Mesoporous silica nanoparticles with dual-targeting agricultural sources for enhanced cancer treatment via tritherapy.

In this study, we introduced dual-targeting folic acid (FA) and hyaluronic acid (HA) modified on the surface of rice husk mesoporous silica nanoparticles (rMSNs). The rMSNs were employed as a drug delivery system loaded with camptothecin (CPT) as a model drug, Eu3+ ions as a photosensitizer for photodynamic therapy (PDT), bismuth (Bi) for photothermal therapy (PTT), and Gd3+ ions for magnetic resonance imaging (MRI) to develop novel nanoparticles, rMSN-EuGd-Bi@CPT-HA-FA, with dual-targeted function and triple therapy for cancer treatment. The results of the cell cytotoxicity experiment showed that the A549 cancer cells had a survival rate of approximately 35% when treated with 200 µg mL-1 of rMSN-EuGd-Bi@CPT-HA-FA under 808 nm irradiation for 15 min. The dual-targeted function and synergistic treatment of CPT, PTT, and PDT were also responsible for the 20% survival rate of the A549 cancer cells treated with 200 µg mL-1 of rMSN-EuGd-Bi@CPT-HA-FA under 808 nm irradiation for 30 min. The results showed that rMSN-EuGd-Bi@CPT-HA-FA can effectively combine chemotherapy (through CPT), PDT, and PTT for cancer treatment.

Diatom-derived mesoporous silica nanoparticles loaded with fucoidan for enhanced chemo-photodynamic therapy.

Combination therapy merges chemical photodynamic therapy (CPDT) to improve cancer treatment. It synergizes chemotherapy with photodynamic therapy (PDT), using photosensitizers to produce reactive oxygen species (ROS) when exposed to light, effectively killing drug-resistant cancer cells. It is not affected by drug resistance, making it an attractive option for combination with chemotherapy. In this study, the focus was on the design of a combination therapy of chemotherapy and PDT. They synthesized diatomaceous earth mesoporous silica nanoparticles (dMSN) containing lanthanide metal ions in a PDT composition. These nanoparticles can generate ROS under near-infrared light irradiation and have MRI and fluorescence imaging capabilities, confirming their phototherapeutic effect on HCT116 cancer cells at a 200 µg/mL concentration. Fucoidan, derived from brown algae, was used as the chemotherapy component. The fucoidan extracted from Sargassum oligocystum in Pingtung Haikou showed the highest anticancer activity, with cell viability of 57.4 % at 200 µg/mL on HCT116 cancer cells. For combination therapy, fucoidan was loaded into nanoparticles (dMSN-EuGd@fucoidan). Cell viability experiments revealed that at 200 µg/mL, the cell survival rate of dMSN-EuGd@Fucoidan on HCT116 cancer cells was 47.7 %. Combination therapy demonstrated superior anticancer efficacy compared to PDT or chemotherapy alone, successfully synthesizing nanoparticles for combined chemotherapy and photodynamic therapy.

Higher prevalence of idiopathic normal pressure hydrocephalus-like MRI features in progressive supranuclear palsy: An imaging reminder of atypical parkinsonism.

OBJECTIVES: The classic triad of idiopathic normal pressure hydrocephalus (NPH) encompass gait disturbance, cognitive impairment, and urinary incontinence. These symptoms overlap with parkinsonism but with distinct treatment. Lacking applicable differentiation also hampers the prediction to therapeutic response. Here, we try to clarify this issue among different Parkinsonian syndromes and propose some innovative thinking while approaching a patient with parkinsonism and hydrocephalus concomitantly. METHODS: Twenty-four patients with clinical probable multiple system atrophy (MSA), 34 with probable progressive supranuclear palsy (PSP), and 58 with sex- and age-matched Parkinson's disease (PD) were enrolled. Evans' index (EI), callosal angle (CA), antero-posterior (AP) diameter of the midbrain, length of the midbrain tegmentum diameter (MBTegm ), and disproportionately enlarged subarachnoid space hydrocephalus (DESH) were evaluated using the conventional MRI. Logistic regression was applied to identify the independent variables in hydrocephalus. RESULTS: Patients with PSP had higher mean EI than those with MSA and PD. Around 38.2% of patients with PSP had accompanied hydrocephalus (EI > 0.3). Parkinsonism subtypes (PD, MSA, or PSP), AP diameter of the midbrain, and MBTegm were significantly different among patients with and without hydrocephalus. After regression analysis, parkinsonism subtype stood out to be the most key risk factor of hydrocephalus. The comparison between patients with PSP with and without hydrocephalus did not disclose specific clinical characteristics or risk factors. CONCLUSIONS: This study demonstrates that the presence of NPH-like MRI features is much higher in PSP patients, and this tendency is decided upon the determination of parkinsonism subtype. Sharing pathophysiological characteristics in these two diseases is implied. More diagnostic tools are needed to better differentiate the two diseases and decide the treatment. To closely observe hydrocephalic parkinsonism patients and well inform the possible limited shunting benefits if PSP core features appear, will be more pivotal and practical at present clinical practice.

