ABSTRACT
The goal of stroke rehabilitation is to establish a robust protocol for patients to live independently in community. Firstly, we examined the impact of 3 hybridized transcranial direct current stimulation (tDCS)-mirror therapy interventions on activities of daily life (ADL) in stroke patients. Secondly, we explored the underlying therapeutic mechanisms with theory-driven electroencephalography (EEG) indexes in the alpha band. This was achieved by identifying the unique contributions of alpha power in motor production to ADL in relation to the premotor cortex (PMC), primary cortex (M1), and Sham tDCS with mirror therapy. The results showed that, although post-intervention ADL improvement was comparable among the three tDCS groups, one of the EEG indexes differentiated the interventions. Neural-behavioral correlation analyses revealed that different types of ADL improvements consistently corresponded with alpha power in the temporal lobe exclusively in the PMC tDCS group (all rs > 0.39). By contrast, alterations in alpha power in the central-frontal region were found to vary, with ADL primarily in the M1 tDCS group (r = -0.6 or 0.7), with the benefit depending on the complexity of the ADL. In conclusion, this research suggested two potential therapeutic mechanisms and demonstrated the additive benefits of introducing theory-driven neural indexes in explaining ADL.
ABSTRACT
BACKGROUND: Pressure injuries are a common and serious issue for bedridden residents in long-term-care facilities. Areas of bony prominences, such as the scapula, sacrum, and heels, are more likely to develop pressure injuries. The management of pressure injury wounds include dressing changes, repositioning, away from moisture, decreasing the occurrence of friction and shear, and more. Some supportive surfaces are also used for pressure injury cases such as gel pads, alternating pressure air mattresses, and air-fluidized beds. The aim of this case study was to determine whether the use of an artificial intelligent mattress can improve a nursing home resident with prolonged pressure injury. CASE PRESENTATION: A retrospective study design was conducted for this case study. A 79-year-old male developed a pressure injury in the sacrum. His pressure injury was initially at stage 4, with a score of 12 by the Braden scale. The PUSH score was 16. During 5.5 months of routine care plus the use of the traditional alternative air mattress, in the nursing home, the wound stayed in stage 3 but the PUSH score increased up to 11. An artificial intelligence mattress utilizing 3D InterSoft was used to detect the bony prominences and redistribute the external pressure of the skin. It implements a color guided schematic of 26 colors to indicate the amount of pressure of the skin. RESULTS: The wound size was decreased and all eczema on the resident's back diminished. The PUSH score was down to 6, as the artificial intelligent mattress was added into the routine care. The staff also reported that the resident's quality of sleep improved and moaning decreased. The hemiplegic side is at greater risk of developing pressure injury. CONCLUSIONS: This novice device appeared to accelerate wound healing in this case. In the future, more cases should be tested, and different care models or mattress can be explored.
Subject(s)
Pressure Ulcer , Male , Humans , Aged , Pressure Ulcer/prevention & control , Pressure Ulcer/epidemiology , Retrospective Studies , Artificial Intelligence , Wound Healing , BedsABSTRACT
Lidocaine is the most frequently applied local infiltration anesthetic agent for treating tendinopathies. However, studies have discovered lidocaine to negatively affect tendon healing. In the current study, the molecular mechanisms and effects of lidocaine on tenocyte migration were evaluated. We treated tenocytes intrinsic to the Achilles tendons of Sprague-Dawley rats with lidocaine. The migration ability of cells was analyzed using electric cell-substrate impedance sensing (ECIS) and scratch wound assay. We then used a microscope to evaluate the cell spread. We assessed filamentous actin (F-actin) cytoskeleton formation through immunofluorescence staining. In addition, we used Western blot analysis to analyze the expression of phospho-focal adhesion kinase (FAK), FAK, phospho-paxillin, paxillin, and F-actin. We discovered that lidocaine had an inhibitory effect on the migration of tenocytes in the scratch wound assay and on the ECIS chip. Lidocaine treatment suppressed cell spreading and changed the cell morphology and F-actin distribution. Lidocaine reduced F-actin formation in the tenocyte during cell spreading; furthermore, it inhibited phospho-FAK, F-actin, and phospho-paxillin expression in the tenocytes. Our study revealed that lidocaine inhibits the spread and migration of tenocytes. The molecular mechanism potentially underlying this effect is downregulation of F-actin, phospho-FAK, and phospho-paxillin expression when cells are treated with lidocaine.
