Vitamin D as a Regulator of Adipocyte Differentiation Effects in vivo and in vitro

2018 ◽  
Vol 69 (3) ◽  
pp. 731-734
Author(s):  
Alin Constantin Pinzariu ◽  
Teodor Oboroceanu ◽  
Florin Zugun Eloae ◽  
Ioana Hristov ◽  
Victor Vlad Costan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipocyte Differentiation ◽  
Dependent Manner ◽  
Omental Adipose Tissue ◽  
In Vivo Experiments ◽  
Dose Dependent ◽  
Stromal Stem Cells

The age-associated adiposity and the effect of long-term vitamin D was studied in vitamin D deficient rats. In in vivo experiments, the influence of a 9 months of vitamin D treatment (weekly oral gavage with 0.125 mg vitamin D3 (5000 IU)/100g body weight) on the adipocyte precursors from the omental adipose tissue was examinated. In in vitro experiment, rat adipose-derived mesenchymal stromal/stem cells (ASCs) were induced to differentiate into adipocytes in the presence or absence of 25(OH)D3 (0.25, 25, and 2500 nmol/L). ASCs derived from vitamin D-treated animals showed an increase adipogenic potential as compared to vitamin D-deficient rats. The addition of 25(OH)D3 inhibits the adipocyte differentiation and lipid deposition in a dose dependent manner.

scholarly journals Deciphering the Formulation Secret Underlying Chinese Huo-Clearing Herbal Drink

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianan Wang ◽  
Bo Zhou ◽  
Xiangdong Hu ◽  
Shuang Dong ◽  
Ming Hong ◽  
...  
Keyword(s):  
Lower Percentage ◽  
Dependent Manner ◽  
Prunella Vulgaris ◽  
Cellular Inflammation ◽  
Optimal Health ◽  
Dose Dependent ◽  
Body Heat

Herbal teas or herbal drinks are traditional beverages that are prevalent in many cultures around the world. In Traditional Chinese Medicine, an herbal drink infused with different types of medicinal plants is believed to reduce the ‘Shang Huo’, or excessive body heat, a status of sub-optimal health. Although it is widely accepted and has a very large market, the underlying science for herbal drinks remains elusive. By studying a group of herbs for drinks, including ‘Gan’ (Glycyrrhiza uralensis Fisch. Ex DC.), ‘Ju’ (Dendranthema morifolium (Ramat.) Tzvelev), ‘Bu’ (Microcos paniculata L.), ‘Jin’ (Lonicera japonica Thunb.), ‘Xia’ (Prunella vulgaris L.), and ‘Ji’ (Plumeria rubra L.), the long-term jargon is connected with the inflammation of modern immunology through a few pro-inflammatory markers. In vitro studies have indicated that cellular inflammation is lowered by Ju and Jin either individually or synergistically with Gan. Among all herbs, only Gan detoxicated cellular toxicity of Bu in a dose dependent manner. The synergistic formulation of Ju and Gan, or Jin and Gan, in a reduction of Shang Huo, was tested in vivo. Both combinations exhibited a lower percentage of neutrophils, monocytes, and CD4+/CD8+ ratio in the blood, as well as inflammatory cytokines. Furthermore, body weight in the combinatory groups was more stable than treatments using single herbs. The combination of old traditional oriental methods with Western science logistics, has resulted in the formulation of different herbs into one concoction for the use of detoxification and synergism.

Selective inhibition of endothelium-dependent dilation in resistance-sized vessels in vivo

1987 ◽  
Vol 253 (2) ◽  
pp. H234-H239 ◽  
Author(s):  
U. Pohl ◽  
L. Dezsi ◽  
B. Simon ◽  
R. Busse
Keyword(s):  
Potent Inhibitor ◽  
Selective Inhibition ◽  
Dependent Manner ◽  
Sham Treatment ◽  
In Vivo Experiments ◽  
Before And After ◽  
Dose Dependent

