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1.
Diabetes ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39024127

ABSTRACT

Diabetic retinopathy is the most common microvascular complication caused by chronic hyperglycemia and is a leading cause of blindness; however, the underlying molecular mechanism has not been clearly elucidated. Thus, we investigated whether regulation of AMPactivated protein kinase (AMPK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by transglutaminase 2 (TGase2) is important for hyperglycemia-induced microvascular leakage in the diabetic retina. In HRECs and diabetic mouse retinas, we found that TGase2, activated by sequential elevation of intracellular Ca2+ and reactive oxygen species (ROS) levels, played an essential role in hyperglycemia-induced vascular leakage. ROS generation and TGsae2 activation were involved in hyperglycemia-induced AMPK dephosphorylation, which resulted in VE-cadherin disassembly and increased fluorescein isothiocyanate-dextran extravasation. Furthermore, high glucose-induced TGase2 activation suppressed GAPDH activity, determined by an on-chip activity assay, through inhibition of AMPK, which induced VE-cadherin disassembly and endothelial permeability in HRECs. Overall, our findings suggest that inhibition of AMPK and GAPDH by TGase2 plays a pivotal role in hyperglycemia-induced microvascular leakage in the retinas of diabetic mice.

2.
medRxiv ; 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38712177

ABSTRACT

Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS-evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other brain-computer interface studies to ensure successful placement of stimulation electrodes.

3.
Nat Commun ; 15(1): 4547, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806514

ABSTRACT

Efficient photovoltaic devices must be efficient light emitters to reach the thermodynamic efficiency limit. Here, we present a promising prospect of perovskite photovoltaics as bright emitters by harnessing the significant benefits of photon recycling, which can be practically achieved by suppressing interfacial quenching. We have achieved radiative and stable perovskite photovoltaic devices by the design of a multiple quantum well structure with long (∼3 nm) organic spacers with oleylammonium molecules at perovskite top interfaces. Our L-site exchange process (L: barrier molecule cation) enables the formation of stable interfacial structures with moderate conductivity despite the thick barriers. Compared to popular short (∼1 nm) Ls, our approach results in enhanced radiation efficiency through the recursive process of photon recycling. This leads to the realization of radiative perovskite photovoltaics with both high photovoltaic efficiency (in-lab 26.0%, certified to 25.2%) and electroluminescence quantum efficiency (19.7 % at peak, 17.8% at 1-sun equivalent condition). Furthermore, the stable crystallinity of oleylammonium-based quantum wells enables our devices to maintain high efficiencies for over 1000 h of operation and >2 years of storage.

4.
Dev Cogn Neurosci ; 66: 101373, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38574406

ABSTRACT

Adolescence has been hypothesized to be a critical period for the development of human association cortex and higher-order cognition. A defining feature of critical period development is a shift in the excitation: inhibition (E/I) balance of neural circuitry, however how changes in E/I may enhance cortical circuit function to support maturational improvements in cognitive capacities is not known. Harnessing ultra-high field 7 T MR spectroscopy and EEG in a large, longitudinal cohort of youth (N = 164, ages 10-32 years old, 347 neuroimaging sessions), we delineate biologically specific associations between age-related changes in excitatory glutamate and inhibitory GABA neurotransmitters and EEG-derived measures of aperiodic neural activity reflective of E/I balance in prefrontal association cortex. Specifically, we find that developmental increases in E/I balance reflected in glutamate:GABA balance are linked to changes in E/I balance assessed by the suppression of prefrontal aperiodic activity, which in turn facilitates robust improvements in working memory. These findings indicate a role for E/I-engendered changes in prefrontal signaling mechanisms in the maturation of cognitive maintenance. More broadly, this multi-modal imaging study provides evidence that human association cortex undergoes physiological changes consistent with critical period plasticity during adolescence.

