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Freesia refracta (FR), a perennial flower of the Iris family (Iridaceae), is widely used in cosmetics despite limited scientific evidence of its skin benefits and chemical composition, particularly of FR callus extract (FCE). This study identified biologically active compounds in FCE and assessed their skin benefits, focusing on anti-aging. FR calli were cultured, extracted with water at 40 °C, and analyzed using Centrifugal Partition Chromatography (CPC), Nuclear Magnetic Resonance (NMR), and HCA, revealing key compounds, namely nicotinamide and pyroglutamic acid. FCE significantly increased collagen I production by 52% in normal and aged fibroblasts and enhanced fibroblast-collagen interaction by 37%. An in vivo study of 43 female volunteers demonstrated an 11.1% reduction in skin roughness and a 2.3-fold increase in collagen density after 28 days of cream application containing 3% FCE. Additionally, the preservation tests of cosmetics containing FCE confirmed their stability over 12 weeks. These results suggest that FCE offers substantial anti-aging benefits by enhancing collagen production and fibroblast-collagen interactions. These findings highlighted the potential of FCE in cosmetic applications, providing significant improvements in skin smoothness and overall appearance. This study fills a gap in the scientific literature regarding the skin benefits and chemical composition of FR callus extract, supporting its use in the development of effective cosmeceuticals.
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Fibroblastos , Estrés Oxidativo , Extractos Vegetales , Envejecimiento de la Piel , Piel , Envejecimiento de la Piel/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Humanos , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Piel/metabolismo , Piel/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Adulto , Colágeno/metabolismo , Cosméticos/farmacología , Persona de Mediana Edad , Niacinamida/farmacología , Ácido Pirrolidona Carboxílico/análogos & derivados , Ácido Pirrolidona Carboxílico/farmacología , Ácido Pirrolidona Carboxílico/metabolismoRESUMEN
We report a case of a 45-year-old man presenting with tachycardia and palpitation. Echocardiography indicated severe tricuspid regurgitation. We suspected traumatic tricuspid damage due to high energy trauma in a motor vehicle accident 17â¯years earlier. He underwent a sternotomy, and his tricuspid valve was repaired with chordal reconstruction, indentation closure, and ring annuloplasty. The postoperative period was uneventful, and he was discharged 10â¯days after the operation. This report highlights the value of echocardiography for diagnosis of primary tricuspid regurgitation related to trauma, and the importance of early diagnosis to allow surgical intervention before irreversible damage occurs. Learning objective: Traumatic tricuspid regurgitation is a rare cardiovascular complication of blunt chest trauma. The mechanism of the tricuspid valve injury is thought to be secondary to sudden impact causing an anteroposterior compression of the right ventricle by the sternum in end-diastole. This injury is often incidentally identified or can be missed until the patient experiences symptoms of right heart failure resulting from severe tricuspid regurgitation.
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In this study, we analyzed the impact of multi-terminal direct current (MTDC) system on the integration of renewable energy resources into the Korean power system. Due to the large-scale renewable energy plants planned to be integrated into the power system, line congestion is expected in the southern part of power system. Given the difficulty in constructing AC transmission lines due to social conflicts, we proposed an alternative solution using an offshore multi-terminal DC offshore transmission system. Firstly, we calculate the effective renewable energy plant generation capacity based on annual wind and solar radiation data. Next, we conduct PSS/E simulations to minimize future line congestion in the Korean power grid. The offshore terminal is designed to transfer the power generated in southern Korea and is verified using different terminal rating cases. The simulation result, including contingency analysis, demonstrate that transferring 80% of the generated renewable power achieves the best line flow condition. Therefore, the MTDC system is a possible candidate for integrating future renewable energy systems into the Korean power grid.
