Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 440
Filtrar
Más filtros

Base de datos
Tipo del documento
Intervalo de año de publicación
1.
Inorg Chem ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39284105

RESUMEN

Although research on nitrosyl (NO) heme complexes and their one-electron reduced form, nitroxyl (or nitroxyl anion, NO-) derivatives, has been going on for decades, there are still disagreements about the electrical configuration of nitroxyl complexes, and the majority of the work on this topic is based on theoretical calculations. Following the initial nitroxyl iron porphyrin crystal structure, we present two further polymorphic forms of [CoCp2][Fe(TFPPBr8)(NO)]. Using the same completely halogenated porphyrin ligand, we also present two polymorphic forms of nitrosyl cobalt(II) complexes, which are another sort of {MNO}8 structure. In addition to the EXANES and EPR studies of these {FeNO}7 and {CoNO}8 complexes, the {FeNO}8 [CoCp2][Fe(TFPPBr8)(NO)] complex is also investigated by temperature-dependent Mössbauer experiments for the first time with the {FeNO}7 precursor as a control sample. The analysis of the Mössbauer and crystal structural parameters between these two types of {MNO}8 (M = Fe or Co) species and previously reported analogous ones allow us to conclude that the electronic configuration of [Fe(TFPPBr8)(NO)]- is best described as an intermediate between low-spin Fe(II)-NO- and Fe(I)-NO•.

2.
J Am Chem Soc ; 146(38): 26427-26434, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39241233

RESUMEN

Realizing topological transformation through supramolecular fusion is particularly challenging, as the self-assembly of disparate components often results in the orthogonal assembly of building blocks into distinct structures rather than the formation of a heteroleptic architecture. This study introduces a topological transformation, transitioning from a figure-eight knot (41 knot) to a Solomon link (412 link) through a supramolecular fusion process. By employing two structurally similar amino acid ligands (L1 and L3) of varying lengths as bridge ligands, we obtained figure-eight knot 1 and a molecular tweezer-like compound 3 when individually complexed with binuclear Cp*Rh acceptor B1. Our results revealed that subtle modifications to bridge ligands can lead to dramatic changes in their structures and recognition properties. Moreover, we successfully achieved the targeted formation of a heteroleptic Solomon link 4 by blending figure-eight knot 1 and compound 3 in a 1:1 ratio without the need for templates. This procedure effortlessly converted the 41 knot into a 412 link, thus marking a significant advancement in the topological transformation. This work not only marks the construction of the first heteroleptic Solomon link comprising two distinct metallamacrocycles but also demonstrates a process of supramolecular fusion-based topological transformation involving three distinct topological structures.

3.
Chem Sci ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39297002

RESUMEN

Various prenylated indoline alkaloids with diverse biological activities, including (-)-debromoflustramine B with significant butyrylcholinesterase inhibitory activity, could be synthesized by dearomative prenylation reactions of tryptophan derivatives. However, previously reported dearomative prenylations were limited to batch reactions at the milligram scale, requiring multistep reactions and complex post-processing to obtain the desired natural products. The more efficient synthesis of alkaloids remains challenging, as does the recovery of expensive catalysts. Herein, we developed a chiral heterogeneous Pd nanoparticle (NP) catalyst supported on a polymer, which produces indoline alkaloids in high yields with excellent enantioselectivities. Additionally, the first gram-scale four-step continuous-flow total synthesis of (-)-debromoflustramine B was successfully achieved with this chiral Pd heterogeneous catalyst, requiring only a simple post-processing step.

