  
Dihydropyridine Derivative ◽  
Nifedipine Analogues ◽  
Hypertensive Drug

Current family planning measures predominantly target a female clientele, with relatively few significant developments in male fertility regulation. At present, only effective methods for contraception in men are those that prevent sperm transport, such as condoms and vasectomy. Thus, in an attempt to synthesize non-hormonal, safe, reversible and oral male contraceptive, we have used nifedipine as a prototype molecule. Nifedipine is a calcium channel blocker and popular anti-hypertensive drug. Its reversible anti-fertility effect is a well-known side effect. In order to develop male oral contraceptive, we have synthesized four analogues; m-hydroxy (D5), m-chloro (D6), p-nitro (D7), p-methoxy (D8) aryl 1, 4-dihydropyridine derivative of nifedipine and monitored their effect on sperm motility and metabolic activity. To highlight their mechanism of action on sperm function through membrane interaction, we have studied their molecular level interactions with model membrane using NMR and DSC technique. One of the synthesized analogues (D5) showed promising results.

scholarly journals Microfluidic Advancements in Classical Biotechnology – A Review

2018 ◽  
Author(s):  
Ishtiaq Ahmed ◽  
Zain Akram ◽  
Mohammed Hussen Bule ◽  
Hafiz M. N. Iqbal
Keyword(s):  
Molecular Level ◽  
Modern Science ◽  
Cellular Communications ◽  
Cellular Interactions ◽  
Science And Engineering ◽  
Microbial Life ◽  
Micro Technology ◽  
Multiple Type

Micro-technology has played a substantial role in bioscience, biomedical and biotechnological research due to its core advantages in modern science and engineering. It has created unique development in various sectors of bio-research and upsurges the efficacy of research at the molecular level in recent years. Microfluidic technology makes it possible to manipulate sample volumes at the micro- and nano-level (called nanofluidics) with terrific control outside in vivo cellular microenvironment, enabling the reduction of discrepancies between in vivo and in vitro environments as well as reducing reaction time and cost. In this review, we discuss various effective integrations of microfluidic technologies into biotechnology and its paradigmatic significance in bio-research, supporting mechanical and chemical in vitro cellular micro-environment. Specific innovations relating to the application of microfluidics to advance microbial life, solitary and co-cultures along with a multiple-type cell culturing, cellular communications, cellular interactions and population dynamics are discussed.

Correlated Studies of Cellular Interactions Using TEM, Freeze Etching, and SEM

1974 ◽  
Vol 32 ◽  
pp. 320-321
Author(s):  
J. P. Revel
Keyword(s):  
Developmental Stages ◽  
Three Dimensional ◽  
Cell Movement ◽  
Cellular Interactions ◽  
Serial Sections ◽  
Cell Sheets ◽  
Freeze Etching ◽  
Early Developmental

Movement of individual cells or of cell sheets and complex patterns of folding play a prominent role in the early developmental stages of the embryo. Our understanding of these processes is based on three- dimensional reconstructions laboriously prepared from serial sections, and from autoradiographic and other studies. Many concepts have also evolved from extrapolation of investigations of cell movement carried out in vitro. The scanning electron microscope now allows us to examine some of these events in situ. It is possible to prepare dissections of embryos and even of tissues of adult animals which reveal existing relationships between various structures more readily than used to be possible vithout an SEM.

scholarly journals Adipo-Derived Stem Cell Features and MCF-7

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1754
Author(s):  
Giuseppe Garroni ◽  
Francesca Balzano ◽  
Sara Cruciani ◽  
Renzo Pala ◽  
Donatella Coradduzza ◽  
...  
Keyword(s):  
Stem Cell ◽  
Molecular Level ◽  
Cancer Cell Line ◽  
Human Adipose Tissue ◽  
Cell Cycle Regulators ◽  
Culturing Conditions ◽  
And Migration ◽  
Related Proteins ◽  
Mcf 7

Human adipose tissue-derived stem cells (hADSCs) are highly suitable for regeneration therapies being easily collected and propagated in vitro. The effects of different external factors and culturing conditions are able to affect hADSC proliferation, senescence, differentiation, and migration, even at the molecular level. In the present paper, we exposed hADSCs to an exhausted medium from the breast cancer cell line (MCF-7) to evaluate whether the soluble factors released by these cells may be able to induce changes in stem cell behavior. In particular, we investigated the expression of stemness-related genes (OCT4; Sox 2; Nanog), the cell-cycle regulators p21 (WAF1/CIP1) p53, epigenetic markers (DNMT1 and Sirt1), and autophagy-related proteins. From our results, we can infer that the exhausted medium from MCF-7 is able to influence the hADSCs behavior increasing the expression of stemness-related genes, cell proliferation, and autophagy. Polyamines detectable in MCF-7 exhausted medium could be related to the higher proliferation capability observed in hADSCs, suggesting direct crosstalk between these molecules and the observed changes in stem cell potency.

scholarly journals In Vitro Human Joint Models Combining Advanced 3D Cell Culture and Cutting-Edge 3D Bioprinting Technologies

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 596
Author(s):  
Christian Jorgensen ◽  
Matthieu Simon
Keyword(s):  
New Technology ◽  
3D Cell Culture ◽  
External Pressure ◽  
New Drugs ◽  
Cellular Interactions ◽  
Joint Models ◽  
Physical Stimulation ◽  
Precise Control ◽  
Diarthrodial Joint

Joint-on-a-chip is a new technology able to replicate the joint functions into microscale systems close to pathophysiological conditions. Recent advances in 3D printing techniques allow the precise control of the architecture of the cellular compartments (including chondrocytes, stromal cells, osteocytes and synoviocytes). These tools integrate fluid circulation, the delivery of growth factors, physical stimulation including oxygen level, external pressure, and mobility. All of these structures must be able to mimic the specific functions of the diarthrodial joint: mobility, biomechanical aspects and cellular interactions. All the elements must be grouped together in space and reorganized in a manner close to the joint organ. This will allow the study of rheumatic disease physiopathology, the development of biomarkers and the screening of new drugs.

scholarly journals Glycan-to-Glycan Binding: Molecular Recognition through Polyvalent Interactions Mediates Specific Cell Adhesion

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 397
Author(s):  
Gradimir Misevic ◽  
Emanuela Garbarino
Keyword(s):  
Cell Adhesion ◽  
Plasma Membranes ◽  
Specific Cell ◽  
Cellular Interactions ◽  
New Paradigm ◽  
Tumor Cell Adhesion ◽  
Self Recognition ◽  
Structural And Functional Properties ◽  
Low Valent

Glycan-to-glycan binding was shown by biochemical and biophysical measurements to mediate xenogeneic self-recognition and adhesion in sponges, stage-specific cell compaction in mice embryos, and in vitro tumor cell adhesion in mammals. This intermolecular recognition process is accepted as the new paradigm accompanying high-affinity and low valent protein-to-protein and protein-to-glycan binding in cellular interactions. Glycan structures in sponges have novel species-specific sequences. Their common features are the large size >100 kD, polyvalency >100 repeats of the specific self-binding oligosaccharide, the presence of fucose, and sulfated and/or pyruvylated hexoses. These structural and functional properties, different from glycosaminoglycans, inspired their classification under the glyconectin name. The molecular mechanism underlying homophilic glyconectin-to-glyconectin binding relies on highly polyvalent, strong, and structure-specific interactions of small oligosaccharide motifs, possessing ultra-weak self-binding strength and affinity. Glyconectin localization at the glycocalyx outermost cell surface layer suggests their role in the initial recognition and adhesion event during the complex and multistep process. In mammals, Lex-to-Lex homophilic binding is structure-specific and has ultra-weak affinity. Cell adhesion is achieved through highly polyvalent interactions, enabled by clustering of small low valent structure in plasma membranes.

Vasorelaxing Activity of Stilbenoid and Phenanthrene Derivatives from Brasiliorchis porphyrostele: Involvement of Smooth Muscle CaV1.2 Channels

Planta Medica ◽  
2020 ◽  
Vol 86 (09) ◽  
pp. 631-642
Author(s):  
Watcharee Waratchareeyakul ◽  
Fabio Fusi ◽  
Miriam Durante ◽  
Amer Ahmed ◽  
Walter Knirsch ◽  
...  
Keyword(s):  
Channel Blocker ◽  
Antihypertensive Agents ◽  
Dependent Manner ◽  
Vascular Effects ◽  
Concentration Dependent Manner ◽  
Spasmolytic Activity ◽  
Depth Analysis ◽  
Cav1.2 Channels ◽  
Vasorelaxant Activity

AbstractFive compounds, 3,4′-dihydroxy-3′,5,5′-trimethoxydihydrostilbene, 1; 3,4′-ihydroxy-3′,5′-dimethoxydihydrostilbene, 2; 3,4′-dihydroxy-5,5′-dimethoxydihydrostilbene, 3; 9,10-dihydro-2,7-dihydroxy-4,6-dimethoxyphenanthrene, 4; and the previously unreported 1,2,6,7-tetrahydroxy-4-methoxyphenanthrene, 5 were isolated from the South American orchid, Brasiliorchis porphyrostele. An in-depth analysis of their vascular effects was performed on in vitro rat aorta rings and tail main artery myocytes. Compounds 1 – 4 were shown to possess vasorelaxant activity on rings pre-contracted by the α 1 receptor agonist phenylephrine, the CaV1.2 stimulator (S)-(−)-Bay K 8644, or depolarized with high K+ concentrations. However, compound 5 was active solely on rings stimulated by 25 mM but not 60 mM K+. The spasmolytic activity of compounds 1 and 4 was significantly affected by the presence of an intact endothelium. The KATP channel blocker glibenclamide and the KV channel blocker 4-aminopyridine significantly antagonized the vasorelaxant activity of compounds 4 and 1, respectively. In patch-clamp experiments, compounds 1 – 4 inhibited Ba2+ current through CaV1.2 channels in a concentration-dependent manner, whereas neither compound 4 nor compound 1 affected K+ currents through KATP and KV channels, respectively. The present in vitro, comprehensive study demonstrates that Brasiliorchis porphyrostele may represent a source of vasoactive agents potentially useful for the development of novel antihypertensive agents that has now to be validated in vivo in animal models of hypertension.

scholarly journals Desethylamiodarone antagonizes the effect of thyroid hormone at the molecular level

2001 ◽  
pp. 59-64 ◽  
Author(s):  
F Bogazzi ◽  
L Bartalena ◽  
S Brogioni ◽  
A Burelli ◽  
F Raggi ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Molecular Mechanisms ◽  
Thyroid Hormone Receptor ◽  
Molecular Level ◽  
Inhibitory Effect ◽  
Mobility Shift ◽  
Down Regulation ◽  
Nih3t3 Cells ◽  
Peripheral Tissues

OBJECTIVE: To evaluate the molecular mechanisms of the inhibitory effects of amiodarone and its active metabolite, desethylamiodarone (DEA) on thyroid hormone action. MATERIALS AND METHODS: The reporter construct ME-TRE-TK-CAT or TSHbeta-TRE-TK-CAT, containing the nucleotide sequence of the thyroid hormone response element (TRE) of either malic enzyme (ME) or TSHbeta genes, thymidine kinase (TK) and chloramphenicol acetyltransferase (CAT) was transiently transfected with RSV-TRbeta into NIH3T3 cells. Gel mobility shift assay (EMSA) was performed using labelled synthetic oligonucleotides containing the ME-TRE and in vitro translated thyroid hormone receptor (TR)beta. RESULTS: Addition of 1 micromol/l T4 or T3 to the culture medium increased the basal level of ME-TRE-TK-CAT by 4.5- and 12.5-fold respectively. Amiodarone or DEA (1 micromol/l) increased CAT activity by 1.4- and 3.4-fold respectively. Combination of DEA with T4 or T3 increased CAT activity by 9.4- and 18.9-fold respectively. These data suggested that DEA, but not amiodarone, had a synergistic effect with thyroid hormone on ME-TRE, rather than the postulated inhibitory action; we supposed that this was due to overexpression of the transfected TR into the cells. When the amount of RSV-TRbeta was reduced until it was present in a limited amount, allowing competition between thyroid hormone and the drug, addition of 1 micromol/l DEA decreased the T3-dependent expression of the reporter gene by 50%. The inhibitory effect of DEA was partially due to a reduced binding of TR to ME-TRE, as assessed by EMSA. DEA activated the TR-dependent down-regulation by the negative TSH-TRE, although at low level (35% of the down-regulation produced by T3), whereas amiodarone was ineffective. Addition of 1 micromol/l DEA to T3-containing medium reduced the T3-TR-mediated down-regulation of TSH-TRE to 55%. CONCLUSIONS: Our results demonstrate that DEA, but not amiodarone, exerts a direct, although weak, effect on genes that are regulated by thyroid hormone. High concentrations of DEA antagonize the action of T3 at the molecular level, interacting with TR and reducing its binding to TREs. This effect may contribute to the hypothyroid-like effect observed in peripheral tissues of patients receiving amiodarone treatment.

scholarly journals in vitro Effects of Calcium Antagonists PN 200-110, Nifedipine, and Nimodipine on Human and Canine Cerebral Arteries

1983 ◽  
Vol 3 (3) ◽  
pp. 354-361 ◽  
Author(s):  
E. Müller-Schweinitzer ◽  
P. Neumann
Keyword(s):  
Rank Order ◽  
Cerebral Arteries ◽  
Isometric Tension ◽  
Mesenteric Arteries ◽  
Organ Bath ◽  
Vasoconstrictor Response ◽  
Dihydropyridine Derivative ◽  
Basilar Arteries ◽  
In Vitro Effects

PN 200–110 [4-(2, 1, 3-benzoxadiazol - 4 -) - 1,4-dihydro - 2,6 - dimethyl - pyridine - 3,5 - dicarboxylic acid methyl 1-methylethyl ester], a new dihydropyridine derivative, was investigated by recording isometric tension on spiral strips from human and canine arteries in tissue baths at 37°C. Responses to increasing concentrations of CaCl2 were investigated in calcium-free depolarizing solution (60 mmol/L KCl in equimolar replacement for NaCl, 50 mmol/L TRIZMA buffer, pH 7.4). Comparison of those concentrations that reduced the vasoconstrictor response to 1.6 mmol/L CaCl2 by 50% revealed the following order of potencies on both human and canine arteries: PN 200–110 > nimodipine > nifedipine. Responses to 5-hydroxytryptamine (5-HT) and blood were investigated in Krebs–Henseleit solution (NaHCO3 buffer). On canine arteries, PN 200–110 antagonized responses to 5-HT when used at 10–30 pmol/L; it was ∼70 times more potent on basilar than on mesenteric arteries, whereas both nifedipine and nimodipine were, respectively, ∼10 and 6 times more potent on basilar than on mesenteric arteries. When canine basilar arteries were constricted by the addition of blood to the organ bath, each of the investigated dihydropyridine derivatives elicited concentration-dependent relaxation, producing the following order of potencies: PN 200–110 > nifedipine = nimodipine. On human anterior cerebral arteries, the blood-induced contractions were counteracted in the following rank order: PN 200–110 = nimodipine > nifedipine. The results suggest that due to its potent calcium-blocking activity on cerebral arteries, PN 200–110 might be of value for the prevention and treatment of cerebrovascular spasms following subarachnoid hemorrhage.

scholarly journals Establishment of Highly Efficient Agrobacterium Rhizogenes-mediated Transformation for Stevia Rebaudiana Bertoni Explants

2016 ◽  
Vol 58 (1) ◽  
pp. 113-118 ◽  
Author(s):  
Żaneta Michalec-Warzecha ◽  
Laura Pistelli ◽  
Francesca D’Angiolillo ◽  
Marta Libik-Konieczny
Keyword(s):  
Agrobacterium Rhizogenes ◽  
Hairy Roots ◽  
Molecular Level ◽  
Stevia Rebaudiana ◽  
Culture Conditions ◽  
Light Conditions ◽  
Inoculum Concentration ◽  
Stevia Rebaudiana Bertoni ◽  
Pcr Method

Abstract Leaves and internodes from Stevia rebaudiana Bertoni plants growing in different conditions were used for transformation with two strains of Agrobacterium rhizogenes: ATCC 15384 and LBA 9402. Hairy roots formation was observed and the percentage of the transformed explants depended on the type of explant, time of inoculation and inoculum concentration. Inoculation of explants from ex vitro and in vitro plants with LBA 9402 strain led to higher efficiency of transformation than inoculation with ATCC 15384 strain. Growth rate of hairy roots in liquid culture was assessed under light and dark conditions. It was found that the growth of hairy roots decreased significantly under light conditions. Transformation of hairy roots growing in different culture conditions was confirmed at the molecular level using PCR method with primers constructed against rolB and rolC genes from A. rhizogenes.

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