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Polylactic acid (PLA) bioplastics have attracted increasing attention from both academic and industrial researchers due to their biomass‐derived nature and low toxicity for the human body and environment. A major drawback of PLA is slow crystallization during processing, which considerably limits its commercial applications. In this study, a simple and low‐cost approach involving the addition of eco‐friendly low molecular weight poly(ethylene glycol) (PEG; 400 g/mole) as a green solvent was developed to enhance the PLA crystallization process. Differential scanning calorimetry and polarized optical microscopy data revealed that the introduction of PEG into PLA considerably increased the PLA crystallization rate. In particular, the isothermal crystallization rate of a system with a PLA/PEG mass ratio of 70/30 was more than seven times greater than that of neat PLA. In addition, the miscibility, thermal properties, and microstructures of various PLA/PEG blends were determined. A substantial reduction in the equilibrium melting temperature of PLA after PEG addition confirmed that these polymer blends were thermodynamically miscible in the melt, which strongly influenced the PLA crystallization rate. Furthermore, the addition of PEG increased the regularity of PLA crystals and induced the formation of ring‐banded PLA spherulites with periodic twisted lamellae. [ABSTRACT FROM AUTHOR]

Aims: We aimed to find where and how noise‐induced cochlear hearing loss affects the central nervous system during the early state and identify the neural substrate for aberrant patterns that mediating noise‐related anxiety−/depression‐ like behaviors. Methods: Broad band noise with 122 dB for 2 hours was conducted to induce hearing loss. We defined 0 day (N0D) and 10 days (N10D) post noise as the acute and sub‐acute period. Behavioral tests (Open field test and light/dark test) and resting‐state fMRI were computed to evaluate emotional conditions and aberrant neural activity. Functional connectivity analysis using the anterior cingulate cortex as a seed was computed to reveal the spatial distribution beyond auditory network during both periods. Results: Anxiety−/depression‐like behaviors were found in rats with noise exposure. Between‐group analysis revealed that N0D rats displayed widespread reductions in functional connectivity, spanning primary somatosensory cortex, medial geniculate body, inferior colliculus, cingulate cortex, cerebellar lobule comparing with N10D rats and a similar pattern was also occurred in comparison with the control group. Conclusion: Taken together, an "acoustic‐causing" network accounting for distress and gating of noise exposure related anxiety/depression was proposed. [ABSTRACT FROM AUTHOR]

The highly practical acetylation of free nucleosides is achieved using acetic anhydride/acetic acid as a reusable solvent and acetylating regent. A series of nucleosides, including ribosyl, deoxyribosyl, arabinosyl, acyclic and pyranosyl, and many clinical drugs were acetylated efficiently, even on large scale (200 g). [ABSTRACT FROM AUTHOR]

High-porosity magnesia phosphate paste (HPMPP) was prepared via the pre-foaming method. In the pre-foaming method, sintering treatment was not required. The bulk density and maximum compressive strength of the HPMPP prepared according to the ratio of water to solids (W/So) of 0.32 reached 464.00 ± 5.00 Kg/m3 and 0.30 ± 0.05 MPa, respectively. The compressive strength increased with the increases in the addition amounts of sodium silicate and polypropylene fibers. The bulk density of HPMPP increased with the increase in the addition of sodium silicate and decreased with the increase in the addition of polypropylene fibers. Besides, the porosity of the magnesia phosphate paste increased from 79.85% to 81.27% and from 80.31% to 83.75% after the addition of sodium silicate and polypropylene fibers respectively. The highest porosity (83.75%) of the prepared HPMPP was realized under the addition proportion (sodium silicate: polypropylene fibers: solids = 0.06:0.0025:1). The average pore size of the prepared HPMPP is about 180 μm and the pore distribution range is relatively narrow. The hydration product (struvite) is combined with MgO particle one by one and then coated on the surface of bubbles. With the decrease of the water content, after breaking bubbles, the porous structure can be achieved. [ABSTRACT FROM AUTHOR]

