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91.
    
Antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics and chemotherapy in the treatment of multidrug-resistant pathogens and drug-resistant cancers. Clinical application of AMPs is limited due to low stability and inefficient transport. Encapsulation in nanocarriers may improve their therapeutic potential. Chitosan nanoparticles (CS-NPs) are efficient carriers for proteins and peptides, improving the treatment of microbial infections and targeted drug delivery. We examined toxicity against cancer cell lines and antibacterial activities of the pleurocidin-like AMP NRC-07 upon encapsulation in CS-NPs by ionotropic gelation. The biological activities of various formulations of free and encapsulated NRC-07 and free nanoparticles were evaluated against Pseudomonas aeruginosa and breast cancer cells, using assays for cell viability and lactate dehydrogenase cytolysis with non-cancer cell lines as controls. NRC-07-containing nanoparticles decreased the bacterial and cancer cell viability in a concentration-dependent manner. Activities of encapsulated peptide were >2-fold higher than those of free NRC-07 peptide. Unloaded CS-NPs and free peptide were not cytotoxic against control cells. Encapsulation of NRC-07 into CS-NPs enhanced the antibacterial and selective cytotoxicity of the peptide, possibly enhancing anticancer activities. Encapsulation presents a promising tool for the development of efficient drug delivery systems.  相似文献   
92.
In this study, two olive mill wastes - exhausted olive cake (EOC) and paste of olive mill wastewater naturally dehydrated (POMW) - were co-composted and mixed with 25% sesame bark (SB). The humification process was evidenced by quantifying the humic substances and the generally accepted humification indices: (i) the ratio of humic acid (HA) carbon to fulvic acid (FA) carbon (CHA/CFA), (ii) the ratio of water soluble organic carbon (CW) to total organic nitrogen (Cw/Norg), (iii) and the ratio of humic acid carbon to total organic carbon CHA/Corg and by determining the absorbance ratios: E2/E4, E2/E6 and E4/E6. The results showed that the time required to reach maturity was dependant on the chemical properties of the initial raw materials used. The compost including EOC had more nitrogen and synthesised more polymerised HA, the POMW compost also had acceptable degrees of stability and maturity at the end of the process. Maturation was confirmed by a decline in Cw below 1.7, an increase in nitrogen, in HA, in CHA/CFA and an elimination of phytotoxicity. Composts produced with olive mill wastes, experimented on potato culture in the field, can be considered beneficial to soils because of their humification indexes and no toxicity.  相似文献   
93.
To determine whether PAX-2 and PAX-8 are involved in Wilms tumor (WT) pathogenesis, we sought mutations in these two genes in 99 Wilms tumors of favorable histology. We screened the entire protein coding sequences as well as the intronic regions adjacent to exons, using denaturing HPLC followed by sequencing of samples displaying abnormal chromatograms. In PAX-2, a silent polymorphism was found within exon 2 and exon 8 in 1% and 21% of cases, respectively. Three apparently silent polymorphisms were also found in PAX-8, two in exon 5 (2 of 99 cases or 2%) and one in exon 6 (22 of 99 cases or 22%), all of which were located 3' to the exons. In conclusion, no evidence for disease causing mutation was found using this technique, and so the direct involvement of either of these two genes in WT is unlikely.  相似文献   
94.
95.
It has been speculated that trace elements may a play role in the pathogenesis of heart diseases. In the present study, we aimed to assess the levels of selenium (Se) and mercury (Hg) in biological samples (whole blood, urine, and scalp hair) of myocardial infarction (MI) patients of both genders (age range 45–60 years) at the first, second, and third heart attack (n?=?130), hospitalized in a cardiac ward of a civil hospital of Hyderabad City (Pakistan). For comparison, healthy age-matched referent subjects (n?=?61) of both genders were also selected. Se and Hg in biological samples were measured by electrothermal atomic absorption spectrometry and cold vapor atomic absorption spectrometry, prior to microwave acid digestion, respectively. The validity of the methodology was checked by biological certified reference materials. During this study, 78 % of the 32 registered patients of third MI attack (aged >50 years) died. The concentration of Se was decreased in scalp hair and blood samples of MI patients, while Hg was higher in all biological samples as compared to referent subjects. Se concentration was inversely associated with the risk of MI attacks in both genders. These results add to an increasing body of evidence that Se is a protective element for cardiovascular health.  相似文献   
96.
    
Altered expression of multiple miRNAs was found to be extensively involved in the pathogenesis of different neurological disorders including Alzheimer's disease, Parkinson's disease, stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. One of the biggest concerns within gene-based therapy is the delivery of the therapeutic microRNAs to the intended place, which is obligated to surpass the biological barriers without undergoing degradation in the bloodstream or renal excretion. Hence, the delivery of modified and unmodified miRNA molecules using excellent vehicles is required. In this light, mesenchymal stem cells (MSCs) have attracted increasing attention. The MSCs can be genetically modified to express or overexpress a particular microRNA aimed with promote neurogenesis and neuroprotection. The current review has focused on the therapeutic capabilities of microRNAs-overexpressing MSCs to ameliorate functional deficits in neurological conditions.  相似文献   
97.
Staphylococcus aureus is a gram positive bacterium, responsible for both community-acquired and hospital-acquired infection, resulting in a mortality rate of 39%. 43.2% resistance to methicilin and emerging resistance to Fluroquinolone and Oxazolidinone, have evoked the necessity of the establishment of alternative and effective therapeutic approach to treat this bacteria. In this computational study, various database and online software are used to determine some specific targets of Staphylococcus aureus N315 other than those used by Penicillin, Quinolone and Oxazolidinone. For this purpose, among 302 essential proteins, 101 nonhomologous proteins were accrued and 64 proteins which are unique in several metabolic pathways of S. aureus were isolated by using metabolic pathway analysis tools. Furthermore, 7 essentially unique enzymes involved in exclusive metabolic pathways were revealed by this research, which can be potential drug target. Along with these important enzymes, 15 non-homologous proteins located on membrane were identified, which can play a vital role as potential therapeutic targets for the future researchers.  相似文献   
98.
In order to gain insight into the function of the Saccharomyces cerevisiae SWI/SNF complex, we have identified DNA sequences to which it is bound genomewide. One surprising observation is that the complex is enriched at the centromeres of each chromosome. Deletion of the gene encoding the Snf2 subunit of the complex was found to cause partial redistribution of the centromeric histone variant Cse4 to sites on chromosome arms. Cultures of snf2Δ yeast were found to progress through mitosis slowly. This was dependent on the mitotic checkpoint protein Mad2. In the absence of Mad2, defects in chromosome segregation were observed. In the absence of Snf2, chromatin organisation at centromeres is less distinct. In particular, hypersensitive sites flanking the Cse4 containing nucleosomes are less pronounced. Furthermore, SWI/SNF complex was found to be especially effective in the dissociation of Cse4 containing chromatin in vitro. This suggests a role for Snf2 in the maintenance of point centromeres involving the removal of Cse4 from ectopic sites.  相似文献   
99.
The purpose of this study was to develop a physicomechanically customizable oral metal chelatory in situ hot melt dispersion mini-pellet entity which could be utilized within a binary drug delivery system. Avicel® RC/CL type R-591 was included within the in situ hot melt dispersion mini-pellet formulations to determine the physicomechanical effect this compound would have on the mini-pellet formulations. The physicomechanical properties of the hot melt in situ mini-pellet formulations were mathematically fitting to regression curves. Physicomechanical adjustment of the in situ hot melt dispersion mini-pellet formulations could be mathematically predicted with the derived regression curve equations. The addition of Avicel® RC/CL type R-591 increased the physicomechanical properties such as matrix hardness and increased total disintegration of the in situ hot melt dispersion mini-pellet formulations. The utilization of a physicomechanically customizable oral metal chelatory in situ hot melt dispersion mini-pellet entity within a binary drug delivery system would to achieve a synergistically enhance the activity of a drug-carrying entity or a permeation enhancing entity within a single drug delivery unit. The experimental results indicated that weights of the pellets that achieved optimal hardness ranged between 35 and 45 mg. The melt–dispersion formulations disintegrated within shorter time periods and maintained higher ethylenediaminetetraacetic acid (EDTA) concentrations whereas melt–dispersion formulations which included Avicel® had superior physicomechanical properties. Disintegration times ranged between 1,000 s for melt–dispersions containing EDTA and methyloxy polyethylene glycol 2000 (mPEG) only, to >6,000 s for melt–dispersions comprising EDTA, mPEG, and Avicel®.  相似文献   
100.

Background

Leishmaniasis is a disease caused by protozoan parasites of genus Leishmania. The frequent involvement of Leishmania tropica in human leishmaniasis has been recognized only recently. Similarly as L. major, L. tropica causes cutaneous leishmaniasis in humans, but can also visceralize and cause systemic illness. The relationship between the host genotype and disease manifestations is poorly understood because there were no suitable animal models.

Methods

We studied susceptibility to L. tropica, using BALB/c-c-STS/A (CcS/Dem) recombinant congenic (RC) strains, which differ greatly in susceptibility to L. major. Mice were infected with L. tropica and skin lesions, cytokine and chemokine levels in serum, and parasite numbers in organs were measured.

Principal Findings

Females of BALB/c and several RC strains developed skin lesions. In some strains parasites visceralized and were detected in spleen and liver. Importantly, the strain distribution pattern of symptoms caused by L. tropica was different from that observed after L. major infection. Moreover, sex differently influenced infection with L. tropica and L. major. L. major-infected males exhibited either higher or similar skin pathology as females, whereas L. tropica-infected females were more susceptible than males. The majority of L. tropica-infected strains exhibited increased levels of chemokines CCL2, CCL3 and CCL5. CcS-16 females, which developed the largest lesions, exhibited a unique systemic chemokine reaction, characterized by additional transient early peaks of CCL3 and CCL5, which were not present in CcS-16 males nor in any other strain.

Conclusion

Comparison of L. tropica and L. major infections indicates that the strain patterns of response are species-specific, with different sex effects and largely different host susceptibility genes.  相似文献   
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