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Background: Refractory gastroesophageal reflux disease (refractory GERD) is a heterogeneous disease characterized by unresponsiveness or poor efficacy to proton-pump inhibitors (PPIs). This chronic disorder substantially weakens patients' mental wellbeing and quality of life, increasing the financial burden on society. Multiple articles have been reported in this area. However, literature involving scientometric analysis of refractory GERD is absent. Therefore, it is necessary to understand the evolution of research themes and the main hotspots of refractory GERD through bibliometric methods. Methods: All documents related to refractory GERD based on the WOS Core Collection from January 2000 to November 2023 were selected for analysis. Citespace V 6.1 R6, VOSviewer V 1.6.20, and Scimago Graphica V 1.0.38 were used to perform bibliometric analysis. Results: We collected a total of 241 research articles from 36 countries and 322 institutions, contributed by over 1,000 authors. Over the last 20 years, the number of articles in this field has increased year by year, and since 2011, the number of publications has increased dramatically, with 85.89% of the papers. These countries are led by the United States and Japan. GUT had the highest number of citations and DIGESTION had the highest number of publications. Research on standardized diagnosis and management, mechanisms, novel monitoring methods, and innovative drugs and procedures for refractory GERD are the main topics and hotspots in this field. This study also found that neuroimmune interaction is closely related to refractory GERD, which may be a new direction for future mechanism research. Conclusion: Our study is the first bibliometric analysis of the global literature on refractory GERD. This research provides valuable insights for researchers, enabling them to quickly understand the research frontier and hot topics of this field.
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Understanding the range shift patterns of foundation species (e.g., macroalgae) under future climatic conditions is critical for biodiversity conservation in coastal ecosystems. These predictions are typically made using species distribution models (SDMs), and severe habitat loss has been predicted for most brown algal forests. Nevertheless, some models showed that local adaptation within species can reduce range loss projections. In this study, we used the brown algae Sargassum fusiforme and Sargassum thunbergii, which are distributed in the Northwest Pacific, to determine whether climate change will cause the Sargassum beds in Northwest Pacific temperate waters to expand or contract. We divided S. fusiforme and S. thunbergii into northern and southern lineages, considering the temperature gradients and phylogeographic structures. We quantified the realized niches of the two lineages using an n-dimensional hypervolume. Significant niche differentiation was detected between lineages for both species, suggesting the existence of local adaptation. Based on these results, lineage-level SDMs were constructed for both species. The prediction results showed the different responses of different lineages to climate change. The suitable distribution area for both species was predicted to move northward, retaining part of the suitable habitat at low latitudes (along the East China Sea). Unfortunately, this expansion could not compensate for losing middle-low latitude areas. Our results have important implications for the future management and protection of macroalgae and emphasize the importance of incorporating intraspecific variation into species distribution predictions.
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Plants delicately regulate endogenous auxin levels through the coordination of transport, biosynthesis, and inactivation, which is crucial for growth and development. While it is well-established that the actin cytoskeleton can regulate auxin levels by affecting polar transport, its potential role in auxin biosynthesis has remained largely unexplored. Using LC-MS/MS-based methods combined with fluorescent auxin marker detection, we observed a significant increase in root auxin levels upon deletion of the actin bundling proteins AtFIM4 and AtFIM5. Fluorescent observation, immunoblotting analysis, and biochemical approaches revealed that AtFIM4 and AtFIM5 affect the protein abundance of the key auxin synthesis enzyme YUC8 in roots. AtFIM4 and AtFIM5 regulate the auxin synthesis enzyme YUC8 at the protein level, with its degradation mediated by the 26S proteasome. This regulation modulates auxin synthesis and endogenous auxin levels in roots, consequently impacting root development. Based on these findings, we propose a molecular pathway centered on the 'actin cytoskeleton-26S proteasome-YUC8-auxin' axis that controls auxin levels. Our findings shed light on a new pathway through which plants regulate auxin synthesis. Moreover, this study illuminates a newfound role of the actin cytoskeleton in regulating plant growth and development, particularly through its involvement in maintaining protein homeostasis via the 26S proteasome.
