Expression of microRNAs related to apoptosis in the aqueous humor and lens capsule of patients with glaucoma.

Background: The aim of this study is to investigate the expression profiles of microRNAs (miRNAs) related to apoptosis in the aqueous humor (AH) and lens capsule (LC) of patients with glaucoma. Methods: AH and LC samples were collected from patients with open-angle glaucoma and control participants who were scheduled for cataract surgery. A miRNA PCR array comprising 84 miRNAs was used to analyze the AH (glaucoma, n = 3; control, n = 3) and LC samples (glaucoma, n = 3; control, n = 4). Additionally, the AH and LC samples (glaucoma, n = 3; control, n = 4) were subjected to quantitative real-time PCR to validate the differentially expressed miRNAs determined using the PCR array. Bioinformatics analysis was performed to identify the interactions between miRNAs and diseases. Additionally, the differential expression of these miRNAs and the target gene was validated through in vitro experiments using a retinal ganglion cell (RGC) model. Results: Expression levels of 19 and 3 miRNAs were significantly upregulated in the AH and LC samples of the glaucoma group, respectively (p < 0.05). Of these, the expression levels of hsa-miR-193a-5p and hsa-miR-222-3p showed significant differences in both AH and LC samples. Bioinformatics analysis showed experimentally validated 8 miRNA:gene pairs. Among them, PTEN was selected to analyze the expression level in AH and LC from separate cohort (glaucoma, n = 5; control, n = 4). The result showed downregulation of PTEN concurrent with upregulation of the two miRNAs in LC samples of glaucoma group. In vitro experiments validated that the expression levels of hsa-miR-193a-5p and hsa-miR-222-3p were significantly upregulated, and that of PTEN was significantly downregulated in the H2O2-treated RGC, while the level of PTEN was recovered through co-treatment with miR-193a inhibitor or miR-222 inhibitor. Conclusion: This is the first study to investigate the differential expression of apoptosis-related miRNAs in the AH and LC of patients with glaucoma. Hsa-miR-193a-5p and hsa-miR-222-3p, which were upregulated in both AH and LC, may be considered potential biomarkers for glaucoma.

Dual stimuli-responsive mesoporous silica nanoparticles for efficient loading and smart delivery of doxorubicin to cancer with RGD-integrin targeting.

The recent progress in nanoparticle applications, such as tumor-targeting, has enabled specific delivery of chemotherapeutics to malignant tissues with enhanced local efficacy while limiting side effects. However, existing delivery systems leave much room for improvement in terms of achieving enhanced colloidal stability in fluid medium, efficient targeting of intended sites, and effective release of therapeutic drugs into diseased cells. Here, an efficient stimuli-responsive nanocarrier for mammalian cells, termed RGD-NAMs, was developed, which enabled temperature- and pH-sensitive release of drug loads. The RGD-NAMs comprise two parts: a stimuli-responsive copolymer shell (NIBIm-AA-RGD) and drug-container core (MSNs). The RGD-NAMs have a stable drug-loading capacity with a marked difference in the release rate depending on the temperature and pH conditions. The RGD-NAMs also exhibit high colloidal stability in SBF (Stimulated body fluid) solutions and minimal toxicity in skeletal myoblasts (C2C12) and bovine arterial endothelial cells (BAEC). The doxorubicin-loaded RGD-NAMs induced a cytotoxic effect in a dose-dependent manner, which was furthered by an increase in temperature from 37 to 40 °C. Moreover, significant control of the release rate and the amount were achieved through pH change. This novel, smart drug-delivery system with high responsiveness to temperature and pH changes has wide application prospects in biomedical fields, including the theragnosis of tumors and vascular diseases.

Improved gliotransmission by increasing intracellular Ca2+ via TRPV1 on multi-walled carbon nanotube platforms.

