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Interfacial science and electroorganic syntheses are inextricably linked because all electrochemical reactions occur at the interface between the electrode and the solution. Thus, the surface chemistry of the electrode material impacts the organic reaction selectivity. In this short review, we highlight emergent examples of electrode surface chemistries that enable selective electroorganic synthesis in three reaction classes: (1) hydrogenation, (2) oxidation, and (3) reductive CâC bond formation between two electrophiles. We showcase the breadth of techniques, including materials and in-situ characterization, requisite to establish mechanistic schemes consistent with the observed reactivity patterns. Leveraging an electrode's unique surface chemistry will provide complementary approaches to tune the selectivity of electroorganic syntheses and unlock an electrode's catalytic properties.
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Pressure-sensitive adhesives are widely utilized due to their instant and reversible adhesion to various dry substrates. Though offering intuitive and robust attachment of medical devices on skin, currently available clinical pressure-sensitive adhesives do not attach to internal organs, mainly due to the presence of interfacial water on the tissue surface that acts as a barrier to adhesion. In this work, a pressure-sensitive, repositionable bioadhesive (PSB) that adheres to internal organs by synergistically combining the characteristic viscoelastic properties of pressure-sensitive adhesives and the interfacial behavior of hydrogel bioadhesives, is introduced. Composed of a viscoelastic copolymer, the PSB absorbs interfacial water to enable instant adhesion on wet internal organs, such as the heart and lungs, and removal after use without causing any tissue damage. The PSB's capabilities in diverse on-demand surgical and analytical scenarios including tissue stabilization of soft organs and the integration of bioelectronic devices in rat and porcine models, are demonstrated.
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Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models. These positive outcomes are associated with enhanced allergen uptake by antigen-sampling dendritic cells in the small intestine, suppressed pathogenic type 2 immune responses, increased interferon-γ+ and interleukin-10+ regulatory T cell populations, and restored ileal abundances of Eggerthellaceae and Enterorhabdus in allergic mice. Overall, our findings underscore the therapeutic potential of the engineered allergen gel as a suitable microbiome-modulating platform for food allergy and other allergic diseases.
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Inside germinal centers (GCs), antigen-specific B cells rely on precise interactions with immune cells and strategic localization between the dark and light zones to clonally expand, undergo affinity maturation, and differentiate into long-lived plasma cells or memory B cells. Follicular helper T (Tfh) cells, the key gatekeepers of GC-dependent humoral immunity, exhibit remarkable dynamic positioning within secondary lymphoid tissues and rely on intercellular interactions with antigen-presenting cells (APCs) during their differentiation and execution of B-cell-facilitating functions within GCs. In this review, we briefly cover the transcriptional regulation of Tfh cell differentiation and function and explore the molecular mechanisms governing Tfh cell motility, their interactions with B cells within GCs, and the impact of their dynamic behavior on humoral responses.
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Regulación de la Expresión Génica , Centro Germinal , Sinapsis Inmunológicas , Humanos , Animales , Sinapsis Inmunológicas/metabolismo , Centro Germinal/inmunología , Centro Germinal/metabolismo , Diferenciación Celular , Linfocitos B/inmunología , Linfocitos B/metabolismo , Células T Auxiliares Foliculares/inmunología , Células T Auxiliares Foliculares/metabolismo , Transcripción Genética , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismoRESUMEN
BACKGROUND: The aim of this study was to compare outcomes and complications in patients with and without a history of prior rotator cuff surgery who underwent reverse total shoulder arthroplasty (RTSA). METHODS: Two-hundred and nine consecutive patients who had undergone RTSA for rotator cuff insufficiency with a minimum 12-months follow-up period were reviewed. A total of 35 patients with a history of prior rotator cuff surgery were made the study group (PS group). Using propensity score matching for age and sex, these patients were matched 1:3 with a control group of 105 patients with no history of prior surgery (NPS group). The mean follow-up period was 41.4 months. RESULTS: Both groups showed a significant improvement of clinical scores and range of motion after RTSA. The PS group showed a significantly higher final visual analog scale (VAS) pain score compared with the NPS group (P = 0.020). The PS group showed a significantly higher incidence of acromial stress fracture compared with the NPS group (17.1% vs 4.8%, P = 0.018), but no significant difference in the overall complication rate was observed (25.7% vs 13.3%, P > 0.05). The PS group showed a significantly higher reoperation rate compared with the NPS group (14.3% vs 1.9%, P = 0.004). CONCLUSIONS: Our study demonstrated that a history of prior rotator cuff surgery was associated with a high incidence of acromial stress fracture and reoperation after RTSA as well as a high final VAS pain score, although satisfactory clinical outcomes after RTSA were achieved in both groups.