Bryophyte substrates and species may affect spore germination through allelopathy. Polytrichum strictum is currently expanding in peatlands in north-eastern China – is this an effect of its superior spore germinability or do its gametophytes have a stronger allelopathic effect than do Sphagnum ? We conducted a spore burial experiment to test the effect of species identity, substrate and water table depth (WTD) on spore germinability and bryophyte allelopathic effect with P. strictum and two Sphagnum species ( S. palustre and S. magellanicum ). After 5 months of burial during a growing season, the spores were tested for germinability. Allelopathic effect of bryophyte substrates was assessed by the difference between spore germinability after being stored inside or outside the substrates. After burial, more than 90% of the spores lost their germinability across all three species due to ageing and allelopathy. Spore germinability differed among species, where the spores in S. palustre had a higher germination frequency than those in P. strictum . The three bryophytes maintained a higher germinability in Sphagnum than in Polytrichum hummocks, probably due to a stronger allelopathic effect of P. strictum . Water table drawdown by 10 cm increased germinability by more than 60% across the three species. The study indicates that P. strictum does not possess an advantage regarding spore germination but rather its gametophytes have a stronger allelopathic effect. Due to the weaker inhibitive effect of Sphagnum gametophytes, P. strictum may have a potential establishment superiority over Sphagnum in peatlands, in addition to a better drought tolerance, which may explain its current expansion. [ABSTRACT FROM AUTHOR]

In this study, a facile emulsion templating method was developed for the preparation of high-performance monolithic porous titania-based humidity-sensing ceramics. High internal phase Pickering emulsions (HIPEs) with internal phase of 70 vol%, stabilized by short-chain amphiphilic molecules in situ modified TiO 2 solid nanoparticles, were employed as templates. The obtained sensors contain a hierarchically ordered three-dimensional interconnected pore structure and exhibit high sensitivity to water vapors as well as linear response in the wide relative humidity (RH) range between 11% and 95%. The observed sensor impedance variation can be as high as four orders of magnitude, depending on the RH value. In addition, the produced sensors are characterized by the reversible response with relatively small hysteresis and thus can be reversibly operated without repeated high-temperature thermal desorption cleaning. [ABSTRACT FROM AUTHOR]

Natucin C (NC) and Natucin P (NP) are two kinds of antimicrobial peptides (AMPs). In the present study, the effects of NC-NP mixture on a tilapia species ( Oreochromis niloticus ) were examined. Animals were fed with either a control diet or one of five AMP-supplemented diets for eight weeks. AMP-supplemented diets contained five increasing levels of NP from G1 to G5 and one level of NC (200 mg/kg). Results showed that fish in the G3, G4 and G5 groups had significantly higher levels of total protein (TP), albumin (ALB) and globulin (GLO) in serum than fish in the control group. Fish fed with G4 and G5 diets exhibited significantly higher high-density lipoprotein cholesterol (HDL-C) levels compared to the control fish. Lipopolysaccharide (LPS) levels in all AMP-supplemented groups were significantly lower than the control. In addition, the total antioxidant capacity (TAOC) and lysozyme (LZM) activities were significantly increased in fish fed with the G3 and G4 diets, respectively compared to the control. The serum malondialdehyde (MDA) levels in fish fed with AMP-supplemented diets were significantly decreased compared to those not supplemented with AMPs. Furthermore, the mRNA expressions of tumor necrosis factor alpha ( TNF-α ), interleukin-1-beta ( IL-1β ), gamma interferon ( IFN-γ ) and heat shock protein 70 (HSP70 ) in the hepatopancreas, spleen, kidney and gill were measured. Overall, the expression levels were enhanced in an NP dose-dependent and tissue-specific manner. The expressions of four genes in four organs (except IL-1β in spleen, and TNF-α and HSP70 in gill) were significantly upregulated in fish fed with the G5 diet. Fish fed with the G4 diet had increased expression levels of IL-1β in spleen and IFN-γ in kidney. The relative expression levels of TNF-α , IL-1β and HSP70 in the hepatopancreas in fish fed with the G3 diet were significantly upregulated compared to the control. Transcriptional levels of IL-1β and HSP70 in the hepatopancreas, IFN-γ and HSP70 in the kidney and IL-1β in the gills of fish fed with the G2 diet were upregulated. Taken together, our results indicated that the NC-NP mixture can enhance the antioxidant capacity and innate immune ability of O . niloticus , indicating that this mixture might be a potential alternative to antibiotics when used as a feed additive. [ABSTRACT FROM AUTHOR]