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Objective: Shoulder pain is a common complaint in outpatient clinics and can result in an inability to work or perform household activities, leading to significant socioeconomic burden. Acupotomy, as one kind acupuncture that has flat knife-shaped tip, has been widely used for treating shoulder pain. However, despite the widespread use of acupotomy in primary medical institutions, large sample size clinical trials have not sufficiently been performed. In this respect, this multi-center retrospective study aimed to investigate the effectiveness and safety of acupotomy in reducing shoulder pain and disability using data from multi-center primary care clinics. Methods: This study was conducted in 25 Korean medicine clinics affiliated with the Korean Medical Society of Acupotomology, Republic of Korea, from August 2021 to December 2021. The medical records of patients who visited the clinics complaining of shoulder pain were gathered, and among them were those of patients who underwent acupotomy treatment and those who received acupuncture combined therapy. The Numeric Rating Scale (NRS), SPADI (Shoulder Pain and Disability Index), Range of Motion (ROM) and adverse event were evaluated at each visit. A linear mixed-effects models and paired t-test were used to identify the effectiveness of the treatment. Results: Overall analysis showed that the NRS score of patients decreased from 4.95 ± 1.97 before treatment to 3.78 ± 2.03 after treatment (n = 332, difference in NRS score, 1.17; 95% CI: 0.96-1.38, t = 10.89 p < 0.001). SPADI score decreased from 19.05 ± 20.44 at baseline before treatment to 12.12 ± 17.26 after the last visit, which was statistically significant (n = 332, mean difference in SPADI score, 6.93; 95% CI: 4.71-9.15, t = 6.150, p < 0.001). No serious adverse event was reported in both groups. Conclusion: This study showed the effectiveness of acupotomy therapy for shoulder pain, and as the treatment sessions increased, the effect of pain reduction and shoulder function improvement were also increased.
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We have been developing new inhibitors for c-Jun N-terminal kinase 3 (JNK3) as a potential treatment for Alzheimer's disease (AD). We identified potential JNK3 inhibitors through pharmacodynamic optimization studies, including benzimidazole compounds 2 and 3, but their unreliable pharmacokinetic properties led us to develop carbamate inhibitors 2h and 3h. In vitro studies validated carbamate inhibitors 2h and 3h as potent and highly selective JNK3 inhibitors with favorable pharmacokinetic profiles. Oral administration of 2h and 3h to both APP/PS1 and 3xTg AD mouse models improved cognitive function, indicating their potential as effective treatments for Alzheimer's disease. Carbamate JNK3 inhibitor 3h, in particular, restored cognitive function to near-normal levels in the 3xTg mice model of AD and led to pTau reduction in the hippocampal tissues of 3xTg-AD mice during in vivo behavioral evaluations. We intend to further develop these carbamate JNK3 inhibitors in preclinical studies as a potential first-in-class treatment for AD.
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Enfermedad de Alzheimer , Ratones , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Carbamatos/farmacología , Carbamatos/uso terapéutico , Modelos Animales de Enfermedad , Cognición , Ratones TransgénicosRESUMEN
PURPOSE: This study aimed to investigate the quality of medical care in North Korea using data from North Korean medical research. MATERIALS AND METHODS: This study included publications containing the keyword "medical" among North Korea's consecutive publications and selected 415 papers related to heart disease, brain disease, and emergency medical care published at The North Korean Data Center of the Ministry of Unification (https://unibook.unikorea.go.kr). Among 40 research articles, we reviewed ten with representative epidemiological data for cardiovascular treatment, and the latest medical materials were selected and analyzed in detail. RESULTS: Few studies reported the experience of large-scale medical facilities or verified professional performance. Proof of the efficacy of the latest drugs was rare, although the treatment results of interventional therapy and conventional heart surgery were reported. Efforts to improve emergency medical care and innovation of treatment materials using new technologies were being actively studied. However, careful interpretation is required due to the lack of objectivity in research data and some deviation in the composition of patients included in the data. CONCLUSION: Research of cardiovascular disease in North Korea is conducted at a very limited scope, although treatment results appear to be recorded. The management of cardiovascular disease and the establishment of an emergency medical system warrant global attention and cooperation for further improvement.
