RESUMEN

Single-molecule surface-enhanced Raman spectroscopy (SM-SERS) is an ultrahigh-resolution spectroscopic method for directly obtaining the complex vibrational mode information on individual molecules. SM-SERS offers a wide range of submolecular information on the hidden heterogeneity in its functional groups and varying structures, dynamics of conformational changes, binding and reaction kinetics, and interactions with the neighboring molecule and environment. Despite the richness in information on individual molecules and potential of SM-SERS in various detection targets, including large and complex biomolecules, several issues and practical considerations remain to be addressed, such as the requirement of long integration time, challenges in forming reliable and controllable interfaces between nanostructures and biomolecules, difficulty in determining hotspot size and shape, and most importantly, insufficient signal reproducibility and stability. Moreover, utilizing and interpreting SERS spectra is challenging, mainly because of the complexity and dynamic nature of molecular fingerprint Raman spectra, and this leads to fragmentary analysis and incomplete understanding of the spectra. In this Perspective, we discuss the current challenges and future opportunities of SM-SERS in views of system approaches by integrating molecules of interest, Raman dyes, plasmonic nanostructures, and artificial intelligence, particularly for detecting and analyzing biomolecules to realize the validation and expansion of information space in SM-SERS.

Asunto(s)

Espectrometría Raman , Espectrometría Raman/métodos , Propiedades de Superficie , Nanoestructuras/química

RESUMEN

Complement component 3 (C3) deficiency has recently been reported as one of the novel causes of constipation. To identify a unique gene specific to constipation caused by C3 deficiency, the total RNA extracted from the mid colon of C3 knockout (C3 KO) mice was hybridized to oligonucleotide microarrays, and the function of the candidate gene was verified in in vitro and in vivo models. C3 KO mice used for microarrays showed definite phenotypes of constipation. Overall, compared to the wild type (WT), 1237 genes were upregulated, and 1292 genes were downregulated in the C3 KO mice. Of these, the major genes included were lysine (K)-specific demethylase 5D (KDM5D), olfactory receptor 870 (Olfr870), pancreatic lipase (PNLIP), and alkaline phosphatase intestinal (ALPI). Specifically, the ALPI gene was selected as a novel gene candidate based on alterations during loperamide (Lop)-induced constipation and intestinal bowel disease (IBD). The upregulation of ALPI expression treated with acetate recovered the expression level of mucin-related genes in primary epithelial cells of C3 KO mice as well as most phenotypes of constipation in C3 KO mice. These results indicate that ALPI plays an important role as the novel gene associated with C3 deficiency-induced constipation.

Asunto(s)

Complemento C3 , Estreñimiento , Ratones Noqueados , Animales , Estreñimiento/genética , Estreñimiento/etiología , Complemento C3/genética , Complemento C3/deficiencia , Complemento C3/metabolismo , Ratones , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/deficiencia , Modelos Animales de Enfermedad , Loperamida , Colon/metabolismo , Colon/patología , Perfilación de la Expresión Génica

RESUMEN

Glutathione peroxidase-1 (GPx1) and cAMP/Ca2+ responsive element (CRE)-binding protein (CREB) regulate neuronal viability by maintaining the redox homeostasis. Since GPx1 and CREB reciprocally regulate each other, it is likely that GPx1-CREB interaction may play a neuroprotective role against oxidative stress, which are largely unknown. Thus, we investigated the underlying mechanisms of the reciprocal regulation between GPx1 and CREB in the male rat hippocampus. Under physiological condition, L-buthionine sulfoximine (BSO)-induced oxidative stress increased GPx1 expression, extracellular signal-regulated kinase 1/2 (ERK1/2) activity and CREB serine (S) 133 phosphorylation in CA1 neurons, but not dentate granule cells (DGC), which were diminished by GPx1 siRNA, U0126 or CREB knockdown. GPx1 knockdown inhibited ERK1/2 and CREB activations induced by BSO. CREB knockdown also decreased the efficacy of BSO on ERK1/2 activation. BSO facilitated dynamin-related protein 1 (DRP1)-mediated mitochondrial fission in CA1 neurons, which abrogated by GPx1 knockdown and U0126. CREB knockdown blunted BSO-induced DRP1 upregulation without affecting DRP1 S616 phosphorylation ratio. Following status epilepticus (SE), GPx1 expression was reduced in CA1 neurons and DGC. SE also decreased CREB activity CA1 neurons, but not DGC. SE degenerated CA1 neurons, but not DGC, accompanied by mitochondrial elongation. These post-SE events were ameliorated by N-acetylcysteine (NAC, an antioxidant), but deteriorated by GPx1 knockdown. These findings indicate that a transient GPx1-ERK1/2-CREB activation may be a defense mechanism to protect hippocampal neurons against oxidative stress via maintenance of proper mitochondrial dynamics.