BACKGROUND: Astrocyte is a key regulator of neuronal activity and excitatory/inhibitory balance via gliotransmission. Recently, gliotransmission has been identified as a novel target for neurological diseases. However, using the properties of nanomaterials to modulate gliotransmission has not been uncovered. RESULTS: We prepared non-invasive CNT platforms for cells with different nanotopography and properties such as hydrophilicity and conductivity. Using CNT platforms, we investigated the effect of CNT on astrocyte functions participating in synaptic transmission by releasing gliotransmitters. Astrocytes on CNT platforms showed improved cell adhesion and proliferation with upregulated integrin and GFAP expression. In addition, intracellular GABA and glutamate in astrocytes were augmented on CNT platforms. We also demonstrated that gliotransmitters in brain slices were increased by ex vivo incubation with CNT. Additionally, intracellular resting Ca2+ level, which is important for gliotransmission, was also increased via TRPV1 on CNT platforms. CONCLUSION: CNT can improve astrocyte function including adhesion, proliferation and gliotransmission by increasing resting Ca2+ level. Therefore, our study suggests that CNT would be utilized as a new therapeutic platform for central nervous system diseases by modulating gliotransmission.

Wearable CNTs-based humidity sensors with high sensitivity and flexibility for real-time multiple respiratory monitoring.

Sensors, such as optical, chemical, and electrical sensors, play an important role in our lives. While these sensors already have widespread applications, such as humidity sensors, most are generally incompatible with flexible/inactive substrates and rely on conventional hard materials and complex manufacturing processes. To overcome this, we develop a CNT-based, low-resistance, and flexible humidity sensor. The core-shell structured CNT@CPM is prepared with Chit and PAMAM to achieve reliability, accuracy, consistency, and durability, resulting in a highly sensitive humidity sensor. The average response/recovery time of optimized sensor is only less than 20 s, with high sensitivity, consistent responsiveness, good linearity according to humidity rates, and low hysteresis (- 0.29 to 0.30 %RH). Moreover, it is highly reliable for long-term (at least 1 month), repeated bending (over 15,000 times), and provides accurate humidity measurement results. We apply the sensor to smart-wear, such as masks, that could conduct multi-respiratory monitoring in real-time through automatic ventilation systems. Several multi-respiratory monitoring results demonstrate its high responsiveness (less than 1.2 s) and consistent performance, indicating highly desirable for healthcare monitoring. Finally, these automatic ventilation systems paired with flexible sensors and applied to smart-wear can not only provide comfort but also enable stable and accurate healthcare in all environments.

Electrical and thermal stimulus-responsive nanocarbon-based 3D hydrogel sponge for switchable drug delivery.

Smart hydrogels that are responsive to various external (e.g. electrical and/or thermal) stimulation have become increasingly popular in recent years for simple, rapid, and precise drug delivery that can be controlled and turned on or off with external stimuli. For such a switchable drug delivery material, highly homogeneous dispersion and distribution of the hydrophobic, electrically conductive nanomaterials throughout a hydrophilic three-dimensional (3D) hydrogel network remains a challenge and is essential for achieving well-connected electrical and thermal conducting paths. Herein we developed electrical and thermal stimulus-responsive 3D hydrogels based on (i) carbon nanotubes (CNTs) as the core unit and an electrical/thermal conductor, (ii) chitosan (Chit) as the shell unit and a hydrophilic dispersant, and (iii) poly(NIPAAm-co-BBVIm) (pNIBBIm) as the drug carrier and a temperature-responsive copolymer. By formulating the CNT-core and Chit-shell units and constructing a CNT sponge framework, uniform distribution and 3D connectivity of the CNTs were improved. The 3D hydrogel based on the CNT sponge, namely the 3D frame CNT-Chit/pNIBBIm hydrogel, delivered approximately 37% of a drug, ketoprofen used for the treatment of musculoskeletal pain, during about 30% shrinkage after electrical and thermal switches on/off and exhibited the best potential for future use in a smart transdermal drug delivery system. The physicochemical, mechanical, electrical, thermal, and biocompatible characteristics of this nanocarbon-based 3D frame hydrogel led to remarkable electrical and thermal stimulus-responsive properties capable of developing an excellent controllable and switchable drug delivery platform for biomedical engineering and medicine applications.

The effects of additional electrical stimulation combined with repetitive transcranial magnetic stimulation and motor imagery on upper extremity motor recovery in the subacute period after stroke: A preliminary study.