The evaluation and optimization of landscape ecological pattern has important implications for the accurate improvement of forest quality and high-quality urban development in the Pearl River Delta urban agglomeration. Based on the "one map" data and digital elevation model data of forest resource management in 2021, we evaluated and optimized landscape ecological pattern of the Pearl River Delta urban agglomeration by morphological spatial pattern analysis and minimum cumulative resistance model. The results showed that there were 435861 patches in the Pearl River Delta urban agglomeration that could be used as ecological source area, covering an area of 7346.60 km 2 and accounting for 13.4% of the Pearl River Delta area. Thirty patches were selected as the ecological source area of the study area by using the area and patch importance index, covering an area of 2792.59 km 2 and accounting for 5.1% of the Pearl River Delta area. The overall natural environment of the Pearl River Delta urban agglomeration was excellent. The ecological resistance level was small. The peripheral ecological resistance was low. The core ecological resistance was high. There was still a large room for adjustment of stand types and landscape patterns, which should be optimized by adjusting the composition and spatial distribution of tree species. The ecological network of the Pearl River Delta urban agglomeration was optimized with 30 ecological sources, 103 key ecological corridors, and 95 ecological nodes. The improvement rates of the optimized probability of connectivity index and integral index of connectivity index were 297.5% and 695.1%, respectively. The optimization results could effectively connect the ecological sources and spread the ecological service functions of ecological sources.

Phosphodiesterase (PDE) inhibitors can improve sperm motility in patients with asthenozoospermia. However, the most commonly reported nonselective PDE inhibitor pentoxifylline and PDE5 inhibitor sildenafil have the disadvantages of requiring a high concentration and destroying sperm integrity. We examined the PDE10A inhibitor PF-2545920 to compare its ability to promote sperm motility with that of pentoxifylline and sildenafil. After seminal plasma was discarded, several semen samples were subjected to four treatments (control, PF-2545920, pentoxifylline, and sildenafil) to evaluate their ability to affect motility, viability, and spontaneous acrosome reactions. Intracellular calcium and adenosine triphosphate (ATP), mitochondrial membrane potential, and penetration through viscous medium were assessed by flow cytometry, luciferase, and hyaluronic acid after treatment with PF-2545920. Statistical analyses were performed using the analysis of variance statistical test. PF-2545920 elevated the percentage of motile spermatozoa compared to the control, pentoxifylline, and sildenafil groups at 10 µmol l -1 ( P < 0.01). It is less toxic to GC-2spd mouse spermatocytes cells and spermatozoa and causes fewer spontaneous acrosomal reactions ( P < 0.05). PF-2545920 also increased mitochondrial membrane potential ( P < 0.001) and altered intracellular calcium ( P < 0.05) in a dose-dependent manner, including increasing sperm hyaluronic acid penetrating ability ( P < 0.05). Therefore, PF-2545920 might be an excellent choice for stimulating the sperm motility., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Activated nucleotide binding to the oligonucleotide receptor protein 3 (NLRP3) inflammasome is possibly involved in the pathogenesis of Alzheimer's disease through oxidative stress and neurogenic inflammation. Low expression of the signal transducer and activator of transcription 3 (STAT3) gene may promote the occurrence of neurodegenerative diseases to some extent. To clarify the roles of the NLRP3 inflammasome and STAT3 expression in oxidative stress, (1) SHSY5Y cells were incubated with 1 mM H 2 O 2 to induce oxidative stress injury, and the expression of human-cell-specific signal transduction, STAT3-shRNA silencing signal transduction and STAT3 were detected. Cells were pretreated with Ca 2+ chelator BAPATA-AM (0.1 mM) for 30 minutes as a control. (2) Western blot assay was used to analyze the expression of caspase-1, NLRP3, signal transduction and STAT3. Enzyme-linked immunosorbent assay was used to analyze interleukin-1β levels. Flow cytometry was carried out to calculate the number of apoptotic cells. We found that H 2 O 2 treatment activated NLRP3 inflammasomes and decreased phosphorylation of signal transduction and STAT3 serine 727. BAPTA-AM pretreatment abolished the H 2 O 2 -induced activation of NLRP3 inflammasomes, caspase-1 expression, interleukin-1β expression and apoptosis in SHSY5Y cells, and had no effect in cells with downregulated STAT3 expression by RNAi. The findings suggest that downregulation of signal transduction and STAT3 expression may enhance the oxidative stress mediated by NLRP3, which may not depend on the Ca 2+ signaling pathway., Competing Interests: None