Post-treatment late complications of nasopharyngeal carcinoma.

Radiotherapy (RT) or concurrent chemoradiation therapy (CCRT) is not only effective at patients' survival rates, but also produces undesirable late complications. The purpose of this study is to investigate the post-treatment late complications in nasopharyngeal carcinoma (NPC) patients, and to analyze the individual impact factors. We enrolled 188 newly diagnosed NPC patients who had received complete treatments and at least 3 years' follow-up between March 1984 and March 2010. Late complications were modified from the Toxicity Criteria of the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer. Of 188 patients, 132 were male and 56 were female. Eighty-eight patients received CCRT and the other 100 patients received RT alone. The median follow-up duration was 7.34 years (range 3.30-26.54). Only 5.3% of patients reported no complication during post-treatment follow-up. The most common major and minor complications were osteoradionecrosis (10.1%) and xerostomia (56.4%), respectively. There was no impact factor for age, underlying disease, and cancer staging. However, there was a negative impact factor for xerostomia and limb numbness in the CCRT group compared with the RT group. Besides, re-radiation for recurrent patients could increase the risk of major complications. Fortunately, these major complications were reduced after the introduction of intensity-modulated radiotherapy in 2003. The improvement of treatment modality decreased the risk of major complications. Physicians should pay more attentions and improve patients' quality of life during follow-up.

Evaluating the performance of whole genome amplification for use in low template DNA typing.

We report on the performance of two whole genome amplification methods, GenomiPhi™ amplification and modified-improved primer extension preamplification (mIPEP), when analysing low template DNA samples. Template as low as 10 pg treated with mIPEP generated more than 1 ng of DNA that could be used in STR typing. Initial templates of 100-10 pg, when treated with mIPEP, generated an increase in alleles compared with control samples. Partial profiles using the AmpFℓSTR(®) Identifiler™ Kit were produced from this suboptimal DNA template, with 70% of the possible alleles (21.7 ± 2.1 in 32 alleles) recorded, using the mIPEP amplified products with an initial template of 100 pg. Allelic imbalance decreased with samples treated with whole genome amplification method (WGA) compared with those without this initial treatment. Further methods for improvement were also analysed including altering the condition of electrokinetic injection, and the successful DNA typing rate was increased to about 80%. This report illustrates the potential use and limitations of WGA for low template samples.

Bioactivity of crude fucoidan extracted from Sargassum ilicifolium (Turner) C. Agardh.

Fucoidan derived from brown algae has been shown to exhibit antitumor and antioxidant effects, so research on sulfated polysaccharides is increasing. The purpose of this study was to evaluate the characteristics and biological activity of fucoidan that was extracted at two temperatures (65 and 80 °C) from Sargassum ilicifolium (Turner) C. Agardh from five regions of Taiwan. The data show that there are significant differences in the yield, sulfate and total sugar content of Sargassum ilicifolium (Turner) C. Agardh grown in different locations in the same sea area. HPLC was used to determine the monosaccharide compositions of the fucoidan, which contains fucose, mannose, mannose, glucose and galactose and have a low molecular weight of less than 5 kDa, and then we will select the algae collected in Fugang, Taitung, for further biological activity research. The sampled Sargassum ilicifolium (Turner) C. Agardh at all five locations has a good polyphenol content, and it shows great DPPH radical scavenging activity, ABTS radical scavenging activity, Ferrous ion-chelating activity and Reducing power. The Sargassum ilicifolium (Turner) C. Agardh that was collected from Taitung Fugang is not toxic to L929 normal cells, but for A549 cancer cells and HCT116 cancer cells, it is known from the results that it has good cytotoxicity for A549 cancer cells. Thus, this study found that the Sargassum ilicifolium (Turner) C. Agardh that was collected from Taitung Fugang has significant antioxidant and anticancer properties.

Mesoporous silica nanoparticles with fluorescent and magnetic dual-imaging properties to deliver fucoidan.

Fucoidan is a sulfated polysaccharide that is mainly extracted from brown algae. In this study, a simple and efficient method of hot water extraction, which is commonly used in industry, was used to obtain crude polysaccharides. Furthermore, agricultural waste was our source of biogenic silica, and it was then synthesized into drug carrier-nanoparticles. In combination with a popular drug delivery system, the carrier was doped with a dual imaging lanthanide metal and loaded with the drug. Fucoidan has decent bioactivities, such as anticancer activity. The extracted fucoidan is expensive, but we can exploit the nanocarrier to reduce the necessary dose of fucoidan. The experimental section is divided into three parts. The first part analyzed the chemical properties and antioxidant activity of the extracted fucoidan. The second part endowed the material with fluorescent and magnetic dual-imaging properties by incorporating Eu3+ and Gd3+ during the synthesis of rice husk mesoporous silica nanoparticles (rMSNs). The third part tested the anti-cancer ability of rMSN-EuGd@Fucoidan. The drug delivery system rMSN-EuGd@Fucoidan, which was synthesized in this research, showed cytotoxicity against A549 cancer cells. The results of the cell viability tests for fucoidan and rMSN-EuGd@Fucoidan were 58% and 47%, respectively. After inverse calculation from the TGA data yielded a value of 54.5%, we determined that the amount of fucoidan loaded in rMSN-EuGd@Fucoidan was 109 µg. Our results showed that rMSN-EuGd@Fucoidan needs less fucoidan to be effective, and its toxicity against A549 cells is higher than that of fucoidan.

Hyaluronidase-Responsive Mesoporous Silica Nanoparticles with Dual-Imaging and Dual-Target Function.

Nanoparticle-based drug delivery systems are among the most popular research topics in recent years. Compared with traditional drug carriers, mesoporous silica nanoparticles (MSN) offer modifiable surfaces, adjustable pore sizes and good biocompatibility. Nanoparticle-based drug delivery systems have become a research direction for many scientists. With the active target factionalized, scientists could deliver drug carriers into cancer cells successfully. However, drugs in cancer cells could elicit drug resistance and induce cell exocytosis. Thus, the drug cannot be delivered to its pharmacological location, such as the nucleus. Therefore, binding the cell membrane and the nuclear target on the nanomaterial so that the anticancer drug can be delivered to its pharmacological action site is our goal. In this study, MSN-EuGd was synthesized by doping Eu3+ and Gd3+ during the synthesis of MSN. The surface of the material was then connected to the TAT peptide as the nucleus target for targeting the cancer nucleus and then loaded with the anticancer drug camptothecin (CPT). Then, the surface of MSN-EuGd was bonded to the hyaluronic acid as an active target and gatekeeper. With this system, it is possible and desirable to achieve dual imaging and dual targeting, as well as to deliver drugs to the cell nucleus under a hyaluronidase-controlled release. The experimental approach is divided into three parts. First, we conferred the material with fluorescent and magnetic dual-imaging property by doping Eu3+ and Gd3+ into the MSN. Second, modification of the cell membrane target molecule and the nucleus target molecule occurred on the surface of the nanoparticle, making the nanoparticle a target drug carrier. Third, the loading of drug molecules into the carrier gave the entire carrier a specific target profile and enabled the ability to treat cancer. In this study, we investigated the basic properties of the drug carrier, including physical properties, chemical properties, and in vitro tests. The result showed that we have successfully designed a drug delivery system that recognizes normal cells and cancer cells and has good anticancer effects.

The Influence of Selected Fingerprint Enhancement Techniques on Forensic DNA Typing of Epithelial Cells Deposited on Porous Surfaces.

Fingerprints deposited at crime scene can be a source of DNA. Previous reports on the effects of fingerprint enhancement methods have focused mainly on fingermarks deposited in blood or saliva. Here, we evaluate the effects of fingerprint enhancement methods on fingerprints deposited on porous surfaces. We performed real-time quantification and STR typing, the results of which indicated that two methods (iodine fuming and 1,2-indanedione in ethyl acetate enhancement) had no effect on the quantity of DNA isolated and resultant STR alleles when compared to control samples. DNA quantities and allele numbers were lower for samples enhanced with silver nitrate and 1,2-indanedione in acetic acid when compared to control samples. Based on DNA quantity, quality, and observable stochastic effects, our data indicated that iodine fuming and 1,2-indanedione in ethyl acetate were the preferred options for the enhancement of fingerprints on porous surfaces.