Preparation and evaluation of curcumin-loaded self-assembled micelles.

OBJECTIVE: Curcumin being used to treat various chronic diseases while its poor bioavailability issue limited its wide clinical application as a therapeutic agent. The aim of this work was to prepare curcumin-loaded self-assembled micelles using soluplus and solutol®HS15 (SSCMs) to enhance curcumin's solubility and thus oral bioavailability. METHODS: Optimum formulation was investigated and the optimized ratio of drugs and excipients was obtained and the SSCMs were prepared via ethanol solvent evaporation method. The optimal SSCMs were characterized by transmission electron microscopy, drug content analysis including loading efficiency (LE%) and entrapment efficiency (EE%), and the cumulative amount of curcumin released from the micelles were all calculated using HPLC method. The in vitro cytotoxicity and the permeability of SSCMs were measured by Caco-2 cell monolayers and the oral bioavailability was evaluated by SD rats. KEY FINDINGS: The solubility of curcumin in self-assembled micelles was dramatically increased by 4200 times as compared to free curcumin. Caco-2 cells transport experiment exhibited that while soluplus and solutol®HS15 were self-assembled into micelles, it could not only promote the permeability of curcumin across membrane for better absorption, but also could restrain the curcumin pumped outside due to the role of P-gp efflux mechanism of soluplus and solutol®HS15. Furthermore, the prepared SSCMs formulation was almost nontoxic and had safety performance on Caco-2 cells model. Moreover, curcumin's oral bioavailability of SSCMs formulation in SD rats had doubled than that of free curcumin. CONCLUSIONS: The prepared SSCMs were characterized by PS, PDI, LE%, EE% data analysis. After the soluplus and solutol®HS15 were self assembled into micelles, both the solubility and membrane permeability of curcumin were evaluated to have been enhanced, as well as the effect of efflux pump of curcumin was inhibited, hence to promote oral absorption and generate an increased bioavailability.

ECG-gated pulmonary artery CTA for evaluation of right ventricular function in patients with acute pulmonary embolism.

OBJECTIVE: To evaluate right ventricular function in patients with acute pulmonary embolism (APE) using electrocardiogram-gated CTA and to discuss the clinical value of pulmonary artery CTA PATIENTS AND METHODS: Based on death risk evaluation, 86 APE patients were divided into high-risk group (n=46) and non-high-risk group (n=40). The CT pulmonary embolism (PE) index and parameters of right ventricular function were analyzed from the CTPA images and compared between the two groups. Potential correlation between the two was also discussed. RESULT: CT PE index (median 24.69%) of the high-risk group was obviously higher than that of the non-high-risk group (median 8.58%) (P<.05). Except the diameter of superior vena cava, all other parameters of right ventricular function were significantly different between the two groups (P<.05). CT PE index was correlated with the parameters of right ventricular function. CONCLUSION: ECG-gated pulmonary artery CTA is suitable for assessing the severity of APE and right ventricular function.

Multislice spiral CT angiography for evaluation of acute aortic syndrome.

OBJECTIVE: To discuss the diagnostic value of multislice CT angiography (MSCTA) in acute aortic syndrome (AAS). MATERIALS AND METHODS: The clinical and imaging data of 36 cases diagnosed as AAS by MSCTA were collected. The manifestations of the MSCTA images were reviewed retrospectively, and the average x-ray dose was calculated. RESULTS: Among 36 AAS cases, 16 cases had aortic dissection (AD), 8 cases had penetrating atherosclerotic ulcer (PAU), 7 cases had intramural hematoma (IMH), and 5 cases had unstable thoracic aneurysm (UTA). Of 16 cases with AD, type A and type B accounted for 43.7% (7/16) and 56.3% (9/16), respectively. Of 7 cases with IMH, type A and type B accounted for 42.9% (3/7) and 57.1% (4/7), respectively. CONCLUSION: In spite of the x-ray radiation, MSCTA proves to be a rapid and noninvasive imaging technique for the diagnosis of AAS.

Acetate-producing bacterium Paenibacillus odorifer hampers lung cancer growth in lower respiratory tract: an in vitro study.