Subject(s)
Achilles Tendon , Actins , Rats , Animals , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Paxillin/metabolism , Paxillin/pharmacology , Actins/metabolism , Phosphorylation , Tenocytes/metabolism , Lidocaine/pharmacology , Cell Movement , Rats, Sprague-Dawley , Cell AdhesionABSTRACT
Muscle injuries are common among athletes and often treated with platelet-rich plasma (PRP). However, whether the leukocyte concentration affects the efficacy of PRP in treating muscle injuries remains unclear. This study investigated the effects of leukocyte-poor platelet-rich plasma (LP-PRP) and leukocyte-rich platelet-rich plasma (LR-PRP) on myoblast proliferation and the molecular mechanisms underlying these effects. Myoblasts were treated with 0.5% LP-PRP, 0.5% LR-PRP, 1% LP-PRP, or 1% LR-PRP for 24 h. The gene expression of the LP-PRP- and LR-PRP-treated myoblasts was determined using RNA sequencing analysis. Cell proliferation was evaluated using an bromodeoxyuridine (BrdU) assay, and cell cycle progression was assessed through flow cytometry. The expression of cyclin A, cyclin-dependent kinase 1 (cdk1), and cdk2 was examined using Western blotting. The expression of myoblast determination protein 1 (MyoD1) was examined through Western blotting and immunofluorescence staining. The LP-PRP and LR-PRP both promoted the proliferation of myoblasts and increased differential gene expression of myoblasts. Moreover, the LP-PRP and LR-PRP substantially upregulated the expression of cyclin A, cdk1, and cdk2. MyoD1 expression was induced in the LP-PRP and LR-PRP-treated myoblasts. Our results corroborate the finding that LP-PRP and LR-PRP have similar positive effects on myoblast proliferation and MyoD1 expression.
Subject(s)
Cyclin A , Myoblasts , Platelet-Rich Plasma , Humans , CDC2 Protein Kinase/metabolism , Cell Proliferation , Cyclin A/metabolism , Leukocytes/physiology , Myoblasts/physiology , Platelet-Rich Plasma/metabolism , Up-RegulationABSTRACT
RNA interference (RNAi) technology has been a promising treatment strategy for combating intractable diseases. However, the applications of RNAi in clinical are hampered by extracellular and intracellular barriers. To overcome these barriers, various siRNA delivery systems have been developed in the past two decades. The first approved RNAi therapeutic, Patisiran (ONPATTRO) using lipids as the carrier, for the treatment of amyloidosis is one of the most important milestones. This has greatly encouraged researchers to work on creating new functional siRNA carriers. In this review, the recent advances in siRNA carriers consisting of lipids, polymers, and polymer-modified inorganic particles for cancer therapy are summarized. Representative examples are presented to show the structural design of the carriers in order to overcome the delivery hurdles associated with RNAi therapies. Finally, the existing challenges and future perspective for developing RNAi as a clinical modality will be discussed and proposed. It is believed that the addressed contributions in this review will promote the development of siRNA delivery systems for future clinical applications.
Subject(s)
Drug Carriers , Nanoparticles , RNA, Small Interfering/chemistry , RNA Interference , Drug Carriers/chemistry , Genetic Therapy , Polymers/chemistry , Lipids/chemistry , Nanoparticles/chemistryABSTRACT
Background: Microsurgical great toe-to-thumb transfer (mGTT) is a widely used procedure when immediate replantation of thumb is not feasible. The aim of this study was to investigate the alteration of plantar pressure profile of the donor foot after mGTT. Methods: Twenty patients receiving microsurgical great toe-to-hand transfer between 1985 to 2014, and 16 healthy subjects were recruited. Group 1 consisted of 20 feet receiving mGTT, whereas group 2 consisted of 32 normal feet as control. The flap design in this study was to preserve 1 cm of the proximal phalanx to maintain the attachment of the plantar aponeurosis and intrinsic muscles. The Taiwan Chinese version of the Foot Function Index was used for patient-reported outcome measurement. A novel Emed-X system was used for dynamic plantar pressure measurement. A total of four parameters were collected, including peak pressure, contact area, contact time, and pressure-time integral. Results: In group 1, the peak pressure redistributed under the first metatarsal bone and was significantly higher than group 2 (P < 0.05). There was no significant change of the contact area between the midfoot region of group 1 and group 2 (P > 0.05). Furthermore, similar foot clearance efficiency was demonstrated in group 1 and group 2 (P > 0.05). Conclusions: The windlass effect of the foot will not be affected when performing mGTT with preservation of 1 cm of the proximal phalanx. Therefore, this surgical procedure is highly recommended for clinical application.