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Investigación Biomédica , Enfermedades Cardiovasculares , Humanos , República Popular Democrática de Corea/epidemiología , Enfermedades Cardiovasculares/terapiaRESUMEN
Recombinant adeno-associated virus (rAAV)-based gene therapies offer an immense opportunity for rare diseases, such as amyotrophic lateral sclerosis (ALS), which is defined by the loss of the upper and the lower motor neurons. Here, we describe generation, characterization, and utilization of a novel vector system, which enables expression of the active form of hepatocyte growth factor (HGF) under EF-1α promoter with bovine growth hormone (bGH) poly(A) sequence and is effective with intrathecal injections. HGF's role in promoting motor neuron survival had been vastly reported. Therefore, we investigated whether intrathecal delivery of HGF would have an impact on one of the most common pathologies of ALS: the TDP-43 pathology. Increased astrogliosis, microgliosis and progressive upper motor neuron loss are important consequences of ALS in the motor cortex with TDP-43 pathology. We find that cortex can be modulated via intrathecal injection, and that expression of HGF reduces astrogliosis, microgliosis in the motor cortex, and help restore ongoing UMN degeneration. Our findings not only introduce a novel viral vector for the treatment of ALS, but also demonstrate modulation of motor cortex by intrathecal viral delivery, and that HGF treatment is effective in reducing astrogliosis and microgliosis in the motor cortex of ALS with TDP-43 pathology.
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Esclerosis Amiotrófica Lateral , Corteza Motora , Animales , Bovinos , Humanos , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/terapia , Proteínas de Unión al ADN/genética , Gliosis , Factor de Crecimiento de Hepatocito/genética , Corteza Motora/patologíaRESUMEN
Dual-ion Li metal batteries based on non-flammable SO2-in-salt inorganic electrolytes ( Li-SO2 batteries) offer high safety and energy density. The use of cupric oxide (CuO) as a self-activating cathode material achieves a high specific capacity with cost-effective manufacturing in Li-SO2 batteries, but its cycle retention performance deteriorates owing to the significant morphological changes of the cathode active materials. Herein, we report the catalytic effect of carbonaceous materials used in the cathode material of Li-SO2 batteries, which act as templates to help recrystallize the active materials in the activation and conversion reactions. We found that the combination of oxidative-cyclized polyacrylonitrile (PAN) with N-doped carbonaceous materials and multi-yolk-shell CuO (MYS-CuO) nanoclusters as cathode active materials can significantly increase the specific capacity to 315.9 mAh g- 1 (93.8% of the theoretical value) at 0.2 C, which corresponds to an energy density of 1295 Wh kgCuO-1, with a capacity retention of 84.46% at the 200th cycle, and the cathode exhibited an atypical blossom-like morphological change.
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Ulcerative colitis (UC), a pathological condition of inflammatory bowel disease, is a chronic inflammatory disorder that involves an abnormal immune response and epithelial barrier dysfunction. Although we have previously reported the anti-inflammatory effects of 7-hydroxyl-1-methylindole-3-acetonitrile (7-HMIA), a synthesized analog of arvelexin on macrophages and paw edema, its anti-colitis effect and its mechanism are not known. In this study, colitis was induced in mice model by 4% (w/v) dextran sodium sulfate (DSS) solution in drinking water for 9 days. At the same time, from the first day of administering drinking water containing DSS, the animals were treated with 5-aminosalicylic acid (5-ASA), 75 mg/kg/day, orally) or 7-HMIA (10 or 20 mg/kg/day, intraperitoneally), depending on the experimental group, respectively. The studies were terminated on the tenth day of the experiment. Our data showed that 7-HMIA reduced the disease activity index and spleen/body weight (S/B) ratio, and improved the shortened colon length comparable to the effects of 5-ASA observed in the DSS-exposed mice. 7-HMIA, like 5-ASA, inhibited the histological damage, such as a thickened colonic muscle layer and shortened crypt length in the colon of the mice with DSS-induced colitis. 7-HMIA restored the tight junction-related proteins (occludin, claudin-1, and claudin-2) and epithelial-mesenchymal transition-mediated proteins (E-cadherin, N-cadherin, and vimentin) in the colon tissue of mice with DSS-induced colitis. Additionally, 7-HMIA (20 mg/kg/day) showed the inhibitory effects similar to that of 5-ASA on the myeloperoxidase activity, interleukin (IL)-6 production, and expression levels of inducible nitric oxide synthase (iNOS), and even showed greater inhibition of IL-1ß production in the DSS-induced mice. Furthermore, the DSS-induced activation of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) were effectively suppressed by 7-HMIA treatment like the effects of 5-ASA. Overall, our findings revealed that 7-HMIA decreased the severity of colitis by protecting the inflamed mucosal barrier by interfering with NF-κB and STAT3 activation.