BACKGROUND: To evaluate the therapeutic effects of additional electrical stimulation (ES) combined with low frequency (LF)-repetitive transcranial magnetic stimulation (rTMS) and motor imagery (MI) training on upper extremity (UE) motor function following stroke. METHODS: The participants with subacute stroke in the experimental group (n = 8) received LF rTMS + MI + active ES interventions, and those in control group (n = 9) received LF rTMS + MI + sham ES interventions. Interventions were performed 5 days a week for 2 weeks, for a total of 10 sessions. All participants were given the same dosage of conventional rehabilitation during the study period. The primary outcome measure was the UE Fugl-Meyer Assessment (FMA). The secondary outcome measures were the shoulder abduction and finger extension scores, modified Barthel Index, Purdue Pegboard Test, and finger tapping test. All scores were measured before and just after the intervention. RESULTS: After the 2-week intervention period, the FMA and modified Barthel Index scores were improved in both groups compared to baseline assessment (P < .001 in the experimental group and P = .008 in the control group). Of note, the change in FMA scores was significantly higher in the experimental group compared with that of the control group (P = .04). CONCLUSION: These results suggest that the use of LF rTMS + MI combined with additional ES lead to greater improvement of UE motor function after stroke. As such, this intervention may be a promising adjuvant therapy in UE motor training.

Changes in Muscle Mass after Botulinum Toxin Injection in Children with Spastic Hemiplegic Cerebral Palsy.

We aimed to evaluate muscle mass changes after injection of botulinum toxin (BoNT) in children with spastic hemiplegic cerebral palsy (CP). Children aged between 2 and 12 years who were diagnosed with hemiplegic CP with spastic equinus foot were prospectively recruited and administered BoNT in the affected leg. Lean body mass (LBM) of both legs and total limbs was measured by dual-energy X-ray absorptiometry (DXA) preinjection and 4 and 12 weeks after injection. A total of 15 children were enrolled into the study. LBM of both legs and total limbs increased significantly over 12 weeks of growth. The ratio of LBM of the affected leg to total limbs and to the unaffected leg significantly reduced at 4 weeks after injection compared with preinjection but significantly increased at 12 weeks after injection compared with 4 weeks after injection. In conclusion, the muscle mass of the affected leg after BoNT injection in children with hemiplegic spastic CP decreased at 4 weeks after BoNT injection but significantly recovered after 12 weeks after injection.

Bilateral Cerebral Ptosis in a Patient with Subdural Hemorrhage: a Case Report.

Although cerebral ptosis is rare, it is commonly associated with unilateral right cerebral hemisphere lesions. We report a case of a 79-year-old woman who presented with bilateral complete ptosis after a traumatic right fronto-temporo-parietal subdural hemorrhage (SDH). Bilateral ptosis was the primary manifestation of the acute right SDH, and the patient had no parenchymal lesion. Her prognosis was good, and she made a complete recovery. Right hemispheric hypoperfusion, as demonstrated on brain perfusion single-photon emission computed tomography, implied that the lateralization of eyelid control was in the right hemisphere, in line with previous reports.

Montreal Cognitive Assessment and Frontal Assessment Battery test as a predictor of performance of unaffected hand function after subcortical stroke.

The objective of this study was to elucidate the association between unaffected hand function and cognitive impairment and to determine whether the cognitive screening test can be a predictor of unaffected upper limb function in patients with unilateral subcortical strokes. A retrospective study of 37 patients with unilateral first-ever subcortical stroke was conducted through a review of medical records. The unaffected hand function and cognitive screening tests were measured upon admission to the neurorehabilitation unit and then 4 weeks later at discharge. The relationship between unaffected hand function and cognitive function was investigated with multiple linear regression analysis. Comparing the initial evaluation of unaffected hand function and cognitive function with the evaluation at discharge, cognitive function improved significantly at discharge; however, grip strength and dexterity of the unaffected hand were stationary except for three-point pinch strength, tip pinch strength, and finger tapping speed. The Montreal cognitive assessment (MoCA) score was found to be a significant predictor of unaffected grip strength (R2 = 0.33, P = 0.004) and three-point pinch strength (R2 = 0.16, P = 0.04) at discharge and the Frontal Assessment Battery (FAB) score to be a predictive value of the unaffected finger tapping test (R2 = 0.46, P < 0.001) at discharge. In subcortical stroke patients with low MoCA and FAB scores, clinicians must ensure that patients participate in rehabilitation therapy including bimanual activity with careful attention to the patient's unaffected hand function.

