Biodegradable Polymers as a Noncoding miRNA Nanocarrier for Multiple Targeting Therapy of Human Hepatocellular Carcinoma.

Therapeutic strategy based on the restoration of tumor suppressor-microRNAs (miRNAs) is a promising approach for cancer therapy, but the low delivery efficiency of miRNA remains a huge hurdle due to the lack of safe and efficient nonviral carriers. In this work, with the use of newly developed PEGylated biodegradable charged polyester-based vectors (PEG-BCPVs) as the carrier, the miR26a and miR122 codelivering therapeutic strategy (PEG-BCPVs/miR26a/miR122 as the delivery formulation) is successfully developed for efficient treatment of human hepatocellular carcinoma (HCC). In vitro study results show that PEG-BCPVs are capable of effectively facilitating miRNA cellular uptake via a cell endocytosis pathway. Consequently, the restoration of miR26a and miR122 remarkably inhibit the cell growth, migration, invasion, colony formation, and induced apoptosis of HepG2 cells. More importantly, the chemosensitivity of HepG2 to anticancer drug is also considerably enhanced. After treatment with the PEG-BCPV-based miRNA delivery system, the expression of the multiple targeted genes corresponding to miR26a and miR122 in HepG2 cells is greatly downregulated. Accordingly, the newly developed miRNA restoration therapeutic strategy via biodegradable PEG-BCPVs as the carrier should be a promising modality for combating HCC.

Biodegradable Polymer-Coated Multifunctional Graphene Quantum Dots for Light-Triggered Synergetic Therapy of Pancreatic Cancer.

In this work, we reported the synthesis of an engineered novel nanocarrier composed of biodegradable charged polyester vectors (BCPVs) and graphene quantum dots (GQDs) for pancreatic cancer (MiaPaCa-2 cells) therapy applications. Such a nanocarrier was utilized to co-load doxorubicin (DOX) and small interfering ribonucleic acid (siRNA), resulting in the formation of GQD/DOX/BCPV/siRNA nanocomplexes. The resulting nanocomplexes have demonstrated high stability in physiologically mimicking media, excellent K-ras downregulation activity, and effective bioactivity inhibition for MiaPaCa-2 cells. More importantly, laser light was used to generate heat for the nanocomplexes via the photothermal effect to damage the cells, which was further employed to trigger the release of payloads from the nanocomplexes. Such triggered release function greatly enhanced the anticancer activity of the nanocomplexes. Preliminary colony formation study also suggested that GQD/DOX/BCPV/siRNA nanocomplexes are qualified carrier candidates in subsequent in vivo tests.

Synthesis of Polylactide-Based Core-Shell Interface Cross-Linked Micelles for Anticancer Drug Delivery.

Well-defined poly(ethylene glycol)-b-allyl functional polylactide-b-polylactides (PEG-APLA-PLAs) are synthesized through sequential ring-opening polymerization. PEG-APLA-PLAs that have amphiphilic properties and reactive allyl side chains on their intermediate blocks are successfully transferred to core-shell interface cross-linked micelles (ICMs) by micellization and UV-initiated irradiation. ICMs have demonstrated enhanced colloidal stability in physiological-mimicking media. Hydrophobic molecules such as Nile Red or doxorubicin (Dox) are readily loaded into ICMs; the resulting drug-ICM formulations possess slow and sustained drug release profiles under physiological-mimicking conditions. ICMs exhibit negligible cytotoxicity in human uterine sarcoma cancer cells by using biodegradable aliphatic polyester as the hydrophobic segments. Relative to free Dox, Dox-loaded ICMs show a reduced cytotoxicity due to the late intracellular release of Dox from ICMs. Overall, ICMs represent a new type of biodegradable cross-linked micelle and can be employed as a promising platform for delivering a broad variety of hydrophobic drugs.

Synthesis of (E)-oxindolylidene acetate using tandem palladium-catalyzed Heck and alkoxycarbonylation reactions.