Asunto(s)

Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Glutatión Peroxidasa GPX1 , Glutatión Peroxidasa , Hipocampo , Sistema de Señalización de MAP Quinasas , Dinámicas Mitocondriales , Neuronas , Estrés Oxidativo , Ratas Sprague-Dawley , Estado Epiléptico , Animales , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Masculino , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/patología , Dinámicas Mitocondriales/efectos de los fármacos , Dinámicas Mitocondriales/fisiología , Estado Epiléptico/inducido químicamente , Estado Epiléptico/metabolismo , Estado Epiléptico/patología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Ratas , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología

RESUMEN

Limited research has been performed to determine if histologic improvement serves as a prognosticator for endoscopic remission, a key therapeutic target for ulcerative colitis (UC). The primary aim of the study was to evaluate if histological activity could predict endoscopic remission in UC patients with Mayo endoscopic subscores (MES) of 0 or 1. In addition, we compared the clinical outcomes between histologic improvement group and active group. This research encompassed 492 individuals with UC with MES of 0 or 1, who underwent histological assessment as per the established protocol of Samsung Medical Center between January 2018 and December 2020. Participants were categorized into two cohorts based on the degree of histological activity: those showing histologic improvement and those with ongoing histologic activity. The endoscopic activity was assessed during follow-up, and the primary outcome was endoscopic remission according to histologic activity. Out of the total participants, endoscopic activity was scrutinized in 435 patients during the colonoscopic follow-up and in 146 during the subsequent one. The histologic improvement group at the index colonoscopy was more likely achieve endoscopic remission than the histologic active group. Clinical relapse was more likely in the histologic active group than in the histologic improvement group.

Asunto(s)

Colitis Ulcerosa , Colonoscopía , Inducción de Remisión , Humanos , Colitis Ulcerosa/patología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Recurrencia

RESUMEN

Policosanol is a blend of long-chain aliphatic alcohols (LCAAs) and is well-known for several health-beneficial activities; however, the functionality of policosanol varied substantially based on the composition of LCAAs. In this study, two distinct policosanols, Raydel® (extracted from Cuban sugarcane wax) and BOC Sciences (extracted from Chinese sugarcane wax), were dietarily supplemented (0.1% w/w) for 12 weeks in hyperlipidemic zebrafish to examine their influence on the blood lipid profile and functionality of the liver, kidney, and reproductive organs. The results demonstrated a noteworthy impact of both policosanols on preventing high-cholesterol diet (HCD, 4% w/w)-induced dyslipidemia by decreasing total cholesterol (TC) and triglyceride (TG) levels in the plasma. However, compared to BOC Sciences, the Raydel® policosanol exhibited a significantly (p < 0.05) higher efficacy in reducing HCD-induced TC and TG levels. A substantial effect was observed exclusively with the Raydel® policosanol in mitigating HCD-impaired low-density-lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C) levels. Hepatic histology and immunohistochemistry (IHC) analysis revealed the higher efficacy of Raydel® policosanol over BOC Sciences policosanol to prevent HCD-provoked fatty liver changes, cellular senescence, oxidative stress, and interleukin (IL)-6 production. Consistently, a significantly higher effect of Raydel® over BOC Sciences policosanol was observed on the protection of kidney, testis, and ovary morphology hampered by HCD consumption. In addition, Raydel® policosanol exhibited a notably stronger effect (~2-fold, p < 0.05) on the egg-laying ability of the zebrafish compared to policosanol from BOC Sciences. Furthermore, Raydel® policosanol plays a crucial role in improving embryo viability and mitigating developmental defects caused by the intake of an HCD. Conclusively, Raydel® policosanol displayed a substantially higher efficacy over BOC Sciences policosanol to revert HCD-induced dyslipidemia, the functionality of vital organs, and the reproductive health of zebrafish.