Congenital Osseous Torticollis that Mimics Congenital Muscular Torticollis: A Retrospective Observational Study.

It may be difficult to diagnose congenital osseous torticollis based on physical examinations or plain X-rays, especially when children have no other accompanying congenital defects. This study reports the children with torticollis caused by the vertebral anomaly with the symptom of abnormal head and neck posture only. We retrospectively reviewed the records of 1015 patients diagnosed with congenital torticollis in a single tertiary hospital (Incheon St. Mary's Hospital, Korea) who were referred from a primary local clinic. We included those with deficits in passive range of motion (PROM) of neck. Ultrasonography of the sternocleidomastoid (SCM) muscles, ophthalmologic and neurologic examinations, and cervical X-rays were performed for all patients. If bony malalignment was suspected from X-ray, three-dimensional volume-rendered computed tomography (3D-CT) was performed. Ten patients were diagnosed with osseous torticollis with no defect other than bony anomalies. Although X-ray images were acquired for all patients, vertebral anomalies were definitely confirmed in three cases (30.0%) only, and the others (70.0%) were confirmed by CT. The most common type of vertebral anomaly was single-level fusion. Identifying congenital vertebral anomalies is challenging especially when the degree of invasion is only one level. Although abnormal findings on X-rays may be subtle, a careful examination must be performed to avoid misdiagnosis.

Peroxiredoxin 4 attenuates glutamate-induced neuronal cell death through inhibition of endoplasmic reticulum stress.

High concentrations of glutamate induce neurotoxicity by eliciting reactive oxygen species (ROS) generation and intracellular Ca2+ influx. The disruption of Ca2+ homeostasis in the endoplasmic reticulum (ER) evokes ER stress, ultimately resulting in neuronal dysfunction. Additionally, glutamate participates in the development of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Peroxiredoxins (Prxs) are members of a family of antioxidant enzymes that protect cells from neurotoxic factor-induced apoptosis by scavenging hydrogen peroxide (H2O2). Prx4 is located in the ER and controls the redox condition within the ER. The present study investigated the protective effects of Prx4 against glutamate-induced neurotoxicity linked to ER stress. HT22 cells in which Prx4 was either overexpressed or silenced were used to elucidate the protective role of Prx4 against glutamate toxicity. The expression of Prx4 in HT22 cells was significantly increased in response to glutamate treatment, while ROS scavengers and ER chemical chaperones reduced Prx4 levels. Moreover, Prx4 overexpression reduces glutamate-induced apoptosis of HT22 cells by inhibiting ROS formation, Ca2+ influx, and ER stress. Therefore, we conclude that Prx4 has protective effects against glutamate-induced HT22 cell damage. Collectively, these results suggest that Prx4 could contribute to the treatment of neuronal disorders.

Continuous-wave operation of DFB laser diodes based on GaN using 10$

Single longitudinal mode continuous-wave operation of distributed-feedback (DFB) laser diodes based on GaN is demonstrated using laterally coupled 10th-order surface Bragg gratings. The gratings consist of V-shaped grooves alongside a 1.5 µm wide p-contact stripe fabricated by using electron-beam lithography and plasma etching. By varying the period of the Bragg grating, the lasing wavelength could be adjusted between 404.8 and 408.5 nm. The feasibility of this device concept was confirmed by mode-hop-free operation up to an optical output power of 90 mW, a low temperature sensitivity of the lasing wavelength, and a Gaussian lateral far-field distribution.

A multifunctional selective "turn-on" fluorescent chemosensor for detection of Group IIIA ions Al3+, Ga3+ and In3.

A versatile chemosensor 1 (E)-2-(((8-hydroxy-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)methylene)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione, based on naphthalimide and julolidine moieties, was developed for highly distinguishable and selective recognition of Group IIIA metal ions (Al3+, Ga3+ and In3+). Sensor 1 exhibited significant 'off-on' fluorescence responses at 488 nm in the presence of Al3+ and at 570 nm in the presence of Ga3+ and In3+. The same emission of Ga3+ and In3+ could be distinguished through different color changes (from colorless to yellow for Ga3+ and no color change for In3+). Binding constants of 1 for Ga3+ and In3+ are the highest reported to date for an organic chemosensor. A 2 : 1 binding mode between 1 with Al3+, Ga3+ and In3+ is proposed based on electrospray ionization mass spectrometry, Job plot analysis, and theoretical calculations.