In vivo experiments were performed in autoperfused hindlimbs of rabbits to investigate the role of endothelium-mediated vasomotion in resistance-sized vessels. The flow responses to the vasodilators acetylcholine (ACh), ATP, and substance P (SP), all of which have been shown to act in an endothelium-dependent manner in large conduit arteries, were studied before and after exposure of the hindleg vasculature to gossypol (a potent inhibitor of endothelium-mediated vasodilation in vitro). The flow responses to adenosine (ADO), nitroglycerin (GTN), and prostaglandin E2 (PGE2), which induce relaxation by a direct effect on vascular smooth muscle, were tested in the same manner. All vasodilators induced dose-dependent increases in femoral flow up to two- to threefold when administered intra-arterially. After gossypol, the flow responses to the endothelium-dependent compounds (ACh, ATP, and SP) were severely reduced (by 88 +/- 3%, P less than 0.01) or sometimes were converted to constrictions (ATP). The flow increases induced by ADO, PGE2, and GTN remained largely unaffected. Sham treatment (gossypol solute only), exposure to indomethacin (10 microM), and ganglionic blockade had no differential effect on the flow responses. The selective action of gossypol in suppressing the flow responses to the endothelium-dependent compounds ACh, ATP, and SP is consistent with a vasomotor role for endothelial cells in resistance-sized vessels in vivo.

scholarly journals Anti-tumor activity of a novel proteasome inhibitor D395 against multiple myeloma and its lower cardiotoxicity compared with carfilzomib

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Xuxing Shen ◽  
Chao Wu ◽  
Meng Lei ◽  
Qing Yan ◽  
Haoyang Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitor ◽  
Osteoclast Differentiation ◽  
Dependent Manner ◽  
Serum Enzyme ◽  
Herg Channels ◽  
Anti Tumor Activity ◽  
Dose Dependent

AbstractCarfilzomib, a second-generation proteasome inhibitor, has significantly improved the survival rate of multiple myeloma (MM) patients, but its clinical application is still restricted by drug resistance and cardiotoxicity. Here, we identified a novel proteasome inhibitor, D395, and assessed its efficacy in treating MM as well as its cardiotoxicity at the preclinical level. The activities of purified and intracellular proteasomes were measured to determine the effect of D395 on the proteasome. CCK-8 and flow cytometry experiments were designed to evaluate the effects of D395 on cell growth and apoptosis. The effects of D395 and carfilzomib on serum enzyme activity, echocardiography features, cardiomyocyte morphology, and hERG channels were also compared. In our study, D395 was highly cytotoxic to MM cell lines and primary MM cells but not normal cells, and it was well tolerated in vivo. Similar to carfilzomib, D395 inhibited osteoclast differentiation in a dose-dependent manner. In particular, D395 exhibited lower cardiotoxicity than carfilzomib in all experiments. In conclusion, D395 is a novel irreversible proteasome inhibitor that has remarkable anti-MM activity and mild cardiotoxicity in vitro and in vivo.

scholarly journals Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Hep G2 ◽  
Time Curve ◽  
Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

Papaya shoot tip associated endophytic bacteria isolated from in vitro cultures and host–endophyte interaction in vitro and in vivo

2007 ◽  
Vol 53 (3) ◽  
pp. 380-390 ◽  
Author(s):  
Pious Thomas ◽  
Sima Kumari ◽  
Ganiga K. Swarna ◽  
T.K.S. Gowda
Keyword(s):  
Culture Medium ◽  
Carica Papaya ◽  
In Vitro Cultures ◽  
Dependent Manner ◽  
16S Rdna Sequence ◽  
16S Rdna Sequence Analysis ◽  
Single Organism ◽  
Dose Dependent

Fourteen distinct bacterial clones were isolated from surface-sterilized shoot tips (~1 cm) of papaya (Carica papaya L. ‘Surya’) planted on Murashige and Skoog (MS)-based papaya culture medium (23/50 nos.) during the 2–4 week period following in vitro culturing. These isolates were ascribed to six Gram-negative genera, namely Pantoea ( P. ananatis ), Enterobacter ( E. cloacae ), Brevundimonas ( B. aurantiaca ), Sphingomonas , Methylobacterium ( M. rhodesianum ), and Agrobacterium ( A. tumefaciens ) or two Gram-positive genera, Microbacterium ( M. esteraromaticum ) and Bacillus ( B. benzoevorans ) based on 16S rDNA sequence analysis. Pantoea ananatis was the most frequently isolated organism (70% of the cultures) followed by B. benzoevorans (13%), while others were isolated from single stocks. Bacteria-harboring in vitro cultures often showed a single organism. Pantoea, Enterobacter, and Agrobacterium spp. grew actively on MS-based normal papaya medium, while Microbacterium, Brevundimonas, Bacillus, Sphingomonas, and Methylobacterium spp. failed to grow in the absence of host tissue. Supplying MS medium with tissue extract enhanced the growth of all the organisms in a dose-dependent manner, indicating reliance of the endophyte on its host. Inoculation of papaya seeds with the endophytes (20 h at OD550 = 0.5) led to delayed germination or slow seedling growth initially. However, the inhibition was overcome by 3 months and the seedlings inoculated with Pantoea, Microbacterium, or Sphingomonas spp. displayed significantly better root and shoot growths.