5.
NMR Biomed ; 37(8): e5146, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38533593

ABSTRACT

The decoupled 8 × 2 transceiver array has been shown to achieve a mean B1 + of 11.7 uT with a coefficient of variation of ~11% over the intracranial brain volume for 7-T MR imaging. However, this array may be thought to give lower signal-to-noise ratio (SNR) and higher g-factors for parallel imaging compared with a radio frequency (RF) receive-only coil due to the latter's higher coil count and use of coil overlap to reduce the mutual impedance. Nonetheless, because the transceiver's highly decoupled design (pertinent for transmission) should also be constructive for reception, we measured the noise correlation, g-factors, and SNR for the decoupled transceiver in comparison with a commercial reference coil. We found that although the transceiver has half the number of receive elements in comparison with the reference coil (16 vs. 32), comparable g-factors and SNR over the head were obtained. From five subjects, the transceiver versus reference coil SNR was 65 ± 10 versus 67 ± 15. The mean noise correlation for all coil pairs was 10% ± 5% and 12% ± 9% (transceiver and reference coil, respectively). As changes in load impedance may alter the S parameters, we also examined the performance of the transceiver with tuned and matched (TM) versus untuned and unmatched (UTM) conditions on five subjects. We found that the noise correlation and SNR are robust to load variation; a noise correlation of 10% ± 5% and 10% ± 6% was determined with TM versus UTM conditions (SNRUTM/SNRTM = 0.97 ± 0.08). Finally, we demonstrate the performance of the array in human brain using T2-weighted turbo spin echo imaging, finding excellent SNR performance in both caudal and rostral brain regions.


Subject(s)
Magnetic Resonance Imaging , Signal-To-Noise Ratio , Humans , Brain/diagnostic imaging , Male , Female , Equipment Design , Adult
6.
Biomed Pharmacother ; 172: 116232, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38310652

ABSTRACT

Proinsulin C-peptide, a biologically active polypeptide released from pancreatic ß-cells, is known to prevent hyperglycemia-induced microvascular leakage; however, the role of C-peptide in migration and invasion of cancer cells is unknown. Here, we investigated high glucose-induced migration and invasion of ovarian cancer cells and the inhibitory effects of human C-peptide on metastatic cellular responses. In SKOV3 human ovarian cancer cells, high glucose conditions activated a vicious cycle of reactive oxygen species (ROS) generation and transglutaminase 2 (TGase2) activation through elevation of intracellular Ca2+ levels. TGase2 played a critical role in high glucose-induced ovarian cancer cell migration and invasion through ß-catenin disassembly. Human C-peptide inhibited high glucose-induced disassembly of adherens junctions and ovarian cancer cell migration and invasion through inhibition of ROS generation and TGase2 activation. The preventive effect of C-peptide on high glucose-induced ovarian cancer cell migration and invasion was further demonstrated in ID8 murine ovarian cancer cells. Our findings suggest that high glucose conditions induce the migration and invasion of ovarian cancer cells, and human C-peptide inhibits these metastatic responses by preventing ROS generation, TGase2 activation, and subsequent disassembly of adherens junctions.


Subject(s)
Ovarian Neoplasms , Humans , Animals , Mice , Female , C-Peptide/pharmacology , Reactive Oxygen Species/pharmacology , Ovarian Neoplasms/pathology , Cell Movement , Glucose/pharmacology
7.
Global Spine J ; : 21925682231218729, 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-38015818

ABSTRACT

STUDY DESIGN: Retrospective Study. OBJECTIVES: Minimally invasive endoscopic spinal surgery is gaining popularity, but our understanding of the lumbar spine's microvascular geometry relies heavily on cadaver studies and textbook illustrations. Additionally, inconsistent nomenclature of vessels in the literature hampers effective communication among surgeons. This study aims to improve the clarity and comprehensibility of the lumbar spinal microvascular geometry under endoscopic view. METHODS: The study included 400 patients who underwent endoscopic spinal surgery for lumbar spinal canal stenosis and foraminal stenosis. The surgeries were performed by an experienced surgeon using either the interlaminar or transforaminal approach. Endoscopic video recordings were further analyzed to map the microvascular geometry and common bleeding foci. The observed results were cross-referenced with existing literature to reconstruct a comprehensive view of the vascular anatomy. RESULTS: The transforaminal approach commonly encounters bleeding foci originating from the major branches of the segmental lumbar artery and the emissary veins within the foramen. The interlaminar approach primarily encounters bleeding foci from the muscle vessels in the dorsal lamina, which are believed to be located near the ends of the three main branches. In the intracanal region, epidural vessels form a rotary loop above the disc, which can contribute to most of the bleeding during discectomy. CONCLUSIONS: This study provides a comprehensive understanding of the microvascular anatomy in the lumbar spine during endoscopic spinal surgery. Recognizing the geometry will help surgeons anticipate and control bleeding, reducing the risk of complications. The findings contribute to the improvement of surgical techniques and patient safety in endoscopic spinal surgery.