A multi-functional chemosensor for highly selective ratiometric fluorescent detection of silver(I) ion and dual turn-on fluorescent and colorimetric detection of sulfide.

A multi-functional chemosensor 1 as silver and sulfide detector was synthesized by the combination of octopamine and 4-dimethylaminocinnamaldehyde. Sensor 1 exhibited a ratiometric fluorescence emission for Ag+ from blue to sky. The binding mode of 1 and Ag+ turned out to be a 1 : 1 ratio as determined using Job plot and electrospray ionization (ESI) mass spectral analyses. The sensing mechanism of 1 with silver ion was unravelled by 1H NMR titrations and theoretical calculations. Sensor 1 also discerned sulfide by enhancing fluorescence intensity and changing colour from yellow to colourless in aqueous solution. The sensing properties of 1 toward S2- were investigated by using ESI-mass analysis, Job plot and 1H NMR titrations. Moreover, 1 could be used as a detector for sulfide in a wide pH range.

Small intestine- and colon-specific smart oral drug delivery system with controlled release characteristic.

In recent years, there has been a significant increase in strategies for the development of small intestine (and colon)-specific oral drug-delivery systems to maximize the efficiency of therapeutic agents and reduce side effects. However, only a few strategies are capable of working in the complicated environment of the human intestinal tract. In this study, the preparation of a basic pH/temperature-responsive co-polymer (p-NIVIm) and its in-vitro-drug delivery function in the pH range of 1-8 and temperature range of 25-42 °C are reported. The basic copolymer was prepared by radical copolymerization of N-isopropyl acryl amide (NIPAAm) and N-vinylimidazole (VIm). The lower critical solution temperature (LCST) of p-NIVIm was higher in stomach pH (~1.0) conditions (36.5-42 °C) and lower in small intestine and/or colon pH (~8.0) conditions (35.8-38.2 °C). The ability to uptake a model protein (BSA) at body temperature and to release it in conditions of 37 °C and pH 1-8 was determined. The drug loading capacity (0.231 mg per 1.0 mg copolymer) and efficiency (92.4%) were high at 37 °C/pH 7. The drug carrier showed a slow release pattern at pH 1 (~0.084 mg; ~35%) and then a sudden release pattern (~0.177 mg; ~73%) at pH 8. The cytotoxicity of p-NIVIm to MCF-7 cells in vitro was minimal at concentrations <168.9 µg/mL after 72 h. The prepared copolymer with its pH-/temperature-responsive protein-entrapping and -releasing behavior at body temperature may potentially be applied as a novel small intestine (and colon)-specific oral drug delivery system.

A Multi-Responsive Naphthalimide-Based "Turn-on" Fluorescent Chemosensor for Sensitive Detection of Trivalent Cations Ga3+, Al3+ and Cr3.

A new multifunctional chemosensor 1, (E)-2-(((2-hydroxynaphthalen-1-yl)methylene)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione, based on naphtalimide and naphthaldehyde was developed, which showed the fluorescence responses to trivalent metal ions (Ga3+, Al3+ and Cr3+). Sensor 1 detected and differentiated selectively trivalent metal ions Ga3+, Al3+ and Cr3+ by fluorescence enhancement at different emissions. The association constant of Ga3+-2∙1 complex is the highest one among those of the organic chemosensors reported, to date. The sensing mechanisms for Ga3+, Al3+ and Cr3+ were explained by UV-vis titrations, Job plots, ESI-mass analyses and theoretical calculations.

Colorimetric detection of iron and fluorescence detection of zinc and cadmium by a chemosensor containing a bio-friendly octopamine.