4.
BMC Infect Dis ; 24(1): 915, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232642

RESUMEN

BACKGROUND: This study aimed to investigate the differential expression levels of the cGAS-STING pathway in peripheral blood mononuclear cells (PBMCs) of spinal tuberculosis (TB) patients with different progression and its feasibility as a diagnostic marker. METHODS: Peripheral blood and medical records of 25 patients with spinal TB and 10 healthy individuals, were prospectively collected and analyzed. PBMCs and serum were extracted from peripheral blood and the expression levels of the cGAS-STING pathway in PBMCs were measured by real-time PCR (RT-PCR) and serum interferon ß (IFN-ß) expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of Interferon regulatory Factor 3 (IRF3) in PBMCs was measured using western blot. Statistical analysis was performed using the SPSS 26.0 statistical package. RESULTS: The results showed that the expression level of the TANK-binding kinase 1 (TBK1) and IRF3 was significantly higher in PBMCs (P < 0.05), in patients with active lesions than in patients with stable lesions. The serum concentration of IFN-ß was significantly higher in patients with active lesions (P = 0.028). Compared with healthy individuals, the expression level of the cGAS-STING pathway was elevated in PBMCs of TB patients (P < 0.05), and the difference in the expression level of IFN-ß was not statistically significant (P > 0.05), and the serum IFN-ß concentration was elevated (P < 0.05). The calculated AUC values for TBK1 and IRF3 in PBMCs, IFN-ß in serum and erythrocyte sedimentation rate (ESR) to distinguish between patients with active and stable lesions were 0.732, 0.714, 0.839, and 0.714 respectively. CONCLUSIONS: The expression level of TBK1 and IRF3 in PBMCs, and IFN-ß in the serum of patients with spinal TB is positively correlated with disease activity. TBK1 has higher specificity and IFN-ß in serum has higher sensitivity when used to differentiate between patients with active and stable lesions.


Asunto(s)
Factor 3 Regulador del Interferón , Leucocitos Mononucleares , Proteínas de la Membrana , Nucleotidiltransferasas , Tuberculosis de la Columna Vertebral , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Femenino , Adulto , Proteínas de la Membrana/sangre , Proteínas de la Membrana/genética , Persona de Mediana Edad , Nucleotidiltransferasas/genética , Factor 3 Regulador del Interferón/genética , Factor 3 Regulador del Interferón/metabolismo , Factor 3 Regulador del Interferón/sangre , Tuberculosis de la Columna Vertebral/sangre , Tuberculosis de la Columna Vertebral/genética , Interferón beta/sangre , Transducción de Señal , Proteínas Serina-Treonina Quinasas/genética , Biomarcadores/sangre , Estudios Prospectivos , Adulto Joven , Anciano
5.
Pestic Biochem Physiol ; 204: 106086, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39277399

RESUMEN

Actinomycetes have emerged as significant biocontrol resources due to their rich array of bioactive natural products. While much research has historically focused on secondary metabolites isolated from their fermentation broth, there remains a dearth of reports on their volatile organic compounds (VOCs). Here, strain ML27, isolated from soil, was identified as Streptomyces albidoflavus based on morphological features, physiological, biochemical, and molecular characteristics (16S rRNA, atpD, recA, and rpoB gene sequences). VOCs from S. albidoflavus strain ML27 were effectively captured using solid-phase microextraction (SPME) and tentatively identified through gas chromatography-mass spectrometry (GC/MS). Among these compounds, 4-ethyl-1,2-dimethoxybenzene exhibited broad-spectrum antifungal activity and demonstrated efficacy in controlling citrus anthracnose, with a control efficacy of 86.67%. Furthermore, the inhibitory mechanism of 4-ethyl-1,2-dimethoxybenzene against Colletotrichum gloeosporioides was revealed. Results indicated that 4-ethyl-1,2-dimethoxybenzene induced swelling, deformity, and breakage in C. gloeosporioides mycelia, and significantly inhibited spore germination. Transcriptome analysis revealed that 4-ethyl-1,2-dimethoxybenzene inhibited the growth and development of C. gloeosporioides primarily by disrupting energy metabolism and the integrity of the cell wall and membrane. Based on these results, it is promising to develop 4-ethyl-1,2-dimethoxybenzene as a novel biopesticide for controlling citrus anthracnose.


Asunto(s)
Colletotrichum , Enfermedades de las Plantas , Streptomyces , Colletotrichum/efectos de los fármacos , Streptomyces/metabolismo , Streptomyces/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Compuestos Orgánicos Volátiles/farmacología , Compuestos Orgánicos Volátiles/química , Cromatografía de Gases y Espectrometría de Masas , Citrus/microbiología , Anisoles/farmacología , Anisoles/química , Fungicidas Industriales/farmacología , Antifúngicos/farmacología
6.
Artículo en Inglés | MEDLINE | ID: mdl-39248252

