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Calcinosis cutis is classified into 5 main types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. However, it is occasionally misdiagnosed as a malignancy and its management remains challenging. Therefore, in this study, we report our diagnostic and treatment experiences with patients with calcinosis cutis and suggest strategies for improving patient care. This retrospective study included 7 patients (4 men, 3 women; 44.4â ±â 32.0 years old) who visited our hospital between March 2013 and December 2022 and were diagnosed with calcinosis cutis through histopathological procedures. The patients underwent complete excision of the mass without a safety margin. Frozen biopsy was not performed during surgery. No significant intraoperative or postoperative complications were noted after the application of various imaging techniques for diagnosis and follow-up. All patients showed complete recovery. Follow-up showed no recurrence or complications in the 6 patients who completed 1 year of follow-up. Radiological tests such as plain radiography, ultrasonography, computed tomography, and magnetic resonance imaging are important for accurate diagnosis and treatment of calcinosis cutis. This approach can ensure precise assessment of preoperative lesions, leading to safe and less invasive patient treatment, recurrence prevention, and complications of calcinosis cutis.
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Calcinose , Dermatopatias , Humanos , Calcinose/diagnóstico , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Estudos Retrospectivos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Dermatopatias/diagnóstico , Dermatopatias/patologia , Dermatopatias/cirurgia , Calcinose CutâneaRESUMO
Arsenic, a hazardous heavy metal with potent carcinogenic properties, significantly affects key rice-producing regions worldwide. In this study, we present a quantitative trait locus (QTL) mapping investigation designed to identify candidate genes responsible for conferring tolerance to arsenic toxicity in rice (Oryza sativa L.) during the seedling stage. This study identified 17 QTLs on different chromosomes, including qCHC-1 and qCHC-3 on chromosome 1 and 3 related to chlorophyll content and qRFW-12 on chromosome 12 related to root fresh weight. Gene expression analysis revealed eight candidate genes exhibited significant upregulation in the resistant lines, OsGRL1, OsDjB1, OsZIP2, OsMATE12, OsTRX29, OsMADS33, OsABCG29, and OsENODL24. These genes display sequence alignment and phylogenetic tree similarities with other species and engaging in protein-protein interactions with significant proteins. Advanced gene-editing techniques such as CRISPR-Cas9 to precisely target and modify the candidate genes responsible for arsenic tolerance will be explore. This approach may expedite the development of arsenic-resistant rice cultivars, which are essential for ensuring food security in regions affected by arsenic-contaminated soil and water.
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Arsênio , Oryza , Locos de Características Quantitativas , Estresse Fisiológico , Oryza/genética , Oryza/efeitos dos fármacos , Oryza/metabolismo , Arsênio/toxicidade , Locos de Características Quantitativas/genética , Estresse Fisiológico/genética , Estresse Fisiológico/efeitos dos fármacos , Haploidia , Mapeamento Cromossômico , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genes de Plantas , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Cromossomos de Plantas/genéticaRESUMO
Menopause is induced by spontaneous ovarian failure and leads to life quality deterioration with various irritating symptoms. Hormonal treatment can alleviate these symptoms, but long-term treatment is closely associated with breast and uterine cancer, and stroke. Therefore, developing alternative therapies with novel anti-menopausal substances and improved safety is needed. In our study, heat-killed Bifidobacterium breve HDB7040 significantly promoted MCF-7 cell proliferation in a dose-dependent manner under estrogen-free conditions, similar to 17ß-estradiol. This strain also triggered ESR2 expression, but not ESR1, in MCF-7 cells. Moreover, administrating HDB7040 to ovariectomized (OVX) Sprague-Dawley (SD) female rats reduced estrogen deficiency-induced weight gain, fat mass, blood triglyceride, and total cholesterol levels. It also recovered collapsed trabecular microstructure by improving trabecular morphometric parameters (bone mineral density, bone volume per tissue volume, trabecular number, and trabecular separation) and decreasing blood alkaline phosphatase levels with no significant changes in uterine size and blood estradiol. HDB7040 also significantly regulated the expression of Tff1, Pgr, and Esr2, but not Esr1 in uteri of OVX rats. Heat-killed B. breve HDB7040 exerts an anti-menopausal effect via the specific regulation of ERß in vitro and in vivo, suggesting its potential as a novel substance for improving and treating menopausal syndrome.