Tandem reactions use consecutive reaction steps to efficiently synthesize compounds of high molecular complexity. This paper presents a tandem Pd-catalyzed Heck and alkoxycarbonylation reaction for the stereoselective synthesis of (E)-oxindolylidene acetates. The mechanism underlying the Pd-catalyzed tandem reaction involves the syn-carbopalladation of ynamides followed by alkoxycarbonylation with CO and alcohol. This method makes it possible to obtain the desired (E)-configuration of oxindolylidene acetates exclusively. We evaluated the scope of the reaction by applying optimal reaction conditions to the facile synthesis of a library of (E)-oxindolylidene acetates. The resulting (E)-oxindolylidene acetates exhibited potent anticancer activities against a variety of human cancer cell lines. The anticancer activities of some (E)-oxindolylidene acetates were even superior to those of known CDK inhibitors indirubin-3'-oxime and roscovitine.

Biodegradable nanoparticle-mediated K-ras down regulation for pancreatic cancer gene therapy.

RNA interference (RNAi) targeting the K-ras oncogene mutation in pancreatic cancer mediated by small interfering RNA (siRNA) transfection is a very promising treatment. However, the rapid degradation and negative charge of naked siRNAs restrict their direct delivery into cells. In this contribution, we propose a safe and effective transmembrane transport nanocarrier formulation based on a newly developed biodegradable charged polyester-based vector (BCPV) for K-ras siRNA delivery into pancreatic cancer cells. Our results have shown that these biodegradable and biocompatible vectors are able to transfect siRNAs targeting mutant K-ras into MiaPaCa-2 cells with high transfection and knockdown efficiency. More importantly, the RNAi process initiated a cascade gene regulation of the downstream proteins of K-ras associated with cell proliferation, migration, invasion and apoptosis. We observed that after the mutant K-ras siRNA transfection, the growth, migration and invasion of the MiaPaCa-2 cells were significantly reduced; also, the apoptosis of the pancreatic cancer cells was promoted. Although in vivo testing data are limited, we propose that the BCPV based nanoparticle formulation could be a promising candidate as non-viral vectors for gene therapy in clinical settings.

Gas discharge plasmas are effective in inactivating Bacillus and Clostridium spores.

Bacterial spores are the most resistant form of life and have been a major threat to public health and food safety. Nonthermal atmospheric gas discharge plasma is a novel sterilization method that leaves no chemical residue. In our study, a helium radio-frequency cold plasma jet was used to examine its sporicidal effect on selected strains of Bacillus and Clostridium. The species tested included Bacillus subtilis, Bacillus stearothermophilus, Clostridium sporogenes, Clostridium perfringens, Clostridium difficile, and Clostridium botulinum type A and type E. The plasmas were effective in inactivating selected Bacillus and Clostridia spores with D values (decimal reduction time) ranging from 2 to 8 min. Among all spores tested, C. botulinum type A and C. sporogenes were significantly more resistant to plasma inactivation than other species. Observations by phase contrast microscopy showed that B. subtilis spores were severely damaged by plasmas and the majority of the treated spores were unable to initiate the germination process. There was no detectable fragmentation of the DNA when the spores were treated for up to 20 min. The release of dipicolinic acid was observed almost immediately after the plasma treatment, indicating the spore envelope damage could occur quickly resulting in dipicolinic acid release and the reduction of spore resistance.

Chilaiditi's syndrome in children.