RESUMEN

Inspired by the functions of biological neural networks, volatile memristors are essential for implementing neuromorphic computing. These devices enable large-scale and energy-efficient data processing by emulating neural functionalities through dynamic resistance changes. The threshold switching characteristics of volatile memristors, which are driven by various mechanisms in materials ranging from oxides to chalcogenides, make them versatile and suitable for neuromorphic computing systems. Understanding these mechanisms and selecting appropriate devices for specific applications are crucial for optimizing the performance. However, the existing literature lacks a comprehensive review of switching mechanisms, their compatibility with different applications, and a deeper exploration of the spatiotemporal processing capabilities and inherent stochasticity of volatile memristors. This review begins with a detailed analysis of the operational principles and material characteristics of volatile memristors. Their diverse applications are then explored, emphasizing their role in crossbar arrays, artificial receptors, and neurons. Furthermore, the potential of volatile memristors in artificial inference systems and reservoir computing is discussed, due to their spatiotemporal processing capabilities. Hardware security applications and probabilistic computing are also examined, where the inherent stochasticity of the devices can improve the system robustness and adaptability. To conclude, the suitability of different switching mechanisms for various applications is evaluated, and future perspectives for the development and implementation of volatile memristors are presented. This review aims to fill the gaps in existing research and highlight the potential of volatile memristors to drive innovation in neuromorphic computing, paving the way for more efficient and powerful computational paradigms.

RESUMEN

Alcoholic liver disease (ALD) significantly affects immune cell function and leads to immunological dysregulation. This study explored the potential of granulocyte colony-stimulating factor (G-CSF) to mitigate the negative effects of alcohol on immune cells in a mouse model of ALD. To investigate the capacity of G-CSF, ALD was induced using a 17-day alcohol-enriched diet, followed by a single G-CSF dose prior to sampling. We focused on the dynamics of peripheral blood mononuclear cells using high-dimensional mass cytometry to detect subtle changes. Alcohol intake reduced the number of B cells, monocytes, dendritic cells, and NK cells while increasing the number of T cells. Notably, G-CSF treatment reversed the alcohol-induced increase in total CD4+ and CD8+ T cell populations. This effect was remarkable in naïve, effector CD4+ T cells and naïve CD8+ T cells. PhenoGraph and FlowSOM analysis further revealed the recovery effect of G-CSF on specific T cell subgroups, including central memory CD8+ T cells and double-negative T cells expressing Ly6chighCD44high, which are adversely affected by alcohol. These results enhance our understanding of the effect of ALD on immune function and suggest that G-CSF is a potential therapeutic agent, laying the foundation for future clinical research.

Asunto(s)

Factor Estimulante de Colonias de Granulocitos , Hepatopatías Alcohólicas , Animales , Masculino , Ratones , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Modelos Animales de Enfermedad , Etanol/farmacología , Factor Estimulante de Colonias de Granulocitos/farmacología , Hepatopatías Alcohólicas/inmunología , Hepatopatías Alcohólicas/tratamiento farmacológico , Hepatopatías Alcohólicas/patología , Ratones Endogámicos C57BL , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología

RESUMEN

BACKGROUND: Remimazolam is not only associated with a lower incidence of respiratory depression than propofol but also in itself has the risk of respiratory depression. OBJECTIVE: We investigated respiratory depression following remimazolam infusion, targeting different effect-site concentrations using target-controlled infusion. DESIGN: A prospective, double-blind, randomised controlled study. SETTING: Tertiary hospital, Suwon, South Korea, from April 2022 to November 2022. PARTICIPANTS: One hundred and seven patients scheduled for general anaesthesia were randomised into three groups targeting remimazolam effect-site concentrations of 500 (RMZ-500) ( n  = 36), 1000 (RMZ-1000) ( n  = 35) and 1500 ng ml -1 (RMZ-1500) ( n  = 36). INTERVENTIONS: Remimazolam was solely infused for 10 min according to target effect-site concentrations. According to the degree of SpO 2 decrease, oxygen desaturations were managed with the following respiratory supports: jaw-thrust for SpO 2 less than 97%, 100% oxygen delivery for SpO 2 less than 93% and assisted ventilation for SpO 2 less than 90%. MAIN OUTCOME MEASURES: The incidence of each respiratory support, along with respiratory variables (at baseline, 5 min and 10 min after remimazolam infusion) and loss of consciousness were observed for 10 min after remimazolam target-controlled infusion. RESULTS: Both RMZ-1000 and RMZ-1500 required more frequent respiratory support than RMZ-500 (both P  < 0.001), with nearly identical frequencies between RMZ-1000 and RMZ-1500. In terms of respiratory support, the incidence of assisted ventilation was significantly lower in RMZ-500 (2.8%) than RMZ-1000 (48.6%) and RMZ-1500 (50%) ( P  < 0.001). RMZ-1000 and RMZ-1500 achieved loss of consciousness in all patients; RMZ-500 only achieved loss of consciousness in 86.1% of patients ( P  = 0.010). In patients who maintained spontaneous respiration, tidal volume decreased by 41 to 48% and respiratory rate increased by 118 to 158% at 5 and 10 min, significantly compared to baseline in all groups ( P  < 0.001). CONCLUSIONS: Remimazolam infusion, like that of other benzodiazepines, led to respiratory depression, which was more prominent at higher target effect-site concentrations. Therefore, appropriate countermeasures should be developed to prevent oxygen desaturation. TRIAL REGISTRATION: CRIS ( https://cris.nih.go.kr ), identifier: KCT0006952.

Asunto(s)

Hipnóticos y Sedantes , Insuficiencia Respiratoria , Humanos , Masculino , Femenino , Persona de Mediana Edad , Método Doble Ciego , Estudios Prospectivos , Adulto , Hipnóticos y Sedantes/administración & dosificación , Infusiones Intravenosas , Anciano , Benzodiazepinas/administración & dosificación , Anestesia General/métodos , Relación Dosis-Respuesta a Droga , República de Corea/epidemiología

RESUMEN

The study investigated the effects of temperature and centrifugation time on the efficacy of removing uncured resin from 3D-printed clear aligners. Using a photo-polymerizable polyurethane resin (Tera Harz TC-85, Graphy Inc., Seoul, Korea), aligners were printed and subjected to cleaning processes using isopropyl alcohol (IPA) or centrifugation (g-force 27.95g) at room temperature (RT, 23 °C) and high temperature (HT, 55 °C) for 2, 4, and 6 min. The control group received no treatment (NT). Cleaning efficiency was assessed through rheological analysis, weight measurement, transparency evaluation, SEM imaging, 3D geometry evaluation, stress relaxation, and cell viability tests. Results showed increased temperature and longer centrifugation times significantly reduced aligner viscosity, weight (P < 0.05), and transmittance. IPA-cleaned aligners exhibited significantly lower transparency and rougher surfaces in SEM images. All groups met ISO biocompatibility standards in cytotoxicity tests. The NT group had higher root mean square (RMS) values, indicating greater deviation from the original design. Stress relaxation tests revealed over 95% recovery in all groups after 60 min. The findings suggest that a 2-min HT centrifugation process effectively removes uncured resin without significantly impacting the aligners' physical and optical properties, making it a clinically viable option.

Asunto(s)

Centrifugación , Impresión Tridimensional , Temperatura , Resinas Sintéticas/química , Poliuretanos/química , Supervivencia Celular/efectos de los fármacos , Ensayo de Materiales , Humanos , Animales

RESUMEN

Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.