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Bifidobacterium breve , Proliferação de Células , Receptor beta de Estrogênio , Ovariectomia , Ratos Sprague-Dawley , Útero , Animais , Feminino , Humanos , Células MCF-7 , Ratos , Receptor beta de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Proliferação de Células/efeitos dos fármacos , Menopausa , Estradiol , Temperatura Alta , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genética , Fator Trefoil-1/metabolismo , Fator Trefoil-1/genética , Probióticos/administração & dosagem , Probióticos/farmacologia , Estrogênios/metabolismo , Receptores de Progesterona/metabolismoRESUMO
The importance of gamma-aminobutyric acid (GABA) in plants has been highlighted due to its critical role in mitigating metal toxicity, specifically countering the inhibitory effects of copper stress on rice plants. This study involved pre-treating rice plants with 1 mM GABA for one week, followed by exposure to varying concentrations of copper at 50 µM, 100 µM, and 200 µM. Under copper stress, particularly at 100 µM and 200 µM, plant height, biomass, chlorophyll content, relative water content, mineral content, and antioxidant activity decreased significantly compared to control conditions. However, GABA treatment significantly alleviated the adverse effects of copper stress. It increased plant height by 13%, 18%, and 32%; plant biomass by 28%, 52%, and 60%; chlorophyll content by 12%, 30%, and 24%; and relative water content by 10%, 24%, and 26% in comparison to the C50, C100, and C200 treatments. Furthermore, GABA treatment effectively reduced electrolyte leakage by 11%, 34%, and 39%, and the concentration of reactive oxygen species, such as malondialdehyde (MDA), by 9%, 22%, and 27%, hydrogen peroxide (H2O2) by 12%, 38%, and 30%, and superoxide anion content by 8%, 33, and 39% in comparison to C50, C100, and C200 treatments. Additionally, GABA supplementation led to elevated levels of glutathione by 69% and 80%, superoxide dismutase by 22% and 125%, ascorbate peroxidase by 12% and 125%, and catalase by 75% and 100% in the C100+G and C200+G groups as compared to the C100 and C200 treatments. Similarly, GABA application upregulated the expression of GABA shunt pathway-related genes, including gamma-aminobutyric transaminase (OsGABA-T) by 38% and 80% and succinic semialdehyde dehydrogenase (OsSSADH) by 60% and 94% in the C100+G and C200+G groups, respectively, as compared to the C100 and C200 treatments. Conversely, the expression of gamma-aminobutyric acid dehydrogenase (OsGAD) was downregulated. GABA application reduced the absorption of Cu2+ by 54% and 47% in C100+G and C200+G groups as compared to C100, and C200 treatments. Moreover, GABA treatment enhanced the uptake of Ca2+ by 26% and 82%, Mg2+ by 12% and 67%, and K+ by 28% and 128% in the C100+G and C200+G groups as compared to C100, and C200 treatments. These findings underscore the pivotal role of GABA-induced enhancements in various physiological and molecular processes, such as plant growth, chlorophyll content, water content, antioxidant capacity, gene regulation, mineral uptake, and copper sequestration, in enhancing plant tolerance to copper stress. Such mechanistic insights offer promising implications for the advancement of safe and sustainable food production practices.