RESUMEN

Although hypertension is highly prevalent among the elderly and significantly contributes to cardiovascular disease risk, studies focusing on male elderly individuals over 85 years old are relatively scarce. This study aimed to investigate ambulatory blood pressure monitoring (ABPM) characteristics in male hypertensive patients aged over 85 years. These included demographic characteristics, antihypertensive drug use, 24-h ABPM values, diabetes, coronary heart disease, sleep disorders, smoking history, and drinking history, and the differences in ABPM between the age groups over and under 85 years old were analyzed. A total of 585 elderly hypertensive patients were included. The mean systolic blood pressure in individuals aged over 85 years was significantly greater throughout the day (131.57 ± 12.52 mmHg vs. 123.75 ± 2.74 mmHg, p < .001). In the 85 years older age group, the nighttime variability coefficient of SBP was lower at 7.84 ± 2.9 than the under 85 years age group 8.92 ± 3.13 (p < .001). The 85 years older age group age group presented a significantly greater whole-day systolic blood pressure standard deviation of ABPM (13.2 ± 3.19 vs. 12.47 ± 3.05, p = .005) compared with those under the age of 85 years. In the 85 years older age group, the proportion of individuals with the reverse dipper pattern was higher (48.15% vs. 38.31%, p = .017) than under 85 years age group. This study revealed that elderly male hypertensive patients aged over 85 years presented elevated average blood pressure levels. The research investigated ABPM characteristics. Older hypertensive individuals are more likely to have a reverse-dipper blood pressure pattern.

7.
Int J Biol Macromol ; 278(Pt 1): 134432, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39097053

RESUMEN

In this study, a combination of adenine and potassium oxonate was utilized to establish a hyperuricemic nephropathy (HN) mouse model, aiming to elucidate the effect through which Imperata Cylindrica polysaccharide (ICPC-a) ameliorates HN. In HN mice, an elevation in the abundance of Erysipelatoclostridium, Enterococcus, Prevotella, and Escherichia-Shigella was observed, whereas Lactobacillus and Bifidobacterium declined. Additionally, the systemic reductions in the levels of acetate, propionate, and butyrate, along with a significant increase in indole content, were noted. HN mice demonstrated intestinal barrier impairment, as evidenced by diminished mRNA expression of ZO-1, Occludin, and Claudin-1 and increased Mmp-9 levels. The pro-inflammatory factors IL-6, IL-17, TNF-α, IFN-γ, and COX-2 were overexpressed. Subsequent gavage intervention with ICPC-a markedly mitigated the inflammatory response and ameliorated colon tissue damage. ICPC-a effectively regulated the abundance of gut microbiota and their metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), and indole, promoting the correction of metabolic and gut microbiota imbalances in HN mice. These findings underscored the capacity of ICPC-a as a prebiotic to modulate gut microbiota and microbial metabolites, thereby exerting a multi-pathway and multi-targeted therapeutic effect on HN.


Asunto(s)
Disbiosis , Microbioma Gastrointestinal , Hiperuricemia , Animales , Ratones , Disbiosis/tratamiento farmacológico , Disbiosis/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Hiperuricemia/tratamiento farmacológico , Masculino , Polisacáridos/farmacología , Polisacáridos/química , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Modelos Animales de Enfermedad
8.
Food Chem ; 461: 140773, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39154459

RESUMEN

Recently we have investigated polysaccharide from Imperata cylindrica (ICP) for its physicochemical structure and biological activities. However, the digestion characteristics have yet to be understood. This study investigated the digestion and metabolism characteristics of ICP through in vivo fluorescence tracking, in vitro simulated digestion, fecal fermentation experiments, and microbial sequencing. The results showed that ICP significant distribution in the gastrointestinal tract and kidneys. ICP underwent slight degradation during simulated gastric and intestinal digestion. During fecal fermentation, the utilization degree of ICP and the concentration of short-chain fatty acids (SCFAs) increased. ICP promoted the increase of beneficial microbial abundance. To understand the impact of ICP on the integrity and health of intestinal tissues, molecular docking was employed to preliminarily predict the interaction between ICP and key proteins. The results revealed that ICP could recognize and bind to key proteins through high-affinity targeting binding sites.


Asunto(s)
Bacterias , Digestión , Heces , Fermentación , Microbioma Gastrointestinal , Polisacáridos , Animales , Polisacáridos/metabolismo , Polisacáridos/química , Heces/microbiología , Heces/química , Bacterias/metabolismo , Bacterias/genética , Simulación del Acoplamiento Molecular , Masculino , Poaceae/química , Poaceae/metabolismo , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/química , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/microbiología , Humanos , Ratas Sprague-Dawley
11.
Technol Health Care ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39093089