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Colitis Ulcerosa , Colitis , Agua Potable , Ratones , Animales , FN-kappa B/metabolismo , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Inflamación/metabolismo , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colon/patología , Mesalamina/farmacología , Mesalamina/uso terapéutico , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Ratones Endogámicos C57BLRESUMEN
Despite innumerable efforts to develop effective therapeutics, it is difficult to achieve breakthrough treatments for Alzheimer's disease (AD), and the main reason is probably the absence of a clear target. Here, we reveal c-Jun N-terminal kinase 3 (JNK3), a protein kinase explicitly expressed in the brain and involved in neuronal apoptosis, with a view toward providing effective treatment for AD. For many years, we have worked on JNK3 inhibitors and have discovered 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile-based JNK3 inhibitors with superb potency (IC50 < 1.0 nM) and excellent selectivity over other protein kinases including isoforms JNK1 (>300 fold) and JNK2 (â¼10 fold). Based on in vitro biological activity and DMPK properties, the lead compounds were selected for further in vivo studies. We confirmed that repeat administration of JNK3 inhibitors improved cognitive memory in APP/PS1 and the 3xTg mouse model. Overall, our results show that JNK3 could be a potential target protein for AD.
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Enfermedad de Alzheimer , Imidazoles , Proteína Quinasa 10 Activada por Mitógenos , Inhibidores de Proteínas Quinasas , Animales , Ratones , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/enzimología , Apoptosis/efectos de los fármacos , Imidazoles/química , Imidazoles/farmacología , Imidazoles/uso terapéutico , Proteína Quinasa 10 Activada por Mitógenos/antagonistas & inhibidores , Isoformas de Proteínas/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
Aging in the peripheral nervous system (PNS) leads to its dysfunction and lowers regenerative capacity after injury. Based on the pro-regenerative effect of hepatocyte growth factor (HGF) in injured peripheral nerves, we investigated whether this growth factor is involved in the age-related degeneration of the PNS. We observed that the capacity for nerve regeneration was significantly reduced under aging conditions as indicated by the decreased level of SCG10-positive axons. Functional recovery was also impaired. We further tested whether the HGF/c-Met pathway was involved, and the activation of the c-Met receptor upon nerve injury was significantly reduced, whereas the production of HGF protein was still comparable to that in young mice. Moreover, the phosphorylation and expression of c-Jun, a key regeneration-associated gene, was also lowered in aged animals. In addition, exogenous administration of the HGF expressing plasmid DNA significantly ameliorated the pain-like behavior in young animals, however, such analgesic activity was impaired in aged mice. These data suggested that the HGF/c-Met pathway might be involved in the age-related impairment of regenerative capacity in the PNS.
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In this study, a deep learning model (deepPLM) is shown to automatically detect periodic limb movement syndrome (PLMS) based on electrocardiogram (ECG) signals. The designed deepPLM model consists of four 1D convolutional layers, two long short-term memory units, and a fully connected layer. The Osteoporotic Fractures in Men sleep (MrOS) study dataset was used to construct the model, including training, validating, and testing the model. A single-lead ECG signal of the polysomnographic recording was used for each of the 52 subjects (26 controls and 26 patients) in the MrOS dataset. The ECG signal was normalized and segmented (10 s duration), and it was divided into a training set (66,560 episodes), a validation set (16,640 episodes), and a test set (20,800 episodes). The performance evaluation of the deepPLM model resulted in an F1-score of 92.0%, a precision score of 90.0%, and a recall score of 93.0% for the control set, and 92.0%, 93.0%, and 90.0%, respectively, for the patient set. The results demonstrate the possibility of automatic PLMS detection in patients by using the deepPLM model based on a single-lead ECG. This could be an alternative method for PLMS screening and a helpful tool for home healthcare services for the elderly population.