BACKGROUND: [corrected] Chilaiditi's syndrome (CS) is the condition for which radiological evidence of symptomatic colonic interposition between the liver and diaphragm is presented, although the syndrome is infrequently seen. METHODS: We reviewed patients with CS in our hospital in the past 15 years (3 patients, from July 1990 to June 2005) and case reports in the literature (10 patients). The diagnosis was made by abdominal computed tomography or roentgenograms of the chest and abdomen. RESULTS: There were thirteen patients (6 males, 7 females) enrolled in our study. Their ages ranged from 6 months to 11 years old. The predisposing factors included aerophagia (46.2%), diaphragmatic eventration (23.1%), constipation (23.1%), and abdominal blunt trauma (7.7%). The common clinical manifestations included abdominal pain (69.2%), vomiting (38.5%), abdominal distension (30.7%), constipation (23.1%), and respiratory distress (23.1%). The roentgenograms of the chest and abdomen (n=13) showed elevation of the right hemidiaphragm occupied with mass-like opacity. Abdominal computed tomography (n=4) revealed hepatodiaphragmatic colonic interposition. Most patients were managed conservatively (n=8). Only four patients with recurrent symptoms received surgical correction. All of them had relief of symptoms after treatment. CS appears to be a clinically and radiologically benign syndrome and has a good outcome. For its management, conservative treatment is the first-line option. Other methods includes surgery. CONCLUSIONS: We concluded that this rare syndrome could be kept in mind when young children present with recurrent respiratory distress, abdominal distension or abdominal pain accompanied by predisposing factors such as aerophagia, constipation, diaphragmatic eventration, or blunt trauma. Operative correction is necessary if recurrent symptoms are present.

Does a normal DMSA obviate the performance of voiding cystourethrography in evaluation of young children after their first urinary tract infection?

OBJECTIVE: To determine whether a normal technetium-99m-labeled dimercaptosuccinic acid (DMSA) renal scan obviates the need for voiding cystourethrography (VCUG) in evaluating young children after their first urinary tract infection (UTI). STUDY DESIGN: This was a 10-year retrospective review of 142 children (age < or = 2 years, 77 boys and 65 girls) who had their first UTI and were admitted to a tertiary care general hospital. The association between DMSA renal scan results and VCUG results performed 48 hours and 1 month after diagnosis was evaluated. RESULTS: DMSA renal scans and VCUG were performed in 142 patients. Of these, 99 patients (69.7%) had evidence of pyelonephritis, although only 2 (1.4%) had evidence of renal scarring; 42 (29.6%) had vesicoureteral reflux (VUR) on VCUG. The sensitivity, specificity, positive and negative predictive values, and likelihood ratio negative for abnormalities on DMSA renal scans for detecting the the presence of VUR on VCUG were 88% (95% confidence interval [CI] = 73% to 100%), 36% (95% CI = 26% to 46%), 37% (95% CI = 27% to 46%), 88 % (95% CI = 73% to 100%), and 0.33 (95% CI = 0 to 0.88), respectively. CONCLUSIONS: Children with a negative DMSA renal scan during their first UTI episode rarely have VUR and may never have high-grade VUR. Avoiding VCUGs in children with negative DMSA renal scans could significantly reduce the use of this potentially traumatic test.

Use of magnetic resonance cholangiopancreatography to diagnose neonatal congenital choledochal cyst.

Antenatal identification of choledochal cysts has become increasingly common with advances in prenatal ultrasonography. However, the antenatal diagnosis needs to be confirmed postnatally and a preoperative radiologic evaluation of the cyst prior to complete resection is required. There have been few reports of the application of magnetic resonance cholangiopancreatography in neonates, or in neonates with large choledochal cysts. We describe a neonate with a progressively growing giant choledochal cyst, which was initially detected at 28 weeks' gestation. After delivery, the baby did not feed well and suffered from jaundice and frequent postprandial bilious vomiting. At the age of 11 days, magnetic resonance cholangiopancreatography was used to confirm the prenatal diagnosis and provide a thorough preoperative evaluation. He underwent early resection of the cyst at 15 days of age and recovered uneventfully. Magnetic resonance cholangiopancreatography is an alternative diagnostic method for confirming the antenatal diagnosis of large choledochal cysts in neonates. It may also provide useful diagnostic information for preoperative evaluation.