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Sinus venosus atrial septal defects (SVASDs), concurrent with partial anomalous pulmonary venous connections (PAPVCs), are a rare congenital heart disease in dogs. Surgical correction is essential when clinical signs or significant hemodynamic changes are present. We aimed to report on the successful surgical correction of an SVASD with PAPVCs, using a computed tomography (CT)-based customized 3D cardiac model. A 10-month-old male poodle was referred for corrective surgery for an ASD. Echocardiography confirmed a hemodynamically significant left-to-right shunting flow through an interatrial septal defect and severe right-sided heart volume overload. For a comprehensive diagnosis, a CT scan was performed, which confirmed an SVASD with PAPVCs. A customized 3D cardiac model was used for preoperative decision-making and surgical rehearsal. The defect was repaired using an autologous pericardial patch under a cardiopulmonary bypass (CPB). Temporary pacing was applied for sinus bradycardia and third-degree atrioventricular block. The patient recovered from the anesthesia without further complications. The pacemaker was removed during hospitalization and the patient was discharged without complications 2 weeks post-surgery. At the three-month follow-up, there was no shunting flow in the interatrial septum and the right-sided volume overload had been resolved. The cardiac medications were discontinued, and there were no complications. This report indicates the validity of surgical correction under CPB for an SVASD with PAPVCs, and the advantages of utilizing a CT-based 3D cardiac model for preoperative planning to increase the surgical success rate.
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We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.
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Metilação de DNA , Células Ependimogliais , Neurocitoma , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos , Humanos , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Neurocitoma/genética , Neurocitoma/patologia , Neurocitoma/metabolismo , Células Ependimogliais/metabolismo , Células Ependimogliais/patologia , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Depression, migraine, insomnia, and fibromyalgia are reportedly comorbidities. Nevertheless, no study has evaluated the comorbidity of all four of these disorders. This study aimed to investigate the comorbidity of these four disorders. METHODS: Cross-sectional analyses were performed using data of the Circannual Change in Headache and Sleep study, an online nationwide population-based survey. Validated questionnaires were used to diagnose the disorders and measure quality of life. The change of clinical characteristics by addition of any comorbidity was analyzed using the Jonckheere-Terpstra trend test. RESULTS: The prevalence rates of depression, migraine, insomnia, and fibromyalgia were 7.2 %, 5.6 %, 13.3 %, and 5.8 %, respectively. Among the 3030 included participants, 494 (16.3 %), 164 (5.4 %), 40 (1.3 %), and 6 (0.2 %) had one, two, three, and four of these conditions, respectively. The number of headache days per 30 days (Jonckheere-Terpstra trend test, p = 0.011) and migraine-related disability (migraine disability assessment score, p = 0.021) increased with an increase in the number of comorbidities but not with the intensity of headache (visual analog scale, p = 0.225) among participants with migraine. The severity of insomnia (Insomnia Severity Index, p < 0.001) and fibromyalgia (fibromyalgia severity score, p = 0.002) increased with additional comorbidities; however, depression (Patient Health Questionnaire-9, p = 0.384) did not show such an increase. LIMITATIONS: The diagnoses of conditions were based on self-reported questionnaires. CONCLUSIONS: The findings confirmed significant comorbidity between depression, migraine, insomnia, and fibromyalgia. Health professionals should be aware of the probable comorbidity of depression, migraine, insomnia, and fibromyalgia when caring for individuals with any of these four disorders.
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Fibromialgia , Transtornos de Enxaqueca , Distúrbios do Início e da Manutenção do Sono , Humanos , Fibromialgia/epidemiologia , Depressão/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estudos Transversais , Qualidade de Vida , Comorbidade , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/diagnóstico , CefaleiaRESUMO
Although coffee is one of the most consumed caffeinated beverages worldwide, the role of coffee consumption in migraine is controversial. This study examined the relationship between coffee consumption and clinical characteristics in participants with migraine compared to those with non-migraine headache. This cross-sectional study used data from a nationwide survey on headache and sleep. Coffee consumption was classified as no-to-low (< 1 cup/day), moderate (1-2 cups/day), or high (≥ 3 cups/day). Of the 3030 survey participants, 170 (5.6%) and 1,768 (58.3%) were identified as having migraine and non-migraine headache, respectively. Coffee consumption tended to increase in the order of non-headache, non-migraine headache, and migraine (linear-by-linear association, p = 0.011). Although psychiatric comorbidities (depression for migraine and anxiety for non-migraine headache) and stress significantly differed according to coffee consumption, most headache characteristics and accompanying symptoms did not differ among the three groups for participants with migraine and non-migraine headache. Response to acute headache treatment-adjusted for age, sex, depression, anxiety, stress, preventive medication use, and current smoking-was not significantly different by coffee consumption in participants with migraine and non-migraine headache. In conclusion, most headache-related characteristics and acute treatment response did not significantly differ by coffee consumption in migraine and non-migraine headache.