Renal ischemia-reperfusion injury (IRI) is regarded as a leading cause of acute kidney failure and renal dysfunction. Previous studies show that kappa opioid receptor (KOR) agonists can attenuate IRI in cardiomycytes and neuronal cells. In this study we explored the effects of a KOR agonist on renal IRI and the underlying mechanisms in vivo and in vitro. An IRI model was established in SD rats, which were intravenously pretreated with a KOR agonist U50448H (1 mg/kg), a KOR antagonist Nor-BNI (2 mg/kg) followed by U50448H (1 mg/kg), or the PI3K inhibitor wortmannin (1.4 mg/kg) followed by U50448H (1 mg/kg). U50448H pretreatment significantly decreased the serum levels of creatinine (Cr) and BUN, the renal tubular injury scores and the apoptotic index (AI) in IRI model rats. Furthermore, U50448H significantly increased SOD activity and NO levels, and reduced the MDA levels in the kidney tissues of IRI model rats. Moreover, U50448H significantly increased the phosphorylation of Akt, eNOS and PI3K in the kidney tissues of IRI model rats. All the beneficial effects of U50448H were blocked by Nor-BNI or wortmannin pre-administered. Similar results were observed in vitro in renal tubular epithelial NRK-52E cells subjected to a hypoxia-reoxygenation (HR) procedure. Our results demonstrate that the KOR agonist U50448H protects against renal IRI via activating the PI3K/Akt signaling pathway.

We investigated the ability of microRNA-93 (miR-93) to influence proliferation, invasion, migration, and apoptosisofrenal cell carcinoma (RCC) cells via transforming growth factor-β/solvated metal atom dispersed (TGF-β/Smad) signaling by targeting runt-related transcription factor 3 ( RUNX3 ). RCC tissues with corresponding adjacent normal tissues were collected from 249 RCC patients. And normal renal tissues were collected from patients without RCC who received nephrectomy. The RCC cell line ACHN was treated with miR-93 mimic, mimic-negative control (NC), miR-93 inhibitor, inhibitor-NC, and miR-93 inhibitor + small interfering RNA (siRNA) against RUNX3 (si-RUNX3). Expression of miR-93, RUNX3, TGF-β, and Smad4 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell proliferation was assessed by the Metallothioneins (MTS) assay, cell invasion by the wound-healing assay, cell migration by the Transwell assay, and cell cycle and apoptosis by flow cytometry. Compared with normal renal tissues, the expression of miR-93 and TGF-β were higher while that of RUNX3 and Smad4 were low in RCC and adjacent normal tissues (all P <0.05). RUNX3 was confirmed as a target of miR-93 by the dual luciferase reporter gene assay. Compared with mimic-NC group, cell proliferation, invasion, migration and cells from G0/G1 to S phase enhanced but the apoptosis decreased in the miR-93 mimic group (all P <0.05). Compared with inhibitor-NC group, proliferation, invasion, and migration reduced, while apoptosis increased, and cells at G0/G1 phase arrested in the miR-93 inhibitor group (all P <0.05). Compared with miR-93 inhibitor group, cell proliferation, invasion, and migration increased with increasing cells from G1 to S phase while the apoptosis decreased, in miR-93 inhibitor + si-RUNX3 group (all P <0.05). In conclusion, miR-93 inhibits apoptosis and promotes proliferation, invasion, and migration of RCC cells via TGF-β/Smad signaling by inhibiting RUNX3 ., Competing Interests: None.