ABSTRACT
AIMS: Chronic hyperglycemia triggers overproduction of AKR1B1 (aldo-keto reductase family 1 member B) and receptor for advanced glycation end product (RAGE), which causes epithelial-mesenchymal transition (EMT) in the lens epithelial cells (LECs) of diabetic mellitus (DM) cataracts. However, it is unclear whether EMT in LECs is related to abnormal increase of SGLT2. Sodium glucose cotransporter 2 (SGLT2) inhibitor, also known as dapagliflozin (Dapa) can be used to treat diabetes. Here, we examined how Dapa or nano eye-drops (DapaN) reduce EMT in LECs of DM cataracts. The nano eye-drop provides an ophthalmic treatment that suppressed diabetic cataract progression and improved potency with reduced side effects. MAIN METHODS: SD rats were injected with streptozocin (STZ) (65 mg/kg, ip), nano-Dapa drops (0.456 mg/10 ml/eye) or Dapa (1.2 mg/kg/day) treatment for 6-12 weeks. Immunofluorescence staining was used for protein quantification of RAGE, SGLT2, N-cadherin and E-cadherin in the LECs of rats. KEY FINDINGS: In this study, Dapa applies nanotechnology-based delivery system and it contains polyvinylpyrrolidone (PVP) and HPBCD. Dapa showed therapeutic effect on DM cataracts, wherein it targeted EMT biomarker, E-cadherin. The nano-Dapa drops or oral Dapa inhibited SGLT2, suppressed AKR1B1 expression, decreased AcSOD2- and RAGE-induced EMT in diabetic cataracts. Our findings suggest that nanotechnology-based Dapa eye drops (Dapa-PVP-HPBCD) can effectively improve solubility of Dapa in aqueous solution. SIGNIFICANCE: Taken together, results suggest that the SGLT2-mediated DM cataract therapy may involve the AKR1B1-RAGE-AcSOD2-EMT pathway. The nano eye drops and Dapa show potential beneficial effects for cataract prevention. This study conveys new insights into cataract treatment and supplementation of nano-Dapa drops shows promising result in preventing diabetic cataracts.
Subject(s)
Cataract , Diabetes Complications , Epithelial-Mesenchymal Transition , Sodium-Glucose Transporter 2 Inhibitors , Animals , Rats , Cadherins/metabolism , Cataract/drug therapy , Cataract/metabolism , Diabetes Complications/drug therapy , Diabetes Complications/metabolism , Diabetes Mellitus/metabolism , Lens, Crystalline/metabolism , Rats, Sprague-Dawley , Sodium-Glucose Transporter 2/metabolism , Sodium-Glucose Transporter 2 Inhibitors/pharmacologyABSTRACT
Nanofiber meshes (NFMs) loaded with therapeutic agents are very often employed to treat hard-to-heal wounds such as diabetic wounds. However, most of the NFMs have limited capability to load multiple or hydrophilicity distinctive-therapeutic agents. The therapy strategy is therefore significantly hampered. To tackle the innate drawback associated with the drug loading versatility, a chitosan-based nanocapsule-in-nanofiber (NC-in-NF) structural NFM system is developed for simultaneous loading of hydrophobic and hydrophilic drugs. Oleic acid-modified chitosan is first converted into NCs by the developed mini-emulsion interfacial cross-linking procedure, followed by loading a hydrophobic anti-inflammatory agent Curcumin (Cur) into the NCs. Sequentially, the Cur-loaded NCs are successfully introduced into reductant-responsive maleoyl functional chitosan/polyvinyl alcohol NFMs containing a hydrophilic antibiotic Tetracycline hydrochloride. Having a co-loading capability for hydrophilicity distinctive agents, biocompatibility, and a controlled release property, the resulting NFMs have demonstrated the efficacy on promoting wound healing either in normal or diabetic rats.