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Café , Transtornos de Enxaqueca , Humanos , Estudos Transversais , Transtornos de Enxaqueca/epidemiologia , Cefaleia/epidemiologia , ComorbidadeRESUMO
PURPOSE: Concomitant with the significant advances in computing technology, the utilization of augmented reality-based navigation in clinical applications is being actively researched. In this light, we developed novel object tracking and depth realization technologies to apply augmented reality-based neuronavigation to brain surgery. METHODS: We developed real-time inside-out tracking based on visual inertial odometry and a visual inertial simultaneous localization and mapping algorithm. The cube quick response marker and depth data obtained from light detection and ranging sensors are used for continuous tracking. For depth realization, order-independent transparency, clipping, and annotation and measurement functions were developed. In this study, the augmented reality model of a brain tumor patient was applied to its life-size three-dimensional (3D) printed model. RESULTS: Using real-time inside-out tracking, we confirmed that the augmented reality model remained consistent with the 3D printed patient model without flutter, regardless of the movement of the visualization device. The coordination accuracy during real-time inside-out tracking was also validated. The average movement error of the X and Y axes was 0.34 ± 0.21 and 0.04 ± 0.08 mm, respectively. Further, the application of order-independent transparency with multilayer alpha blending and filtered alpha compositing improved the perception of overlapping internal brain structures. Clipping, and annotation and measurement functions were also developed to aid depth perception and worked perfectly during real-time coordination. We named this system METAMEDIP navigation. CONCLUSIONS: The results validate the efficacy of the real-time inside-out tracking and depth realization technology. With these novel technologies developed for continuous tracking and depth perception in augmented reality environments, we are able to overcome the critical obstacles in the development of clinically applicable augmented reality neuronavigation.
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Realidade Aumentada , Neoplasias Encefálicas , Cirurgia Assistida por Computador , Humanos , Neuronavegação/métodos , Cirurgia Assistida por Computador/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Procedimentos Neurocirúrgicos/métodosRESUMO
Alopecia areata (AA) is a T-cell-mediated autoimmune disease that causes chronic, relapsing hair loss; however, its precise pathogenesis remains to be elucidated. Recent studies have provided compelling evidence of crosstalk between inflammasomes and mitophagy-a process that contributes to the removal of damaged mitochondria. Our previous studies showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome is important for eliciting and progressing inflammation in AA. In this study, we detected mitochondrial DNA damage in AA-affected scalp tissues and IFNγ and poly(I:C) treated outer root sheath (ORS) cells. In addition, IFNγ and poly(I:C) treatment increased mitochondrial reactive oxygen species (ROS) levels in ORS cells. Moreover, we showed that mitophagy induction alleviates IFNγ and poly(I:C)-induced NLRP3 inflammasome activation in ORS cells. Lastly, PTEN-induced kinase 1 (PINK1) knockdown increased NLRP3 inflammasome activation, indicating that PINK1-mediated mitophagy plays a critical role in NLRP3 inflammasome activation in ORS cells. This study supports previous studies showing that oxidative stress disrupts immune privilege status and promotes autoimmunity in AA. The results emphasize the significance of crosstalk between mitophagy and inflammasomes in the pathogenesis of AA. Finally, mitophagy factors regulating mitochondrial dysfunction and inhibiting inflammasome activation could be novel therapeutic targets for AA.