RESUMEN

BACKGROUND: Current treatments do not support direct exposure of fracture fragments, resulting in the inability to directly observe the articular surface during surgery for accurate reduction and firm fixation. OBJECTIVE: The aim of the study was to explore the treatment effect of digital virtual reduction combined with individualized guide plate of lateral tibial condyle osteotomy on tibial plateau fracture involving the lateral posterior condyle collapse. METHODS: 41 patients with tibial plateau fracture involving the lateral posterior condyle collapse were recruited in the trial. All patients underwent Computed Tomography (CT) scanning before operation. After operation, fracture reduction was evaluated using Rasmussen score and function of knee joint was assessed using hospital for special surgery (HSS) score. RESULTS: 41 patients were followed-up 6-26 months (mean, 15.2 months). Fracture reduction was good after operation, with an average of 13.3 weeks of fracture healing without serious complications. The excellent and good rate was 97.6%. The joint movement degree was -5∘∼0∘∼135∘ with an average of 125.5∘. CONCLUSIONS: Digital virtual reduction combined with individualized guide plate of lateral tibial condyle osteotomy was effectively for treating tibial plateau fracture involving the lateral posterior condyle collapse.

12.
Arch Dermatol Res ; 316(7): 474, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39007937

RESUMEN

Psoriasis, a chronic and easily recurring inflammatory skin disease, causes a great economic burden to the patient's family because the etiology and mechanism are still unclear and the treatment cycle is long. In this study, the function and related mechanisms of Momordin Ic in psoriasis were investigated. The IMQ-induced mouse psoriasis model was constructed. The protective effects of different doses of Momordin Ic on psoriasis skin damage in mice were detected by PASI score, HE staining and Ki-67 staining. A psoriasis-like keratinocyte model was established at the cellular level using M5 (IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α) triggered HaCaT. The effects of Momordin Ic upon HaCaT cell biological behavior were examined using MTT and CCK-8 assays. In terms of mechanism, the expression level of each inflammatory factor was assessed using IHC staining and/or ELISA, qRT-PCR, the expression of oxidative stress-related indicators was detected biochemically, and western blot was performed to detect the levels of key proteins of the Wnt signaling and VEGF. As the results shown,  at the in vivo level, Momordin Ic significantly alleviated skin damage, reduced PASI score and inhibited hyperproliferation of keratinized cells in psoriasis mice. At the cellular level, Momordin Ic also significantly reversed M5-induced hyperproliferation of HaCaT keratinocytes. In terms of mechanism, Momordin Ic significantly inhibited the IL-23/IL-17 axis, dramatically elevated the levels of intracellular antioxidants including SOD, GSH-Px, and CAT, and significantly down-regulated the levels of the indicator of oxidative damage, malondialdehyde (MDA). In addition, Momordin Ic also significantly inhibited the level of ß-catenin, a pivotal protein of the Wnt signaling, C-Myc, a target gene of the Wnt signaling, and VEGF, a critical protein of angiogenesis. In conclusion, Momordin Ic can be involved in the skin-protective effects of psoriasis by multiple mechanisms, including inhibition of the Wnt signaling pathway and the IL-23/IL-17 axis, and suppression of oxidative damageand VEGF expression. Momordin Ic has been proven to be an underlying therapeutic drug for the treatment of psoriasis.


Asunto(s)
Modelos Animales de Enfermedad , Interleucina-17 , Interleucina-23 , Queratinocitos , Psoriasis , Piel , Vía de Señalización Wnt , Animales , Humanos , Ratones , Proliferación Celular/efectos de los fármacos , Células HaCaT , Imiquimod , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Ratones Endogámicos BALB C , Estrés Oxidativo/efectos de los fármacos , Psoriasis/tratamiento farmacológico , Psoriasis/patología , Psoriasis/inducido químicamente , Psoriasis/inmunología , Piel/patología , Piel/efectos de los fármacos , Piel/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Vía de Señalización Wnt/efectos de los fármacos
13.
Sci Rep ; 14(1): 15854, 2024 07 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982139