Lung cancer accounts for the large majority of cancer incidence and mortality worldwide for decades. The dysbiotic microbiome and its metabolite secretions in the gut have been regarded as the dominant biological factors in oncogenesis, development, and progression, adding probiotic components of which have come to be potential therapeutic regimes. However, there still exists little knowledge about whether probiotic microorganisms in lower airways inhibit lung cancer by lung microenvironment remodulation. In this study, we performed bioinformatics analysis from previous sequencing data and specific microbiome databases to identify the potent protective microbes in lower airways, followed by bacterial cultivation and morphological verifications in vitro. We found that Paenibacillus odorifer was correlated closely with the anti-tumorous by-product acetic acid in lower respiratory tract. Additionally, the enrichment of this microorganism in the health, rather than in lung neoplasms from public data sets, further confirmed its protective activity in preserving pulmonary homeostasis. Colony cultivation of this strain and targeted metabolite analysis indicated that Paenibacillus odorifer proliferation was weakened at 37°C but lasted longer than it did at the optimal temperature. And performing as a candidate origin of acetic acid, this strain was liable to inhibit the growth of lung cancer cells in time- and dose-dependent approaches which was validated by colony formation assays. These results suggested that Paenibacillus odorifer functions as a candidate probiotic in lower airways to restrict lung cancer cell growth by releasing protective molecules, indicating a potential preventive microbial strategy.IMPORTANCEVarious types of microorganisms in lower respiratory tracts protect local homeostasis against oncogenesis. Although extensive efforts engaged in gut microbiome-mediated pulmonary carcinogenesis, emerging evidence suggested the crucial role of microbial metabolites from respiratory tracts in modulating carcinogenesis-related host inflammation and DNA damage in lung cancer, which was still not fully understood in lower respiratory tract microbes and its metabolite-mediated microecological environment homeostasis in preventing or alleviating lung cancer. In this study, we analyzed the lower respiratory tract microbiome and SCFAs expression among different lung segments from the same participants, further identifying that Paenibacillus odorifer was correlated closely with anti-tumorous by-product, acetate acid in lower respiratory tract by multi-omics analysis. And previous experiments showed this strain could inhibit the growth of lung cancer cells in vitro. These findings indicated that Paenibacillus odorifer in lower respiratory tracts might perform as a candidate probiotic against lung carcinogenesis by releasing protective factor acetate, which further presented a promising diagnostic and interventional approach in clinical settings of lung cancer.

BL02, a phage against carbapenem- and polymyxin-B resistant Klebsiella pneumoniae, isolated from sewage: A preclinical study.

The emergence of Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a threat to public health. Polymyxin-B is generally considered a last-resort antibiotic. In this study, we isolated a carbapenem- and polymyxin-B resistant K. pneumoniae phage BL02 for the first time in Southwestern China and evaluated its biological characteristics and whole-genome sequence. Polymyxin-B resistant K. pneumoniae, (CK02), was isolated from the blood of a male with severe septic shock, and phage BL02 was screened and purified from the hospital sewage. BL02 could lyse 40 out of 46 CRKP isolates (86.96%) and has high activity in the pH range of 6-10 and the temperature range of 4-55 °C. The latency period of BL02 was about 10 min and the lysis period was about 50 min. The genome results showed that BL02 was a linear dsDNA with a total length of 175,595 bp and a GC content of 41.83%. A total of 275 ORFs were predicted and no tRNA, rRNA, drug resistance genes, or virulence genes were found in the genome. Phylogenetic analysis showed that BL02 belongs to the family Straboviridae. Treatment of infected mice with two antibiotics (tigecycline or ceftazidime/avibactam) resulted in 7-day survival rates of 28.57% and 42.86%, respectively. In contrast, the survival rate of mice in the single-dose BL02-treated group was 71.43%. In summary, this preclinical study isolated a phage capable of lysing polymyxin-B resistant K. pneumoniae and validated its safety and efficacy in an in vivo model, which provides a reference for further research on controlling MDR pathogens.

Histology transformation-mediated pathological atypism in small-cell lung cancer within the presence of chemotherapy: A case report.

BACKGROUND: The treatment of small-cell lung cancer (SCLC) has progressed little in recent years because of its unique biological activities and complex genomic alterations. Chemotherapy combined with radiotherapy has been widely accepted as the first-line treatment for SCLC. CASE SUMMARY: Here, we present a 68-year-old male smoker who was diagnosed with SCLC of the right lung. After several cycles of concurrent chemoradiotherapy, the tumor progressed with broad metastasis to liver and bone. Histopathological examination showed an obvious transformation to adenocarcinoma, probably a partial recurrence mediated by the chemotherapy-based regimen. A mixed tumor as the primary lesion and transformation from SCLC or/and tumor stem cells may have accounted for the pathology conversion. We adjusted the treatment schedule in accord with the change in phenotype. CONCLUSION: Although diffuse skeletal and hepatic metastases were seen on a recent computed tomography scan, the patient is alive, with intervals of progression and shrinkage of his cancer.

[Extraction of triterpenoids from fruiting [corrected] bodies of Ganoderma lucidum by supercritical fluid extraction].

OBJECTIVE: To optimize the extracting condition for triterpenoids from the fruits of Ganoderma lucidum by supercritical fluid extraction (SFE). METHOD: Optimum extraction conditions were studied by orthogonal tests. The total triterpenoids were determined by ultraviolet spectrophotometry and ganoderic acid B was determined by RP-HPLC. RESULT: The optimal extraction conditions were that the pressure 25 MPa, the temperature was 45 degrees C, the extraction time was 1.5 hour, and the ethanol was employed as modifier carrier at the volume of 3 mL x g(-1). CONCLUSION: SFE is superior and it is feasible to extract triterpenoids from fruits of Ganoderma lucidum.