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Alopecia em Áreas , Inflamassomos , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Mitofagia/fisiologia , Espécies Reativas de Oxigênio , Proteínas Quinases , PTEN Fosfo-HidrolaseRESUMO
BACKGROUND: Exercise stimulates the activation of muscle satellite cells, which facilitate the maintenance of stem cells and their myogenic conversion during muscle regeneration. However, the underlying mechanism is not yet fully understood. This study shows that the transcriptional co-activator with PDZ-binding motif (TAZ) stimulates muscle regeneration via satellite cell activation. METHODS: Tazf/f mice were crossed with the paired box gene 7 (Pax7)creERT2 mice to generate muscle satellite cell-specific TAZ knockout (sKO) mice. Mice were trained in an endurance exercise programme for 4 weeks. Regenerated muscles were harvested and analysed by haematoxylin and eosin staining. Muscle tissues were also analysed by immunofluorescence staining, immunoblot analysis and quantitative reverse transcription PCR (qRT-PCR). For the in vitro study, muscle satellite cells from wild-type and sKO mice were isolated and analysed. Mitochondrial DNA was quantified by qRT-PCR using primers that amplify the cyclooxygenase-2 region of mitochondrial DNA. Quiescent and activated satellite cells were stained with MitoTracker Red CMXRos to analyse mitochondria. To study the p38 mitogen-activated protein kinase (MAPK)-TAZ signalling axis, p38 MAPK was activated by introducing the MAPK kinase 6 plasmid into satellite cells and also inhibited by treatment with the p38 MAPK inhibitor, SB203580. RESULTS: TAZ interacts with Pax7 to induce Myf5 expression and stimulates mammalian target of rapamycin signalling for satellite cell activation. In sKO mice, TAZ depletion reduces muscle satellite cell number by 38% (0.29 ± 0.073 vs. 0.18 ± 0.034, P = 0.0082) and muscle regeneration. After muscle injury, TAZ levels (2.59-fold, P < 0.0001) increase in committed cells compared to self-renewing cells during asymmetric satellite cell division. Mechanistically, the polarity protein Pard3 induces TAZ (2.01-fold, P = 0.008) through p38 MAPK, demonstrating that the p38 MAPK-TAZ axis is important for muscle regeneration. Physiologically, endurance exercise training induces muscle satellite cell activation and increases muscle fibre diameter (1.33-fold, 43.21 ± 23.59 vs. 57.68 ± 23.26 µm, P = 0.0004) with increased TAZ levels (1.76-fold, P = 0.017). However, sKO mice had a 39% reduction in muscle satellite cell number (0.20 ± 0.03 vs. 0.12 ± 0.02, P = 0.0013) and 24% reduction in muscle fibre diameter compared to wild-type mice (61.07 ± 23.33 vs. 46.60 ± 24.29 µm, P = 0.0006). CONCLUSIONS: Our results demonstrate a novel mechanism of TAZ-induced satellite cell activation after muscle injury and exercise, suggesting that activation of TAZ in satellite cells may ameliorate the muscle ageing phenotype and may be an important target protein for the drug development in sarcopenia.
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Células Satélites de Músculo Esquelético , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Camundongos , DNA Mitocondrial/metabolismo , Mamíferos/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Células Satélites de Músculo Esquelético/metabolismo , Transdução de Sinais , Proteína Quinase 14 Ativada por MitógenoRESUMO
Removal of trace CO impurities is an essential step in the utilization of Hydrogen as a clean energy source. While various solutions are currently employed to address this challenge, there is an urgent need to improve their efficiency. Here, we show that a bead-structured Mg, Cu, and Ce-based sorbent, Mg13CuCeOx, demonstrates superior removal capacity of trace CO from H2 with high stability. The incorporation of Mg boosts sorption performance by enhancing the porous structure and Cu+ surface area. Remarkably, compared to existing pelletized sorbents, Mg13CuCeOx exhibits 15.5 to 50 times greater equilibrium capacity under pressures below 10 Pa CO and 31 times longer breakthrough time in removing 50 ppm CO in H2. Energy-efficient oxidative regeneration using air at 120 °C allows its stable sorption performance over 20 cycles. Through in-situ DRIFTS analysis, we elucidate the reaction mechanism that Mg augments the surface OH groups, promoting the formation of bicarbonate and formate species. This study highlights the potential of MgCuCeOx sorbents in advancing the hydrogen economy by effectively removing trace CO from H2.
