Glutaraldehyde (GLA) Loaded Albumin Nanoparticles Mediated p53 Targeting Cervical Cancer

2021 ◽  
Vol 13 (8) ◽  
pp. 1430-1436
Author(s):  
Jianghong Zhou ◽  
Shuo Zhang ◽  
Yin Tao ◽  
Jinjin Wang ◽  
Huan Chen ◽  
...  

Nano-albumin-mediated different doses of glutaraldehyde (GLA) were used in cervical cancer nude mice to observe the expression of p53, Bax protein and genes in transplanted tumors and explore the mechanism of GLA on cervical cancer. Cervical cancer Hela cells were cultured. 20 nude BALB/C-nu female mice were selected to establish transplanted tumor models and separated into control group (n = 5) and GLA group (n = 15). Grouping of glutaraldehyde (GLA)-loaded human serum albumin nano-carriers (GLA-HSANC) drugs was done and separated into GLA low-dose (0.06 µmol/mg) and medium-dose (0.12 µmol/mg) and high-dose group (0.18 µmol/mg) followed by assessing xenograft tumor apoptosis, p53 and Bax expression and Hela cell cycle. The shape and structure of various organs of nude mice were normal. The volume of transplanted tumors, tumor markers CA125 and CEA in different dose groups were lower than the control group. The tumor inhibition rate, growth inhibition rate of transplanted tumors, the number of apoptotic cells in transplanted tumors, p53, Bax protein and mRNA expression were all opposite in a dose dependent manner. Compared with the control group, the number of cells in G1 phase of other groups was higher with lower cell number in S phase dose-dependently. GLA nano-albumin particles-mediated p53 targeting cervical cancer tumors can significantly promote tumor cell apoptosis possibly via upregulating p53 and Bax, and increasing cells in G1 phase.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh

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).


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Jin He ◽  
Ru Han ◽  
Gongchang Yu ◽  
Martin F. Lavin ◽  
Qiang Jia ◽  
...  

Benzene (BZ) is an important occupational and environmental pollutant. Exposure to BZ may cause aplastic anemia which is characterized as bone marrow hematopoietic failure. In order to reduce the harmful effects of this pollutant, it is necessary to identify additional preventative measures. In this study, we investigated the protective effects of epimedium polysaccharide (EPS), a natural compound with antioxidant and immune-enhancing potency, on aplastic anemia induced by benzene exposure in mice. Male CD-1 mice were randomly divided into five groups including control, BZ (880 mg/kg), LE (EPS low-dose, 20 mg/kg + BZ), ME (EPS middle-dose, 100 mg/kg + BZ), and HE (EPS high-dose, 200 mg/kg + BZ) groups. Animals were exposed to BZ by subcutaneous injection in the presence or absence of EPS via oral administration. All mice were treated 3 times a week for 8 consecutive weeks to develop a mouse model of benzene-induced aplastic anemia (BIAA). Results showed that BZ induced a significant decrease in both white and red blood cells, platelet counts, and hemoglobin level compared with that in the control group (p<0.01). Treatment of EPS led to a protective effect against these changes particularly in the highest-dose group (HE, p<0.01). EPS also recovered the decreased number of nucleated cells in peripheral blood cell smears and femur biopsies by BZ exposure. The increased level of reactive oxygen species (ROS) in bone marrow mononuclear cells (BMMNCs) in mice from the BZ group was significantly lower (p<0.01) in the mice from the highest concentration of EPS (HE) group when compared with that from the control group. In addition, BZ exposure led to a significant increase in the apoptosis rate in BMMNCs which was prevented by EPS in a dose-dependent manner (p<0.01). The antiapoptosis effect of EPS was through reversing apoptotic proteins such as BAX, Caspase-9 and Caspase-3, and Bcl-2. Finally, EPS treatment partially restored the levels of T cells and the different subtypes except CD80+ and CD86+ compared with the BZ group (HE, p<0.05). These results suggest that EPS has protective effects against BIAA via antioxidative stress, immune modulation, and antiapoptosis mechanisms.


2003 ◽  
Vol 284 (2) ◽  
pp. R550-R557 ◽  
Author(s):  
Roy D. Goldfarb ◽  
Thomas S. Parker ◽  
Daniel M. Levine ◽  
Dana Glock ◽  
Imran Akhter ◽  
...  