ABSTRACT
In this study, we synthesized two conjugated microporous polymers (CMPs), An-Ph-TPA and An-Ph-Py CMPs, using the Suzuki cross-coupling reaction. These CMPs are organic polymers with p-conjugated skeletons and persistent micro-porosity and contain anthracene (An) moieties linked to triphenylamine (TPA) and pyrene (Py) units. We characterized the chemical structures, porosities, thermal stabilities, and morphologies of the newly synthesized An-CMPs using spectroscopic, microscopic, and N2 adsorption/desorption isotherm techniques. Our results from thermogravimetric analysis (TGA) showed that the An-Ph-TPA CMP displayed better thermal stability with Td10 = 467 °C and char yield of 57 wt% compared to the An-Ph-Py CMP with Td10 = 355 °C and char yield of 54 wt%. Furthermore, we evaluated the electrochemical performance of the An-linked CMPs and found that the An-Ph-TPA CMP had a higher capacitance of 116 F g-1 and better capacitance stability of 97% over 5000 cycles at 10 A g-1. In addition, we assessed the biocompatibility and cytotoxicity of An-linked CMPs using the MTT assay and a live/dead cell viability assay and observed that they were non-toxic and biocompatible with high cell viability values after 24 or 48 h of incubation. These findings suggest that the An-based CMPs synthesized in this study have potential applications in electrochemical testing and the biological field.
Subject(s)
Amines , Polymers , Polymers/chemistry , Adsorption , AnthracenesABSTRACT
A flexible, hydrophobic, and multilayered poly(vinyl alcohol) (PVA) film evolved to replace a commercially available nonbiodegradable easy seal-paper (ES-PAPER) sealing film. First, environmentally friendly fillers, such as cellulose nanocrystals (CNCs) or cellulose nanofibers (CNFs), were added to produce PVA + CNC/CNF composites via blade coating and solution casting to strengthen the mechanical properties of PVA. Subsequently, biodegradable and hydrophobic materials, such as poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) and neat PLA, were added to prepare multilayered PEG-PLA and PLA hydrophobic composites using double-sided solution casting. The hydrophobicity of PVA was enhanced through heat treatment. Finally, the mechanical properties of the as-prepared PVA film were compared with those of a commercially available ES-PAPER sealing film. PVA + CNC/CNF composites exhibit excellent transparency and mechanical properties, whereas PVA + CNCs 3.0â wt% have the highest Young's modulus and tensile strength, which are, respectively, 3% and 96% higher than the Young's modulus and tensile strength of an ES-PAPER sealing film. With regard to strain at break, the prepared PVA film also exhibited a value many times larger than that of the ES-PAPER sealing film because of good filler dispersibility, which significantly enhanced the durability of the sealing film.
ABSTRACT
Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease that mainly affects the axial bones, and dementia is characterized by a decline in cognitive function, leading to dependence in everyday activity. Although the association between dementia and ankylosing spondylitis has been investigated, the influence of axSpA medication on dementia risk is unclear. The aim of this study was to investigate the risk of dementia among axSpA patients and if the conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) can reduce the risk of dementia. Patients with axSpA whose data were recorded during 2004-2008 and who were followed up until the end of 2010 were recruited. A control cohort was matched by age and sex. A Cox multivariate proportional hazards model was applied to analyze the risk factors for dementia. The hazard ratio (HR) and adjusted HR (aHR) were estimated between the study and control cohorts. The effects of csDMARDs and steroid use on the risk of different types of dementia were also analyzed. In total, 2341 and 11,705 patients constituted the axSpA and control cohort, respectively. The axSpA cohort had a greater risk of vascular dementia (aHR = 2.09 (1.36-3.20). The risk of dementia (aHR = 1.01 (0.55-1.85) did not significantly differ between patients with axSpA who received csDMARDs. In conclusion, patients with axSpA are at a risk of vascular dementia, which could be reduced by csDMARDs.