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Synapses in the brain utilize two distinct communication mechanisms: chemical and electrical. For a comprehensive investigation of neural circuitry, neural interfaces should be capable of both monitoring and stimulating these types of physiological interactions. However, previously developed interfaces for neurotransmitter monitoring have been limited in interaction modality due to constraints in device size, fabrication techniques, and the usage of flexible materials. To address this obstacle, we propose a multifunctional and flexible fiber probe fabricated through the microwire codrawing thermal drawing process, which enables the high-density integration of functional components with various materials such as polymers, metals, and carbon fibers. The fiber enables real-time monitoring of transient dopamine release in vivo, real-time stimulation of cell-specific neuronal populations via optogenetic stimulation, single-unit electrophysiology of individual neurons localized to the tip of the neural probe, and chemical stimulation via drug delivery. This fiber will improve the accessibility and functionality of bidirectional interrogation of neurochemical mechanisms in implantable neural probes.
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Encéfalo , Neuronas , Sinapsis , Animales , Encéfalo/metabolismo , Sinapsis/metabolismo , Sinapsis/química , Neuronas/metabolismo , Optogenética , Dopamina/metabolismo , Ratones , TemperaturaRESUMEN
We identified a new human voltage-gated potassium channel blocker, NnK-1, in the jellyfish Nemopilema nomurai based on its genomic information. The gene sequence encoding NnK-1 contains 5408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the fifth peptide, NnK-1, which was chemically synthesized, is an effective blocker of hKv1.3, hKv1.4, and hKv1.5. Multiple-sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that three residues (3Asp, 25Lys, and 34Thr) of NnK-1, together with six cysteine residues, were conserved. Therefore, we hypothesized that these three residues are crucial for the binding of the toxin to voltage-gated potassium channels. This notion was confirmed by an electrophysiological assay with a synthetic peptide (NnK-1 mu) where these three peptides were substituted with 3Glu, 25Arg, and 34Met. In conclusion, we successfully identified and characterized a new voltage-gated potassium channel blocker in jellyfish that interacts with three different voltage-gated potassium channels. A peptide that interacts with multiple voltage-gated potassium channels has many therapeutic applications in various physiological and pathophysiological contexts.
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Péptidos , Bloqueadores de los Canales de Potasio , Canales de Potasio con Entrada de Voltaje , Escifozoos , Animales , Humanos , Bloqueadores de los Canales de Potasio/farmacología , Bloqueadores de los Canales de Potasio/química , Canales de Potasio con Entrada de Voltaje/antagonistas & inhibidores , Péptidos/farmacología , Péptidos/química , Secuencia de Aminoácidos , Venenos de Cnidarios/farmacología , Venenos de Cnidarios/química , Alineación de SecuenciaRESUMEN
This study aimed to investigate the impact of the cumulative burden of metabolic syndrome (MetS) on the incidence of retinal vein occlusion (RVO) in young adults. We included 1,408,093 subjects aged ≥20 and <40 years without a history of RVO who underwent four consecutive annual health examinations during 2009-2012 from the database of the Korean National Health Insurance Service. The metabolic burden was evaluated based on the cumulative number of MetS diagnoses at each health examination (0-4 times) and the cumulative number of each MetS component diagnosed at each health examination (0-4 times per MetS component). Cox proportional hazards models were used to estimate the risk of RVO according to metabolic burden. The risk of RVO was positively correlated with the cumulative number of MetS diagnoses over the four health examinations. All five MetS components were independently associated with an increased risk of RVO. Subgroup analysis for the impact of MetS on RVO occurrence revealed that MetS had a greater impact on female subjects (P <0.001). Prompt detection of metabolic derangements and their treatment might be important to decrease the risk of RVO in young adults, especially women.
