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121.
BackgroundTriple negative breast cancer (TNBC) is the most aggressive form of breast cancer with limited treatment modalities. It is associated with high propensity of cancer recurrence.MethodsUV Spectroscopy, FTIR, DLS, Zeta potential, TEM and SEM were employed to characterize nanoparticles. MTT assay, Wound healing assay, SEM, Immunocytochemistry analysis, Western blot, RT-PCR, mammosphere formation assay were employed to study apoptosis, cell migration and stemness. Tumor regression was studied in chick embryo xenograft and BALB/c mice model.ResultsHylaluronic acid engrafted metformin loaded graphene oxide (HA-GO-Met) nanoparticles exhibited an anti-cancer efficacy at much lower dosage as compared to metformin alone. HA-GO-Met nanoparticles induced apoptosis and inhibited cell migration of TNBC cells by targeting miR-10b/PTEN axis via NFkB-p65. Upregulation of PTEN affected pAKT(473) expression that induced apoptosis. Cell migration was inhibited by reduction of pFAK/integrinβ1 expressions. Treatment inhibited epithelial mesenchymal transition (EMT) and reduced stemness as evident from the increase in E-cadherin expression, inhibition of mammosphere formation and low expression levels of stemness markers including nanog, oct4 and sox2 as compared to control. Moreover, tumor regression was studied in chick embryo xenograft and BALB/c mice model. HA-GO-Met nanoparticle treatment reduced tumor load and nullified toxicity in peripheral organs imparted by tumor.ConclusionsHA-GO-Met nanoparticles exhibited an enormous anti-cancer efficacy in TNBC in vitro and in vivo.General significanceHA-GO-Met nanoparticles induced apoptosis and attenuated cell migration in TNBC. It nullified overall toxicity imparted by tumor load. It inhibited EMT and reduced stemness and thereby addressed the issue of cancer recurrence.  相似文献   
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Escherichia coli PBP5, a DD-carboxypeptidase (DD-CPase), helps in maintaining cell shape and intrinsic β-lactam resistance. Though PBP5 does not have β-lactamase activity under physiological pH, it has a common but shorter Ω-like loop resembling class A β-lactamases. However, such Ω-like loop lacks the key glutamic acid residue that is present in β-lactamases. It is speculated that β-lactamases and DD-CPases might have undergone divergent evolution leading to distinct enzymes with different substrate specificities and functions indicating the versatility of the Ω-loops. Nonetheless, direct experimental evidence favoring the idea is insufficient. Here, aiming to investigate the effect of introducing a glutamic acid residue in the PBP5 Ω-like loop, we substituted A184 to E to create PBP5_A184E. Expression of PBP5_A184E in E. coli ?PBP5 mutant elevates the β-lactam resistance, especially for cephalosporins. However, like PBP5, PBP5_A184E has the ability to complement the aberrantly shaped E. coli septuple PBP mutant indicating an unaffected in vivo DD-CPase activity. Biochemical and bioinformatics analyses have substantiated the dual enzyme nature of the mutated enzyme possessing both DD-CPase and β-lactamase activities. Therefore, substitution of A184 to E of Ω-like loop alone can introduce the cephalosporinase activity in E. coli PBP5 supporting the phenomenon of a single amino acid polymorphism.  相似文献   
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Ledebouria revoluta are important ethnomedicinal plant found in India and South Africa. Micropropagation via indirect shoot organogenesis had been established from three types of explant (i.e. scale leaf, leaf lamina and root) of L. revoluta. Scale leaf was found superior as compared to leaf lamina and root explant with respect to their organogenic callus induction potentiality. Murashige and Skoog (1962) [MS] media supplemented with 3.0?mg?L?1 2,4-dichlorophenoxyacetic acid, 0.75?mg?L?1 β-naphthoxyacetic acid were best effective for inducing organogenic callus. Maximum 17.0?±?0.52 bulblets were induced from about 500?mg of callus within 42–46?days sub-culturing on a medium containing 0.75?mg?L?1 kinetin. The bulblets were matured (86.7% success) after one month culture on the same medium composition. The best result of in vitro root induction with 100% response and 8.4?±?0.31 roots per bulb was achieved after 18?days of implantation on MS medium containing 2.0?mg?L?1 indole-3-butyric acid. Plantlets were acclimatized with a 96.0% survival rate. Chromosomal studies revealed cytological stability of callus cells and all regenerants containing 2n?=?30 chromosomes, same as parental plants. Antimicrobial activity of L. revoluta was tested against two Gram-positive bacteria, three Gram-negative bacteria and two fungi. The methanol and ethanol extract proved more effective against bacteria, whereas acetone and chloroform extract shows potential anti-fungal activities. Present protocol can be applied reliably to produce uniform planting materials in large scale. In addition, this efficient indirect regeneration pathway via callus culture opens a way for improvement through genetic transformation.  相似文献   