Lipoprotein phospholipid (PL) plays a major role in neutralization of endotoxin. This study tested the hypothesis that prophylactic administration of a PL-enriched emulsion (PRE), which augments PL content of serum lipoproteins and neutralizes endotoxin in vitro, would preserve cardiovascular function and improve survival in porcine septic peritonitis. A control group was compared with low-, mid-, and high-dose treatment groups that received PRE by primed continuous infusion for 48 h. A fibrin clot containing live Escherichia coli 0111.B4 was implanted intraperitoneally 30 min after the priming dose. Survival increased in a dose-dependent manner and was correlated with serum PL. Infused PL was associated with high-density lipoprotein in the low-dose group and all serum lipoproteins at higher doses. Treatment significantly lowered serum endotoxin and tumor necrosis factor (TNF)-α, preserved cardiac output and ejection fraction, and attenuated increases in systemic and pulmonary vascular resistances. This study demonstrated that augmentation of lipoprotein PL via administration of PRE improved survival and offered a novel therapeutic approach to sepsis.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Shaodong Deng ◽  
Hongmei Lu ◽  
Honggang Chi ◽  
Ying Wang ◽  
Xiao Li ◽  
...  

Morinda officinalis F.C. How. (Rubiaceae) is a herbal medicine. It has been recorded that its oligosaccharides have neuroprotective properties. In order to understand the oligosaccharides extracted from Morinda officinalis (OMO), a systematic study was conducted to provide evidence that supports its use in neuroprotective therapies for Alzheimer’s disease (AD). AD rat models were prepared with D-galactose and Aβ25–35. The following groups were used in the present experiment: normal control group, sham-operated group, model group, Aricept group, OMO low-dose group, OMO medium-dose group, and OMO high-dose group. The effects on behavioral tests, antioxidant levels, energy metabolism, neurotransmitter levels, and AD-related proteins were detected with corresponding methodologies. AD rats administered with different doses of OMO all exhibited a significant (P<0.05) decrease in latency and an increase (P<0.05) in the ratio of swimming distance to total distance in a dose-dependent manner in the Morris water maze. There was a significant (P<0.05) increase in antioxidant enzyme activities (SOD, GSH-Px, and CAT), neurotransmitter levels (acetylcholine, γ-GABA, and NE and DA), energy metabolism (Na+/K+-ATPase), and relative synaptophysin (SYP) expression levels in AD rats administered with OMO. Furthermore, there was a significant (P<0.05) decrease in MDA levels and relative expression levels of APP, tau, and caspase-3 in AD rats with OMO. The present research suggests that OMO protects against D-galactose and Aβ25–35-induced neurodegeneration, which may provide a novel strategy for improving AD in clinic.


2020 ◽  
Vol 36 (1) ◽  
pp. 30-40 ◽  
Author(s):  
Feng Liang ◽  
Biao Yan

As a general alternative, diisononyl phthalate (DINP) has gradually replaced di(2-ethylhexyl) phthalate (DEHP) as the main plasticizer used in polyvinyl chloride. Like DEHP, DINP can also be released into the environment, resulting in humans being exposed through skin contact. This study aims to explore whether oxidative damage to hepatic and renal tissues can be induced by dermal exposure to DINP in mice. Forty-two male Balb/c mice were divided into six groups. The five DINP dermal exposure groups were exposed to different doses of DINP (0.02, 0.2, 2, 20, and 200 mg/kg) for 28 consecutive days. The pathological alterations to the skin, liver, and kidney in the mice were examined. Levels of reactive oxygen species (ROS), reduced glutathione (GSH), malondialdehyde (MDA), and DNA-protein cross-links (DPC) in the liver and kidney were also determined to investigate oxidative damage. The experimental results showed that the levels of ROS, MDA, and DPC coefficients increased gradually in a dose-dependent manner, whereas the level of GSH decreased accordingly. When the exposure dose was ≥20 mg/kg, ROS, GSH, MDA content, and the DPC coefficient were significantly different compared to the control group ( p < 0.05). These results suggest that a high dose of DINP can induce oxidative stress and histopathological alterations in the liver and kidney via dermal exposure.