Asunto(s)

Histona Desacetilasas , Fibrosis Peritoneal , Animales , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Fibrosis Peritoneal/metabolismo , Fibrosis Peritoneal/prevención & control , Fibrosis Peritoneal/patología , Ratones , Humanos , Masculino , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Diálisis Peritoneal/efectos adversos , Peritoneo/patología , Peritoneo/metabolismo

RESUMEN

BACKGROUND: The Oxidative Balance Score (OBS) is a comprehensive metric that assesses the state of a person's oxidative balance. This study aimed to investigate the relationship between the oxidative balance score and moderate and severe periodontitis in a representative sample of Korean adults. METHODS: Healthcare big data from the 7th Korea National Health and Nutrition Examination Survey (2016-2018) was used, and 16,489 adults aged ≥19 years were included. Multivariate logistic regression analysis was performed to investigate the effect of sex-specific oxidative balance scores on periodontitis. RESULTS: In comparison with participants with a lower oxidative balance score, those with a higher oxidative balance score had a lower incidence of moderate and severe periodontitis (p < 0.05). After adjusting for covariates, the oxidative balance score was negatively associated with moderate (odds ratio [OR] = 0.952; 95% confidence interval [CI]: 0.934-0.971) and severe (OR = 0.958; 95% CI: 0.931-0.986) periodontitis; however, the result was not significant for severe periodontitis in women's (OR = 0.975; 95% CI: 0.934-1.018). Our study showed a statistically significant association between OBS and moderate and severe periodontitis, the small effect size should be interpreted with caution. CONCLUSIONS: The oxidative balance score was associated with moderate and severe periodontitis in Korean adults. Therefore, managing this score may help reduce the risk of periodontitis.

RESUMEN

In recent years, there has been increasing interest in exploring the potential therapeutic advantages of Citrullus mucosospermus extracts (CME) for nonalcoholic steatohepatitis (NASH). In this study, we investigated the therapeutic effects of CME on NASH using a mice model. High-performance liquid chromatography (HPLC) was employed to identify cucurbitacin E and cucurbitacin E-2-O-glucoside from the CME. Although CME did not significantly alter the serum lipid levels in methionine- and choline-deficient (MCD) mice, it demonstrated a protective effect against MCD diet-induced liver damage. CME reduced histological markers, reduced alanine transaminase (ALT) and aspartame transaminase (AST) levels, and modulated key NASH-related genes, including C/EBPα, PPARγ, Fas, and aP2. In addition, CME was found to restore hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) activity, both crucial for fat catabolism, and reduced the levels of pro-inflammatory cytokines. Furthermore, CME demonstrated the potential to mitigate oxidative stress by maintaining or enhancing the activation and expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide dismutase (SOD), both pivotal players in antioxidant defense mechanisms. These findings underscore the promising therapeutic potential of CME in ameliorating liver damage, inflammation, and oxidative stress associated with NASH.

RESUMEN

Recently, the need to develop a robust three-dimensional (3D) cell culture system that serves as a valuable in vitro tumor model has been emphasized. This system should closely mimic the tumor growth behaviors observed in vivo and replicate the key elements and characteristics of human tumors for the effective discovery and development of anti-tumor therapeutics. Therefore, in this study, we developed an effective 3D in vitro model of human prostate cancer (PC) using a marine collagen-based biomimetic 3D scaffold. The model displayed distinctive molecular profiles and cellular properties compared with those of the 2D PC cell culture. This was evidenced by (1) increased cell proliferation, migration, invasion, colony formation, and chemoresistance; (2) upregulated expression of crucial multidrug-resistance- and cancer-stemness-related genes; (3) heightened expression of key molecules associated with malignant progressions, such as epithelial-mesenchymal transition transcription factors, Notch, matrix metalloproteinases, and pluripotency biomarkers; (4) robust enrichment of prostate cancer stem cells (CSCs); and (5) enhanced expression of integrins. These results suggest that our 3D in vitro PC model has the potential to serve as a research platform for studying PC and prostate CSC biology, as well as for screening novel therapies targeting PC and prostate CSCs.

Asunto(s)

Antineoplásicos , Proliferación Celular , Colágeno , Células Madre Neoplásicas , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Células Madre Neoplásicas/efectos de los fármacos , Técnicas de Cultivo Tridimensional de Células/métodos , Animales , Movimiento Celular/efectos de los fármacos , Andamios del Tejido , Transición Epitelial-Mesenquimal/efectos de los fármacos , Organismos Acuáticos , Descubrimiento de Drogas/métodos