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Rice (Oryza sativa L.) seedlings were grown under NaCl stress. The leaf growth of resistant cv. Damodar was less affected than that of the susceptible cv. Jaya. The leaf protein content showed no distinct cultivar or age dependent differences under NaCl salinity. There was a significant increase in chlorophyll (Chl) and carotenoid (Car) contents of 25-d-oldseedlings of both cv. Jaya and cv. Damodar. However, Chl and Car content of 15-d-old seedlings of cv. Jaya decreased and that of cv. Damodar increased, under NaCl stress. This revised version was published online in July 2006 with corrections to the Cover Date.  相似文献   
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Analyses of sedimentation equilibrium data   总被引:1,自引:0,他引:1  
A numerical procedure is presented which can quite adequately compute the molecular weight averages as a function of solute concentration from sedimentation equilibrium data for homogeneous systems and for monomer-dimer associating systems with a possible extension to heterogeneous systems where monotonic variation in the weight average molecular weight is observed such as in weakly associating or dissociating systems. The procedure utilizes the method of orthogonal polynomials for curve fitting which allows for a rapid determination of best fit with minimal round off error. The procedure is particularly applicable in cases where the concentration of solute at the meniscus can be considered to be neither appreciable and reasonably well determined as in low speed sedimentation equilibrium experiments, nor essentially zero as in high speed sedimentation equilibrium experiments where the calculations become somewhat more simplified. The use of moderate speed sedimentation equilibrium has the advantage of providing a more broad concentration distribution in the centrifuge cell which yields more extensive information concerning dissociating systems yet still provides results at low solute concentrations where most solutes can be considered to be behaving ideally.  相似文献   
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This study concerns the effect of graded doses of estrogen, alone or in combinations with progesterone, on the biochemical composition of the rat seminiferous tubules. Data on the accessory genital organs and pituitary gonadotrophic activity are added. Adult male albino rats received estradiol dipropionate (.1, 1 and 5 mcg/rat) injected intramuscularly, in .1 ml olive oil, daily for 30 days. Animals given the 5 mcg dose were given a 30 day rest period to determine reversibility of effects. In another group estrogen (5 mcg/rat) and progesterone (1 mg/rat) were given concurrently but at different sites for 30 days. Controls received vehicle only. Animals were sacrificed 24 hours after the last injection or rest period and genital organs and the pituitary were removed for study. A progessive reduction in testis weight with dosage was found after estrogen or the combination (p is less that .01). The low dose (.1mcg) had an inconsistent effect on spermatogenesis and endocrine function of the testis. Diameter of the tubules was reduced. Spermatogenesis was arrested in 25% of the tubules at the spermatid of secondary spermatocyte stage. Some normal spermatozoa were seen. Tunica propria was thickened. Some Leydig cells showed atrophy. Vascularity was increased. The median dose (1 mcg) caused spermatogenic arrest at the spermatid or secondary spermatocyte stage but the Sertoli cells were prominent. Only a few spermatozoa were seen. There was some desquamation of seminiferous epithilium. Tubular diameter was still further reduced and the tunica propria thickened. Leydig cells were atrophied. Few spermatozoa were found although 25-30% showed some spermatogenesis. The high dose (5 mcg) caused marked reduction in the diameter of the tubules. Spermatogenesis was arrested at the primary spermatocyte or spermatogonial stage. The tunica popria was much thickened. There was much desquamation and tubular lumeus were filled with debris. The Sertoli cells were hypertrophied. The Leydig cells were atrophied. The tunica albuginea was thickened. There were no spermatozoa. In the recovery group estrogen effects had disappeared, but the tubular diameter remained reduced. Tunica propria was normal. Spermatogenesis progressed to the spermatid stage and in 50% of the tubules many spermatozoa were present. The Leydig cells appeared normal. However spermatozoa were not found in the vas defereus. The histological appearance of the teatis in the estrogen and progesterone group was of the high dose estrogen type but with arrest of spermatogenesis at the spermatid, spermatocye or spermatogonial stage. The Sertoli cells remained hypertrophied. Leydig cells were atrophic. The large blood vessels were engorged. Weight of organs returned almost to normal. Estrogen .1 and 1 mcg had no effect on pituitary weight or gonadotrophin content. The high dose (5 mcg) alone or with progesterone caused a significant increase in pituitary weight (p is less than .0). Estrogen alone (5 mcg) caused a significant decline in pituitary gonadotrophin content (p is less than .0) but the combined therapy had no effect. None of the biochemical constituents of the seminiferous tubules showed any change after injection of .1 mcg of estrogen but 1 mcg dose caused an increase in protein nitrogen, alkaline phosphatase activity and total lipids. The high dose (5 mcg) provoked higher levels.  相似文献   
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