Chemosensor 1 was synthesized by the reaction of octopamine with 2,3-dihydroxybenzaldehyde. Sensor 1 determined iron with an obvious color change from pale yellow to brown in nearly-pure water. The detection limits (0.55 and 0.25 µM) for Fe2+ and Fe3+, respectively, were far lower than the EPA (Environmental Protection Agency) guideline concentration for drinking water (5.37 µM). In addition, 1 could be employed to quantify iron in environmental water samples. Moreover, sensor 1 exhibited different fluorescence emissions in response to zinc (green) and cadmium (blue). The binding structures and sensing mechanisms of 1 for iron, zinc and cadmium were proposed from various spectroscopic studies and theoretical calculations.

Gelidium amansii extract ameliorates obesity by down-regulating adipogenic transcription factors in diet-induced obese mice.

BACKGROUND/OBJECTIVES: In this study, we investigated whether Gelidium amansii extract (GAE) ameliorates obesity in diet-induced obese (DIO) mice. MATERIALS/METHODS: The mice were maintained on a high-fat diet (HD) for 5 weeks to generate the DIO mouse model. And then mice fed HD plus 0.5% (GAE1), 1% (GAE2) or 2% (GAE3) for 8 weeks. RESULTS: After the experimental period, GAE-supplemented groups were significantly lower than the HD group in body weight gain and liver weight. GAE supplemented groups were significantly lower than the HD group in both epididymal and mesenteric adipose tissue mass. The plasma leptin level was significantly higher in the HD group than in GAE-supplemented groups. The leptin level of HD+GAE3 group was significantly lower than that of the HD+conjugated linoleic acid (CLA) group. In contrast, plasma adiponectin level of the HD group was significantly lower than those of HD+GAE2 and HD+GAE3 groups. The expression levels of adipogenic proteins such as fatty acid synthase, sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer binding protein α in the GAE supplemented groups were significantly decreased than those in HD group, respectively. In addition, the expression levels of HD+GAE2 and HD+GAE3 groups are significantly decreased compared to those of HD+CLA group. On the contrary, the expression levels of hormone-sensitive lipase and phospho-AMP-activated protein kinase, proteins associated with lipolysis, were significantly increased in the GAE supplemented groups compared to those in the HD group. HD+GAE3 group showed the highest level among the GAE supplemented groups. CONCLUSIONS: These results suggested that GAE supplementation stimulated the expressions of lipid metabolic factors and reduced weight gain in HD-fed C57BL/6J obese mice.

Gelidium amansii ethanol extract suppresses fat accumulation by down-regulating adipogenic transcription factors in ob/ob mice model.

The purpose of this study was to determine the anti-obesity effects of Gelidium amansii extract (GAE) in the C57BL/6J-ob/ob mice. The ob/ob mice were fed GAE at 0.5% for 4 weeks, after which body weight, epididymal adipose tissue weight, plasma triglycerides, and hepatic lipid accumulation were significantly reduced in GAE-fed mice compared with ob/ob control mice. Plasma adiponectin levels were significantly higher in GAE-fed mice than in ob/ob control mice. These findings were supported by the expression levels of enzymes and proteins related to lipid metabolism assessed by western blotting: protein expression levels of the peroxisome proliferator-activated receptor γ and CCATT/enhancer binding protein α decreased significantly, while hormone-sensitive lipase and phospho-AMP-activated protein kinase levels increased in the GAE-fed mice compared with ob/ob control mice. These findings demonstrate that GAE regulates plasma lipid profiles and increasing highdensity lipoprotein cholesterol levels as well as by regulating the expression levels of lipid metabolic factors, resulting in reduced weight gain in ob/ob mice.

Differences in two-point discrimination and sensory threshold in the blind between braille and text reading: a pilot study.

[Purpose] This study investigated two-point discrimination (TPD) and the electrical sensory threshold of the blind to define the effect of using Braille on the tactile and electrical senses. [Subjects and Methods] Twenty-eight blind participants were divided equally into a text-reading and a Braille-reading group. We measured tactile sensory and electrical thresholds using the TPD method and a transcutaneous electrical nerve stimulator. [Results] The left palm TPD values were significantly different between the groups. The values of the electrical sensory threshold in the left hand, the electrical pain threshold in the left hand, and the electrical pain threshold in the right hand were significantly lower in the Braille group than in the text group. [Conclusion] These findings make it difficult to explain the difference in tactility between groups, excluding both palms. However, our data show that using Braille can enhance development of the sensory median nerve in the blind, particularly in terms of the electrical sensory and pain thresholds.