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Síndrome Metabólico , Oclusión de la Vena Retiniana , Humanos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/complicaciones , Oclusión de la Vena Retiniana/epidemiología , Oclusión de la Vena Retiniana/etiología , Femenino , Masculino , Adulto , República de Corea/epidemiología , Factores de Riesgo , Adulto Joven , Modelos de Riesgos Proporcionales , IncidenciaRESUMEN
Trichospira verticillata is an annual herb that belongs to the family Asteraceae. Trichospira verticillata extract (TVE) elicits anti-plasmodial activity; however, there has been no detailed report about its anti-inflammatory effects and molecular mechanisms. In addition, herbal plants exhibit anti-inflammatory effects by suppressing the NLRP3 inflammasome. Therefore, the primary goal of this study was to examine the effects of TVE on NLRP3 inflammasome activation by measuring interleukin-1ß (IL-1ß) secretion. We treated lipopolysaccharides (LPS)-primed J774A.1 and THP-1 cells with TVE, which attenuated NLRP3 inflammasome activation. Notably, TVE did not affect nuclear factor-kappa B (NF-κB) signalling or intracellular reactive oxygen species (ROS) production and potassium efflux, suggesting that it inactivates the NLRP3 inflammasome via other mechanisms. Moreover, TVE suppressed the formation of apoptosis-associated speck-like protein (ASC) speck and oligomerization. Immunoprecipitation data revealed that TVE reduced the binding of NLRP3 to NIMA-related kinase 7 (NEK7), resulting in reduced ASC oligomerization and speck formation. Moreover, TVE alleviated neutrophilic asthma (NA) symptoms in mice. This study demonstrates that TVE modulates the binding of NLPR3 to NEK7, thereby reporting novel insights into the mechanism by which TVE inhibits NLRP3 inflammasome. These findings suggest TVE as a potential therapeutic of NLRP3 inflammasome-mediated diseases, particularly NA.
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Antiinflamatorios , Asma , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Neutrófilos , Especies Reactivas de Oxígeno , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Animales , Inflamasomas/metabolismo , Asma/metabolismo , Asma/tratamiento farmacológico , Asma/inmunología , Asma/patología , Ratones , Antiinflamatorios/farmacología , Humanos , Neutrófilos/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Especies Reactivas de Oxígeno/metabolismo , Lipopolisacáridos , Quinasas Relacionadas con NIMA/metabolismo , Interleucina-1beta/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Modelos Animales de Enfermedad , Extractos Vegetales/farmacología , Células THP-1RESUMEN
BACKGROUND: Neutrophilic asthma (NA) is a severe asthma phenotype associated with steroid resistance and IL-1ß overproduction; however, the exact mechanism remains unclear. Moreover, the dysfunction of TNF-α signaling pathway, a regulator of IL-1ß production, was associated with the deficiency of ovarian tumor protease deubiquitinase with linear linkage specificity (otulin) in autoimmune patients. OBJECTIVE: We hypothesized that otulin downregulation in macrophages (Mφ) could trigger Mφ activation via the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome signaling pathway. METHODS: We assessed the expressions of otulin in blood monocyte subsets from NA patients and in alveolar Mφ from NA mice. Additionally, we evaluated the functional consequences of otulin deficiency in bone marrow-derived Mφ. The effects of inhibiting receptor-interacting protein kinase (RIPK)-1 and RIPK-3 on neutrophils and group 3 innate lymphoid cells (ILC3s) were assessed in vitro and in vivo. RESULTS: When comparing nonclassical monocytes, a significant downregulation of otulin in the intracellular components was observed in NA patients compared to healthy controls (P = .005). Moreover, isolated alveolar Mφ from the NA mice exhibited lower otulin expression compared to those from control mice. After otulin knockdown in bone marrow-derived Mφ, we observed spontaneous IL-1ß production depending on NLRP3 inflammasome. Moreover, the infiltrated neutrophils and ILC3s were significantly decreased by combined treatment of RIPK-1 and RIPK-3 inhibitors through blocking IL-1ß release in NA. CONCLUSIONS: IL-1ß overproduction caused by a deficiency of otulin, an upstream triggering factor, could be a promising diagnostic and therapeutic target for NA.