Novel composite gel electrolytes were prepared using self-assembled organogels as scaffolds. Mixing silica with the low-molecular-weight poly(ethylene glycol) (PEG)-based electrolytes resulted in precipitation due to significant aggregation of silica. However, clear and transparent PEG-silica composite gel electrolytes were obtained with 1,3:2,4-dibenzylidene-d-sorbitol (DBS) organogels. The organogels resulted from the formation of DBS nanofibrillar networks in which the diameter sizes of the nanofibrils ranged from 10 to 100 nm, as observed by transmission electron microscopy. These three-dimensional nanofibrillar networks entrapped the silica and prevented its aggregation. The thermal properties, such as gel dissolution and thermal degradation temperatures, of the composite gels significantly increased with increasing silica content, as determined by polarizing optical microscopy and thermogravimetric analysis. The conductivity of the prepared composite gel electrolytes was clearly enhanced by increasing the silica content. The silica was well dispersed along the DBS nanofibrillar networks, establishing homogeneous microstructures and effective contact with other components of the electrolytes, leading to an increase in the conductivity.

Aim: To investigate the expression and localization of paxillin in rat pancreas during development., Methods: Pancreata from Sprague Dawley rat fetuses, embryos, young animals, and adult animals were used in this study. Expression levels of paxillin in pancreata of different development stages were detected by reverse transcription polymerase chain reaction and Western blotting. To identify the cell location of paxillin in the developing rat pancreas, immunohistochemistry and double-immunofluorescent staining were performed using antibodies for specific cell markers and paxillin, respectively., Results: The highest paxillin mRNA level was detected at E15.5 (embryo day 15.5) following a decrease in the later developmental periods (P < 0.05 vs E18.5, P0 and adult, respectively), and a progressively increased paxillin protein expression through the transition from E15.5 to adult was detected. The paxillin positive staining was mainly localized in rat islets of Langerhans at each stage tested during pancreas development., Conclusion: The dynamic expression of paxillin in rat pancreas from different stages indicates that paxillin might be involved in some aspects of pancreatic development.

In many instances, multidrug resistance (MDR) is mediated by increasing the expression at the cell surface of the MDR1 gene product, P-glycoprotein (P-gp), a 170-kD energy-dependent efflux pump. The aim of this study was to investigate the potential benefit of combination therapy with magnetic Fe(3)O(4) nanoparticle [MNP (Fe(3)O(4))] and MDR1 shRNA expression vector in K562/A02 cells. For stable reversal of "classical" MDR by short hairpin RNA (shRNA) aiming directly at the target sequence (3491-3509, 1539-1557, and 3103-3121 nucleotide) of MDR1 mRNA. PGC silencer-U6-neo-GFP-shRNA/MDR1 called PGY1-1, PGY1-2, and PGY1-3 were constructed and transfected into K562/A02 cells by lipofectamine 2000. After transfected and incubated with or without MNP (Fe(3)O(4)) for 48 hours, the transcription of MDR1 mRNA and the expression of P-gp were detected by quantitative real-time PCR and Western-blot assay respectively. Meanwhile intracellular concentration of DNR in K562/A02 cells was detected by flow cytometry (FCM). PGC silencer-U6-neo-GFP-shRNA/MDR1 was successfully constructed, which was confirmed by sequencing and PGY1-2 had the greatest MDR1 gene inhibitory ratio. Analysis of the reversal ratio of MDR, the concentration of daunorubicin (DNR) and the transcription of MDR1 gene and expression of P-gp in K562/A02 showed that combination of DNR with either MNP (Fe(3)O(4)) or PGY1-2 exerted a potent cytotoxic effect on K562/A02 cells, while combination of MNP (Fe(3)O(4)) and PGY1-2 could synergistically reverse multidrug resistance. Thus our in vitro data strongly suggested that a combination of MNP (Fe(3)O(4)) and shRNA expression vector might be a more sufficient and less toxic anti-MDR method on leukemia.