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BACKGROUND: The intricate relationship between type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) presents a challenge in understanding the significance of various biomarkers in diagnosis. AIM: To elucidate the roles and diagnostic values of α2-macroglobulin (α2-MG), podocalyxin (PCX), α-L-fucosidase (AFU), retinol-binding protein-4 (RBP-4), and cystatin C (CysC) in DN. METHODS: From December 2018 to December 2020, 203 T2DM patients were enrolled in the study. Of these, 115 were diagnosed with DN (115 patients), while the remaining 88 patients were classified as non-DN. The urinary levels of α2-MG, PCX, and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility. RESULTS: After adjustments for age and gender, significant positive correlations were observed between the biomarkers CysC, RBP-4, α2-MG/urinary creatinine (UCr), PCX/UCr, and AFU/UCr, and clinical indicators such as urinary albumin-to-creatinine ratio (UACR), serum creatinine, urea, 24-h total urine protein, and neutrophil-to-lymphocyte ratio (NLR). Conversely, these biomarkers exhibited negative correlations with the estimated glomerular filtration rate (P < 0.05). Receiver operating characteristic (ROC) curve analysis further demonstrated the diagnostic performance of these biomarkers, with UACR showcasing the highest area under the ROC curve (AUCROC) at 0.97. CONCLUSION: This study underscores the diagnostic significance of α2-MG, PCX, and AFU in the development of DN. The biomarkers RBP-4, CysC, PCX, AFU, and α2-MG provide promising diagnostic insights, while UACR is the most potent diagnostic biomarker in assessing DN.
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OBJECTIVES: To evaluate the clinical efficacy of dexamethasone (DEX) implant, for the treatment of macular edema (ME) caused by retinal vein occlusion (RVO) and diabetic retinopathy (DR) through a systematic review and meta-analysis. METHODS: The PubMed, Embase and Cochrane Library databases were comprehensively searched from inception to November 21, 2022, for studies evaluating the clinical efficacy of DEX implant for patients with retinal vein occlusion macular edema (RVO-ME) or diabetic macular edema (DME). Randomized controlled trials (RCTs) published in English were considered eligible. The Cochrane Collaboration tool was applied to assess the risk of bias in each study. Effect estimates with 95% confidence intervals (CIs) were pooled using the random effects model. We also conducted subgroup analyses to explore the sources of heterogeneity and the stability of the results. RESULTS: This meta-analysis included 8 RCTs (RVO-ME [n = 2] and DME [n = 6]) assessing a total of 336 eyes. Compared with anti-VEGF therapy, DEX implant treatment achieved superior outcomes in terms of best corrected visual acuity (BCVA) (mean difference [MD] = -3.68 ([95% CI, -6.11 to -1.25], P = 0.003), and no heterogeneity was observed (P = 0.43, I2 = 0%). DEX implant treatment also significantly reduced central macular thickness (CMT) compared with anti-VEGF treatment (MD = -31.32 [95% CI, -57.92 to -4.72], P = 0.02), and there was a high level of heterogeneity between trials (P = 0.04, I2 = 54%). In terms of severe adverse events, DEX implant treatment had a higher risk of elevated intraocular pressure than anti-VEGF therapy (RR = 6.98; 95% CI: 2.16 to 22.50; P = 0.001), and there was no significant difference in cataract progression between the two groups (RR = 1.83; 95% CI: 0.63 to 5.27, P = 0.31). CONCLUSIONS: Compared with anti-VEGF therapy, DEX implant treatment is more effective in improving BCVA and reducing ME. Additionally, DEX implant treatment has a higher risk of elevated intraocular pressure. Due to the small number of studies and the short follow-up period, the results should be interpreted with caution. The long-term effects of the two treatments need to be further determined. TRIAL REGISTRATION: Prospero Registration Number CRD42021243185.
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Dexametasona , Retinopatía Diabética , Implantes de Medicamentos , Edema Macular , Factor A de Crecimiento Endotelial Vascular , Edema Macular/tratamiento farmacológico , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Humanos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Retinopatía Diabética/tratamiento farmacológico , Agudeza Visual/efectos de los fármacos , Oclusión de la Vena Retiniana/tratamiento farmacológico , Oclusión de la Vena Retiniana/complicaciones , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificaciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Hyssopus cuspidatus Boriss., a classic Uyghur medicine, is used to treat inflammatory lung diseases such as asthma. But the therapeutic effect and mechanism of the volatile oil of Hyssopus cuspidatus Boriss.(HVO) in asthma therapy remain unclear. AIM OF THE STUDY: We aim to characterize the constituents of HVO, investigate the therapeutic effect in OVA-induced allergic asthmatic mice and further explore the molecular mechanism. MATERIALS AND METHODS: In this study, we applied two-dimensional gas chromatography quadrupole time-of-flight mass spectrometry (GC × GC-QTOF MS) to identify the ingredients of HVO. We established OVA-induced asthmatic model to investigate the therapeutic effect of HVO. To further explore the potential molecular pathways, we used network pharmacology approach to perform GO and KEGG pathways enrichment, and then built an ingredient-target-pathway network to identify key molecular pathways. Finally, LPS-induced RAW 264.7 macrophages and OVA-induced asthmatic model were used to validate the potential signaling pathways. RESULTS: GC × GC-QTOF MS analysis revealed the presence of 123 compounds of HVO. The sesquiterpenes and monoterpenes are the main constituents. The in vivo study indicated that HVO suppressed OVA-induced eosinophilic infiltration in lung tissues, inhibited the elevation of IgE, IL-4, IL-5, and IL-13 levels, downregulated the expressions of phosphorylated PI3K, Akt, JNK and P38, and maintained epithelial barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin. The in vitro study also revealed an inhibition of NO release and downregulation of phosphorylated PI3K, Akt, JNK and P38 levels. CONCLUSION: HVO alleviates airway inflammation in OVA-induced asthmatic mice by inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin.
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Asma , Aceites Volátiles , Ovalbúmina , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Animales , Femenino , Ratones , Antiasmáticos/farmacología , Asma/tratamiento farmacológico , Asma/inducido químicamente , Modelos Animales de Enfermedad , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos BALB C , Aceites Volátiles/farmacología , Aceites Volátiles/química , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pyroglyphidae/inmunología , Células RAW 264.7 , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND AND OBJECTIVES: Collateral status is a pivotal determinant of clinical outcomes in acute ischemic stroke (AIS); however, its evaluation can be challenging. We investigated the predictive value of CT perfusion (CTP) derived time and density alterations versus CTP for collateral status prediction in AIS. METHODS: Consecutive patients with anterior circulation occlusion within 24 h were retrospectively included. Time-density curves of the CTP specified ischemic core, penumbra, and the corresponding contralateral unaffected brain were obtained. The collateral status was dichotomised into robust (4-5 scores) and poor (0-3 scores) using multiphase collateral scoring, as described by Menon et al.. Receiver operating characteristic curves and multivariable regression analysis were performed to assess the predictive ability of CTP-designated tissue time and density alterations, CTP for robust collaterals, and favourable outcomes (mRS score of 0-2 at 90 days). RESULTS: One-hundred patients (median age, 68 years; interquartile range, 57-80 years; 61 men) were included. A smaller ischemic core, shorter peak time delay, lower peak density decrease, lower cerebral blood volume ratio, and cerebral blood flow ratio in the CTP specified ischemic core were significantly associated with robust collaterals (PFDR ≤ 0.004). The peak time delay demonstrated the highest diagnostic value (AUC, 0.74; P < 0.001) with 66.7 % sensitivity and 73.7 % specificity. Furthermore, the peak time delay of less than 8.5 s was an independent predictor of robust collaterals and favourable clinical outcomes. CONCLUSIONS: Robust collateral status was significantly associated with the peak time delay in the ischemic core. It is a promising image marker for predicting collateral status and functional outcomes in AIS.
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Circulación Cerebrovascular , Circulación Colateral , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología , Sensibilidad y Especificidad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Angiografía por Tomografía Computarizada/métodosRESUMEN
Metabolic syndrome (MetS) represents a constellation of metabolic abnormalities, typified by obesity, hypertension, hyperglycemia, and hyperlipidemia. It stems from intricate dysregulations in metabolic pathways governing energy and substrate metabolism. While comprehending the precise etiological mechanisms of MetS remains challenging, evidence underscores the pivotal roles of aberrations in lipid metabolism and insulin resistance (IR) in its pathogenesis. Notably, nicotinamide N-methyltransferase (NNMT) has recently surfaced as a promising therapeutic target for addressing MetS. Single nucleotide variants in the NNMT gene are significantly correlated with disturbances in energy metabolism, obesity, type 2 diabetes (T2D), hyperlipidemia, and hypertension. Elevated NNMT gene expression is notably observed in the liver and white adipose tissue (WAT) of individuals with diabetic mice, obesity, and rats afflicted with MetS. Knockdown of NNMT elicits heightened energy expenditure in adipose and hepatic tissues, mitigates lipid accumulation, and enhances insulin sensitivity. NNMT catalyzes the methylation of nicotinamide (NAM) using S-adenosyl-methionine (SAM) as the donor methyl group, resulting in the formation of S-adenosyl-l-homocysteine (SAH) and methylnicotinamide (MNAM). This enzymatic process results in the depletion of NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and the generation of SAH, a precursor of homocysteine (Hcy). Consequently, this cascade leads to reduced NAD+ levels and elevated Hcy levels, implicating NNMT in the pathogenesis of MetS. Moreover, experimental studies employing RNA interference (RNAi) strategies and small molecule inhibitors targeting NNMT have underscored its potential as a therapeutic target for preventing or treating MetS-related diseases. Nonetheless, the precise mechanistic underpinnings remain elusive, and as of yet, clinical trials focusing on NNMT have not been documented. Therefore, further investigations are warranted to elucidate the intricate roles of NNMT in MetS and to develop targeted therapeutic interventions.
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The complex process of aging leads to a gradual deterioration in the function of cells, tissues, and the entire organism, thereby increasing the risk of disease and death. Nicotinamide N-methyltransferase (NNMT) has attracted attention as a potential target for combating aging and its related pathologies. Studies have shown that NNMT activity increases over time, which is closely associated with the onset and progression of age-related diseases. NNMT uses S-adenosylmethionine (SAM) as a methyl donor to facilitate the methylation of nicotinamide (NAM), converting NAM into S-adenosyl-L-homocysteine (SAH) and methylnicotinamide (MNA). This enzymatic action depletes NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and generates SAH, a precursor of homocysteine (Hcy). The reduction in the NAD+ levels and the increase in the Hcy levels are considered important factors in the aging process and age-related diseases. The efficacy of RNA interference (RNAi) therapies and small-molecule inhibitors targeting NNMT demonstrates the potential of NNMT as a therapeutic target. Despite these advances, the exact mechanisms by which NNMT influences aging and age-related diseases remain unclear, and there is a lack of clinical trials involving NNMT inhibitors and RNAi drugs. Therefore, more in-depth research is needed to elucidate the precise functions of NNMT in aging and promote the development of targeted pharmaceutical interventions. This paper aims to explore the specific role of NNMT in aging, and to evaluate its potential as a therapeutic target.
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The prevalence of papillary thyroid cancer (PTC) has been rising in recent years. Despite its relatively low mortality, PTC frequently metastasizes to lymph nodes and often recurs, posing significant health and economic burdens. The role of iodine in the pathogenesis and advancement of thyroid cancer remains poorly understood. Circular RNAs (circRNAs) are recognized to function as competing endogenous RNAs (ceRNAs) that modulate gene expression and play a role in various cancer stages. Consequently, this research aimed to elucidate the mechanism by which circRNA influences the impact of iodine on PTC. Our research indicates that high iodine levels can exacerbate the malignancy of PTC via the circ_0004851/miR-296-3p/FGF11 axis. These insights into iodine's biological role in PTC and the association of circRNA with the disease could pave the way for novel biomarkers and potentially effective therapeutic strategies to mitigate PTC progression.
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Regulación Neoplásica de la Expresión Génica , Yodo , MicroARNs , ARN Circular , Cáncer Papilar Tiroideo , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Humanos , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Yodo/metabolismo , Línea Celular Tumoral , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Secuencia de BasesRESUMEN
One promising approach to overcome drug resistance in asthma treatments involves dual-target therapy, specifically targeting the ß2 adrenergic receptor (ß2-AR) and muscarinic-3 acetylcholine receptor (M3R). This study investigated the anti-asthma effects and dual-target mechanisms of glycyrrhizic acid, hesperidin, and platycodin D (GHP) from Zhisou San. GHP administration effectively attenuated OVA-induced inflammatory infiltration and overproduction of mucus in asthmatic mice. Additionally, GHP treatment significantly suppressed M3R and promoted ß2-AR activation, resulting in the relaxation of tracheal smooth muscle. These findings concluded that GHP mitigated asthma by targeting ß2-AR and M3R to ameliorate airway inflammation and modulate airway smooth muscle relaxation.
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KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed. From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features. Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years. Of the 49 cases with known clinical information, 94% were current or ex-smokers, and 49% were stage IV at diagnosis with median survival of 12 months. Sixty-three percent were histology cases and the remainder were cytology cases. Eighty-two percent were non-mucinous adenocarcinomas, with conventional histology including lepidic, acinar, solid, single cells and micropapillary patterns, and 62% were poorly differentiated. There were five (6%) cases of mucinous adenocarcinoma, one case of pleomorphic carcinoma and one case of high-grade fetal adenocarcinoma. TTF1 was positive in the majority (89%) of cases. Nineteen (23%) cases had TP53 co-mutation, and these cases had trends towards higher PD-L1 expression, poor differentiation, and presentation as stage IV disease, but the differences were not statistically significant. KRAS G12C mutated NSCLCs almost exclusively occurred in smokers and were mostly non-mucinous adenocarcinomas with conventional histological patterns which ranged from well to poorly differentiated. Around a quarter had TP53 co-mutation, the histological impacts and immune profile of which need to be assessed in a larger study.
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The tumor microenvironment is a complex network of cells, extracellular matrix, and signaling molecules that plays a critical role in tumor progression and metastasis. Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits. However, recent studies have shown that lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) also play multifaceted roles in the tumor microenvironment beyond their structural functions, particularly in hepatocellular carcinoma (HCC). This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC, including their involvement in angiogenesis, immune modulation, lymphangiogenesis, and metastasis. By providing a detailed account of the complex interplay between LECs, BECs, and tumor cells, this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.
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BACKGROUND: Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-editing enzyme that significantly impacts cancer progression and various biological processes. The expression of ADAR1 mRNA has been examined in multiple cancer types using The Cancer Genome Atlas (TCGA) dataset, revealing distinct patterns in kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and liver hepatocellular carcinoma (LIHC) compared to normal controls. However, the reasons for these differential expressions remain unclear. METHODS: In this study, we performed RT-PCR and western blotting (WB) to validate ADAR1 expression patterns in clinical tissue samples. Survival analysis and immune microenvironment analysis (including immune score and stromal score) were conducted using TCGA data to determine the specific cell types associated with ADAR1, as well as the key genes in those cell types. The relationship between ADAR1 and specific cell types' key genes was verified by immunohistochemistry (IHC), using clinical liver and kidney cancer samples. RESULTS: Our validation analysis revealed that ADAR1 expression was downregulated in KICH, KIRC, and KIRP, while upregulated in LIHC compared to normal tissues. Notably, a significant correlation was found between ADAR1 mRNA expression and patient prognosis, particularly in KIRC, KIRP, and LIHC. Interestingly, we observed a positive correlation between ADAR1 expression and stromal scores in KIRC, whereas a negative correlation was observed in LIHC. Cell type analysis highlighted distinct relationships between ADAR1 expression and the two stromal cell types, blood endothelial cells (BECs) and lymphatic endothelial cells (LECs), and further determined the signature gene claudin-5 (CLDN5), in KIRC and LIHC. Moreover, ADAR1 was inversely related with CLDN5 in KIRC (n = 26) and LIHC (n = 30) samples, verified via IHC. CONCLUSIONS: ADAR1 plays contrasting roles in LIHC and KIRC, associated with the enrichment of BECs and LECs within tumors. This study sheds light on the significant roles of stromal cells within the complex tumor microenvironment (TME) and provides new insights for future research in tumor immunotherapy and precision medicine.
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Adenosina Desaminasa , Carcinoma Hepatocelular , Carcinoma de Células Renales , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales , Neoplasias Hepáticas , Proteínas de Unión al ARN , Microambiente Tumoral , Adenosina Desaminasa/genética , Adenosina Desaminasa/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Neoplasias Renales/mortalidad , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Pronóstico , Femenino , Masculino , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Persona de Mediana EdadRESUMEN
To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.
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Enfermedades Gastrointestinales , Glicina , Sepsis , Sulfonamidas , Humanos , Sepsis/tratamiento farmacológico , Sepsis/complicaciones , Sepsis/sangre , Masculino , Femenino , Glicina/análogos & derivados , Glicina/uso terapéutico , Persona de Mediana Edad , Anciano , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Enfermedades Gastrointestinales/tratamiento farmacológico , Proteínas Inhibidoras de Proteinasas Secretoras , Biomarcadores/sangre , Resultado del TratamientoRESUMEN
The developmental toxicity of fenvalerate, a representative pyrethroid insecticide, is well documented. The present study aimed to explore whether prenatal exposure to fenvalerate causes depression-like behavior in adulthood. Pregnant mice were orally administrated with either corn oil or fenvalerate (2 or 20 mg/kg) during pregnancy. Depressive-like behaviors were assessed by tail suspension test (TST), forced swim test (FST) and sucrose preference test (SPT). Immobility times in TST and FST were increased in offspring whose mothers were exposed to fenvalerate throughout pregnancy. By contrast, sugar preference index, as determined by SPT, was decreased in fenvalerate-exposed offspring. Prefrontal PSD95, a postsynaptic membrane marker, was downregulated in fenvalerate-exposed adulthood offspring. Fenvalerate-induced reduction of prefrontal PSD95 began at GD18 fetal period. Accordingly, prefrontal 5-HT, a neurotransmitter for synaptogenesis, was also reduced in fenvalerate-exposed GD18 fetuses. Tryptophan hydroxylase 2 (TPH2), a key enzyme for 5-HT synthesis, was downregulated in the midbrain of fenvalerate-exposed GD18 fetuses. Additional experiment showed that GRP78 and p-eIF2α, two endoplasmic reticulum stress-related proteins, were increased in the midbrain of fenvalerate-exposed fetal mice. The present results suggest that prenatal exposure to fenvalerate causes depressive-like behavior in adulthood, partially by inhibiting brain-derived 5-HT synthesis.
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Depresión , Insecticidas , Nitrilos , Efectos Tardíos de la Exposición Prenatal , Piretrinas , Serotonina , Animales , Piretrinas/toxicidad , Femenino , Embarazo , Ratones , Nitrilos/toxicidad , Depresión/metabolismo , Serotonina/metabolismo , Insecticidas/toxicidad , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Chaperón BiP del Retículo Endoplásmico , Conducta Animal/efectos de los fármacos , Masculino , Exposición MaternaRESUMEN
Two metal borate-carbonates, M6[Cd2(CO3)2(B12O18)(OH)6] [M = K (1), Rb (2)], were obtained under surfactant-thermal conditions. In 1 and 2, each cyclic [(B12O18)(OH)6]6- anion captures two CdCO3 in two sides of the rings and finally forms the unusual (CdCO3)2@[(B12O18)(OH)6] cluster. Both 1 and 2 show moderate birefringence. Density functional theory calculations indicate that carbonate groups have a major contribution to electron-related optical transition.
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Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas F-Box , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Transducción de Señal , Ubiquitinas/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas F-Box/genética , Proteínas F-Box/metabolismoRESUMEN
OBJECTIVE: To investigate the clinical efficacy of fire acupuncture (FA) on plaque psoriasis (PP), exploring its suitable syndrome types, in order to achieve better therapeutic effects, accelerate the possibility of psoriasis skin lesion recovery, and provide assistance for clinical treatment. METHODS: A total of 8 patients with PP aged between 18 and 60 years were recruited and treated with FA once a week, and the lesion area and severity index (PASI), visual analog scale and pruritus were measured before, 2, 4 and 8 weeks after treatment and at the follow-up period (week 12), respectively. Visual analog scale, and dermoscopy were used for assessment. RESULTS: All patients showed improvement in pruritus after 1 FA treatment, and lesions were reduced to varying degrees after 2 weeks. Except for patients 5 and 8, who only achieved effective results due to severe disease, all other patients with psoriasis achieved significant results at 8 weeks after treatment. CONCLUSION: FA can significantly control the development of lesions, reduce the symptoms of PP lesions and pruritus, and help prevent psoriasis recurrence.