RESUMEN

Optimal fluid management during major surgery is of considerable concern to anesthesiologists. Although crystalloids are the first choice for fluid management, the administration of large volumes of crystalloids is associated with poor postoperative outcomes. Albumin can be used for fluid management and may protect renal function. However, data regarding the effects of albumin administration on kidney function are conflicting. As such, the present study aimed to investigate the effect of albumin administration on renal function in patients undergoing major surgery and compare its effects with those of crystalloid fluid. The Embase, Medline, Web of Science, Cochrane Library, and KoreaMed databases were searched for relevant studies. The primary endpoint of the meta-analysis was the incidence of postoperative kidney injury, including acute kidney injury and renal replacement therapy. Twelve studies comprising 2311 patients were included; the primary endpoint was analyzed in four studies comprising 1749 patients. Perioperative albumin levels in patients undergoing major surgery did not significantly influence kidney dysfunction (p = 0.98). Postoperative fluid balance was less positive in patients who underwent major surgery and received albumin than in those who received crystalloids. Owing to the limitations of this meta-analysis, it remains unclear whether albumin administration during major surgery is better than crystalloid fluid for improving postoperative renal function.

Asunto(s)

Complicaciones Posoperatorias , Humanos , Complicaciones Posoperatorias/etiología , Riñón/efectos de los fármacos , Riñón/fisiopatología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Fluidoterapia/métodos , Soluciones Cristaloides/administración & dosificación , Albúminas/administración & dosificación , Periodo Posoperatorio , Albúmina Sérica Humana/administración & dosificación

RESUMEN

Neuropathic pain (NP) results from lesions or diseases affecting the peripheral or central somatosensory system. However, there are currently no drugs that are particularly effective in treating this condition. SKI306X is a blend of purified extracts of three oriental herbs (Clematis mandshurica, Trichosanthes kirilowii, and Prunella vulgaris) commonly used to treat osteoarthritis for their chondroprotective effects. Chronic postischemic pain (CPIP) and spinal nerve ligation (SNL) models were created by binding the upper left ankle of mice with an O-ring for 3 h and ligating the L5 spinal nerve, respectively. Mice with allodynia were injected intraperitoneally with 0.9% normal saline (NS group) or different doses (25, 50, or 100 mg/kg) of SKI306X (SKI groups). We assessed allodynia using von Frey filaments before injection and 30, 60, 90, 120, 180, and 240 min and 24 h after injection to confirm the antiallodynic effect of SKI306X. We also measured glial fibrillary acidic protein (GFAP) levels in the spinal cord and dorsal root ganglia to confirm the change of SKI306X administration. Both models exhibited significant mechanical allodynia. The intraperitoneal injection of SKI306X significantly increased the paw withdrawal threshold in a dose-dependent manner, as the paw withdrawal threshold was significantly increased after SKI306X administration compared with at baseline or after NS administration. GFAP levels in the SKI group decreased significantly (p < 0.05). Intraperitoneal administration of SKI306X dose-dependently attenuated mechanical allodynia and decreased GFAP levels, suggesting that GFAP is involved in the antiallodynic effect of SKI306X in mice with CPIP and SNL-induced NP.

RESUMEN

This study aimed to investigate the therapeutic potential of Citrullus mucosospermus extract (CME) in counteracting adipogenesis and its associated metabolic disturbances in murine models. In vitro experiments utilizing 3T3-L1 preadipocytes revealed that CME potently inhibited adipocyte differentiation, as evidenced by a dose-dependent reduction in lipid droplet formation. Remarkably, CME also attenuated glucose uptake and intracellular triglyceride accumulation in fully differentiated adipocytes, suggesting its ability to modulate metabolic pathways in mature adipose cells. Translating these findings to an in vivo setting, we evaluated the effects of CME in C57BL/6N mice fed a high-fat diet (HFD) for 10 weeks. CME administration, concomitantly with the HFD, resulted in a significant attenuation of body weight gain compared to the HFD control group. Furthermore, CME treatment led to substantial reductions in liver weight, total fat mass, and deposits of visceral and retroperitoneal adipose tissue, underscoring its targeted impact on adipose expansion. Histological analyses revealed the remarkable effects of CME on hepatic steatosis. While the HFD group exhibited severe lipid accumulation within liver lobules, CME dose-dependently mitigated this pathology, with the highest dose virtually abolishing hepatic fat deposition. An examination of adipose tissue revealed a progressive reduction in adipocyte hypertrophy upon CME treatment, culminating in a near-normalization of adipocyte morphology at the highest dose. Notably, CME exhibited potent anti-inflammatory properties, significantly attenuating the upregulation of pro-inflammatory cytokines' mRNA levels (TNF-α, IL-1ß and IL-6) in the livers of HFD-fed mice. This suggests a potential mechanism through which CME may exert protective effects against inflammation associated with obesity and fatty liver disease.