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Inflammation is implicated as a cause in many diseases. Most of the anti-inflammatory agents in use are synthetic and there is an unmet need for natural substance-derived anti-inflammatory agents with minimal side effects. Aiouea padiformis belongs to the Lauraceae family and is primarily found in tropical regions. While some members of the Aiouea genus are known to possess anti-inflammatory properties, the anti-inflammatory properties of Aiouea padiformis extract (AP) have not been investigated. In this study, we aimed to examine the anti-inflammatory function of AP through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and elucidate the underlying mechanisms. Treatment with AP inhibited the secretion of interleukin-1 beta (IL-1ß) mediated by NLRP3 inflammasome in J774A.1 and THP-1 cells without affecting the viability. In addition, AP treatment did not influence NF-κB signaling, potassium efflux, or intracellular reactive oxygen species (ROS) production-all of which are associated with NLRP3 inflammasome activation. However, intriguingly, AP treatment significantly reduced the ATPase activity of NLRP3, leading to the inhibition of ASC oligomerization and speck formation. Consistent with cellular experiments, the anti-inflammatory property of AP in vivo was also evaluated using an LPS-induced inflammation model in zebrafish, demonstrating that AP hinders NLRP3 inflammasome activation.
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Lauraceae , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Inflamasomas , Pez Cebra , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Adenosina Trifosfatasas , Extractos Vegetales/farmacologíaRESUMEN
Recently identified human FOXP3lowCD45RA- inflammatory non-suppressive (INS) cells produce proinflammatory cytokines, exhibit reduced suppressiveness, and promote antitumor immunity unlike conventional regulatory T cells (Tregs). In spite of their implication in tumors, the mechanism for generation of FOXP3lowCD45RA- INS cells in vivo is unclear. We showed that the FOXP3lowCD45RA- cells in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator. Mice with CRIF1 deficiency in Tregs bore Foxp3lowINS-Tregs with mitochondrial dysfunction and metabolic reprograming. The enhanced glutaminolysis activated α-ketoglutarate-mTORC1 axis, which promoted proinflammatory cytokine expression by inducing EOMES and SATB1 expression. Moreover, chromatin openness of the regulatory regions of the Ifng and Il4 genes was increased, which facilitated EOMES/SATB1 binding. The increased α-ketoglutarate-derived 2-hydroxyglutarate down-regulated Foxp3 expression by methylating the Foxp3 gene regulatory regions. Furthermore, CRIF1 deficiency-induced Foxp3lowINS-Tregs suppressed tumor growth in an IFN-γ-dependent manner. Thus, CRIF1 deficiency-mediated mitochondrial dysfunction results in the induction of Foxp3lowINS-Tregs including FOXP3lowCD45RA- cells that promote antitumor immunity.
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Proteínas de Unión a la Región de Fijación a la Matriz , Enfermedades Mitocondriales , Neoplasias , Humanos , Ratones , Animales , Linfocitos T Reguladores , Ácidos Cetoglutáricos/metabolismo , Proteínas de Unión a la Región de Fijación a la Matriz/metabolismo , Citocinas/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismoRESUMEN
PURPOSE: To evaluate the prevalence and risk factors of age-related macular degeneration (AMD) in the Korean population. METHODS: In this cross-sectional study based on the Korea National Health and Nutrition Examination Survey (2017-2020) data 13,737 participants aged ≥ 40 years with assessable fundus images were included. The prevalence and risk factors of AMD were evaluated. The prevalence of early AMD, geographic atrophy (GA), and neovascular AMD were also assessed. Logistic regression analyses were used to identify risk factors. RESULTS: The prevalence (95% confidence interval [CI]) of AMD was 13.94% (13.15-14.72). The prevalence (95% CI) of early AMD, GA, and neovascular AMD was 13.07% (12.29-13.85), 0.26% (0.17-0.35), and 0.61% (0.47-0.75), respectively. The prevalence increased with age; it was 3.61%, 11.33%, 20.31%, 31.37%, and 33.98% in participants in their 40s, 50s, 60s, 70s, and ≥ 80 years, respectively. In multivariate analysis, AMD was positively associated with older age (p < 0.001; odds ratio [OR], 1.08; 95% CI, 1.07-1.09), male sex (p = 0.014; OR, 1.27; 95% CI, 1.05-1.53), and lower degree of education (p < 0.001; OR, 1.36 (for junior high school graduates); 95% CI, 1.12-1.65). CONCLUSIONS: AMD was detected in approximately one-third of individuals aged ≥ 70 years, thus indicating that AMD is a common disease among older Koreans. Regular fundus examinations in populations with risk factors for AMD as well as education on methods to prevent or delay AMD progression, such as the Mediterranean diet, are necessary.
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The ectopic gut colonization by orally derived pathobionts has been implicated in the pathogenesis of various gastrointestinal diseases, including inflammatory bowel disease (IBD). For example, gut colonization by orally derived Klebsiella spp. has been linked to IBD in mice and humans. However, the mechanisms whereby oral pathobionts colonize extra-oral niches, such as the gut mucosa, remain largely unknown. Here, we performed a high-density transposon (Tn) screening to identify genes required for the adaptation of an oral Klebsiella strain to different mucosal sites - the oral and gut mucosae - at the steady state and during inflammation. We find that K. aerogenes, an oral pathobiont associated with both oral and gut inflammation in mice, harbors a newly identified genomic locus named "locus of colonization in the inflamed gut (LIG)" that encodes genes related to iron acquisition (Sit and Chu) and host adhesion (chaperon usher pili [CUP] system). The LIG locus is highly conserved among K. aerogenes strains, and these genes are also present in several other Klebsiella species. The Tn screening revealed that the LIG locus is required for the adaptation of K. aerogenes in its ectopic niche. In particular, we determined K. aerogenes employs a CUP system (CUP1) present in the LIG locus for colonization in the inflamed gut, but not in the oral mucosa. Thus, oral pathobionts likely exploit distinct adaptation mechanisms in their ectopically colonized intestinal niche compared to their native niche.
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Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Humanos , Animales , Ratones , Klebsiella/genética , Enfermedades Inflamatorias del Intestino/patología , Inflamación , Mucosa BucalRESUMEN
Neural probe engineering is a dynamic field, driving innovation in neuroscience and addressing scientific and medical demands. Recent advancements involve integrating nanomaterials to improve performance, aiming for sustained in vivo functionality. However, challenges persist due to size, stiffness, complexity, and manufacturing intricacies. To address these issues, a neural interface utilizing freestanding CNT-sheets drawn from CNT-forests integrated onto thermally drawn functional polymer fibers is proposed. This approach yields a device with structural alignment, resulting in exceptional electrical, mechanical, and electrochemical properties while retaining biocompatibility for prolonged periods of implantation. This Structurally Aligned Multifunctional neural Probe (SAMP) employing forest-drawn CNT sheets demonstrates in vivo capabilities in neural recording, neurotransmitter detection, and brain/spinal cord circuit manipulation via optogenetics, maintaining functionality for over a year post-implantation. The straightforward fabrication method's versatility, coupled with the device's functional reliability, underscores the significance of this technique in the next-generation carbon-based implants. Moreover, the device's longevity and multifunctionality position it as a promising platform for long-term neuroscience research.