2021 ◽  
Vol 11 (10) ◽  
pp. 1924-1931
Author(s):  
Meineng Huang ◽  
Sheng Jiang ◽  
Tong Chen ◽  
Xu Han ◽  
Xinyu Yang ◽  
...  

Objective: To evaluate the curative effect of blue shark skin collagen composite gel on oral mucosal ulcer using the rat oral ulcers model stimulated by glacial acetic acid. Methods: Collagen from blue shark skin was isolated and physiochemically characterized by FTIR, SDS-PAGE and scanning electron microscopy (SEM). Seventy standard male rats were divided into seven groups. The surface and the area of the ulcer were observed and calculated daily. After 12 days of administration, rats in the model group and the control group were killed and the ulcer and surrounding tissues were cut to pieces about one mm3 size. The specimens were stained with 10% formalin solution, paraffinembedded sections, HE staining and light microscope were used to observe the histopathological changes in ulcer tissues. Results: The high-dose group had the fastest ulcer healing effects after 12 days of treatment with blue shark skin collagen composite gel. The composite gel was found to significantly accelerate the healing of oral ulcers in a dose-dependent manner. Conclusion: The blue shark skin collagen composite gel in this study may be a good biomedical material candidate for the treatment of oral ulcers in the near future. Potential of other marine fish skin collagen comples on healing oral ulcers should be also considered.


2014 ◽  
Vol 912-914 ◽  
pp. 1961-1964 ◽  
Author(s):  
Wei Zhang ◽  
Wen He Zhu ◽  
Yan Li ◽  
Jun Luo ◽  
Shi Jie Lv

Abstract: To investigate whether juglone could inhibits the proliferation on human cervical cancer cells (HeLa) in vitro. Cells were divided into control group, different concentration (10μM, 20μM, 50μM, 100μM and200μM) juglone groups for different durations. The viability of HeLa cells was detected by methyl thiazolyl tetrazolium (MTT) assay. The morphology changes of HeLa cells were observed by inverted microscope .The results showed that the viability of HeLa cells was decreased and the cell morphology was changed in a dose-dependent manner after treatment different concentration juglone for 24h when compared with control group. The results suggest that Juglone may be effective for the treatment of HeLa cells.


2013 ◽  
Vol 41 (06) ◽  
pp. 1439-1457 ◽  
Author(s):  
Yi-Chuan Chen ◽  
Heng-Yuan Chang ◽  
Jeng-Shyan Deng ◽  
Jian-Jung Chen ◽  
Shyh-Shyun Huang ◽  
...  

Hispolon (a phenolic compound isolated from Phellinus linteus) has been shown to possess strong antioxidant, anti-inflammatory, anticancer, and antidiabetic properties. In this study, we investigated the antiproliferative effect of hispolon on human hepatocellular carcinoma NB4 cells using the MTT assay, DNA fragmentation, DAPI (4, 6-diamidino-2-phenylindole dihydrochloride) staining, and flow cytometric analysis. Hispolon inhibited the cellular growth of NB4 cells in a dose-dependent manner through the induction of cell cycle arrest at G0/G1 phase measured using flow cytometric analysis and apoptotic cell death, as demonstrated by DNA laddering. Exposure of NB4 cells to hispolon-induced apoptosis-related protein expressions, such as the cleavage form of caspase 3, caspase 8, caspase 9, poly (ADP ribose) polymerase, and the proapoptotic Bax protein. Western blot analysis showed that the protein levels of extrinsic apoptotic proteins (Fas and FasL), intrinsic related proteins (cytochrome c), and the ratio of Bax/Bcl-2 were increased in NB4 cells after hispolon treatment. Hispolon-induced G0/G1-phase arrest was associated with a marked decrease in the protein expression of p53, cyclins D1, and cyclins E, and cyclin-dependent kinases (CDKs) 2, and 4, with concomitant induction of p21waf1/Cip1 and p27Kip1. We conclude that hispolon induces both of extrinsic and intrinsic apoptotic pathways in NB4 human leukemia cells in vitro.


