Microorganisms develop biofilms on indwelling medical devices and are associated with device-related infections, resulting in substantial morbidity and mortality. This study investigated the effect of pretreating hydrogel-coated catheters with Pseudomonas aeruginosa bacteriophages on biofilm formation by P. aeruginosa in an in vitro model. Hydrogel-coated catheters were exposed to a 10 log ₁₀ PFU ml ⁻¹ lysate of P. aeruginosa phage M4 for 2 h at 37°C prior to bacterial inoculation. The mean viable biofilm count on untreated catheters was 6.87 log ₁₀ CFU cm ⁻² after 24 h. The pretreatment of catheters with phage reduced this value to 4.03 log ₁₀ CFU cm ⁻² ( P < 0.001). Phage treatment immediately following bacterial inoculation also reduced biofilm viable counts (4.37 log ₁₀ CFU cm ⁻² reduction; P < 0.001). The regrowth of biofilms on phage-treated catheters occurred between 24 and 48 h, but supplemental treatment with phage at 24 h significantly reduced biofilm regrowth ( P < 0.001). Biofilm isolates resistant to phage M4 were recovered from catheters pretreated with phage. The phage susceptibility profiles of these isolates were used to guide the development of a five-phage cocktail from a larger library of P. aeruginosa phages. The pretreatment of catheters with this cocktail reduced the 48-h mean biofilm cell density by 99.9% (from 7.13 to 4.13 log ₁₀ CFU cm ⁻² ; P < 0.001), but fewer biofilm isolates were resistant to these phages. These results suggest the potential of applying phages, especially phage cocktails, to the surfaces of indwelling medical devices for mitigating biofilm formation by clinically relevant bacteria.

Terahertz (THz = 10 ¹² Hz) spectroscopy has shown great potential in biomedical research due to its unique features, such as the non-invasive and label-free identification of living cells and medical imaging.

Background and Purpose—: Inflammatory injury plays a critical role in intracerebral hemorrhage (ICH)–induced secondary brain injury. Recently, dopamine D2 receptor (DRD2) is identified as an important component controlling innate immunity and inflammatory response in central nervous system, and αB-crystallin (CRYAB) is a potent negative regulator on inflammatory pathways. Here, we sought to investigate the role of DRD2 on neuroinflammation after experimental ICH and the potential mechanism mediated by CRYAB. Methods—: Two hundred and twenty-four (224) male CD-1 mice were subjected to intrastriatal infusion of bacterial collagenase or autologous blood. Two DRD2 agonists quinpirole and ropinirole were administrated by daily intraperitoneal injection starting at 1 hour after ICH. DRD2 and CRYAB in vivo knockdown was performed 48 hours before ICH insult. Behavioral deficits and brain water content, Western blots, immunofluorescence staining, coimmunoprecipitation (Co-IP) assay, and proteome cytokine array were evaluated. Results—: Endogenous DRD2 and CRYAB expressions were increased after ICH. DRD2 knockdown aggravated the neurobehavioral deficits and the pronounced cytokine expressions. DRD2 activation by quinpirole and ropinirole ameliorated neurological outcome, brain edema, interleukin-1β, and monocyte chemoattractant protein-1 expression, as well as microglia/macrophages activation, in the perihematomal region. These effects were abolished by pretreatment with CRYAB siRNAs. Quinpirole enhanced cytoplasmic binding activity between CRYAB and NF-κB and decreased nuclear NF-κB expression. Similar therapeutic benefits were observed using autologous blood injection model and intranasal delivery of quinpirole. Conclusions—: DRD2 may have anti-inflammatory effects after ICH. DRD2 agonists inhibited neuroinflammation and attenuated brain injury after ICH, which is probably mediated by CRYAB and enhanced cytoplasmic binding activity with NF-κB.

Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in the mitogen-activated protein kinase (MAPK) signaling cascade during CRC. The presence of BRAF^V600E mutation can determine the response of a tumor to chemotherapy. However, the association between the BRAF^V600E mutation and the clinicopathological features of CRC remains controversial. We performed a systematic review and meta-analysis to estimate the effect of BRAF^V600E mutation on the clinicopathological characteristics of CRC. We identified studies that examined the effect of BRAF^V600E mutation on CRC within the PubMed, ISI Science Citation Index, and Embase databases. The effect of BRAF^V600E on outcome parameters was estimated by odds ratios (ORs) with 95% confidence intervals (CIs) for each study using a fixed effects or random effects model. 25 studies with a total of 11,955 CRC patients met inclusion criteria. The rate of BRAF^V600 was 10.8% (1288/11955). The BRAF^V600E mutation in CRC was associated with advanced TNM stage, poor differentiation, mucinous histology, microsatellite instability (MSI), CpG island methylator phenotype (CIMP). This mutation was also associated with female gender, older age, proximal colon, and mutL homolog 1 (MLH1) methylation. This meta-analysis demonstrated that BRAF^V600E mutation was significantly correlated with adverse pathological features of CRC and distinct clinical characteristics. These data suggest that BRAF^V600E mutation could be used to supplement standard clinical and pathological staging for the better management of individual CRC patients, and could be considered as a poor prognostic marker for CRC.