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Nanotubos de Carbono , Polímeros , Animales , Polímeros/química , Nanotubos de Carbono/química , Temperatura , Optogenética/métodos , Neuronas/fisiología , Neuronas/citología , Materiales Biocompatibles/química , Encéfalo , Neurotransmisores , Médula Espinal , RatonesRESUMEN
PURPOSE: To evaluate the bilateral involvement of age-related macular degeneration (AMD) in South Koreans. METHODS: This was a cross-sectional study of the Korean National Health and Nutrition Examination Survey (2017-2020). This study included 13,737 participants aged 40 years or older. Participants were evaluated to determine the prevalence of bilateral early and late AMD. In cases in which exudative AMD or geographic atrophy (GA) was diagnosed in a single eye, the fellow eye was evaluated to determine the presence and type of late AMD. RESULTS: The overall prevalence of bilateral AMD was 6.12% (95% confidence interval [CI], 5.63-6.61). The prevalence of bilateral early AMD was 5.71% (95% CI, 5.24-6.18), while that of late AMD was 0.14% (95% CI, 0.08-0.20). The prevalence of the bilateral involvement of late AMD increased with age. A 0.02% prevalence (95% CI, 0.00-0.06) of late AMD was observed in participants aged 50-59. The prevalence increased to 0.08% (95% CI, 0.00-0.18) in participants aged 60-69, while the prevalence in participants aged 70-79 and over 80 was 0.45% (95% CI, 0.12-0.78) and 1.97% (95% CI, 0.75-3.19), respectively. The prevalence of early AMD in one eye and late AMD in the fellow eye was 0.26% (95% CI, 0.16-0.36). CONCLUSIONS: An assessment of the incidence of AMD revealed that a significant number of persons had bilateral involvement. The treatment burden may significantly increase for participants with bilateral late AMD compared to those with unilateral involvement. Therefore, the study may be helpful with the establishment of private and national insurance policies.
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ETHNOPHARMACOLOGICAL RELEVANCE: Guarea genus comprises tropical and subtropical terrestrial herbs inhabiting Central and South America. These plants, including Guarea guidonia (L.) Sleumer, have anti-inflammatory, analgesic, antibacterial, antiviral, and immune-enhancing properties. AIM OF THE STUDY: Although various species of the Guarea genus are known for their medicinal properties, comprehensive data on their anti-inflammatory effects remain limited. Therefore, we investigated the NLRP3 inflammasome-inhibiting effects of the Guarea genus in this study. MATERIALS AND METHODS: To evaluate the anti-inflammatory activities of 18 members of the Guarea genus, we treated NLRP3 inflammasome activators with their extracts in LPS-primed J774A.1 and THP-1 cells. Cell viability was determined by water soluble tetrazolium salt (WST) and cytokine production, protein expression, and nuclear fractionation were determined by western blotting. Reactive oxygen species (ROS) production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization were measured using confocal microscopic analysis. Inflammation-induced zebrafish was used in the in vivo experiments. RESULTS: Among the 18 Guarea members tested, Guarea microcarpa C. DC. extract (GM) exhibited no cytotoxicity and specifically suppressed the activation of the NLRP3 inflammasome, but not of the AIM2 or NLRC4 inflammasomes, by inhibiting the ATPase activity of NLRP3. This was achieved without affecting NF-κB signaling, potassium efflux, or intracellular ROS production, all of which are involved in NLRP3 activation. The reduced ATPase activity of NLRP3 led to decreased ASC oligomerization. Furthermore, GM exhibited anti-inflammatory effects in vivo. Additionally, GM treatment alleviated inflammation at the organismal level in an LPS-induced inflammation model using zebrafish embryos. CONCLUSION: Our results demonstrate the anti-inflammatory effects of GM via suppressing the NLRP3 inflammasome. Therefore, GM can be a potential therapeutic candidate for various inflammatory diseases caused by aberrant NLRP3 inflammasome activation.
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Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pez Cebra , Especies Reactivas de Oxígeno/metabolismo , Lipopolisacáridos/farmacología , Caspasa 1/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , FN-kappa B/metabolismo , Antiinflamatorios no Esteroideos/uso terapéutico , Adenosina Trifosfatasas , Interleucina-1beta/metabolismoRESUMEN
High-fidelity and comfortable recording of electrophysiological (EP) signals with on-the-fly setup is essential for health care and human-machine interfaces (HMIs). Microneedle electrodes allow direct access to the epidermis and eliminate time-consuming skin preparation. However, existing microneedle electrodes lack elasticity and reliability required for robust skin interfacing, thereby making long-term, high-quality EP sensing challenging during body movement. Here, we introduce a stretchable microneedle adhesive patch (SNAP) providing excellent skin penetrability and a robust electromechanical skin interface for prolonged and reliable EP monitoring under varying skin conditions. Results demonstrate that the SNAP can substantially reduce skin contact impedance under skin contamination and enhance wearing comfort during motion, outperforming gel and flexible microneedle electrodes. Our wireless SNAP demonstration for exoskeleton robot control shows its potential for highly reliable HMIs, even under time-dynamic skin conditions. We envision that the SNAP will open new opportunities for wearable EP sensing and its real-world applications in HMIs.
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Dispositivo Exoesqueleto , Robótica , Humanos , Adhesivos , Reproducibilidad de los Resultados , Piel , ElectrodosRESUMEN
BACKGROUND: Sex disparities in cardiogenic shock (CS) treatment are controversial, and the prognostic implications of sex remain unclear in CS caused by acute myocardial infarction (AMI). OBJECTIVES: This study aimed to evaluate the prognostic effect of sex according to the severity of CS in patients undergoing percutaneous coronary intervention (PCI) for AMI complicated by CS. METHODS: We assessed 695 patients from 12 tertiary centers in South Korea who underwent PCI for AMI complicated by CS, and analyzed outcomes by sex (female [n = 184] vs. male [n = 511]). We compared a 12-month patient-oriented composite endpoint (POCE, defined as a composite of all-cause mortality, myocardial infarction, re-hospitalization due to heart failure, and repeat revascularization) between the sexes, respective of SCAI shock stage C&D or E. Propensity score-matched analysis was performed to reduce bias. RESULTS: We found that the female group was older and had higher vasoactive-inotropic and IABP-SHOCK II scores than the male group, with findings consistent across SCAI shock stages. During the 12-month follow-up period, multivariate analysis revealed no significant differences in POCE (HR 1.01, 95% CI 0.67-1.53, p = 0.963 for SCAI stage C&D, HR 1.24, 95% CI 0.84-1.84, p = 0.286 for SCAI stage E) between females and males. After propensity score matching, the incidence of POCE (HR 1.47, 95% CI 0.79-2.72, p = 0.220 for SCAI stage C&D, HR 0.88, 95% CI 0.49-1.57, p = 0.665 for SCAI stage E) was similar between sexes. CONCLUSIONS: Sex does not appear to influence the risk of 12-month POCE in patients treated with PCI for CS caused by AMI, irrespective of shock severity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02985008. RESCUE (REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy of left ventricular assist device for Korean patients with cardiogenic shock), NCT02985008, Registered December 5, 2016 - retrospectively and prospectively. IRB INFORMATION: This study was approved by the institutional review board of Samsung Medical Center (Reference number: 2016-03-130).
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The therapeutic potential of Mesenchymal stem cells (MSCs) for the treatment of Intervertebral disc (IVD) degeneration can be enhanced by amplifying specific cytokines and proteins. This study aimed to investigate the therapeutic potential of tetracycline-off system-engineered tonsil-derived mesenchymal stem cells (ToMSC-Tetoff-TGFß1-IGF1-BMP7) for treating intervertebral disc (IVD) degeneration. ToMSCs were isolated from a tonsillectomy patient and genetically modified with four distinct plasmids via CRISPR/Cas9-mediated knock-in gene editing. Transgene expression was confirmed through immunofluorescence, western blots, and an enzyme-linked immunosorbent assay for transforming growth factor beta 1 (TGFß1) protein secretion, and the effect of MSC-TetOff-TGFß1-IGF1-BMP7 on disc injury was assessed in a rat model. The ToMSC-Tetoff-TGFß1-IGF1-BMP7 treatment exhibited superior therapeutic effects compared to ToMSC-TGFß1, and ToMSC-SDF1α implantation groups, stimulating the regeneration of nucleus pulposus (NP) cells crucial for IVD. The treatment showed potential to restore the structural integrity of the extracellular matrix (ECM) by upregulating key molecules such as aggrecan and type II collagen. It also exhibited anti-inflammatory properties and reduced pain-inducing neuropeptides. ToMSC-Tetoff-TGFß1-IGF1-BMP7 holds promise as a novel treatment for IVD degeneration. It appears to promote NP cell regeneration, restore ECM structure, suppress inflammation, and reduce pain. However, more research and clinical trials are required to confirm its therapeutic potential.