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Obesity has been increasing in many regions of the world, including Europe, USA, and Korea. To manage obesity, we should consider it as a disease and apply therapeutic methods for its treatment. Molecular and therapeutic approaches for obesity management involve regulating biomolecules such as DNA, RNA, and protein in adipose-derived stem cells to prevent to be fat cells. Multiple factors are believed to play a role in fat differentiation, with one of the most effective factor is Ca2+. We recently reported that the electromagnetic perceptive gene (EPG) regulated intracellular Ca2+ levels under various electromagnetic fields. This study aimed to investigate whether EPG could serve as a therapeutic method against obesity. We confirmed that EPG serves as a modulator of Ca2+ levels in primary adipose cells, thereby regulating several genes such as CasR, PPARγ, GLU4, GAPDH during the adipogenesis. In addition, this study also identified EPG-mediated regulation of myogenesis that myocyte transcription factors (CasR, MyoG, MyoD, Myomaker) were changed in C2C12 cells and satellite cells. In vivo experiments carried out in this study confirmed that total weight/ fat/fat accumulation were decreased and lean mass was increased by EPG with magnetic field depending on age of mice. The EPG could serve as a potent therapeutic agent against obesity.
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Adipogenia , Obesidade , Animais , Camundongos , Células 3T3-L1 , Adipogenia/genética , Diferenciação Celular/genética , Fenômenos Eletromagnéticos , Desenvolvimento Muscular/genética , Obesidade/terapia , PPAR gama/metabolismo , Proteínas de Peixes/farmacologia , Proteínas de Peixes/uso terapêuticoRESUMO
Cor triatriatum dexter (CTD) is an uncommon congenital cardiac anomaly in dogs. This case report describes successful membranectomy for CTD via partial venous inflow occlusion under mild hypothermia in a dog. A 7-month-old intact male mixed-breed dog weighing 20.5 kg presented with a history of abdominal distention, lethargy, and anorexia. Clinical examination, radiography, echocardiography, microbubble testing, and computed tomography revealed a remnant right atrium membrane obscuring the venous blood inflow from the vena cava. Considering the potential risk of re-stenosis following interventional treatment, curative resection involving surgical membranectomy via venous inflow occlusion was performed. By performing partial venous inflow occlusion under mild hypothermia (34.5 °C), sufficient time was obtained to explore the defect and resect the remnant membrane. The dog recovered without any complications, and the clinical signs were relieved. This case illustrates that partial venous inflow occlusion under mild hypothermia is feasible for achieving curative resection of cor triatriatum dexter in dogs.
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BACKGROUND: A hyaluronic acid filler is a viscoelastic substance that can be evaluated by rheology. Rheological properties are important for the longevity of the filler, which can be deformed due to the various forces that exist on the face. This study aimed to evaluate the maintenance of the lifting capacity of hyaluronic acid filler injection. METHODS: Rheological evaluation of five different products was performed on nine patients who had undergone hyaluronic acid filler injection from Jan 18, 2021 to Jan 27, 2022. Photographs from different time points up to 1 year after filler injection were used to determine the maintenance of the lifting effect of the filler injection. RESULTS: After 1 year of follow-up, the filler on the forehead, temple area, nose, chin, nasojugal fold, and mid-cheek groove areas showed good maintenance, while the nasolabial fold slightly improved. CONCLUSIONS: Appropriate rheological parameters of hyaluronic acid fillers should be considered before injection into different facial areas. A good choice of filler can result in a good aesthetic effect 1 year after injection. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Despite the therapeutic potential of recombinant proteins, their cell permeabilities and stabilities remain significant challenges. Here we demonstrate that cyclized recombinant proteins can be used as universal cargos for permeable and stable delivery into cells and polydiacetylene liposomes. Utilizing a split intein-mediated process, cyclized model fluorescent proteins containing short tetraarginine (R4) and hexahistidine (H6) tags were generated without compromising their native protein functions. Strikingly, as compared to linear R4/H6-tagged proteins, the cyclized counterparts have substantially increased permeabilities in both cancer cells and synthetic liposomes, as well as higher resistances to enzymatic degradation in cancer cells. These properties are likely a consequence of structural constraints imposed on the proteins in the presence of short functional peptides. Additionally, photodynamic therapy by cyclized photoprotein-loaded liposomes in cancer cells was significantly improved in comparison to that by their non-cyclized counterparts. These findings suggest that our strategy will be universally applicable to intercellular delivery of proteins and therapeutics.
