Search

Cisplatin is a widely used standard chemotherapy for various cancers. However, cisplatin treatment is associated with severe ototoxicity. Fucoidan is a complex sulfated polysaccharide mainly derived from brown seaweeds, and it shows multiple bioactivities such as antimicrobial, anti-inflammatory, anticancer, and antioxidant activities. Despite evidence of the antioxidant effects of fucoidan, research on its otoprotective effects remains limited. Therefore, the present study investigated the otoprotective effects of fucoidan in vitro using the mouse cochlear cell line UB/OC-2 to develop new strategies to attenuate cisplatin-induced ototoxicity. We quantified the cell membrane potential and analyzed regulators and cascade proteins in the apoptotic pathway. Mouse cochlear UB/OC-2 cells were pre-treated with fucoidan before cisplatin exposure. The effects on cochlear hair cell viability, mitochondrial function, and apoptosis-related proteins were determined via flow cytometry, Western blot analysis, and fluorescence staining. Fucoidan treatment reduced cisplatin-induced intracellular reactive oxygen species production, stabilized mitochondrial membrane potential, inhibited mitochondrial dysfunction, and successfully protected hair cells from apoptosis. Furthermore, fucoidan exerted antioxidant effects against oxidative stress by regulating the Nrf2 pathway. Therefore, we suggest that fucoidan may represent a potential therapeutic agent for developing a new otoprotective strategy.

This study investigated the effects of yelling intervention on symptoms and autonomic responses in motion sickness. Forty-two healthy participants were recruited, and they participated in Coriolis stimulation, a technique for inducing motion sickness. The experimental procedure comprised five 1-min rotating stimuli with 1-min rest after each stimulus. Then, the symptom severity was assessed using the Motion Sickness Symptom Rating (MSSR). The d2 Test of Attention scores and cardiovascular responses were recorded before and after Coriolis stimulation. The electrocardiogram results were documented to analyze heart rate variability (HRV). During Coriolis stimulus, the participants were required to yell 5-8 times in the experimental trial, and to keep quiet for each minute of rotation in the control trial. The yelling intervention significantly reduced the MSSR score ( p < 0.001). Nevertheless, it did not significantly affect the d2 Test of Attention scores. Yelling while rotating did not significantly affect the heart rate nor blood pressure. However, it decreased the normalized low frequency of HRV ( p = 0.036). Moreover, it improved motion sickness, but its effect on attention was not evident. Motion sickness could significantly affect cardiovascular responses and HRV. However, yelling did not affect cardiovascular response, and it reduced sympathetic nervous system activity.

For highly viscous polymer melts, considerable fluid temperature rises produced by viscous heating can be a disturbing factor in viscosity measurements. By scrutinizing the experimental and simulated capillary pressure losses for polymeric liquids, we demonstrate the importance of applying a viscous heating correction to the shear viscosity, so as to correct for large errors introduced by the undesirable temperature rises. Specifically, on the basis of a theoretical derivation and 3-D nonisothermal flow simulation, an approach is developed for retrieving the equivalent shear viscosity in capillary rheometry, and we show that the shear viscosity can be evaluated by using the average fluid temperature at the wall, instead of the bulk temperature, as previously assumed. With the help of a viscous Cross model in analyzing the shear-dominated capillary flow, it is possible to extract the viscous heating contribution to capillary pressure loss, and the general validity of the methodology is assessed using the experiments on a series of thermoplastic melts, including polymers of amorphous, crystalline, and filler-reinforced types. The predictions of the viscous model based on the equivalent viscosity are found to be in good to excellent agreement with experimental pressure drops. For all the materials studied, a near material-independent scaling relation between the dimensionless temperature rise (Θ) and the Nahme number (Na) is found, Θ ~ Na 0.72 , from which the fluid temperature rise due to viscous heating as well as the resultant viscosity change can be predicted.

All aircrews are required to undertake the altitude hypoxia training and be familiarized with the hypobaric effect on their physiological regulation. Due to the characteristics of the helicopter aircrafts, few researches have reported in-flight hypoxia events among the helicopter aircrews. The main goal of this study was designed to compare the hypoxia symptoms of helicopter aircrews between the altitude hypoxia training and during flight. We developed a questionnaire to collect the details of chamber flights and in-flight hypoxia events in 2019. All data were managed by the SPSS software and two-tailed 0.05 alpha level was considered as a significant level. Of the 213 study participants, there were eight (3.8%) cases that experienced hypoxia symptoms during the flight. The top five symptoms that appeared both in the last and current altitude hypoxia trainings were visual impairment (20.7%), difficulty concentrating (12.7%), tiredness (12.2%), cognitive impairment (8.0%), and air hunger (5.2%). Meanwhile, the frequency of those symptoms above was not significantly different from the last or current training compared with those in-flight hypoxia events. The survey unveiled a series of consistency correlations of hypoxia symptoms between the chamber flights and in-flight environment for the helicopter aircrew group.

In the treatment of cancers, small interfering ribonucleic acids (siRNAs) are delivered into cells to inhibit the oncogenic protein's expression; however, polyanions, hydrophilicity, and rapid degradations in blood, endosomal or secondary lysosomal degradation hamper clinal applications. In this study, we first synthesized and characterized two copolymers: methoxy poly(ethylene glycol)-b-poly(2-hydroxy methacrylate-ketal-pyridoxal) and methoxy poly(ethylene glycol)-b-poly(methacrylic acid-co-histidine). Afterwards, we assembled two polymers with the focal adhesion kinase (FAK) siRNA, forming polyplex-mixed micelles for the treatment of the human colon cancer cell line HCT116. In terms of the physiological condition, the cationic pyridoxal molecules that were conjugated on the copolymer with ketal bonds could electrostatically attract the siRNA. Additionally, the pyridoxal could form a hydrophobic core together with the hydrophobic deprotonated histidine molecules in the other copolymer and the hydrophilic polyethylene glycol (PEG) shell to protect the siRNA. In an acidic condition, the pyridoxal would be cleaved from the polymers due to the breakage of the ketal bonds and the histidine molecules can simultaneously be protonated, resulting in the endosome/lysosome escape effect. On the basis of our results, the two copolymers were successfully prepared and the pyridoxal derivatives were identified to be able to carry the siRNA and be cleavable by the copolymers in an acidic solution. Polyplex-mixed micelles were prepared, and the micellar structures were identified. The endosome escape behavior was observed using a confocal laser scanning microscopy (CLSM). The FAK expression was therefore reduced, and the cytotoxicity of siRNA toward human colon cancer cells was exhibited, rapidly in 24 h. This exceptional anticancer efficiency suggests the potential of the pH-sensitive polyplex-mixed micellar system in siRNA delivery.

This study proposes a shape approximation approach to portray the regions of interest (ROI) from medical imaging data. An effective algorithm to achieve an optimal approximation is proposed based on the framework of Particle Swarm Optimization. The convergence of the proposed algorithm is derived under mild assumptions on the selected family of shape equations. The issue of detecting Parkinson's disease (PD) based on the Tc-99m TRODAT-1 brain SPECT/CT images of 634 subjects, with 305 female and an average age of 68.3 years old from Kaohsiung Chang Gung Memorial Hospital, Taiwan, is employed to demonstrate the proposed procedure by fitting optimal ellipse and cashew-shaped equations in the 2D and 3D spaces, respectively. According to the visual interpretation of 3 experienced board-certified nuclear medicine physicians, 256 subjects are determined to be abnormal, 77 subjects are potentially abnormal, 174 are normal, and 127 are nearly normal. The coefficients of the ellipse and cashew-shaped equations, together with some well-known features of PD existing in the literature, are employed to learn PD classifiers under various machine learning approaches. A repeated hold-out with 100 rounds of 5-fold cross-validation and stratified sampling scheme is adopted to investigate the classification performances of different machine learning methods and different sets of features. The empirical results reveal that our method obtains 0.88 ±0.04 classification accuracy, 0.87 ±0.06 sensitivity, and 0.88 ±0.08 specificity for test data when including the coefficients of the ellipse and cashew-shaped equations. Our findings indicate that more constructive and useful features can be extracted from proper mathematical representations of the 2D and 3D shapes for a specific ROI in medical imaging data, which shows their potential for improving the accuracy of automated PD identification.

Excessive levels of reactive oxygen species (ROS) lead to mitochondrial damage and apoptotic cell death in gentamicin-induced ototoxicity. 2,3,4',5-Tetrahydroxystilbene-2- O -β-d-glucoside (THSG), a bioactive constituent, isolated from Polygonum multiflorum Thunb., exhibits numerous biological benefits in treating aging-related diseases by suppressing oxidative damage. However, its protective effect on gentamicin-induced ototoxicity remains unexplored. Therefore, here, we aimed to investigate the otoprotective effect of THSG on gentamicin-induced apoptosis in mouse cochlear UB/OC-2 cells. We evaluated the effect of gentamicin and THSG on the ROS level, superoxide dismutase (SOD) activity, mitochondrial membrane potential, nuclear condensation, and lactate dehydrogenase (LDH) release, and the expression of apoptosis-related proteins was assessed to understand the molecular mechanisms underlying its preventive effects. The findings demonstrated that gentamicin increased ROS generation, LDH release, and promoted apoptotic cell death in UB/OC-2 cells. However, THSG treatment reversed these effects by suppressing ROS production and downregulating the mitochondrial-dependent apoptotic pathway. Additionally, it increased the SOD activity, decreased the expression of apoptosis-related proteins, alleviated the levels of the apoptotic cells, and impaired cytotoxicity. To the best of our knowledge, this is the first study to demonstrate that THSG could be a potential therapeutic option to attenuate gentamicin-induced ototoxicity.

Background: Tumor markers are used to screen tens of millions of individuals worldwide at annual health check-ups, especially in East Asia. Machine learning (ML)-based algorithms that improve the diagnostic accuracy and clinical utility of these tests can have substantial impact leading to the early diagnosis of cancer., Methods: ML-based algorithms, including a cancer screening algorithm and a secondary organ of origin algorithm, were developed and validated using a large real world dataset (RWD) from asymptomatic individuals undergoing routine cancer screening at a Taiwanese medical center between May 2001 and April 2015. External validation was performed using data from the same period from a separate medical center. The data set included tumor marker values, age, and gender from 27,938 individuals, including 342 subsequently confirmed cancer cases., Results: Separate gender-specific cancer screening algorithms were developed. For men, a logistic regression-based algorithm outperformed single-marker and other ML-based algorithms, with a mean area under the receiver operating characteristic curve (AUROC) of 0.7654 in internal and 0.8736 in external cross validation. For women, a random forest-based algorithm attained a mean AUROC of 0.6665 in internal and 0.6938 in external cross validation. The median time to cancer diagnosis (TTD) in men was 451.5, 204.5, and 28 days for the mild, moderate, and high-risk groups, respectively; for women, the median TTD was 229, 132, and 125 days for the mild, moderate, and high-risk groups. A second algorithm was developed to predict the most likely affected organ systems for at-risk individuals. The algorithm yielded 0.8120 sensitivity and 0.6490 specificity for men, and 0.8170 sensitivity and 0.6750 specificity for women., Conclusions: ML-derived algorithms, trained and validated by using a RWD, can significantly improve tumor marker-based screening for multiple types of early stage cancers, suggest the tissue of origin, and provide guidance for patient follow-up.

To reduce the side effects of immune drugs and the sustainable release of immune drugs on local parts, we have designed an injectable thermal-sensitive hydrogel containing an imiquimod-loaded liposome system. In the extracellular environment of tumor tissues (pH 6.4), 50% of the drug was released from the carrier, which could be a result of the morphological changes of the liposomal microstructure in the acidic environment. According to the results in animals, the drug-containing liposomes combined with hydrogel can be effectively applied in breast cancer therapy to delay the growth of tumors as well as to dramatically reduce the death rate of mice.

By treating with histone-deacetylase inhibitor valproate sodium, three new heterdimeric tetrahydroxanthone⁻chromanone lactones chrysoxanthones A⁻C ( 1 ⁻ 3 ), along with 17 known compounds were isolated from a sponge-associated Penicillium chrysogenum HLS111. The planar structures of chrysoxanthones A⁻C were elucidated by means of spectroscopic analyses, including MS, 1D, and 2D NMR. Their absolute configurations were established by electronic circular dichroism (ECD) calculations. Chrysoxanthones A⁻C exhibited moderate antibacterial activities against Bacillus subtilis with minimum inhibitory concentration (MIC) values of 5⁻10 μg/mL.

pH-sensitive polymer⁻liposomes can rapidly release their payloads. However, it is difficult to simultaneously achieve stability and pH-responsiveness in the polymer⁻liposomes. In this study, stable and pH-sensitive crosslinked polymer⁻liposomes were fabricated through electrostatic interactions. The pH-sensitive copolymer methoxy poly(ethylene glycol)- block -poly(methacrylic acid)-cholesterol (mPEG- b -P(MAAc)-chol) and crosslinking reagent poly(ethylene glycol) with end-capped with lysine (PEG-Lys2) were synthesized and characterized. At physiological conditions, the pH-sensitive copolymers were anionic and interacted electrostatically with the cationic crosslinker PEG-Lys2, forming the electrostatically-crosslinked polymer⁻liposomes and stabilizing the liposomal structure. At pH 5.0, the carboxylic groups in mPEG- b -P(MAAc)-chol were neutralized, and the liposomal structure was destroyed. The particle size of the crosslinked polymer⁻liposomes was approximately 140 nm and the polymer⁻liposomes were loaded with the anticancer drug doxorubicin. At pH 7.4, the crosslinked polymer⁻liposomes exhibited good stability with steady particle size and low drug leakage, even in the presence of fetal bovine serum. At pH 5.0, the architecture of the crosslinked polymer⁻liposomes was damaged following rapid drug release, as observed by using transmission electron microscopy and their apparent size variation. The crosslinked polymer⁻liposomes were pH-sensitive within the endosome and in the human breast cancer cells MDA-MB-231, as determined by using confocal laser scanning microscopy. The intracellular drug release profiles indicated cytotoxicity in cancer cells. These results indicated that the highly-stable and pH-sensitive electrostatically-crosslinked polymer⁻liposomes offered a potent drug-delivery system for use in anticancer therapies.

Multifunctional polymer nanoparticles have been developed for cancer treatment because they could be easily designed to target cancer cells and to enhance therapeutic efficacy according to cancer hallmarks. In this study, we synthesized a pH-sensitive polymer, poly(methacrylic acid- co -histidine/doxorubicin/biotin) (HBD) in which doxorubicin (DOX) was conjugated by a hydrazone bond to encapsulate an immunotherapy drug, imiquimod (IMQ), to form dual cancer-targeting and dual drug-loaded nanoparticles. At low pH, polymeric nanoparticles could disrupt and simultaneously release DOX and IMQ. Our experimental results show that the nanoparticles exhibited pH-dependent drug release behavior and had an ability to target cancer cells via biotin and protonated histidine., Competing Interests: The authors declare no conflict of interest.