2020 ◽  
Vol 7 ◽  
Author(s):  
Zeyang Sun ◽  
Haihua Li ◽  
Yupeng Li ◽  
Jiayun Qiao

Intestinal health is a critical issue for piglets during their weaning transition period. Previous reports have emphasized the promise of distinct probiotics in improving the enteric health. Here in this research, a newly isolated Lactobacillus salivarius strain was pretreated to Lipopolysaccharide (LPS)-challenged piglets and its association with integrity of the intestinal barrier coupled with effective dosage were expected to be signified. In the present study, 72 piglets (Landrace × Yorkshiere × Duroc) were randomly allotted to four groups, each group with six replicates. The subjects in the control group were provided with basal diet while those in other tested groups with extra 0.05, 0.1, and 0.2% L. salivarius, respectively. Fourteen days later, LPS was intraperitoneally injected and sodium pentobarbital was then delivered to euthanize those LPS-challenged piglets. An increase of average daily gain and body weight along with an apparent decline of diarrhea rate were observed in L. salivarius-treated groups. Both 0.1 and 0.2% L. salivarius supplement in total diet had the capability to markedly elevate levels of CAT, GSH-Px, SOD, anti-inflammatory cytokine from the serum as well as tight junction proteins (Claudin-1, Occludin, and ZO-1) extracted from intestine in LPS-challenged piglets. These changes were accompanied by the obvious downregulation of D-lactic acid, DAO, MDA and pro-inflammatory mediators in the serum, including IL-1β, IL-6, IFN-γ, and TNF-α. Meanwhile, the expression levels of TLR2 and TLR4 in spleen and mesenteric lymph nodes were significantly lower whereas the oxidation-related gene, ho-1 was up-regulated with L. salivarius administration. Our findings suggested that relatively high dose L. salivarius (0.1–0.2%) could regulate the progression of inflammatory response and oxidative stress when individuals were exposed to LPS, thus probably offering valuable assistance in restoring barrier function and improving overall performance.


2021 ◽  
Vol 8 ◽  
Author(s):  
Chunyan Shao ◽  
Moufeng Zheng ◽  
Ziwei Yu ◽  
Sheng Jiang ◽  
Bin Zhou ◽  
...  

The purpose of this study was to investigate the effects of dietary Selenohomolanthionine (SeHLan) on antioxidant status and immune response in canine parvovirus (CPV) vaccinated puppies. In this study, 30 weaned puppies were randomly divided into six groups: control group (–Se/–Vacc), immunization group (–Se/+Vacc), supplementation of sodium selenite group (SS/+Vacc, 0.35 mg/kg DM), low-dose SeHLan group (SeHLan-L/+Vacc, 0.35 mg/kg DM), mid-dose SeHLan group (SeHLan-M/+Vacc, 1.0 mg/kg DM), and high-dose SeHLan group (SeHLan-H/+Vacc, 2.0 mg/kg DM). The puppies were fed for 42 days and vaccinated with Vanguard Plus 5 on day 0 and day 21. Blood samples were collected on 7, 14, 21, 28, 35, 42 days post-immunization (PI) for determination of antioxidant indicators, lymphocyte proliferation index, serum cytokine concentration (IL-2, IL-4), canine polymorphonuclear neutrophils (PMN) phagocytic function, and the level of CPV antibody titers. The results showed that SeHLan supplementation raised the serum Se concentration and glutathione peroxidase (GSH-Px) activity in a dose-dependent manner (P &lt; 0.05). It also increased the activity of serum superoxide dismutase (SOD) and decreased serum malondialdehyde (MDA) content, especially in SeHLan-M/+Vacc group (1.0 mg/kg DM) (P &lt; 0.01). SeHLan supplementation significantly increased lymphocyte proliferation, IL-2, and IL-4 levels in canine serum, and enhanced phagocytosis of PMN in vaccinated puppies (P &lt; 0.05). Moreover, SeHLan supplementation shortened the CPV antibody production time and increased the CPV antibody titers (P &lt; 0.05). Of note, the beneficial effects of SeHLan were superior to those of SS. In conclusion, dietary SeHLan supplementation improved antioxidant activity, increased CPV antibody titers, and enhanced immune function in puppies after weaning. An appropriate dosage of SeHLan (1~2 mg/kg DM) may confer nutritional benefits in puppies.


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