A temperature sensitive variant of p53 drives p53-dependent MicroRNA expression without evidence of widespread post-transcriptional gene silencing

The p53 tumour suppressor is a transcription factor that can regulate the expression of numerous ge

Terazosin Interferes with Quorum Sensing and Type Three Secretion System and Diminishes the Bacterial Espionage to Mitigate the Salmonella Typhimurium Pathogenesis

Salmonella enterica is an invasive intracellular pathogen and hires diverse systems to manipulate its survival in the host cells. Salmonella could eavesdrop on the host cells, sensing and responding to the produced adrenergic hormones and other neurotransmitters, which results in the augmentation of its virulence and establishes its accommodation in host cells. The current study aims to assess the anti-virulence effect of α-adrenergic antagonist terazosin on S. Typhimurium. Our findings show that terazosin significantly reduced S. Typhimurium adhesion and biofilm formation. Furthermore, terazosin significantly decreased invasion and intracellular replication of S. Typhimurium. Interestingly, in vivo, terazosin protected the mice from S. Typhimurium pathogenesis. To understand the terazosin anti-virulence activity, its effect on quorum sensing (QS), bacterial espionage, and type three secretion system (T3SS) was studied. Strikingly, terazosin competed on the membranal sensors that sense adrenergic hormones and down-regulated their encoding genes, which indicates the ability of terazosin to diminish the bacterial eavesdropping on the host cells. Moreover, terazosin significantly reduced the Chromobacterium violaceum QS-controlled pigment production and interfered with the QS receptor Lux-homolog Salmonella SdiA, which indicates the possible terazosin-mediated anti-QS activity. Furthermore, terazosin down-regulated the expression of T3SS encoding genes. In conclusion, terazosin may mitigate S. Typhimurium virulence owing to its hindering QS and down-regulating T3SS encoding genes besides its inhibition of bacterial espionage

Terazosin Interferes with Quorum Sensing and Type Three Secretion System and Diminishes the Bacterial Espionage to Mitigate the <i>Salmonella</i> Typhimurium Pathogenesis

Salmonella enterica is an invasive intracellular pathogen and hires diverse systems to manipulate its survival in the host cells. Salmonella could eavesdrop on the host cells, sensing and responding to the produced adrenergic hormones and other neurotransmitters, which results in the augmentation of its virulence and establishes its accommodation in host cells. The current study aims to assess the anti-virulence effect of α-adrenergic antagonist terazosin on S. Typhimurium. Our findings show that terazosin significantly reduced S. Typhimurium adhesion and biofilm formation. Furthermore, terazosin significantly decreased invasion and intracellular replication of S. Typhimurium. Interestingly, in vivo, terazosin protected the mice from S. Typhimurium pathogenesis. To understand the terazosin anti-virulence activity, its effect on quorum sensing (QS), bacterial espionage, and type three secretion system (T3SS) was studied. Strikingly, terazosin competed on the membranal sensors that sense adrenergic hormones and down-regulated their encoding genes, which indicates the ability of terazosin to diminish the bacterial eavesdropping on the host cells. Moreover, terazosin significantly reduced the Chromobacterium violaceum QS-controlled pigment production and interfered with the QS receptor Lux-homolog Salmonella SdiA, which indicates the possible terazosin-mediated anti-QS activity. Furthermore, terazosin down-regulated the expression of T3SS encoding genes. In conclusion, terazosin may mitigate S. Typhimurium virulence owing to its hindering QS and down-regulating T3SS encoding genes besides its inhibition of bacterial espionage

Fabrication of Celecoxib PVP Microparticles Stabilized by Gelucire 48/16 via Electrospraying for Enhanced Anti-Inflammatory Action

Electrospraying (ES) technology is considered an efficient micro/nanoparticle fabrication technique with controlled dimensions and diverse morphology. Gelurice® 48/16 (GLR) has been employed to stabilize the aqueous dispersion of Celecoxib (CXB) for enhancing its solubility and oral bioavailability. Our formula is composed of CXB loaded in polyvinylpyllodine (PVP) stabilized with GLR to formulate microparticles (MPs) (CXB-GLR-PVP MPs). CXB-GLR-PVP MPs display excellent in vitro properties regarding particle size (548 ± 10.23 nm), zeta potential (−20.21 ± 2.45 mV), and drug loading (DL, 1.98 ± 0.059 mg per 10 mg MPs). CXB-GLR-PVP MPs showed a significant (p p < 0.05) in CXB-GLR-PVP MPs treated group alongside an enhancement in the histological features was revealed. CXB-GLR-PVP MPs is an up-and-coming delivery system that could be elucidated in future clinical investigations