Asunto(s)

Células 3T3-L1 , Adipogénesis , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Extractos Vegetales , Aumento de Peso , Animales , Dieta Alta en Grasa/efectos adversos , Extractos Vegetales/farmacología , Ratones , Aumento de Peso/efectos de los fármacos , Masculino , Adipogénesis/efectos de los fármacos , Adipocitos/efectos de los fármacos , Obesidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo

RESUMEN

Policosanol is a mixture of long-chain aliphatic alcohols (LCAAs) derived from various plant and insect origins that are marketed by various companies with distinct formulations and brand names. Policosanols offer several beneficial effects to treat dyslipidemia and hypertension; however, a comprehensive functionality comparison of various policosanol brands has yet to be thoroughly explored. In the present study five distinct policosanol brands from different origins and countries, Raydel-policosanol, Australia (PCO1), Solgar-policosanol, USA (PCO2), NutrioneLife-monacosanol, South Korea (PCO3), Mothernest-policosanol, Australia (PCO4), and Peter & John-policosanol, New Zealand (PCO5) were compared via dietary supplementation (1% in diet, final wt/wt) to zebrafish for six weeks to investigate their impact on survivability, blood lipid profile, and functionality of vital organs under the influence of a high-cholesterol diet (HCD, final 4%, wt/wt). The results revealed that policosanol brands (PCO1-PCO5) had a substantial preventive effect against HCD-induced zebrafish body weight elevation and hyperlipidemia by alleviating total cholesterol (TC) and triglycerides (TG) in blood. Other than PCO3, all the brands significantly reduced the HCD's elevated low-density lipoprotein cholesterol (LDL-C). On the contrary, only PCO1 displayed a significant elevation in high-density lipoprotein cholesterol (HDL-C) level against the consumption of HCD. The divergent effect of PCO1-PCO5 against HCD-induced hepatic damage biomarkers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), was observed. PCO1, PCO2, and PCO4 efficiently curtailed the AST and ALT levels; however, PCO3 and PCO5 potentially aggravated the HCD's elevated plasma AST and ALT levels. Consistently, the hepatic histology outcome revealed the least effectiveness of PCO3 and PCO5 against HCD-induced liver damage. On the contrary, PCO1 exhibited a substantial hepatoprotective role by curtailing HCD-induced fatty liver changes, cellular senescent, reactive oxygen species (ROS), and interleukin-6 (IL-6) production. Likewise, the histological outcome from the kidney, testis, and ovary revealed the significant curative effect of PCO1 against the HCD-induced adverse effects. PCO2-PCO5 showed diverse and unequal results, with the least effective being PCO3, followed by PCO5 towards HCD-induced kidney, testis, and ovary damage. The multivariate interpretation based on principal component analysis (PCA) and hierarchical cluster analysis (HCA) validated the superiority of PCO1 over other policosanol brands against the clinical manifestation associated with HCD. Conclusively, different brands displayed distinct impacts against HCD-induced adverse effects, signifying the importance of policosanol formulation and the presence of aliphatic alcohols on the functionality of policosanol products.