8.
NMR Biomed ; 36(12): e5021, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37586403

ABSTRACT

While B0 shimming is an important requirement for in vivo brain spectroscopy, for single voxel spectroscopy (SVS), the role for advanced shim methods has been questioned. Specifically, with the small spatial dimensions of the voxel, the extent to which inhomogeneities higher than second order exist and the ability of higher order shims to correct them is controversial. To assess this, we acquired SVS from two loci of neurophysiological interest, the rostral prefrontal cortex (rPFC; 8 cc) and hippocampus (Hc; 9 cc). The rPFC voxel was placed using SUsceptibility Managed Optimization (SUMO) and an initial B0 map that covers the entire cerebrum to cerebellum. In each location, we compared map-based shimming (Bolero) with projection-based shimming (FAST(EST)MAP). We also compared vendor-provided spherical harmonic first- and second-order shims with additional third- and fourth-order shim hardware. The 7T SVS acquisition used stimulated echo acquisition mode (STEAM) TR/TM/TE of 6 s/20 ms/8 ms, a tissue water acquisition for concentration reference, and LCModel for spectral analysis. In the rPFC (n = 7 subjects), Bolero shimming with first- and second-order shims reduced the residual inhomogeneity σ B 0 from 9.8 ± 4.5 Hz with FAST(EST)MAP to 6.5 ± 2.0 Hz. The addition of third- and fourth-order shims further reduced σ B 0 to 4.0 ± 0.8 Hz. In the Hc (n = 7 subjects), FAST(EST)MAP, Bolero with first- and second-order shims, and Bolero with first- to fourth-order shims achieved σ B 0 values of 8.6 ± 1.9, 5.6 ± 1.0, and 4.6 ± 0.9 Hz, respectively. The spectral linewidth, Δ v σ B 0 , was estimated with a Voigt lineshape using σ B 0 and T2 = 130 ms. Δ v σ B 0 significantly correlated with the Cramer-Rao lower bounds and concentrations of several metabolites, including glutamate and glutamine in the rPFC. In both loci, if the B0 distribution is well described by a Gaussian model, the variance of the metabolite concentrations is reduced, consistent with the LCModel fit based on a unimodal lineshape. Overall, the use of the high order and map-based B0 shim methods improved the accuracy and consistency of spectroscopic data.


Subject(s)
Brain , Head , Humans , Brain/diagnostic imaging , Magnetic Resonance Spectroscopy/methods , Magnetic Resonance Imaging/methods , Image Processing, Computer-Assisted/methods
9.
Curr Oncol ; 30(5): 4632-4647, 2023 04 30.
Article in English | MEDLINE | ID: mdl-37232808

ABSTRACT

This review article gives an overview of the current state of the art of bladder cancer imaging and then discusses in depth the scientific and technical merit of a novel imaging approach, tracing its evolution from murine cancer models to cancer patients. While the poor resolution of soft tissue obtained by widely available imaging options such as abdominal sonography and radiation-based CT leaves them only suitable for measuring the gross tumor volume and bladder wall thickening, dynamic contrast-enhanced magnetic resolution imaging (DCE MRI) is demonstrably superior in resolving muscle invasion. However, major barriers still exist in its adoption. Instead of injection for DCE-MRI, intravesical contrast-enhanced MRI (ICE-MRI) instills Gadolinium chelate (Gadobutrol) together with trace amounts of superparamagnetic agents for measurement of tumor volume, depth, and aggressiveness. ICE-MRI leverages leaky tight junctions to accelerate passive paracellular diffusion of Gadobutrol (604.71 Daltons) by treading the paracellular ingress pathway of fluorescein sodium and of mitomycin (<400 Daltons) into bladder tumor. The soaring cost of diagnosis and care of bladder cancer could be mitigated by reducing the use of expensive operating room resources with a potential non-surgical imaging option for cancer surveillance, thereby reducing over-diagnosis and over-treatment and increasing organ preservation.


Subject(s)
Organometallic Compounds , Urinary Bladder Neoplasms , Humans , Animals , Mice , Neoplasm Staging , Magnetic Resonance Imaging/methods , Urinary Bladder Neoplasms/diagnostic imaging
10.
Int J Mol Sci ; 24(9)2023 Apr 22.
Article in English | MEDLINE | ID: mdl-37175389

ABSTRACT

N-acetylaspartate (NAA) and choline (Cho) are two brain metabolites implicated in several key neuronal functions. Abnormalities in these metabolites have been reported in both early course and chronic patients with schizophrenia (SCZ). It is, however, unclear whether NAA and Cho's alterations occur even before the onset of the disorder. Clinical high risk (CHR) individuals are a population uniquely enriched for psychosis and SCZ. In this exploratory study, we utilized 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to examine differences in total NAA (tNAA; NAA + N-acetylaspartylglutamate [NAAG]) and major choline-containing compounds, including glycerophosphorylcholine and phosphorylcholine [tCho], over the creatine (Cre) levels between 26 CHR and 32 healthy control (HC) subjects in the subcortical and cortical regions. While no tCho/Cre differences were found between groups in any of the regions of interest (ROIs), we found that CHR had significantly reduced tNAA/Cre in the right dorsal lateral prefrontal cortex (DLPFC) compared to HC, and that the right DLPFC tNAA/Cre reduction in CHR was negatively associated with their positive symptoms scores. No tNAA/Cre differences were found between CHR and HC in other ROIs. In conclusion, reduced tNAA/Cre in CHR vs. HC may represent a putative molecular biomarker for risk of psychosis and SCZ that is associated with symptom severity.


Subject(s)
Hippocampus , Magnetic Resonance Imaging , Humans , Magnetic Resonance Spectroscopy , Hippocampus/metabolism , Creatine/metabolism , Aspartic Acid/metabolism , Choline/metabolism
11.
BMC Musculoskelet Disord ; 24(1): 426, 2023 May 27.
Article in English | MEDLINE | ID: mdl-37244983

ABSTRACT

BACKGROUND: The NASS guideline cannot recommend any of the surgical treatment options toward adult isthmic spondylolisthesis (AIS) since 2014. After the introduction of endoscopic decompression, instead of treating the spondylolysis itself, treatment can specifically target the refractory radicular pain developed during the degeneration progress without devastating the peripheral soft tissue. However, we noticed that endoscopic transforaminal decompression seems to be less effective in AIS compared to other types of degenerative spondylolisthesis. Thus, we came up with a novel craniocaudal interlaminar approach, utilizing the proximal adjacent interlaminar space to perform bilateral decompression and observed the pathoanatomy of pars defect directly and tried to identify the cause of decompression failure. METHODS: From January 2022 to June 2022, 13 patients with AIS underwent endoscopic decompression via the endoscopic craniocaudal interlaminar approach and were followed up for at least 6 months. Visual Analogue Scale, Oswestry Disability Index and MacNab scores were recorded to monitor patients' clinical recovery. All endoscopic procedures were recorded and reviewed to illustrate the pathoanatomy. RESULTS: Four patients required minor revision via the same technique. One of them required it due to incomplete isthmic spur resection, two due to neglected disc protrusion, and the other due to root subpedicular kinking in higher grade anterolisthesis. All patients' clinical condition improved significantly subsequently. After reviewing the endoscopic video, we have observed that the hook-like, ragged spur originating from the isthmic defect extends beyond the region around the foramen. Instead, it extends proximally into the adjacent lateral recess, resulting in impingement along the fracture edge above the index foramen and, in some cases, even in the extraforaminal area. CONCLUSIONS: The broad spanning isthmic spur extending to the proximal adjacent lateral recess might be the reason why the transforaminal approach yielded less satisfactory results due to the incomplete decompression result from approach related restriction. Our study demonstrated an optimistic outcome by applying decompression from the upper level. Therefore, we propose that the craniocaudal interlaminar approach might be a better route for decompression in adult isthmic spondylolisthesis.


Subject(s)
Spinal Stenosis , Spondylolisthesis , Humans , Adult , Spondylolisthesis/complications , Spondylolisthesis/diagnostic imaging , Spondylolisthesis/surgery , Decompression, Surgical/methods , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Endoscopy/methods , Treatment Outcome , Spinal Stenosis/surgery , Retrospective Studies
12.
Pain Physician ; 26(3): E181-E189, 2023 05.
Article in English | MEDLINE | ID: mdl-37192241

ABSTRACT

BACKGROUND: Chronic discogenic pain includes degeneration-driven changes under the mechanical macroenvironment of an internal disc, which leads to the progressive changes of biochemical microenvironment that induce abnormal ingrowth of the nociceptor. The propriety of the animal model reflecting the pathologic natural history has not been assessed. OBJECTIVES: This study investigated the biochemical evidence of chronic discogenic pain by employing a discogenic pain animal model induced by shear force. STUDY DESIGN: Animal study utilizing rats in vivo model of a shear force device. METHODS: Fifteen rats were divided into 3 groups (n = 5/group) according to the period for which sustained dorsoventral shear force was applied (1 week or 2 weeks); the control group received the spinous attachment unit, without a spring. Pain data were collected using von Frey hairs on the hind paws. Growth factor and cytokine abundance was analyzed in the dorsal root ganglion (DRG) and plasma. RESULTS: After the shear force devices were installed, the significant variables were found to markedly increase in the DRG tissues of the 2-week group; however, they were not altered in the 1-week group. Specifically, interleukin (IL)-6, neurogrowth factor (NGF), transforming growth factor (TGF)-alpha, platelet-derived growth factor (PDGF)-beta, and vascular endothelial growth factor (VEGF) were increased. Meanwhile, the plasma levels of tumor necrosis factor-alpha, IL-1beta, IL-5, IL-6, IL-12, and NGF were increased in the 1-week group; whereas, TGF-alpha, PDGF-beta, and VEGF were increased in the 2-week group. LIMITATIONS: The limitations include the general limitations of quadrupedal animals, the poor precision and flexural deformation of shear force devices, inaccuracies regarding the evaluation of histological denaturation, and short intervention and observational periods. CONCLUSIONS: This animal model effectively generated biochemical responses to shear loading with evidence of neurological changes induced without direct macrodamage to the outer annulus fibrosus. Chemical internals were induced by mechanical externals among the contributing factors of chronic discogenic pain.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Rats , Animals , Vascular Endothelial Growth Factor A , Nerve Growth Factor/metabolism , Nerve Growth Factor/pharmacology , Pain , Disease Models, Animal
13.
Theranostics ; 13(8): 2424-2438, 2023.
Article in English | MEDLINE | ID: mdl-37215567

ABSTRACT

Rationale: Neovascularization is a hallmark of the late stages of diabetic retinopathy (DR) leading to blindness. The current anti-DR drugs have clinical disadvantages including short circulation half-lives and the need for frequent intraocular administration. New therapies with long-lasting drug release and minimal side effects are therefore needed. We explored a novel function and mechanism of a proinsulin C-peptide molecule with ultra-long-lasting delivery characteristics for the prevention of retinal neovascularization in proliferative diabetic retinopathy (PDR). Methods: We developed a strategy for ultra-long intraocular delivery of human C-peptide using an intravitreal depot of K9-C-peptide, a human C-peptide conjugated to a thermosensitive biopolymer, and investigated its inhibitory effect on hyperglycemia-induced retinal neovascularization using human retinal endothelial cells (HRECs) and PDR mice. Results: In HRECs, high glucose conditions induced oxidative stress and microvascular permeability, and K9-C-peptide suppressed those effects similarly to unconjugated human C-peptide. A single intravitreal injection of K9-C-peptide in mice resulted in the slow release of human C-peptide that maintained physiological levels of C-peptide in the intraocular space for at least 56 days without inducing retinal cytotoxicity. In PDR mice, intraocular K9-C-peptide attenuated diabetic retinal neovascularization by normalizing hyperglycemia-induced oxidative stress, vascular leakage, and inflammation and restoring blood-retinal barrier function and the balance between pro- and anti-angiogenic factors. Conclusions: K9-C-peptide provides ultra-long-lasting intraocular delivery of human C-peptide as an anti-angiogenic agent to attenuate retinal neovascularization in PDR.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Hyperglycemia , Retinal Neovascularization , Humans , Mice , Animals , Retinal Neovascularization/drug therapy , Diabetic Retinopathy/drug therapy , C-Peptide/pharmacology , C-Peptide/therapeutic use , Endothelial Cells , Neovascularization, Pathologic/drug therapy , Hyperglycemia/drug therapy
14.
Neuroimage Clin ; 38: 103398, 2023.
Article in English | MEDLINE | ID: mdl-37086647

ABSTRACT

Stability of precision grip depends on the ability to regulate forces applied by the digits. Increased frequency composition and temporal irregularity of oscillations in the force signal are associated with enhanced force stability, which is thought to result from increased voluntary drive along the corticospinal tract (CST). There is limited knowledge of how these oscillations in force output are regulated in the context of dexterous hand movements like precision grip, which are often impaired by CST damage due to stroke. The extent of residual CST volume descending from primary motor cortex may help explain the ability to modulate force oscillations at higher frequencies. Here, stroke survivors with longstanding hand impairment (n = 17) and neurologically-intact controls (n = 14) performed a precision grip task requiring dynamic and isometric muscle contractions to scale and stabilize forces exerted on a sensor by the index finger and thumb. Diffusion spectrum imaging was used to quantify total white matter volume within the residual and intact CSTs of stroke survivors (n = 12) and CSTs of controls (n = 14). White matter volumes within the infarct region and an analogous portion of overlap with the CST, mirrored onto the intact side, were also quantified in stroke survivors. We found reduced ability to stabilize force and more restricted frequency ranges in force oscillations of stroke survivors relative to controls; though, more broadband, irregular output was strongly related to force-stabilizing ability in both groups. The frequency composition and temporal irregularity of force oscillations observed in stroke survivors did not correlate with maximal precision grip force, suggesting that it is not directly related to impaired force-generating capacity. The ratio of residual to intact CST volumes contained within infarct and mirrored compartments was associated with more broadband, irregular force oscillations in stroke survivors. Our findings provide insight into granular aspects of dexterity altered by corticospinal damage and supply preliminary evidence to support that the ability to modulate force oscillations at higher frequencies is explained, at least in part, by residual CST volume in stroke survivors.


Subject(s)
Pyramidal Tracts , Stroke , Humans , Pyramidal Tracts/diagnostic imaging , Fingers , Hand Strength/physiology , Infarction
15.
BMC Med ; 21(1): 49, 2023 02 13.
Article in English | MEDLINE | ID: mdl-36782199

ABSTRACT

BACKGROUND: Hyperglycemic memory (HGM) is a pivotal phenomenon in the development of diabetic complications. Although coincident diabetic complications are reported, research on their development and treatment is limited. Thus, we investigated whether C-peptide can simultaneously inhibit HGM-induced retinal, pulmonary, and glomerular dysfunctions in diabetic mice supplemented with insulin. METHODS: Insulin-treated diabetic mice were supplemented with human C-peptide by subcutaneous implantation of K9-C-peptide depots for 4 weeks, and reactive oxygen species (ROS) generation, transglutaminase (TGase) activity, and vascular leakage were examined in the retina, lung, and kidney. RESULTS: We found hyperglycemia-induced persistent ROS generation and TGase activation after blood glucose normalization in the retina, lung, and kidney of insulin-supplemented diabetic mice. These pathological events were inhibited by systemic supplementation of human C-peptide via subcutaneous implantation of a thermosensitive biopolymer-conjugated C-peptide depot. ROS generation and TGase activation were in a vicious cycle after glucose normalization, and C-peptide suppressed the vicious cycle and subsequent endothelial permeability in human retinal endothelial cells. Moreover, C-peptide supplementation ameliorated HGM-induced retinal vascular leakage and neurodegeneration, pulmonary vascular leakage and fibrosis, and glomerular adherens junction disruption and vascular leakage. CONCLUSIONS: Overall, our findings demonstrate that C-peptide supplementation simultaneously attenuates vascular and neuronal dysfunctions in the retina, lung, and glomerulus of insulin-supplemented diabetic mice.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Retinopathy , Humans , Mice , Animals , C-Peptide , Reactive Oxygen Species , Endothelial Cells , Diabetes Mellitus, Experimental/complications , Retina , Transglutaminases/physiology , Insulin/pharmacology , Lung , Diabetic Retinopathy/complications
16.
FASEB J ; 37(2): e22763, 2023 02.
Article in English | MEDLINE | ID: mdl-36625326

ABSTRACT

Diabetic retinopathy (DR) is caused by retinal vascular dysfunction and neurodegeneration. Intraocular delivery of C-peptide has been shown to be beneficial against hyperglycemia-induced microvascular leakage in the retina of diabetes; however, the effect of C-peptide on diabetes-induced retinal neurodegeneration remains unknown. Moreover, extraocular C-peptide replacement therapy against DR to avoid various adverse effects caused by intravitreal injections has not been studied. Here, we demonstrate that systemic C-peptide supplementation using osmotic pumps or biopolymer-conjugated C-peptide hydrogels ameliorates neurodegeneration by inhibiting vascular endothelial growth factor-induced pathological events, but not hyperglycemia-induced vascular endothelial growth factor expression, in the retinas of diabetic mice. C-peptide inhibited hyperglycemia-induced activation of macroglial and microglial cells, downregulation of glutamate aspartate transporter 1 expression, neuronal apoptosis, and histopathological changes by a mechanism involving reactive oxygen species generation in the retinas of diabetic mice, but transglutaminase 2, which is involved in retinal vascular leakage, is not associated with these pathological events. Overall, our findings suggest that systemic C-peptide supplementation alleviates hyperglycemia-induced retinal neurodegeneration by inhibiting a pathological mechanism, involving reactive oxygen species, but not transglutaminase 2, in diabetes.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Retinopathy , Hyperglycemia , Animals , Mice , Vascular Endothelial Growth Factor A/metabolism , C-Peptide/metabolism , Reactive Oxygen Species/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Retina/metabolism , Vascular Endothelial Growth Factors , Diabetic Retinopathy/metabolism , Hyperglycemia/metabolism , Dietary Supplements
17.
Food Sci Anim Resour ; 42(6): 953-967, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36415581

ABSTRACT

The objective of this study was to determine effects of aging methods (wet-aged, dry-aged, and packaged dry-aged) during 60 d on quality traits and microbial characteristics of beef. Wet-aged beef was packed by vacuum packaging and stored in a 4°C refrigerator. Dry-aged beef was used without packaging. Packaged dry-aged beef was packaged in commercial bags. Dry-aged and packaged dry-aged samples were stored in a meat ager at 2°C-4°C with 85%-90% relative humidity. Meat color, crust thickness, aging loss, cooking loss, Warner-Bratzler shear force (WBSF), texture profile analysis, Torrymeter, meat pH, water activity, volatile basic nitrogen (VBN), thiobarbituric acid reactant substances (TBARS), and microbial analysis were measured or performed every 15 d until 60 d of aging time. Meat color changed significantly with increasing aging time. Differences in meat color among aging methods were observed. Aging losses of dry-aged and packaged dry-aged samples were higher than those of wet-aged samples. Wet-aged beef showed higher cooking loss, but lower WBSF than dry-aged and packaged dry-aged beef. VBN and TBARS showed an increasing tendency with increasing aging time. Differences of VBN and TBARS among aging methods were found. Regarding microbial analysis, counts of yeasts and molds were different among aging methods at the initial aging time. Packaged dry-aged and dry-aged beef showed similar values or tendency. Significant changes occurred during aging in all aging methods. Packaged dry aging and dry aging could result in similar quality traits and microbial characteristics of beef.

18.
Prog Neurobiol ; 219: 102370, 2022 12.
Article in English | MEDLINE | ID: mdl-36309210

ABSTRACT

Animal and human postmortem studies provide evidence for changes in gamma-aminobutyric acid (GABA) and glutamate in prefrontal cortex (PFC) during adolescence, suggesting shifts in excitation and inhibition balance consistent with critical period plasticity. However, how GABA and glutamate change through adolescence and how the balance of these inhibitory and excitatory neurotransmitters changes is not well understood in vivo in humans. High field (7 Tesla) Magnetic Resonance Spectroscopic Imaging was used to investigate age-related changes in the balance of GABA/creatine (Cr) and glutamate/Cr in multiple developmentally-relevant regions of frontal cortex in 144 10-30-year-olds. Results indicated a homogenous pattern of age-related Glu/Cr decreases across regions, while age-related changes in GABA/Cr were heterogenous, with a mix of stable and decreasing age effects. Importantly, balance between glutamate/Cr and GABA/Cr in areas of frontal cortex increased through adolescence, suggesting the presence of critical period plasticity in frontal cortex at this significant time of development when adult trajectories are established.


Subject(s)
Glutamic Acid , gamma-Aminobutyric Acid , Adult , Adolescent , Humans , Inhibition, Psychological , Prefrontal Cortex , Magnetic Resonance Imaging/methods , Creatine
19.
ACS Appl Mater Interfaces ; 14(2): 3334-3343, 2022 Jan 19.
Article in English | MEDLINE | ID: mdl-34981919

ABSTRACT

Icephobic coatings have been extensively studied for decades to overcome the potential damage associated with ice formation in various devices that are operated under harsh weather conditions. Superhydrophobic surface coatings have been applied for icephobic coating applications owing to their low surface energy. In this study, an icephobic coating of a self-formed superhydrophobic surface using polydimethylsiloxane (PDMS) and SiO2 powder was investigated. The effect of superhydrophobicity on icephobicity was determined by varying the experimental parameters. Polyvinylidene fluoride (PVDF) was added to the PDMS solution to improve the mechanical properties of the icephobic layer. The PDMS-PVDF solution also showed a self-formation behavior into a superhydrophobic surface. In addition, the icephobicity and mechanical properties of the PDMS-PVDF mixture coating improved because of the multilevel nanostructure formed by physical and chemical interactions between the mixture and SiO2 powder. We believe that the proposed approach will be a suitable candidate for various practical applications of icephobicity and a model system to understand the correlation between superhydrophobicity and icephobicity.

20.
Small Methods ; 5(5): e2001248, 2021 May.
Article in English | MEDLINE | ID: mdl-34928076

ABSTRACT

Perovskite solar cells in an n-i-p structure record high power conversion efficiency, but issues of insufficient thermal stability and the high cost of p-type hole transporting materials have been raised as drawbacks. H2 -phthalocyanine (Pc) is introduced as a hole transport material to ensure the thermal stability and simultaneously have served surface passivation effects on hybrid halide perovskites as a Lewis base. Pyrrolic nitrogen in the Pc reacts with uncoordinated Pb2+ ions on the perovskite surface. Upon enhancing the interfacial interaction between phthalocyanine and the perovskite, the open circuit voltage in devices increases as compared to that of devices using a metal-phthalocyanine complex. While the phthalocyanine-applied device maintains superior thermal long-term stability, the power conversion efficiency also exceeds 20%.

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