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Hepatocyte growth factor (HGF) is a multifunctional protein that plays a critical role in the angiogenic, neurotrophic, antifibrotic, and antiapoptotic activities of various cell types. It has been previously reported that intramuscular injection of pCK-HGF-X7 (or VM202), a plasmid DNA designed to express both native isoforms of human HGF (Pyun et al., 2010), significantly reduced the level of neuropathic pain in clinical studies as well as in a variety of animal models. In clinical studies, it has been observed that pCK-HGF-X7 appeared to give much higher pain-relieving effects in subjects not taking pregabalin or gabapentin, α2δ1 calcium channel blockers frequently prescribed for reducing pain in patients with diabetic peripheral neuropathy. In this study, we tested the effects of gabapentin on HGF-mediated pain reduction and nerve regeneration in vivo. Consistent with the data from clinical studies, gabapentin administration inhibited the pain reduction and axon regeneration effects mediated by HGF expression from pCK-HGF-X7. In the context of nerve regenerative effects, treatment with gabapentin or EGTA, a Ca2+ chelator, inhibited HGF-mediated axon outgrowth of injured sciatic nerves in vivo. Taken together, i.m. injection of HGF-encoding plasmid DNA ameliorated pain symptoms and enhanced the regeneration of injured nerves, and these therapeutic effects of HGF were significantly hindered by gabapentin treatment, suggesting the possible involvement of Ca2+ in the pro-regenerative activities of native HGF derived from treatment with pCK-HGF-X7.
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Neuralgia , Traumatismos de los Nervios Periféricos , Analgésicos/farmacología , Analgésicos/uso terapéutico , Animales , Axones/metabolismo , ADN/genética , ADN/farmacología , Modelos Animales de Enfermedad , Gabapentina/farmacología , Gabapentina/uso terapéutico , Terapia Genética , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/farmacología , Factor de Crecimiento de Hepatocito/uso terapéutico , Humanos , Regeneración Nerviosa , Neuralgia/tratamiento farmacológico , Traumatismos de los Nervios Periféricos/tratamiento farmacológicoRESUMEN
Digital health-based lifestyle interventions (e.g., mobile applications, short messaging service, wearable devices, social media, and interactive websites) are widely used to manage metabolic syndrome (MetS). This study aimed to confirm the utility of self-care for prevention or management of MetS. We recruited 106 participants with one or more MetS risk factors from December 2019 to September 2020. Participants were provided five healthcare devices and applications. Characteristics were compared at baseline and follow-up to examine changes in risk factors, engagement, persistence, and physical activity (analyzed through device use frequency and lifestyle interventions performed). Participants with 1-2 MetS risk factors showed statistically significant reductions in waist circumference (WC) and blood pressure (BP). Participants with ≥3 MetS risk factors showed statistically significant reductions in risk factors including weight, body mass index, WC, BP, and fasting blood sugar (FBS). The prevention and improvement groups used more healthcare devices than the other groups. Smartwatch was the most frequently used device (5 times/week), and physical activity logged more than 7000 steps/week. WC, BP, and FBS of the improvement group were reduced by more than 40%. Based on engagement, persistence, and physical activity, digital health-based lifestyle interventions could be helpful for MetS prevention and management.
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Insulin-like growth factor-1 (IGF-1) plays a significant role in the development of various organs, and several studies have suggested that IGF-1 isoforms, IGF-1 Ea and IGF-1 Ec, are expressed in skeletal muscle to control its growth. In this study, we designed a novel nucleotide sequence, IGF-1-X10, consisting of IGF-1 exons and introns to simultaneously express both IGF-1 Ea and IGF-1 Ec. When transfected into human cells, the expression of both isoforms was observed at the transcript and protein levels. In an animal study, intramuscular injection of plasmid DNA comprising IGF-1-X10 induced the expression of IGF-1 Ea and IGF-1 Ec, leading to the production of functional IGF-1 protein. Finally, the efficacy of this plasmid DNA was tested in a cardiotoxin (CTX)-mediated muscle injury model and age-related muscle atrophy model. We found that IGF-1-X10 increased the muscle mass and controlled several key factors involved in the muscle atrophy program in both models. Taken together, these data suggest that IGF-1-X10 may be utilized in the form of gene therapy for the treatment of various muscle diseases related to IGF-1 deficiency.
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Factor I del Crecimiento Similar a la Insulina , Enfermedades Musculares , Animales , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Plásmidos/genética , Enfermedades Musculares/metabolismo , ADNRESUMEN
BACKGROUND: Diabetic wounds account for 25 to 50 percent of total diabetic health care costs annually, and present overall healing rates of less than 50 percent. Because delayed diabetic wound healing is associated with impaired fibroblast function, the authors hypothesize that tyrosine kinase Met (cMet) agonistic monoclonal antibody will promote diabetic wound healing by means of stable activation of hepatocyte growth factor/cMet signaling. METHODS: Two 6-mm dorsal wounds were created in each mouse (6-week-old, male BKS.Cg-Dock7 m +/+Lepr db /J; n = 5). After subcutaneous injections of agonist (20 mg/kg) at 0 and 72 hours, the wound sizes were measured at days 0, 1, 3, 6, and 10. Histologic and immunohistochemical analyses were performed at day 10 (cMet, α-smooth muscle actin, CD68, and transforming growth factor-ß). In vitro cytotoxicity and migration tests with diabetic fibroblasts were performed with or without agonist treatment (1 or 10 nM). cMet pathway activation of fibroblasts was confirmed through p-p44/42 mitogen-activated protein kinase, p-mTOR, p-cMet, and ROCK-1 expression. RESULTS: The cMet agonistic monoclonal antibody-treated group showed 1.60-fold lower wound area ( p = 0.027), 1.54-fold higher collagen synthesis ( p = 0.001), and 1.79-fold lower inflammatory cell infiltration ( p = 0.032) than the saline-treated control. The agonist increased cMet (1.86-fold; p = 0.029), α-smooth muscle actin (1.20-fold; p = 0.018), and vascular endothelial growth factor (1.68-fold, p = 0.029) expression but suppressed CD68 (1.25-fold; p = 0.043), transforming growth factor-ß (1.25-fold; p = 0.022), and matrix metalloproteinase-2 (2.59-fold; p = 0.029) expression. In vitro agonist treatment (10 nM) of diabetic fibroblasts increased their migration by 8.98-fold ( p = 0.029) and activated the hepatocyte growth factor/cMet pathway. CONCLUSIONS: Tyrosine kinase Met agonistic monoclonal antibody treatment improved diabetic wound healing in mice and reduced wound-site inflammatory cell infiltration. These results need to be validated in large animals before piloting human trials. CLINICAL RELEVANCE STATEMENT: Although further clinical studies are necessary to evaluate its therapeutic efficacy, our study suggested that cMet agonistic monoclonal antibody can be the alternative modality in order to improve wound healing cascade in diabetic foot patients.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Actinas , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Colágeno , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Factor de Crecimiento de Hepatocito , Humanos , Inflamación , Masculino , Metaloproteinasa 2 de la Matriz , Ratones , Factores de Crecimiento Transformadores , Factor A de Crecimiento Endotelial VascularRESUMEN
Hepatocyte growth factor (HGF) is a secretory protein that is involved in various biological activities such as angiogenesis, neuroprotection, and anti-inflammatory effects. Intramuscular injection of an HGF-encoding plasmid DNA (pCK-HGF-X7) has been shown to produce pain-relieving effects in a rodent model and patients with neuropathic pain.To further investigate the underlying mechanism, we investigated the anti-inflammatory effects of HGF in the context of neuropathic pain. Consistent with previous data, intramuscular injection of pCK-HGF-X7 showed pain relieving effects up to 8 weeks and pharmacological blockade of the c-Met receptor hindered this effect, which suggest that the analgesic effect was c-Met receptor-dependent. At the histological level, macrophage infiltration in the dorsal root ganglion (DRG) was significantly decreased in the pCK-HGF-X7 injected group. Moreover, HGF treatment significantly downregulated the LPS-mediated induction of pro-inflammatory cytokines in primary cultured DRG neurons. Taken together, these data suggest that HGF-encoding plasmid DNA attenuates neuropathic pain via controlling the expression of pro-inflammatory cytokines.
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Factor de Crecimiento de Hepatocito , Neuralgia , Animales , Antiinflamatorios/metabolismo , ADN/metabolismo , Modelos Animales de Enfermedad , Ganglios Espinales/metabolismo , Terapia Genética , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Inyecciones Intramusculares , Neuralgia/genética , Neuralgia/metabolismo , Neuralgia/terapia , Plásmidos/genéticaRESUMEN
PURPOSE: To measure and explore complex cardiac anatomy in research and preoperative simulation, a virtual imaging technology-the Vesalius 3D suite (PS Medtech, Amsterdam, Netherlands)-combines Vesalius three-dimensional (3D) image-processing software with an optic-tracking navigation system running PST-Client software. We present a novel method of evaluating dynamic aortic root geometry in vivo using this visualization system. DESCRIPTION: Based on electrocardiography-gated cardiac computed tomography data in systole and diastole, images of the aortic root in a healthy adult were reconstructed for 3D visualization. Virtual interaction tools were used to explore and measure the aortic root structures. EVALUATION: Virtually reconstructed images revealed the aortic root internal structures in exquisite detail. Highly accessible 3D interpretation promptly permitted precise measurements of repair-relevant anatomic parameters, including geometrically complex curves of the aortic root wall and dynamic changes in the aortic valves. Measurement accuracy examined against a known prosthesis showed within 1 mm of error (less than 0.5%). CONCLUSIONS: This technology may promote understanding of aortic root form and function, and facilitate valve-sparing surgery, and seems valuable for 3D exploration and measurement of cardiac anatomy in vivo.