RESUMEN

The chloroplast genome plays a crucial role in elucidating genetic diversity and phylogenetic relationships. Vitis vinifera L. (grapevine) is an economically important species, prompting exploration of wild genetic resources to enhance stress resilience. We meticulously assembled the chloroplast genomes of two Korean Vitis L. species, V. flexuosa Thunb. and V. amurensis Rupr., contributing valuable data to the Korea Crop Wild Relatives inventory. Through exhaustive specimen collection spanning diverse ecological niches across South Korea, we ensured comprehensive representation of genetic diversity. Our analysis, which included rigorous codon usage bias assessment and repeat analysis, provides valuable insights into amino acid preferences and facilitates the identification of potential molecular markers. The assembled chloroplast genomes were subjected to meticulous annotation, revealing divergence hotspots enriched with nucleotide diversity, thereby presenting promising candidates for DNA barcodes. Additionally, phylogenetic analysis reaffirmed intra-genus relationships and identified related crops, shedding light on evolutionary patterns within the genus. Comparative examination with chloroplast genomes of other crops uncovered conserved sequences and variable regions, offering critical insights into genetic evolution and adaptation. Our study advances the understanding of chloroplast genomes, genetic diversity, and phylogenetic relationships within Vitis species, thereby laying a foundation for enhancing grapevine genetic diversity and resilience to environmental challenges.

Asunto(s)

Genoma del Cloroplasto , Filogenia , Vitis , Vitis/genética , Genoma del Cloroplasto/genética , Evolución Molecular , Variación Genética , República de Corea , Cloroplastos/genética , Genoma de Planta

RESUMEN

In the biological nervous system, the integration and cooperation of parallel system of receptors, neurons, and synapses allow efficient detection and processing of intricate and disordered external information. Such systems acquire and process environmental data in real-time, efficiently handling complex tasks with minimal energy consumption. Memristors can mimic typical biological receptors, neurons, and synapses by implementing key features of neuronal signal-processing functions such as selective adaption in receptors, leaky integrate-and-fire in neurons, and synaptic plasticity in synapses. External stimuli are sensitively detected and filtered by "artificial receptors," encoded into spike signals via "artificial neurons," and integrated and stored through "artificial synapses." The high operational speed, low power consumption, and superior scalability of memristive devices make their integration with high-performance sensors a promising approach for creating integrated artificial sensory systems. These integrated systems can extract useful data from a large volume of raw data, facilitating real-time detection and processing of environmental information. This review explores the recent advances in memristor-based artificial sensory systems. The authors begin with the requirements of artificial sensory elements and then present an in-depth review of such elements demonstrated by memristive devices. Finally, the major challenges and opportunities in the development of memristor-based artificial sensory systems are discussed.

RESUMEN

BACKGROUND AND HYPOTHESIS: End-stage kidney disease (ESKD) has an elevated risk of osteoporotic fractures in relation to mineral and bone disorder (MBD) as well as conventional risks of osteoporosis. We investigated the association between oral phosphate binders, the mainstay of MBD treatment, and osteoporotic fracture in dialysis patients. METHODS: We obtained data from the National Health Insurance database for incident dialysis patients without a history of osteoporotic fractures. Participants were categorized into four groups based on their initial 1-year prescription profiles: calcium-based phosphate binder (CBPB), non-calcium-based phosphate binder (NCBPB), both calcium and non-calcium-based binders (Mixed), and non-phosphate binder (non-user) groups. The primary outcome was the occurrence of new-onset osteoporotic fractures after 1 year of dialysis. Secondary outcomes included cardiovascular events and mortality. RESULTS: Out of 69 368 incident dialysis patients, 22 326, 5020, 2853, and 39 169 were included in the CBPB, NCBPB, mixed, and non-user groups, respectively. The overall risk of osteoporotic fractures was lower in patients taking any phosphate binders compared to non-users. Specifically, only the CBPB group showed a reduced risk of vertebral (adjusted hazard ratio (aHR) 0.83 [0.76-0.92]), hip (aHR 0.81 [0.74-0.89]), and distal radius (aHR 0.88 [0.78-0.99]) fractures compared to non-users. This relationship was represented by a time-dependent manner with fracture risk reduction in patients taking CBPB for 3-6 months (aHR 0.9 [0.83-0.99]) and ≥ 6 months (aHR 0.83 [0.78-0.89]), compared to those using CBPB for less than 3 months. Additionally, only the CBPB group had a lower risk of MACE, cardiac arrest, and ventricular arrhythmia than non-users. All phosphorus binder groups showed a reduced mortality risk compared to non-users. CONCLUSIONS: Our findings indicate that the using phosphate binders in ESKD patients is lowers the risk of osteoporotic fractures. Notably, those taking CBPB had a reduced risk without increasing cardiovascular events or mortality compared to non-users.