RESUMEN

This study aimed to assess the current status and changing trends of the disease burden of stroke and its subtypes due to low dietary fiber intake in China from 1990 to 2019. In cases of stroke and its subtypes attributable to low dietary fiber, deaths, disability-adjusted life-years (DALYs), age-standardized mortality rates (ASMR), age-standardized DALYs rates (ASDR), and percentage change were used to assess disease burden. Data were obtained from the 2019 global burden of disease study. Trends were assessed using Joinpoint regression and age-period-cohort analysis. Between 1990 and 2019, there was a declining trend in stroke and its subtypes, ASDR and ASMR, as well as the corresponding number of deaths and DALYs, due to low dietary fiber intake in China. Subarachnoid hemorrhage (SH) showed the greatest decrease, followed by intracerebral hemorrhage (IH) and ischemic stroke (IS). Local drift curves showed a U-shaped distribution of stroke, IS, and IH DALYs across the whole group and sex-based groups. For mortality, the overall and male trends were similar to those for DALYs, whereas female stroke, IH, and IS showed an upward trend. The DALYs for stroke and IH showed a clear bimodal distribution, IS showed an increasing risk with age. For mortality, the SH subtype showed a decreasing trend, whereas other subtypes showed an increasing risk with age. Both the period and cohort rates of stroke DALYs and motality due to low dietary fiber have declined. Males had a higher risk of DALYs and mortality associated with low fiber levels. The burden of stroke and its subtypes associated with a low-fiber diet in China has been declining over the past 30 years, with different patterns of change for different stroke subtypes and a higher burden for males, highlighting the differential impact of fiber intake on stroke and its subtypes.


Asunto(s)
Fibras de la Dieta , Accidente Cerebrovascular , Humanos , China/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/mortalidad , Hemorragia Subaracnoidea/mortalidad , Hemorragia Subaracnoidea/epidemiología , Adulto , Años de Vida Ajustados por Discapacidad , Años de Vida Ajustados por Calidad de Vida , Anciano de 80 o más Años , Costo de Enfermedad , Factores de Riesgo , Carga Global de Enfermedades/tendencias , Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/epidemiología , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/mortalidad
14.
J Am Heart Assoc ; 13(14): e034915, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38979821

RESUMEN

BACKGROUND: The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient-specific factors predicting the RDN response. METHODS AND RESULTS: We focused on individuals with hypertension who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the overall quality of evidence. A total of 50 studies were ultimately included in this systematic review, among which 17 studies were for meta-analysis. Higher baseline heart rate and lower pulse wave velocity were shown to be associated with significant antihypertensive efficacy of RDN on 24-hour systolic BP reduction (weighted mean difference, -4.05 [95% CI, -7.33 to -0.77]; weighted mean difference, -7.20 [95% CI, -9.79 to -4.62], respectively). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension, impaired baroreflex sensitivity, and several biomarkers are also reported to be associated with significant BP reduction after RDN. CONCLUSIONS: In patients with hypertension treated with the RDN, higher heart rate, and lower pulse wave velocity were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with orthostatic hypertension, BP variability, impaired cardiac baroreflex sensitivity, and some biomarkers are also reported to be associated with a better BP response to RDN.


Asunto(s)
Presión Sanguínea , Hipertensión , Riñón , Humanos , Hipertensión/fisiopatología , Hipertensión/cirugía , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Riñón/inervación , Riñón/fisiopatología , Presión Sanguínea/fisiología , Resultado del Tratamiento , Simpatectomía/métodos , Frecuencia Cardíaca/fisiología , Análisis de la Onda del Pulso , Arteria Renal/inervación , Barorreflejo/fisiología
15.
Nat Sci Sleep ; 16: 965-977, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39050367

RESUMEN

Background: Identifying risk factors for cardiovascular disease (CVD) is critical for effective prevention and management. While classic CVD risk factors have been extensively studied, there is a scarcity of research on the association between snoring and CVD risk, particularly in the context of sex differences. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2015 and 2020. Participants were initially categorized based on the severity of snoring or the presence of snoring.Within the snoring group, they were further classified by sex. Analysis was carried out using multivariate logistic regression. Results: Our study included 12,681 participants aged 18 years or older. When compared to the non-snoring group, individuals in the moderate snoring group had a higher odds ratio (OR) of 1.418 (95% CI 1.083 to 1.857, p = 0.011), while those in the severe snoring group had a higher OR of 1.882 (95% CI 1.468 to 2.409, p < 0.001). In the snoring group, individuals were further categorized by gender: 4527 males and 4131 females. Importantly, male patients showed a higher OR for atrial fibrillation (4.945, 95% CI 1.187 to 20.598, p = 0.028) compared to females. Additionally, male patients had a higher OR for coronary heart disease (2.002, 95% CI 1.152 to 3.479, p = 0.014) compared to females. Conclusion: Sex plays a significant role in the relationship between snoring and CVD risk. Males with snoring have a higher risk of developing CVD compared to females. In particular, male snorers are nearly five times more likely to develop atrial fibrillation and about twice as likely to experience coronary artery disease in comparison to female snorers. It is recommended that healthcare providers and public health officials prioritize cardiovascular risk assessments for male individuals who exhibit symptoms of snoring.