Triphenyltin chloride induces spindle microtubule depolymerisation and inhibits meiotic maturation in mouse oocytes

2014 ◽  
Vol 26 (8) ◽  
pp. 1084 ◽  
Author(s):  
Yu-Ting Shen ◽  
Yue-Qiang Song ◽  
Xiao-Qin He ◽  
Fei Zhang ◽  
Xin Huang ◽  
...  
Keyword(s):  
Polar Body ◽  
Meiotic Maturation ◽  
Dependent Manner ◽  
Germinal Vesicle Breakdown ◽  
Mouse Oocytes ◽  
First Polar Body ◽  
Triphenyltin Chloride ◽  
Dose Dependent

Meiosis produces haploid gametes for sexual reproduction. Triphenyltin chloride (TPTCL) is a highly bioaccumulated and toxic environmental oestrogen; however, its effect on oocyte meiosis remains unknown. We examined the effect of TPTCL on mouse oocyte meiotic maturation in vitro and in vivo. In vitro, TPTCL inhibited germinal vesicle breakdown (GVBD) and first polar body extrusion (PBE) in a dose-dependent manner. The spindle microtubules completely disassembled and the chromosomes condensed after oocytes were exposed to 5 or 10 μg mL–1 TPTCL. γ-Tubulin protein was abnormally localised near chromosomes rather than on the spindle poles. In vivo, mice received TPTCL by oral gavage for 10 days. The general condition of the mice deteriorated and the ovary coefficient was reduced (P < 0.05). The number of secondary and mature ovarian follicles was significantly reduced by 10 mg kg–1 TPTCL (P < 0.05). GVBD decreased in a non-significant, dose-dependent manner (P > 0.05). PBE was inhibited with 10 mg kg–1 TPTCL (P < 0.05). The spindles of in vitro and in vivo metaphase II oocytes were disassembled with 10 mg kg–1 TPTCL. These results suggest that TPTCL seriously affects meiotic maturation by disturbing cell-cycle progression, disturbing the microtubule cytoskeleton and inhibiting follicle development in mouse oocytes.

scholarly journals The Antiinfective Effects of Velvet Antler of Formosan Sambar Deer (Cervus unicolor swinhoei) onStaphylococcus aureus-Infected Mice

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Ting-Yeu Dai ◽  
Chih-Hua Wang ◽  
Kun-Nan Chen ◽  
I-Nung Huang ◽  
Wei-Sheng Hong ◽  
...  
Keyword(s):  
Lipoteichoic Acid ◽  
Lavage Fluid ◽  
Dependent Manner ◽  
Protective Mechanisms ◽  
Velvet Antler ◽  
Sambar Deer ◽  
Dose Dependent ◽  
Cervus Unicolor

We assayed the effects of velvet antler (VA) of Formosan sambar deer (Cervus unicolor swinhoei) and its extracts on the anti-infective activity against pathogenicStaphylococcus aureus in vitroandin vivoin this study.In vitrodata indicated that the VA extracts stimulated the proliferation of resting splenocytes and macrophages in a dose-dependent manner up to the highest concentration used (150 μg mL−1). The production of proinflammatory cytokines (TNF-α, IL-6, IL-12) by lipoteichoic acid was significantly suppressed after being cocultured with the VA extracts in a dose-dependent manner. Animal test inS. aureus-infected mice demonstrated that the numbers of bacteria determined in the kidneys and peritoneal lavage fluid ofS. aureus-infected mice were significantly higher than those found in the same organs of mice pretreated with the VA samples. Moreover, the highly enhanced phagocytic activity of macrophages was further verified afterin vitrotreatment with the VA samples. The protective mechanisms of the VA samples might include an immune enhancer and an inflammatory cytokine suppressor.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

scholarly journals Prostaglandin A1 inhibits the phosphorylation of tau via activating protein phosphotase 2A in a michael addition mechanism at the site of cysteine 377