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Estenosis de la Válvula Aórtica/diagnóstico , Válvula Aórtica/diagnóstico por imagen , Ecocardiografía Tridimensional/métodos , Ecocardiografía Transesofágica/métodos , Prótesis Valvulares Cardíacas , Procesamiento de Imagen Asistido por Computador/métodos , Realidad Virtual , Adulto , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Femenino , Humanos , Masculino , Diseño de Prótesis , Valores de Referencia , Estudios Retrospectivos , Reemplazo de la Válvula Aórtica Transcatéter/métodosRESUMEN
ß-Lactam antibiotics target penicillin-binding proteins and inhibit the synthesis of peptidoglycan, a crucial step in cell wall biosynthesis. Staphylococcus aureus acquires resistance against ß-lactam antibiotics by producing a penicillin-binding protein 2a (PBP2a), encoded by the mecA gene. PBP2a participates in peptidoglycan biosynthesis and exhibits a poor affinity towards ß-lactam antibiotics. The current study was performed to determine the diversity and the role of missense mutations of PBP2a in the antibiotic resistance mechanism. The methicillin-resistant Staphylococcus aureus (MRSA) isolates from clinical samples were identified using phenotypic and genotypic techniques. The highest frequency (60%, 18 out of 30) of MRSA was observed in wound specimens. Sequence variation analysis of the mecA gene showed four amino acid substitutions (i.e., E239K, E239R, G246E, and E447K). The E239R mutation was found to be novel. The protein-ligand docking results showed that the E239R mutation in the allosteric site of PBP2a induces conformational changes in the active site and, thus, hinders its interaction with cefoxitin. Therefore, the present report indicates that mutation in the allosteric site of PBP2a provides a more closed active site conformation than wide-type PBP2a and then causes the high-level resistance to cefoxitin.
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We aimed to investigate the role of cMet agonistic antibody (cMet Ab) in preventing kidney fibrosis during acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Additionally, we explored the effect of cMet Ab on TGF-ß1/Smad pathway during the pathogenesis of kidney fibrosis. A unilateral ischemia-reperfusion injury (UIRI) mouse model was established to induce AKI-to-CKD transition. Furthermore, we incubated human proximal tubular epithelial cells (hPTECs) under hypoxic conditions as in vitro model of kidney fibrosis. We analyzed the soluble plasma cMet level in patients with AKI requiring dialysis. Patients who did not recover kidney function and progressed to CKD presented a higher increase in the cMet level. The kidneys of mice treated with cMet Ab showed fewer contractions and weighed more than the controls. The mice in the cMet Ab-treated group showed reduced fibrosis and significantly decreased expression of fibronectin and α-smooth muscle actin. cMet Ab treatment decreased inflammatory markers (MCP-1, TNF-α, and IL-1ß) expression, reduced Smurf1 and Smad2/3 level, and increased Smad7 expressions. cMet Ab treatment increased cMet expression and reduced the hypoxia-induced increase in collagen-1 and ICAM-1 expression, thereby reducing apoptosis in the in vitro cell model. After cMet Ab treatment, hypoxia-induced expression of Smurf1, Smad2/3, and TGF-ß1 was reduced, and suppressed Smad7 was activated. Down-regulation of Smurf1 resulted in suppression of hypoxia-induced fibronectin expression, whereas treatment with cMet Ab showed synergistic effects. cMet Ab can successfully prevent fibrosis response in UIRI models of kidney fibrosis by decreasing inflammatory response and inhibiting the TGF-ß1/Smad pathway.