This study was aimed to explore the potential therapy of Gambogic acid (GA) combined with magnetic nanoparticle of Fe3O4 (Fe3O4-MNP) on leukemia. The proliferation of U937 cells and the cytotoxicity were evaluated by MTT assay. Cell apoptosis was observed and analyzed by microscopy and flow cytometry respectively. The expressions of gene and protein were detected by quantitative real-time polymerase chain reaction and Western blot respectively. The results showed that GA enhanced the cytotoxicity for U937 cells in dose- and time-dependent manners. The Fe3O4-MNP itself had not cytotoxicity, but could enhance the inhibitory effect of GA on proliferation of U937 cells. The apoptotic rate of U937 cells induced by combination of GA with Fe3O4-MNP was higher than that by GA alone. The typical apoptotic features of cells treated with GA and Fe3O4-MNP were observed. The expression levels of caspase-3 and bax after co-treatment of GA and Fe3O4-MNP were higher than that exposed to GA or Fe3O4-MNP alone, but the expressions of bcl-2, NF-kappaB and survivin were down-regulated. It is concluded that Fe3O4-MNP can promote GA-induced apoptosis in U937 cells, and the combination of GA with Fe3O4-MNP may be a safer and less toxic new therapy for leukemia.

The present study was aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet) in vitro and in vivo. The inhibitory effects of adriamycin (ADM) used alone or in combination with BrTet or Tet on the proliferation of K562 and K562/A02 cells were evaluated by MTT assay. The ADM accumulation and the protein levels of P-glycoprotein (P-gp) were detected by flow cytometry. The mRNA levels of P-gp were determined by RT-PCR. The in vivo effect of BrTet and Tet was investigated by using nude mice grafted with sensitive human leukemia cell line K562 and MDR cell line K562/A02. The results showed that BrTet at 0.25, 0.5 and 1 micromol/L reversed the resistance to ADM in MDR K562/A02 cells in a dose-dependent manner. Flow cytometry suggested that BrTet significantly increased the intracellular accumulation of ADM in K562/A02 cells in a dose-dependent manner. BrTet also inhibited the overexpression of P-gp in K562/A02 cells, and down-regulated mdr1 expression. In nude mice bearing K562 xenografts on the left flank and K562/A02 xenografts on the right flank, intraperitoneal injection of 10 mg/kg BrTet significantly enhanced the antitumor activity of ADM against K562/A02 xenografts with inhibitory rates of 26.1%, while ADM alone inhibited the growth of K562/A02 xenografts only by 5.8%. No enhancement effect by BrTet was seen in K562 xenografts. It is concluded that BrTet shows significant MDR reversal activity in vitro and in vivo. Its activity may be related to the inhibition of P-gp overexpression and the increase intracellular accumulation of anticancer drugs. BrTet may be a promising-MDR modulator for eventual assessment in the clinic.

Multidrug resistance (MDR) plays a major role in the failure of cancer chemotherapy. Since Fe(3)O(4)-magnetic nanoparticle loaded with daunorubicin (DNR) can overcome multidrug-resistance of K562 cells in vitro, the effect of Fe(3)O(4)-magnetic nanoparticle loaded with DNR on multidrug-resistant K562 cells was studied in vivo, the K562-n and its MDR counterpart K562-n/VCR cells were inoculated subcutaneously into both sides of the back of nude mice to establish a human leukemia xenograft model. The mice were randomly divided into group A receiving normal saline, group B receiving DNR, group C receiving Fe(3)O(4)-magnetic nanoparticle, group D receiving Fe(3)O(4)-magnetic nanoparticle loaded with DNR and group E receiving Fe(3)O(4)-magnetic nanoparticle containing DNR with a magnetic field built on the surface of the tumor tissue. The tumor volume was measured on the day 1, 5, 9, 13, 17 and 21 after the first treatment. Tumor tissues were isolated for examination of the expression of mdr-1 by reverse transcription polymerase chain reaction and Western blotting. The results showed that for K562-n/VCR tumor, the tumor volume was markedly lower in groups D and E than that in groups A, B and C. Pathological observation revealed that the tumor cells of group A and B grew well, some disseminated necrosis and some cells with karyorrhexis and karyopyknosis existed in group C. However, significant fracture, necrosis of cell and subsequently fibrosis were seen in group D and E. The transcription of mdr-1 gene in groups D and E was significantly lower than that in groups A, B and C (group D and E vs group A, B or C, p < 0.05). However, there were no differences about the protein expression of P-gp between these groups. The tumor volume of K562-n in groups C, D and E was markedly lower than that in groups A and B (group C, D and E vs group A or B, p < 0.05). Pathological observation showed that the tumor cell of group A and B grew well, and no obvious necrosis was observed. Significant fracture, necrosis of cell and subsequently fibrosis were seen in group C, D and E. It is concluded that DNR-loaded Fe(3)O(4) magnetic nanoparticles can suppress the growth of the MDR K562-n/VCR tumor in vivo, but can not further enhance its efficacy on the sensitive K562-n tumor as compared to DNR alone. The additional external magnetic field failed to further improve the antitumor effect in vivo.