ABSTRACT
Osteosarcoma often occurs in children and adolescents with high invasiveness and high mortality. Polo-like kinase 1 (PLK1) overexpressed in most tumors promotes cancer cell proliferation and transformation. PLK1 is considered as a therapeutic target for osteosarcoma. RNA interference-based therapies are employed to combat osteosarcoma through silencing PLK1 gene expression. However, the treatment results remain unsatisfactory due to the lack of a safe and efficient nonviral gene vector. To tackle this hurdle, biodegradable and CO2 -derivative cationic poly(vinylcyclohexene carbonates) (CPCHCs) are used as gene vectors to perform a siPLK1 therapeutic strategy for osteosarcoma treatment. Of those CPCHCs, CPCHC60 demonstrates the most excellent performance in gene transfection efficiency, endo-lysosome escaping, biodegradability, and biosafety. With the treatment of CPCHCs/siRNA nanoparticles, the expression level of PLK1 gene in osteosarcoma cells is significantly down-regulated. Subsequently, cells are arrested in the G2 /M phase and subsequently dead in the form of apoptosis, resulting in significant tumor regression both in vitro and in vivo. This study brings a new insight into the development of superior nonviral gene vectors for practical cancer treatment. Based on the results, the resulting nanoparticle-based gene drug formation is considered to have a highly successful chance in further translational nanomedicine applications.
Subject(s)
Bone Neoplasms , Genetic Vectors , Osteosarcoma , Humans , Apoptosis , Carbon Dioxide , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Genetic Therapy/methods , RNA, Small Interfering/geneticsABSTRACT
BACKGROUND: Walking entails orchestration of the sensory, motor, balance, and coordination systems, and walking disability is a critical concern after stroke. How and to what extent these systems influence walking disability after stroke and recovery have not been comprehensively studied. METHODS: We retrospectively analyzed patients with stroke in the Post-acute care-Cerebrovascular Diseases (PAC-CVD) program. We compared the characteristics of patient groups stratified by their ability to complete the 5-m walk test across various time points of rehabilitation. We then used stepwise linear regression to examine the degree to which each stroke characteristic and functional ability could predict patient gait performance. RESULTS: Five hundred seventy-three patients were recruited, and their recovery of walking ability was defined by the timing of recovery in a 5-m walk test. The proportion of patients who could complete the 5-m walk test at admission, at 3 weeks of rehabilitation, at 6 weeks of rehabilitation, between 7 and 12 weeks of rehabilitation, and who could not complete the 5-m walk test after rehabilitation was 52.2%, 21.8%, 8.7%, 8.7%, and 8.6%, respectively. At postacute care discharge, patients who regained walking ability earlier had a higher chance of achieving higher levels of walking activity. Stepwise linear regression showed that Berg Balance Scale (BBS) (ß: 0.011, p < .001), age (ß: -0.005, p = .001), National Institutes of Health Stroke Scale (NIHSS) (6a + 6b; ß: -0.042, p = .018), Mini-Nutritional assessment (MNA) (ß: -0.007, p < .027), and Fugl-Meyer upper extremity assessment (FuglUE) (ß: 0.002, p = .047) scores predicted patient's gait speed at discharge. CONCLUSION: Balance, age, leg strength, nutritional status, and upper limb function before postacute care rehabilitation are predictors of walking performance after stroke.
Subject(s)
Stroke Rehabilitation , Stroke , Humans , Subacute Care , Retrospective Studies , Stroke/diagnosis , WalkingABSTRACT
Utilizing CO2 as one of the monomer resources, poly(vinylcyclohexene carbonates) (PVCHCs) are used as the precursor for preparing cationic PVCHCs (CPVCHCs) via thiol-ene click functionalization. Through the functionalization, CPVCHC-43 with a tertiary amine density of 43% relative to the backbone is able to display a significantly antibacterial ability against Staphylococcus aureus (S. aureus). Blending CPVCHC-43 with polyacrylonitrile (PAN), CPVCHC/PAN nanofiber meshes (NFMs) have been successfully prepared by electrospinning. More importantly, two crucial fibrous structural factors including CPVCHC/PAN weight ratio and fiber diameter have been systematically investigated for the effects on the antibacterial performance of the NFMs. Sequentially, a quaternization treatment has been employed on the NFMs with an optimal fibrous structure to enhance the antibacterial ability. The resulting quaternized NFMs have demonstrated the great biocidal effects against Gram-positive and Gram-negative bacteria. Moreover, the excellent biocompatibility of the quaternized NFMs have also been thoroughly evaluated and verified.