16.
Int J Surg ; 110(9): 5334-5341, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38833338

RESUMEN

BACKGROUND: The demand for telesurgery is rapidly increasing. Augmented reality (AR) remote surgery is a promising alternative, fulfilling a worldwide need in fracture surgery. However, previous AR endoscopic and Google Glass remotes remain unsuitable for fracture surgery, and the application of remote fracture surgery has not been reported. The authors aimed to evaluate the safety and clinical effectiveness of a new AR remote in fracture surgery. MATERIALS AND METHODS: This retrospective non-inferiority cohort study was conducted at three centres. Between 1 January 2018 and 31 March 2022, 800 patients who underwent fracture surgery were eligible for participation. The study enroled 551 patients with fractures (132 patellae, 128 elbows, 126 tibial plateaus, and 165 ankles) divided into an AR group (specialists used AR to remotely guide junior doctors to perform surgeries) and a traditional non-remote group (specialists performed the surgery themselves). RESULTS: Among 364 patients (182 per group) matched by propensity score, seven (3.8%) in the AR group and six (3%) in the non-remote group developed complications. The 0.005 risk difference (95% CI: -0.033 to 0.044) was below the pre-defined non-inferiority margin of a 10% absolute increase. A similar distribution in the individual components of all complications was found between the groups. Hierarchical analysis following propensity score matching revealed no statistical difference between the two groups regarding functional results at 1-year follow-up, operative time, amount of bleeding, number of fluoroscopies, and injury surgery interval. A Likert scale questionnaire showed positive results (median scores: 4-5) for safety, efficiency, and education. CONCLUSION: This study is the first to report that AR remote surgery can be as safe and effective as that performed by a specialist in person for fracture surgery, even without the physical presence of a specialist, and is associated with improving the skills and increasing the confidence of junior surgeons. This technique is promising for remote fracture surgery and other open surgeries, offering a new strategy to address inadequate medical care in remote areas.


Asunto(s)
Realidad Aumentada , Fracturas Óseas , Humanos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Fracturas Óseas/cirugía , Adulto , Anciano , Estudios de Cohortes , Cirugía Asistida por Computador/métodos
17.
Mol Cancer Res ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38888574

RESUMEN

Metabolic reprogramming of aerobic glycolysis contributes to tumorigenesis. High plasma lactate is a critical regulator in the development of many human malignancies; however, the underlying molecular mechanisms of cancer progression in the response to lactate (LA) remain elusive. Here we show that reduction of Yin-Yang 1 (YY1) expression correlated with high LA commonly occurs in various cancer cell types, including B-lymphoma and cervical cancer. Mechanistically, LA induces YY1 nuclear export and degradation via HSP70-mediated autophagy adjacent to mitochondria in a Histidine-rich LAR (LA-responsive) motif-dependent manner. Mutation of the LAR motif blocks LA-mediated YY1 cytoplasmic accumulation and in turn enhances cell apoptosis. Furthermore, low expression of YY1 promotes the colony formation, invasion, angiogenesis and growth of cancer cells in response to LA in vitro and in vivo using a murine xenograft model. Taken together, our findings reveal that a key lactate-responsive` element and may serve as therapeutic target for intervening cancer progression. Implications: We have shown lactate can induce YY1 degradation via its Histidine-rich LAR motif, and low expression of YY1 promotes cancer cell progression in response to lactate, leading to better prediction of YY1-targeting therapy.

18.
Nat Commun ; 15(1): 5048, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871723

RESUMEN

Despite the advent of genomic sequencing, molecular diagnosis remains unsolved in approximately half of patients with Mendelian disorders, largely due to unclarified functions of noncoding regions and the difficulty in identifying complex structural variations. In this study, we map a unique form of central iris hypoplasia in a large family to 6q15-q23.3 and 18p11.31-q12.1 using a genome-wide linkage scan. Long-read sequencing reveals a balanced translocation t(6;18)(q22.31;p11.22) with intergenic breakpoints. By performing Hi-C on induced pluripotent stem cells from a patient, we identify two chromatin topologically associating domains spanning across the breakpoints. These alterations lead the ectopic chromatin interactions between APCDD1 on chromosome 18 and enhancers on chromosome 6, resulting in upregulation of APCDD1. Notably, APCDD1 is specifically localized in the iris of human eyes. Our findings demonstrate that noncoding structural variations can lead to Mendelian diseases by disrupting the 3D genome structure and resulting in altered gene expression.