The aim of this study was to investigate the potential benefit of combination therapy with magnetic nanoparticle of Fe(3)O(4) and 5-Bromotetrandrine (5-BrTet) on chronic leukemia. The apoptosis was detected by flow cytometry (FCM), Wright staining and light microscope; the expressions of BAX and BCL-2 were measured by Western blot. The results showed that combination of daunorubicin (DNR) with either MNP (Fe(3)O(4)) or 5-BrTet exerted a potent cytotoxic effect on K562/A02 cells, while MNP (Fe(3)O(4)) and 5-BrTet co-treatment could synergistically enhance DNR-induced apoptosis. After treated with this regimen, the typical apoptotic morphological features were found in K562/A02 cells; the expression level of BCL-2 decreased and BAX increased markedly. It is concluded that MNP (Fe(3)O(4)) or 5-BrTet with DNR can induce apoptosis in K562/A02 cells, and they show distinct synergism when used together. The down-regulation of BCL-2 and the up-regulation of BAX may play important roles.

This study was aimed to investigate the reversal effect of 5-bromotetrandrine (5-BrTet) and magnetic nanoparticle of Fe(3)O(4) (Fe(3)O(4)-MNPs) combined with DNR in vivo. The xenograft leukemia model with stable multiple drug resistance in nude mice was established. The two sub-clones of K562 and K562/A02 cells were respectively inoculated subcutaneously into back of athymic nude mice (1 x 10(7) cells/each) to establish the leukemia xenograft models. Drug resistant and the sensitive tumor-bearing nude mice were both assigned randomly into 5 groups: group A was treated with NS; group B was treated with DNR; group C was treated with nanoparticle of Fe(3)O(4) combined with DNR; group D was treated with 5-BrTet combined with DNR; group E was treated with 5-bromotetrandrine and magnetic nanoparticle of Fe(3)O(4) combined with DNR. The incidence of tumor formation, growth characteristics, weight and volume of tumor were observed. The histopathologic examination of tumors and organs were carried out. The protein levels of BCL-2, BAX, and Caspase-3 in resistant tumors were detected by Western blot. The results indicated that 5-BrTet and magnetic nanoparticle of Fe(3)O(4) combined with DNR significantly suppressed growth of K562/A02 cell xenograft tumor, histopathologic examination of tumors showed the tumors necrosis obviously. Application of 5-BrTet and magnetic nanoparticle of Fe(3)O(4) inhibited the expression of BCL-2 protein and up-regulated the expression of BAX, and Caspase-3 protein in K562/A02 cell xenograft tumor. It is concluded that 5-bromotetrandrine and magnetic nanoparticle of Fe(3)O(4) combined with DNR have significant tumor-suppressing effect on MDR leukemia cell xenograft model.

Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy. We evaluated the effect of daunorubicin (DNR)-loaded magnetic nanoparticles of Fe3O4 (MNPs-Fe3O4) on K562-n/VCR cells in vivo. K562-n and its MDR counterpart K562-n/VCR cell were inoculated into nude mice subcutaneously. The mice were randomly divided into four groups: group A received normal saline, group B received DNR, group C received MNPs-Fe3O4, and group D received DNR-loaded MNPs-Fe3O4. For K562-n/VCR tumor, the weight was markedly lower in group D than that in groups A, B, and C. The transcriptions of Mdr-1 and Bcl-2 gene were significantly lower in group D than those in groups A, B, and C. The expression of Bcl-2 was lower in group D than those in groups A, B, and C, but there was no difference in the expression of P-glycoprotein. The transcriptions and expressions of Bax and caspase-3 in group D were increased significantly when compared with groups A, B, and C. In conclusion, DNR-loaded MNPs-Fe3O4 can overcome MDR in vivo.