Effect of Zinc Oxide Nanoparticles on Capsular Gene Expression in Klebsiella pneumoniae Isolated from Clinical Samples.

Klebsiella pneumoniae is an opportunistic pathogen with various virulence factors that give it the capability to invade a host. Nevertheless, the treatment of bacterial infection is gradually complicated as the bacteria can develop resistance to antimicrobial agents. As nanotechnology is a prosperous field for researchers, we employed zinc oxide (ZnO) nanoparticles (NPs) on isolates of Klebsiella pneumoniae. Here, we studied the effect of three NP concentrations-0.25, 0.50, and 0.75 mM-on the gene expression of Klebsiella pneumoniae capsules in isolates collected from different samples. After conducting an anti-bacterial test, the highest nine types of bacteria that resisted the antibacterial agent were chosen for further examination. The gene expression of four genes responsible for capsule manufacturing, namely magA, k2A, rmpA, and kfu, were investigated. When the NP concentration was 0.25 mM, the lowest efficiency was obtained. However, when the concentration increased to 0.50 mM, a noticeable effect on gene expression was detected; consequently, at a concentration of 0.75 Mm, the highest impact was achieved and the gene expression was stopped.

Direct Reprogramming of Mice Skin Fibroblasts into Insulin-Producing Cells In Vitro.

Transdifferentiation means mature cell conversion into other mature cells. Ethical issues, epigenetic failure, or teratoma development are found in cellular reprogramming strategies. Thus, new methods are needed. This study aimed to develop a new novel formula of chemical molecules and growth factors that differentiate skin fibroblasts into insulin-producing cells (IPCs). Newborn mice fibroblasts differentiated using four induction methods into IPCs to search for the best method. Fibroblasts, stem cells, and pancreatic markers were identified using an immunocytochemistry (ICC) assay. Insulin was measured using ELISA and dithizone (DTZ) assays. The skin fibroblasts were induced successfully into IPCs. The best method to obtain IPCs was indicated by measuring insulin concentration in differentiated cell supernatant from all induced cells by the four methods. The protein expression of the pancreatic markers of induced cells increased with time, as indicated by the ICC assay. OCT3/4 increased on day 9, after which the expression tended to decrease. DTZ-positive clusters were observed on day 16. Secreted insulin of differentiated cells was injected in streptozotocin-induced diabetic mice, which decreased blood glucose levels after injection. This study indicated an efficient new chemical method for transdifferentiating skin fibroblasts into functional IPCs, which is a promising method for diabetes mellitus therapy.

Peripheral Anti-nociceptive and Anti-inflammatory Effect of Oleanolic Acid in a Rat Model of Osteoarthritis.

BACKGROUND: Oleanolic acid (OA) is a naturally occurring pentacyclic triterpenoid with multifarious actions. The anti-inflammatory effect it exerts when taken orally is the most important; however, the underpinning mechanisms of such effects have not yet been fully explored. METHODS: In the present study, we evaluated the anti-inflammatory and anti-nociceptive effect of OA by injecting it directly into the knee joint using an animal model of osteoarthritis. Behavioral and electrophysiological studies were conducted to determine whether OA exerts a direct modulatory effect on primary sensory afferents that can lead to a decrease in pain-related behaviors and inflammatory responses. Rats were divided into two main groups: a pre- and a post-treatment group. Knee joint inflammation was induced by injecting a mixture of 3% kaolin and carrageenan (K/C). In the pre-treatment group, two different doses of OA [5 mg/ml (n=5) and 30 mg/ml (n=4); 0.1 ml per injection] were administered into the synovial cavity of the knee joint before induction of inflammation. In the post-treatment group, rats received only one dose [5 mg/ml (n=5)] of OA after induction of inflammation. RESULTS: Results indicate that intra-articular injection of OA improves motor coordination and attenuates nociceptive behavior and inflammatory reactions. More importantly, we observed a direct depolarizing action of OA on articular sensory fibers, a crucial mechanism that activates descending inhibitory pathways and controls incoming nociceptive signals to the spinal cord. CONCLUSION: Overall, our findings suggest that OA can be used as a preventive and therapeutic approach for the management of osteoarthritis.

The Lateral Hypothalamus: An Uncharted Territory for Processing Peripheral Neurogenic Inflammation.

The roles of the hypothalamus and particularly the lateral hypothalamus (LH) in the regulation of inflammation and pain have been widely studied. The LH consists of a parasympathetic area that has connections with all the major parts of the brain. It controls the autonomic nervous system (ANS), regulates feeding behavior and wakeful cycles, and is a part of the reward system. In addition, it contains different types of neurons, most importantly the orexin neurons. These neurons, though few in number, perform critical functions such as inhibiting pain transmission and interfering with the reward system, feeding behavior and the hypothalamic pituitary axis (HPA). Recent evidence has identified a new role for orexin neurons in the modulation of pain transmission associated with several inflammatory diseases, including rheumatoid arthritis and ulcerative colitis. Here, we review recent findings on the various physiological functions of the LH with special emphasis on the orexin/receptor system and its role in mediating inflammatory pain.