In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives

This study demonstrates high drug-loading of novel pyridine derivatives (S1–S4) in lipid- and polymer-based core–shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation technique and characterized for particle size, surface morphology, and entrapment efficiency. The prepared nanocapsules exhibited a particle size ranging from 185.0 ± 17.4 to 223.0 ± 15.3 nm and a drug entrapment of >90%. The microscopic evaluation demonstrated spherical-shaped nanocapsules with distinct core–shell structures. The in vitro release study depicted a biphasic and sustained release pattern of test compounds from the nanocapsules. In addition, it was obvious from the cytotoxicity studies that the nanocapsules showed superior cytotoxicity against both MCF-7 and A549 cancer cell lines, as manifested by a significant decrease in the IC50 value compared to free test compounds. The in vivo antitumor efficacy of the optimized nanocapsule formulation (S4-loaded LPNCs) was investigated in an Ehrlich ascites carcinoma (EAC) solid tumor-bearing mice model. Interestingly, the entrapment of the test compound (S4) within LPNCs remarkably triggered superior tumor growth inhibition when compared with either free S4 or the standard anticancer drug 5-fluorouracil. Such enhanced in vivo antitumor activity was accompanied by a remarkable increase in animal life span. Furthermore, the S4-loaded LPNC formulation was tolerated well by treated animals, as evidenced by the absence of any signs of acute toxicity or alterations in biochemical markers of liver and kidney functions. Collectively, our findings clearly underscore the therapeutic potential of S4-loaded LPNCs over free S4 in conquering EAC solid tumors, presumably via granting efficient delivery of adequate concentrations of the entrapped drug to the target site

The Association of Smoking with Contact Dermatitis: A Cross-Sectional Study

Contact dermatitis is a chronic inflammatory skin disorder with a highly variable prevalence worldwide. Smoking plays a crucial role in mediating inflammatory skin conditions such as contact dermatitis. The present study aimed to investigate the association between smoking status and contact dermatitis in the Saudi population. The patients in the present study were individuals older than 18 years who were diagnosed with contact dermatitis and received a patch test at the Department of Dermatology of King Saud University Medical City from March 2003 through February 2019. All patients were interviewed by phone to complete a specific pre-designed questionnaire to assess tobacco use or exposure history. The total number of enrolled patients in the study was 308 (91 males and 217 females), all with contact dermatitis. Data from the present study suggest that the prevalence of allergic contact dermatitis in smokers may be less than that in non-smokers. Moreover, the prevalence of irritant contact dermatitis in smokers is more significant than in non-smokers. Finally, left-hand contact dermatitis is significantly associated with smoking. Therefore, there is a strong association between smoking and irritant contact dermatitis, especially in the Saudi population, regarding the left hand. Further epidemiologic studies are needed to further explore the role of smoking in the occurrence of contact dermatitis and to explore the possible mechanisms

The Association of Smoking with Contact Dermatitis: A Cross-Sectional Study

Contact dermatitis is a chronic inflammatory skin disorder with a highly variable prevalence worldwide. Smoking plays a crucial role in mediating inflammatory skin conditions such as contact dermatitis. The present study aimed to investigate the association between smoking status and contact dermatitis in the Saudi population. The patients in the present study were individuals older than 18 years who were diagnosed with contact dermatitis and received a patch test at the Department of Dermatology of King Saud University Medical City from March 2003 through February 2019. All patients were interviewed by phone to complete a specific pre-designed questionnaire to assess tobacco use or exposure history. The total number of enrolled patients in the study was 308 (91 males and 217 females), all with contact dermatitis. Data from the present study suggest that the prevalence of allergic contact dermatitis in smokers may be less than that in non-smokers. Moreover, the prevalence of irritant contact dermatitis in smokers is more significant than in non-smokers. Finally, left-hand contact dermatitis is significantly associated with smoking. Therefore, there is a strong association between smoking and irritant contact dermatitis, especially in the Saudi population, regarding the left hand. Further epidemiologic studies are needed to further explore the role of smoking in the occurrence of contact dermatitis and to explore the possible mechanisms