Background/Aims: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. Methods: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund’s adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. Results: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. Conclusion: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.
Antibacterial resistance remains a major global problem due to frequent prescriptions, leading to significant toxicities. To overcome the limitations of antibiotic therapy, it is highly desirable to provide site-specific delivery of drugs with controlled release. Inspired by the biocompatible, biodegradable, and site-specific mimicking behavior of poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL), we developed vancomycin-PEG-PCL-PEG conjugates to maximize the pharmacological effects and minimize the side effects. Drug-loaded vancomycin-PEG-PCL-PEG conjugates are influenced by size, shape, surface area, encapsulation efficiency, in vitro drug release, hemolysis assay, cytotoxicity, and antibacterial activity against methicillinresistant Staphylococcus aureus (MRSA) and bacterial kill kinetics. The results demonstrated that vancomycin (VCM) release from PEG-PCL-PEG triblock revealed a biphasic manner. Hemolysis assay showed the nonprescription nature of VCM-PEG-PCL-PEG. Cytotoxicity studies confirmed the biocompatibility of VCM-PEG-PCL-PEG. The in vitro antibacterial results showed enhance activity with minimum inhibitory concentration compared to bare VCM. Molecular dynamics simulation study revealed that binding between VCM and PEG-PCL-PEG by hydrophobic interactions offers molecular encapsulation and steric barrier to drug degradation. This newly developed therapeutic delivery system can offer to enhance activity and delivery VCM against MRSA.
Background:
Quinolones are among the most effective antibiotics against
Pseudomonas
spp. Several chromosomal and/or plasmid-mediated quinolone-resistance mechanisms have been found in
Pseudomonas
. Plasmid-mediated quinolone-resistance (PMQR) is mediated by quinolone-resistance (QNR) proteins, modifying enzymes or efflux pumps. Only a few previous studies examined the prevalence of quinolone-resistance in the Kingdom of Saudi Arabia (KSA) and showed it is increasing. Mechanisms of quinolone-resistance among
Pseudomonas
spp. in the KSA; examined herein; have not been extensively studied.
Methods:
Ninety-two
Pseudomonas
isolates were collected and their resistance to seven different types of quinolones was determined by the microbroth dilution method. PMQR mechanisms were examined using a PCR screen to identify six PMQR genes including
qnrA
,
qnrB
,
qnrD
,
qnrS,
aac(6´)-Ib-cr
, and
qepA
. Clonal relatedness of the quinolone-resistant isolates was determined by ERIC-PCR.
Results:
Of the isolates, 42.4% (39/92) were resistant to 1-7 of the tested quinolones. Gemifloxacin resistance was the lowest (28.3%) while resistance to the other six quinolones were ≥ 35%. The most common biotype among the 39 quinolone-resistant isolates was resistance to the seven tested quinolones (26/39; 66.7%).
qnrD
,
qnrS
, and
aac(6´)-Ib-cr
were found in 31 (79.5%), 31 (79.5%) and 28 (71.8%) of the 39 isolates, respectively, and all three genes together were found in 22 of the 39 isolates (56.4%).
qnrA, qnrB
, and
qepA
were not detected in any of the isolates and two isolates did not harbor any of the six tested genes. The isolates showed 38 different ERIC profiles and only two isolates (Pa16 and Pa17) had an identical profile.
Conclusion:
This is the first description of PMQR mechanisms among clinical
Pseudomonas
isolates from the KSA, which appears to be mainly mediated by
qnrD
,
qnrS
, and
aac(6´)-Ib-cr
.
The present research work describes development of dual drug‐loaded lipid–polymer hybrid nanoparticles (LPHNPs) of anticancer therapeutics for the management of colon cancer. The epidermal growth factor (EGF)‐functionalized LPHNPs coloaded with 5‐fluorouracil (FU) and sulforaphane (SFN) were prepared by one‐step nanoprecipitation method. Box–Behnken design was applied for optimizing the material attributes and process parameters. The optimized LPHNPs revealed particle size 198 nm, polydispersity index 0.3, zeta potential
−25.3 mV, and drug loading efficiency 19–20.3% for 5‐FU and SFN, respectively. EGF functionalization on LPHNPs was confirmed from positive magnitude of zeta potential to 21.3 mV as compared with the plain LPHNPs. In vitro drug release performance indicated sustained and non‐Fickian mechanism release nature of the drugs from LPHNPs. Anticancer activity evaluation in HCT‐15 colon cancer cells showed significant reduction (p < 0.001) in the cell growth and cytotoxicity of the investigated drugs from various treatments in the order: EGF‐functionalized LPHNPs > plain LPHNPs > free drug suspensions. Overall, the research work corroborated improved treatment efficacy of EGF‐functionalized LPHNPs for delivering chemotherapeutic agents for the management of colon carcinoma.
Epidemiological studies on the heavy and toxic metal content in the human blood and hair of some smokers from Saudi Arabia were carried out by modern analytical techniques. The levels of some selected heavy and toxic metals (e.g.; Hg, Pb, Cd, As, Se, Mn, Zn, Ni, and Cr) were determined using inductively coupled plasma-atomic emission spectrometer (ICP-AES). Prior to the analysis, the blood and hair samples of Saudi Arabia smokers were collected, treated, and digested by microwave digestion system. The number of cigarettes per day as well as the smoking period was taken in consideration in this study. The tested elements concentrations in the investigated smoker blood and hair samples were compared with those obtained from some nonsmoking control samples. The samples were collected from the psychiatric hospital in Taif city after issuing the ethical committee license in this regard. The results obtained from this study represent a very important guide for the antismoking organizations. The assessment of some side effects of the smoking in such studies presents vital challenge for the social antismoking authorities and the stakeholder governments to attain the sustainable investment for their people.
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