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Lipossomos , Peptídeos , Peptídeos/metabolismo , Proteínas Recombinantes , Proteínas LuminescentesRESUMO
To resolve the problem of target specificity and light transmission to deep-seated tissues in photodynamic therapy (PDT), we report a cancer cell-targeted photosensitizer using photoprotein-conjugated upconversion nanoparticles (UCNPs) with high target specificity and efficient light transmission to deep tissues. Core-shell UCNPs with low internal energy back transfer were conjugated with recombinant proteins that consists of a photosensitizer (KillerRed; KR) and a cancer cell-targeted lead peptide (LP). Under near infrared (NIR)-irradiating condition, the UCNP-KR-LP generated superoxide anion radicals as reactive oxygen species via NIR-to-green light conversion and exhibited excellent specificity to target cancer cells through receptor-mediated cell adhesion. Consequently, this photosensitizing process facilitated rapid cell death in cancer cell lines (MCF-7, MDA-MB-231, and U-87MG) overexpressing integrin beta 1 (ITGB1) receptors but not in a cell line (SK-BR-3) with reduced ITGB1 expression and a non-invasive normal breast cell line (MCF-10A). In contrast to green light irradiation, NIR light irradiation exhibited significant PDT efficacy in cancer cells located beneath porcine skin tissues up to a depth of 10 mm, as well as in vivo tumor xenograft mouse models. This finding suggests that the designed nanocomposite is useful for sensing and targeting various deep-seated tumors.
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Nanopartículas , Neoplasias , Humanos , Animais , Camundongos , Suínos , Fármacos Fotossensibilizantes/farmacologia , Luz , Mama , Proteínas Luminescentes , Neoplasias/tratamento farmacológicoRESUMO
Modern irrigation practices and industrial pollution can contribute to the simultaneous occurrence of salinity and heavy metal contamination in large areas of the world, resulting in significant negative effects on crop productivity and sustainability. This study aimed to investigate the growth-promoting potentials of an important endophytic fungal strain SL3 and to compare its potential with exogenous IAA (indole-3-acetic acid) in the context of salt and heavy metal stress. The strain was assessed for plant growth-promoting traits such as the production of indole-3-acetic acid, gibberellins (GA), and siderophore. We selected two important crops, mung bean and maize, and examined various physiological and biochemical characteristics under 300 mM NaCl and 2.5 mM Pb stress conditions, with and without the application of IAA and SL3. This study's results demonstrated that both IAA and SL3 positively impacted the growth and development of plants under normal and stressed conditions. In NaCl and Pb-induced stress conditions, the growth of mung bean and maize plants was significantly reduced. However, the application of IAA and SL3 helped to alleviate stress, leading to a significant increase in shoot/root length and weight compared to IAA and SL3 non-treated plants. The results revealed that photosynthetic pigments, accumulation of catalase (CAT), phenolic contents, polyphenol oxidase, and flavanols are higher in the IAA and SL3-treated plants than in the non-inoculated plants. This study's findings revealed that applying the SL3 fungal strain positively influenced various physiological and biochemical processes in tested plant species under normal and stress conditions of NaCl and Pb. These findings also suggested that SL3 could be a potential replacement for widely used IAA to promote plant growth by improving photosynthetic efficiency, reducing oxidative stress, and enhancing metabolic activities in plants, including mung and maize. Moreover, this study highlights that SL3 has synergistic effects with IAA in enhancing resilience to salt and heavy stress and offers a promising avenue for future agricultural applications in salt and heavy metal-affected regions.