2020 ◽  
Author(s):  
Guo-Biao Xu ◽  
Pei-Pei Guan ◽  
Pu Wang
Keyword(s):  
Cognitive Decline ◽  
Michael Addition ◽  
Dependent Manner ◽  
Western Blots ◽  
Michael Adduct ◽  
Term Administration ◽  
Prostaglandin A1

Abstract Background: Prostaglandin (PG) A1 is a metabolic product of cyclooxygenase 2 (COX-2), which potentially involved in regulating the development and progression of Alzheimer’s disease (AD). As a cyclopentenone (cy) PG, PGA1 is characterized by the presence of a chemically reactive α, β-unsaturated carbonyl. Although PGA1 is potentially involved in regulating multiple biological processes via michael addition, its specific roles in AD remained unclear.Methods: The tauP301S transgenic (Tg) mice were employed as in vivo AD models and neuroblastoma (N) 2a cells as in vitro neuronal models. By intracerebroventricular injected (i.c.v) with PGA1, the binding proteins to PGA1 are analyzed by HPLC-MS-MS. In addition, western blots are used to determine the phosphorylation of tau in PGA1 treated Tg mice in the absence or presence of okadaic acid (OA), an inhibitor of protein phosphotase (PP) 2A. Combining a synthesis of pull down assay, immunoprecipitation, western blots and HPLC-MS-MS, PP2A scaffold subunit A alpha (PPP2R1A) was identified to be activated by directly binding on PGA1 in cysteine 377-dependent manner. Via inhibiting the hyperphosphorylation of tau, morris maze test was employed to determine the inhibitory effects of PGA1 on cognitive decline of tauP301S Tg mice.Results: By incubation with neuroblastoma (n)2a cells and pull down assay, mass spectra (MS) analysis revealed that PGA1 binds with more than 1000 proteins, among which contains the proteins of AD, especially tau protein. Moreover, short-term administration of PGA1 to tauP301S Tg mice significantly decreased the phosphorylation of tau at the sites of Thr181, Ser202 and Ser404 in a dose-dependent manner. To the reason, it’s caused by activating PPP2R1A in tauP301S Tg mice. More importantly, PGA1 has the ability to form michael adduct with PPP2R1A via its cysteine 377 motif, which is critical for the enzymatic activity of PP2A. By activating PP2A, long-term application of PGA1 to tauP301S Tg mice significantly reduced the phosphorylation of tau, which results in improving the cognitive decline of tauP301S Tg mice.Conclusion: Our data provided the first insights needed to decipher the mechanisms underlying the ameliorating effects of PGA1 on cognitive decline of tauP301S Tg mice via activating PP2A in a PPP2R1AC377-dependent Michael adducting mechanisms.

scholarly journals In vitro inhibitory effect of obtusofolin on the activity of CYP3A4, 2C9, and 2E1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Na Liu ◽  
Ping Chen ◽  
Xiaojun Du ◽  
Junxia Sun ◽  
Shasha Han
Keyword(s):  
Human Liver ◽  
Competitive Inhibition ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Inhibition Model ◽  
Dose Dependent

Abstract Background Obtusofolin is the major active ingredient of Catsia tora L., which possesses the activity of improving eyesight and protecting the optic nerve. Investigation on the interaction of obtusofolin with cytochrome P450 enzymes (CYP450s) could provide a reference for the clinical application of obtusofolin. Methods The effect of obtusofolin on the activity of CYP450s was investigated in the presence of 100 μM obtusofolin in pooled human liver microsomes (HLMs) and fitted with the Lineweaver–Burk plots to characterize the specific inhibition model and kinetic parameters. Results Obtusofolin was found to significantly inhibited the activity of CYP3A4, 2C9, and 2E1. In the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM obtusofolin, the inhibition of these CYP450s showed a dose-dependent manner with the IC50 values of 17.1 ± 0.25, 10.8 ± 0.13, and 15.5 ± 0.16 μM, respectively. The inhibition of CYP3A4 was best fitted with the non-competitive inhibition model with the Ki value of 8.82 μM. While the inhibition of CYP2C9 and 2E1 was competitive with the Ki values of 5.54 and 7.79 μM, respectively. After incubating for 0, 5, 10, 15, and 30 min, the inhibition of CYP3A4 was revealed to be time-dependent with the KI value of 4.87 μM− 1 and the Kinact value of 0.0515 min− 1. Conclusions The in vitro inhibitory effect of obtusofolin implying the potential drug-drug interaction between obtusofolin and corresponding substrates, which needs further in vivo validations.

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