Subject(s)
Nanofibers , Acrylic Resins , Amines , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Carbon Dioxide , Carbonates , Gram-Negative Bacteria , Gram-Positive Bacteria , Nanofibers/chemistry , Polycarboxylate Cement , Staphylococcus aureus , Sulfhydryl CompoundsABSTRACT
Objective: To determine the pain and electromyographic (EMG) amplitude ratio of the vastus medialis oblique (VMO) to the vastus lateralis (VL) after botulinum toxin type A (BTA) was injected in the bilateral osteoarthritic knee of patients with patellar malalignment for analysis. Material and methods: A total of fifteen patients were recruited; the more symptomatic knee of each patient received a BTA injection (BTA side). The other set of patients were left untreated. In all, fifteen healthy participants comprised the control group. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and numeric rating scale (NRS) for pain were assessed. The EMG amplitude of VL and VMO activity was recorded using an isokinetic dynamometer and synchronized using the BIOPAC MP100. The data were collected before and at 4, 8, and 12 weeks post−BTA injection. Results: The EMG ratios of the patient group were lower than those of the control group at all testing velocities (p < 0.05). The VMO/VL ratio improved significantly on the BTA side only. The VMO/VL ratios on the BTA side were higher than those on the untreated side (p < 0.05). Knee pain decreased significantly after the BTA injection. The EMG ratios were negatively correlated with the NRS and WOMAC scores. Conclusion: BTA injection effectively reduces knee pain and restores the EMG ratio between the VMO and VL.
ABSTRACT
Since the conceptualization of nanomedicine, numerous nanostructure-mediated drug formulations have progressed into clinical trials for treating cancer. However, recent clinical trial results indicate such kind of drug formulations has a limited improvement on the antitumor efficacy. This is due to the biological barriers associated with those formulations, for example, circulation stability, extravasation efficiency in tumor, tumor penetration ability, and developed multi-drug resistance. When employing for nanomedicine formulations, pristine organic-based and inorganic-based nanostructures have their own limitations. Accordingly, organic/inorganic (O/I) hybrids have been developed to integrate the merits of both, and to minimize their intrinsic drawbacks. In this context, the recent development in O/I hybrids resulting from a self-assembly strategy will be introduced. Through such a strategy, organic and inorganic building blocks can be self-assembled via either chemical covalent bonds or physical interactions. Based on the self-assemble procedure, the hybridization of four organic building blocks including liposomes, micelles, dendrimers, and polymeric nanocapsules with five functional inorganic nanoparticles comprising gold nanostructures, magnetic nanoparticles, carbon-based materials, quantum dots, and silica nanoparticles will be highlighted. The recent progress of these O/I hybrids in advanced modalities for combating cancer, such as, therapeutic agent delivery, photothermal therapy, photodynamic therapy, and immunotherapy will be systematically reviewed.
Subject(s)
Nanoparticles , Nanostructures , Neoplasms , Gold , Humans , Nanomedicine/methods , Nanoparticles/chemistry , Nanostructures/chemistry , Neoplasms/drug therapyABSTRACT
An environmentally friendly, hydrophobic polyvinyl alcohol (PVA) film was developed as an alternative to commercial straws for mitigating the issue of plastic waste. Nontoxic and biodegradable cellulose nanocrystals (CNCs) and nanofibers (CNFs) were used to prepare PVA nanocomposite films by blade coating and solution casting. Double-sided solution casting of polyethylene-glycol-poly(lactic acid) (PEG-PLA) + neat PLA hydrophobic films was performed, which was followed by heat treatment at different temperatures and durations to hydrophobize the PVA composite films. The hydrophobic characteristics of the prepared composite films and a commercial straw were compared. The PVA nanocomposite films exhibited enhanced water vapor barrier and thermal properties owing to the hydrogen bonds and van der Waals forces between the substrate and the fillers. In the sandwich-structured PVA-based hydrophobic composite films, the crystallinity of PLA was increased by adjusting the temperature and duration of heat treatment, which significantly improved their contact angle and water vapor barrier. Finally, the initial contact angle and contact duration (at the contact angle of 20°) increased by 35% and 40%, respectively, which was a significant increase in the service life of the biodegradable material-based straw.
ABSTRACT
Prediction of post-stroke functional outcomes is crucial for allocating medical resources. In this study, a total of 577 patients were enrolled in the Post-Acute Care-Cerebrovascular Disease (PAC-CVD) program, and 77 predictors were collected at admission. The outcome was whether a patient could achieve a Barthel Index (BI) score of >60 upon discharge. Eight machine-learning (ML) methods were applied, and their results were integrated by stacking method. The area under the curve (AUC) of the eight ML models ranged from 0.83 to 0.887, with random forest, stacking, logistic regression, and support vector machine demonstrating superior performance. The feature importance analysis indicated that the initial Berg Balance Test (BBS-I), initial BI (BI-I), and initial Concise Chinese Aphasia Test (CCAT-I) were the top three predictors of BI scores at discharge. The partial dependence plot (PDP) and individual conditional expectation (ICE) plot indicated that the predictors' ability to predict outcomes was the most pronounced within a specific value range (e.g., BBS-I < 40 and BI-I < 60). BI at discharge could be predicted by information collected at admission with the aid of various ML models, and the PDP and ICE plots indicated that the predictors could predict outcomes at a certain value range.
ABSTRACT
Pancreatic cancer is an aggressive malignancy associated with poor prognosis and a high tendency in developing infiltration and metastasis. K-ras mutation is a major genetic disorder in pancreatic cancer patient. RNAi-based therapies can be employed for combating pancreatic cancer by silencing K-ras gene expression. However, the clinical application of RNAi technology is appreciably limited by the lack of a proper siRNA delivery system. To tackle this hurdle, cationic poly (cyclohexene carbonate) s (CPCHCs) using widely sourced CO2 as the monomer are subtly synthesized via ring-opening copolymerization (ROCOP) and thiol-ene functionalization. The developed CPCHCs could effectively encapsulate therapeutic siRNA to form CPCHC/siRNA nanoplexes (NPs). Serving as a siRNA carrier, CPCHC possesses biodegradability, negligible cytotoxicity, and high transfection efficiency. In vitro study shows that CPCHCs are capable of effectively protecting siRNA from being degraded by RNase and promoting a sustained endosomal escape of siRNA. After treatment with CPCHC/siRNA NPs, the K-ras gene expression in both pancreatic cancer cell line (PANC-1 and MiaPaCa-2) are significantly down-regulated. Subsequently, the cell growth and migration are considerably inhibited, and the treated cells are induced into cell apoptotic program. These results demonstrate the promising potential of CPCHC-mediated siRNA therapies in pancreatic cancer treatment.
ABSTRACT
Intracerebral hemorrhage (ICH) is a devastating neurological disorder characterized by an exacerbation of neuroinflammation and neuronal injury, for which few effective therapies are available at present. Inhibition of excessive neuroglial activation has been reported to alleviate ICH-related brain injuries. In the present study, the anti-ICH activity and microglial mechanism of ergosta-7,9(11),22-trien-3ß-ol (EK100), a bioactive ingredient from Asian medicinal herb Antrodia camphorate, were evaluated. Post-treatment of EK100 significantly attenuated neurobehavioral deficit and MRI-related brain lesion in the mice model of collagenase-induced ICH. Additionally, EK100 alleviated the inducible expression of cyclooxygenase (COX)-2 and the activity of matrix metalloproteinase (MMP)-9 in the ipsilateral brain regions. Consistently, it was shown that EK100 concentration-dependently inhibited the expression of COX-2 protein in Toll-like receptor (TLR)-4 activator lipopolysaccharide (LPS)-activated microglial BV-2 and primary microglial cells. Furthermore, the production of microglial prostaglandin E2 and reactive oxygen species were attenuated by EK100. EK100 also attenuated the induction of astrocytic MMP-9 activation. Among several signaling pathways, EK100 significantly and concentration-dependently inhibited activation of c-Jun N-terminal kinase (JNK) MAPK in LPS-activated microglial BV-2 cells. Consistently, ipsilateral JNK activation was markedly inhibited by post-ICH-treated EK100 in vivo. In conclusion, EK100 exerted the inhibitory actions on microglial JNK activation, and attenuated brain COX-2 expression, MMP-9 activation, and brain injuries in the mice ICH model. Thus, EK100 may be proposed and employed as a potential therapeutic agent for ICH.