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Fungos , Metais Pesados , Microbiologia do Solo , Vigna , Zea mays , Vigna/efeitos dos fármacos , Vigna/crescimento & desenvolvimento , Vigna/metabolismo , Vigna/microbiologia , Zea mays/efeitos dos fármacos , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo , Zea mays/microbiologia , Irrigação Agrícola , Fungos/classificação , Fungos/metabolismo , Salinidade , Poluentes do Solo , Reguladores de Crescimento de PlantasRESUMO
BACKGROUND: Conventional 2-Dimensional magnetic resonance imaging-based neuronavigation systems can improve the maximal safe resection in brain tumor surgery but can be unintuitive. A 3-Dimensional (3D)-printed brain tumor model allows for a more intuitive and stereoscopic understanding of brain tumors and adjacent neurovascular structures. This study aimed to identify the clinical efficacy of a 3D-printed brain tumor model in presurgical planning by focusing on differences in the extent of resection (EOR). METHODS: Thirty two neurosurgeons (14 faculty members, 11 fellows, 7 residents) randomly selected the two 3D-printed brain tumor models from the 10 manufactured models and performed presurgical planning following a standardized questionnaire. To compare the 2-Dimensional magnetic resonance imaging-based planning results with the 3D-printed model-based planning results, we analyzed the changing patterns and characteristics of the EOR. RESULTS: Of 64 randomly generated cases, the resection goal changed in 12 cases (18.8%). When the tumor was located intra-axially, the surgical posture required a prone position, and when the neurosurgeon was dexterous in surgery, there was a higher rate of EOR changes. 3D-printed models 2, 4, and 10, which all represented tumors in the posterior of the brain, had high rates of changing EOR. CONCLUSIONS: A 3D-printed brain tumor model could be utilized in presurgical planning to effectively determine the EOR.
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OBJECTIVE: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging-derived tractography (DTI-t) contribute to the localization of language areas, but their accuracy remains controversial. This study aimed to investigate the diagnostic performance of preoperative fMRI and DTI-t obtained with a simultaneous multi-slice technique using intraoperative direct cortical stimulation (DCS) or corticocortical evoked potential (CCEP) as reference standards. MATERIALS AND METHODS: This prospective study included 26 patients (23-74 years; male:female, 13:13) with tumors in the vicinity of Broca's area who underwent preoperative fMRI and DTI-t. A site-by-site comparison between preoperative (fMRI and DTI-t) and intraoperative language mapping (DCS or CCEP) was performed for 226 cortical sites to calculate the sensitivity and specificity of fMRI and DTI-t for mapping Broca's areas. For sites with positive signals on fMRI or DTI-t, the true-positive rate (TPR) was calculated based on the concordance and discordance between fMRI and DTI-t. RESULTS: Among 226 cortical sites, DCS was performed in 100 sites and CCEP was performed in 166 sites. The specificities of fMRI and DTI-t ranged from 72.4% (63/87) to 96.8% (122/126), respectively. The sensitivities of fMRI (except for verb generation) and DTI-t were 69.2% (9/13) to 92.3% (12/13) with DCS as the reference standard, and 40.0% (16/40) or lower with CCEP as the reference standard. For sites with preoperative fMRI or DTI-t positivity (n = 82), the TPR was high when fMRI and DTI-t were concordant (81.2% and 100% using DCS and CCEP, respectively, as the reference standards) and low when fMRI and DTI-t were discordant (≤ 24.2%). CONCLUSION: fMRI and DTI-t are sensitive and specific for mapping Broca's area compared with DCS and specific but insensitive compared with CCEP. A site with a positive signal on both fMRI and DTI-t represents a high probability of being an essential language area.