Asunto(s)
Cromatina , Iris , Linaje , Translocación Genética , Humanos , Cromatina/metabolismo , Cromatina/genética , Iris/metabolismo , Masculino , Femenino , Cromosomas Humanos Par 6/genética , Cromosomas Humanos Par 18/genética , Células Madre Pluripotentes Inducidas/metabolismo , Adulto , Enfermedades del Iris/genética , Enfermedades del Iris/metabolismo , Enfermedades del Iris/patología , Ligamiento Genético
19.
Medicine (Baltimore) ; 103(24): e38426, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38875426

RESUMEN

Previous observational studies revealed controversy about the effect of circulating antioxidants on risk of alopecia. In the present study, we investigated the causal relationships between diet-derived circulating antioxidants and 2 non-scarring alopecia using Mendelian randomization (MR). Instrumental variables for antioxidants (lycopene, retinol, ascorbate, ß-carotene, α-tocopherol, and γ-tocopherol) were selected from published studies. Data for alopecia areata (AA) and androgenetic alopecia (AGA) was obtained from the FinnGen study project (R9 released in 2023), including 195 cases and 201,019 controls for AGA and 682 cases and 361,140 controls for AA. We used the inverse variance weighted method as the primary MR method. Three additional methods were used as sensitivity analysis to validate the robustness of the results. We found a causal relationship between absolute ß-carotene levels and AGA risk (P = .039), but not with AA (P = .283). The results of Wald ratio showed a protective effect of absolute ß-carotene levels against AGA, with per 0.1 ln-transformed ß-carotene being associated with a 76% lower risk of AGA (OR: 0.24, 95% CI: 0.06-0.93). Based on the fixed effects inverse variance weighting results, we found that α-tocopherol was protective against both AGA (P = .026) and AA (P = .018). For each unit increase in α-tocopherol, the effects of change in AGA and AA were 0.02 (95% CI: 0.00-0.61) and 0.10 (95% CI: 0.01-0.67), respectively. The results did not reveal any other causal relationships. Our study identified 3 causal associations of antioxidants with the risk of non-scarring alopecia. These results provide new insights into the prevention of non-scarring alopecia through diet.


Asunto(s)
Alopecia , Antioxidantes , Dieta , Análisis de la Aleatorización Mendeliana , beta Caroteno , Humanos , Antioxidantes/metabolismo , beta Caroteno/sangre , Alopecia/genética , Alopecia/sangre , alfa-Tocoferol/sangre , Femenino , Masculino , Alopecia Areata/sangre , Alopecia Areata/genética , Alopecia Areata/epidemiología , Factores de Riesgo
20.
JCI Insight ; 9(15)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38916964

RESUMEN

Little is known about the expression patterns and functions of circular RNAs (circRNAs) in the heart of large mammals. In this study, we examined the expression profiles of circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in neonatal pig hearts. Pig heart samples collected on postnatal days 1 (P1), 3 (P3), 7 (P7), and 28 (P28) were sent for total RNA sequencing. Our data revealed a total of 7,000 circRNAs in the 24 pig hearts. Pathway enrichment analysis of hallmark gene sets demonstrated that differentially expressed circRNAs were engaged in different pathways. The most significant difference was observed between P1 and the other 3 groups (P3, P7, and P28) in pathways related to cell cycle and muscle development. Out of the 10 circRNAs that were validated through real-time quantitative PCR to verify their expression, 6 exhibited significant effects on cell cycle activity in human induced pluripotent stem cell-derived cardiomyocytes following small interfering RNA-mediated knockdown. circRNA-miRNA-mRNA networks were constructed to understand the potential mechanisms of circRNAs in the heart. In conclusion, our study provided a data set for exploring the roles of circRNAs in pig hearts. In addition, we identified several circRNAs that regulate cardiomyocyte cell cycle.


Asunto(s)
Animales Recién Nacidos , Proliferación Celular , MicroARNs , Miocitos Cardíacos , ARN Circular , Animales , ARN Circular/genética , ARN Circular/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/citología , Porcinos , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Humanos , ARN Mensajero/metabolismo , ARN Mensajero/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA