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1.
Nat Commun ; 15(1): 3884, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38719909

RESUMEN

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.


Asunto(s)
Antígeno B7-1 , Antígeno B7-H1 , Vesículas Extracelulares , Receptor de Muerte Celular Programada 1 , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Humanos , Antígeno B7-1/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/inmunología , Animales , Ratones , Línea Celular Tumoral , Femenino , Neoplasias/inmunología , Neoplasias/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Tolerancia Inmunológica , Ratones Endogámicos C57BL , Masculino , Microambiente Tumoral/inmunología
2.
Adv Sci (Weinh) ; : e2403120, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38728591

RESUMEN

The DNA-guided (gDNA) Argonaute from Thermus thermophilus (TtAgo) has little potential for nucleic acid detection and gene editing due to its poor dsDNA cleavage activity at relatively low temperature. Herein, the dsDNA cleavage activity of TtAgo is enhanced by using 2'-fluorine (2'F)-modified gDNA and developes a novel nucleic acid testing strategy. This study finds that the gDNA with 2'F-nucleotides at the 3'-end (2'F-gDNA) can promote the assembly of the TtAgo-guide-target ternary complex significantly by increasing its intermolecular force to target DNA and TtAgo, thereby providing ≈40-fold activity enhancement and decreasing minimum reaction temperature from 65 to 60°C. Based on this outstanding advance, a novel nucleic acid testing strategy is proposed, termed FAST, which is performed by using the 2'F-gDNA/TtAgo for target recognition and combining it with Bst DNA polymerase for nucleic acid amplification. By integrating G-quadruplex and Thioflavin T, the FAST assay achieves one-pot real-time fluorescence analysis with ultra-sensitivity, providing a limit of detection up to 5 copies (20 µL reaction mixture) for miR-21 detection. In summary, an atom-modification-based strategy has been developed for enhancing the cleavage activity of TtAgo efficiently, thereby improving its practicability and establishing a TtAgo-based nucleic acid testing technology with ultra-sensitivity and high-specificity.

3.
Int J Rheum Dis ; 27(5): e15151, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38720573

RESUMEN

BACKGROUND: Observational studies have found an association between autoimmune liver disease (AILD) and Sjögren's syndrome (SS). However, the causal relationship between the two remains unknown. Clinical guidelines indicate that the coexistence of AILD with other autoimmune diseases may impact prognosis and quality of life; hence, early recognition and management of extrahepatic autoimmune diseases is particularly crucial. Against this backdrop, this study aimed to utilize Mendelian randomization (MR) methods to investigate the potential causal relationship between AILD and SS. METHODS: We extracted summary statistics on AILD and SS from publicly available genome-wide association studies (GWAS) databases to identify appropriate instrumental variables (IVs). The inverse-variance weighted (IVW) method was utilized as the primary approach, with the weighted median (WM) method and MR-Egger method employed as supplementary methods to evaluate the potential causal relationship between the two conditions. Sensitivity analyses, including Cochran's Q test, MR-polynomial residuals and outliers (MR-PRESSO), MR-Egger intercept test, and the leave-one-out test, were performed to assess the stability of the results. RESULTS: The MR study results indicate a significant causal relationship between PBC and PSC with the risk of SS in the European population (IVW: odds ratio [OR] = 1.155, 95% confidence interval [CI]: 1.092-1.222, p < .001; IVW: OR = 1.162, 95% CI: 1.051-1.284, p = .003). A series of sensitivity analyses have confirmed the reliability of the results. CONCLUSIONS: Our study indicates that the presence of both PBC and PSC increases the susceptibility to SS. However, no reliable causal relationship was found between SS and the risk of PBC or PSC. These findings contribute to elucidating the potential pathogenic mechanisms of the disease and are of significant importance for the management of patients with PBC and PSC.


Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/genética , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/epidemiología , Factores de Riesgo , Medición de Riesgo , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/diagnóstico , Fenotipo , Cirrosis Hepática Biliar/genética , Cirrosis Hepática Biliar/epidemiología , Cirrosis Hepática Biliar/diagnóstico
4.
Sci Transl Med ; 16(745): eadh1763, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38691618

RESUMEN

An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. We identified plasma insulin-like growth factor 1 (IGF1) as an independent risk factor in patients with AAA by correlating plasma IGF1 with risk. Smooth muscle cell- or fibroblast-specific knockout of Igf1r, the gene encoding the IGF1 receptor (IGF1R), attenuated AAA formation in two mouse models of AAA induced by angiotensin II infusion or CaCl2 treatment. IGF1R was activated in aortic aneurysm samples from human patients and mice with AAA. Systemic administration of IGF1C, a peptide fragment of IGF1, 2 weeks after disease development inhibited AAA progression in mice. Decreased AAA formation was linked to competitive inhibition of IGF1 binding to its receptor by IGF1C and modulation of downstream alpha serine/threonine protein kinase (AKT)/mammalian target of rapamycin signaling. Localized application of an IGF1C-loaded hydrogel was developed to reduce the side effects observed after systemic administration of IGF1C or IGF1R antagonists in the CaCl2-induced AAA mouse model. The inhibitory effect of the IGF1C-loaded hydrogel administered at disease onset on AAA formation was further evaluated in a guinea pig-to-rat xenograft model and in a sheep-to-minipig xenograft model of AAA formation. The therapeutic efficacy of IGF1C for treating AAA was tested through extravascular delivery in the sheep-to-minipig model with AAA established for 2 weeks. Percutaneous injection of the IGF1C-loaded hydrogel around the AAA resulted in improved vessel flow dynamics in the minipig aorta. These findings suggest that extravascular administration of IGF1R antagonists may have translational potential for treating AAA.


Asunto(s)
Aneurisma de la Aorta Abdominal , Modelos Animales de Enfermedad , Factor I del Crecimiento Similar a la Insulina , Receptor IGF Tipo 1 , Animales , Receptor IGF Tipo 1/metabolismo , Receptor IGF Tipo 1/antagonistas & inhibidores , Humanos , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/tratamiento farmacológico , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/prevención & control , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Porcinos , Ratones , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Ratas
5.
BMC Nephrol ; 25(1): 137, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641839

RESUMEN

C57BL/6 mice are frequently utilized as murine models with the desired genetic background for altertion in multiple research contexts. So far, there is still a lack of comprehensive kidney morphology and single-cell transcriptome atlas at all stages of growth of C57BL/6 mice. To provide an interactive set of reference standards for the scientific community, we performed the current study to investigate the kidney's development throughout the capillary-loop stage until senescence. Eight groups, with five to six mice each, represented embryonic stage (embryos 18.5 days), suckling period (1 day after birth), juvenile stage (1 month old), adulthood (containing 3 months old, 6 months old and 10 months old), reproductive senescence stage (20 months old), and post-senescence stage (30 months old), respectively. With age, the thickness of the glomerular basement membrane (GBM) was increased. Notably, GBM knobs appeared at three months and became frequent with age. Using single-cell transcriptome data, we evaluated how various biological process appear in particular cell types and investigated the potential mechanism of formation of GBM konbs. In conclusion, having access to detailed kidney morphology and single-cell transcriptome maps from C57BL/6 mice at various developmental stages of C57BL/6 mice would be a novel and major resource for biological research and testing of prospective therapeutic approaches.


Asunto(s)
Riñón , Transcriptoma , Ratones , Animales , Ratones Endogámicos C57BL , Membrana Basal Glomerular , Envejecimiento/genética
6.
Heliyon ; 10(8): e29291, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38644851

RESUMEN

Tongue squamous cell carcinoma (TSCC) occupies a high proportion of oral squamous cell carcinoma. TSCC features high lymph node metastasis rates and chemotherapy resistance with a poor prognosis. Therefore, an effective therapy strategy is needed to improve patient prognosis. Melatonin (MT) is a natural indole compound shown to have anti-tumor effects in several cancers. This study focused on the role and mechanism of MT in TSCC cells. The results of the study suggest that MT could inhibit cell proliferation in CRL-1623 cells. Western blot analysis showed the down-regulate of cyclin B1 and the up-regulate P21 protein by MT. MT was also shown to down-regulate the expression of Zeb1, Wnt5A/B, and ß-catenin protein and up-regulate E-cadherin to inhibit the migration of CRL-1623 cells. MT also promoted the expression of ATF4, ATF6, Bip, BAP31 and CHOP in CRL-1623 cells leading to endoplasmic reticulum stress, and induced autophagy and apoptosis in CRL-1623 cells. Western blots showed that MT could promote the expression of Bax, LC3, and Beclin1 proteins and inhibit the expression of p62. We screened differentially expressed long non-coding RNAs (lncRNAs) in MT-treated cells and found that the expression of MALAT1 and H19 decreased. Moreover, MT inhibited tumor growth in nude mice inoculated with CRL-1623 cells. These results suggest that MT could induce autophagy, promote apoptosis, and provide a potential natural compound for the treatment of TSCC.

7.
Heliyon ; 10(7): e28565, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38601664

RESUMEN

Objective: This article aims to identify genetic features associated with immune cell infiltration in cerebral ischemia-reperfusion injury (CIRI) development through bioinformatics, with the goal of discovering diagnostic biomarkers and potential therapeutic targets. Methods: We obtained two datasets from the Gene Expression Omnibus (GEO) database to identify immune-related differentially expressed genes (IRDEGs). These genes' functions were analyzed via Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Tools such as CIBERSORT and ssGSEA assessed immune cell infiltration. The Starbase and miRDB databases predicted miRNAs interacting with hub genes, and Cytoscape software mapped mRNA-miRNA interaction networks. The ENCORI database was employed to predict RNA binding proteins interacting with hub genes. Key genes were identified using a random forest algorithm and constructing a Support Vector Machine (SVM) model. LASSO regression analysis constructed a diagnostic model for hub genes to determine their diagnostic value, and PCR analysis validated their expression in cerebral ischemia-reperfusion. Results: We identified 10 IRDEGs (C1qa, Ccl4, Cd74, Cd8a, Cxcl10, Gmfg, Grp, Lgals3bp, Timp1, Vim). The random forest algorithm, and SVM model intersection revealed three key genes (Ccl4, Gmfg, C1qa) as diagnostic biomarkers for CIRI. LASSO regression analysis, further refined this to two key genes (Ccl4 and C1qa), With ROC curve, analysis confirming their diagnostic efficacy (C1qa AUC = 0.75, Ccl4 AUC = 0.939). PCR analysis corroborated these findings. Conclusions: Our study elucidates immune and metabolic response mechanisms in CIRI, identifying two immune-related genes as key biomarkers and potential therapeutic targets in response to cerebral ischemia-reperfusion injury.

8.
Eur J Radiol ; 175: 111458, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38613868

RESUMEN

PURPOSE: The importance of structured radiology reports has been fully recognized, as they facilitate efficient data extraction and promote collaboration among healthcare professionals. Our purpose is to assess the accuracy and reproducibility of ChatGPT, a large language model, in generating structured thyroid ultrasound reports. METHODS: This is a retrospective study that includes 184 nodules in 136 thyroid ultrasound reports from 136 patients. ChatGPT-3.5 and ChatGPT-4.0 were used to structure the reports based on ACR-TIRADS guidelines. Two radiologists evaluated the responses for quality, nodule categorization accuracy, and management recommendations. Each text was submitted twice to assess the consistency of the nodule classification and management recommendations. RESULTS: On 136 ultrasound reports from 136 patients (mean age, 52 years ± 12 [SD]; 61 male), ChatGPT-3.5 generated 202 satisfactory structured reports, while ChatGPT-4.0 only produced 69 satisfactory structured reports (74.3 % vs. 25.4 %, odds ratio (OR) = 8.490, 95 %CI: 5.775-12.481, p < 0.001). ChatGPT-4.0 outperformed ChatGPT-3.5 in categorizing thyroid nodules, with an accuracy of 69.3 % compared to 34.5 % (OR = 4.282, 95 %CI: 3.145-5.831, p < 0.001). ChatGPT-4.0 also provided more comprehensive or correct management recommendations than ChatGPT-3.5 (OR = 1.791, 95 %CI: 1.297-2.473, p < 0.001). Finally, ChatGPT-4.0 exhibits higher consistency in categorizing nodules compared to ChatGPT-3.5 (ICC = 0.732 vs. ICC = 0.429), and both exhibited moderate consistency in management recommendations (ICC = 0.549 vs ICC = 0.575). CONCLUSIONS: Our study demonstrates the potential of ChatGPT in transforming free-text thyroid ultrasound reports into structured formats. ChatGPT-3.5 excels in generating structured reports, while ChatGPT-4.0 shows superior accuracy in nodule categorization and management recommendations.

9.
World J Clin Cases ; 12(9): 1578-1584, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38576730

RESUMEN

BACKGROUND: Frey syndrome, also known as ototemporal nerve syndrome or gustatory sweating syndrome, is one of the most common complications of parotid gland surgery. This condition is characterized by abnormal sensations in the facial skin accompanied by episodes of flushing and sweating triggered by cognitive processes, visual stimuli, or eating. AIM: To investigate the preventive effect of acellular dermal matrix (ADM) on Frey syndrome after parotid tumor resection and analyzed the effects of Frey syndrome across various surgical methods and other factors involved in parotid tumor resection. METHODS: Retrospective data from 82 patients were analyzed to assess the correlation between sex, age, resection sample size, operation time, operation mode, ADM usage, and occurrence of postoperative Frey syndrome. RESULTS: Among the 82 patients, the incidence of Frey syndrome was 56.1%. There were no significant differences in sex, age, or operation time between the two groups (P > 0.05). However, there was a significant difference between ADM implantation and occurrence of Frey syndrome (P < 0.05). ADM application could reduce the variation in the incidence of Frey syndrome across different operation modes. CONCLUSION: ADM can effectively prevent Frey syndrome and delay its onset.

10.
Mol Cancer ; 23(1): 70, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38576002

RESUMEN

BACKGROUND: Cellular senescence frequently occurs during anti-cancer treatment, and persistent senescent tumor cells (STCs) unfavorably promote tumor progression through paracrine secretion of the senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) have recently emerged as a novel component of the SASP and primarily mediate the tumor-promoting effect of the SASP. Of note, the potential effect of EVs released from STCs on tumor progression remains largely unknown. METHODS: We collected tumor tissues from two cohorts of colorectal cancer (CRC) patients to examine the expression of p16, p21, and SERPINE1 before and after anti-cancer treatment. Cohort 1 included 22 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgical resection. Cohort 2 included 30 patients with metastatic CRC (mCRC) who received first-line irinotecan-contained treatment. CCK-8, transwell, wound-healing assay, and tumor xenograft experiments were carried out to determine the impacts of EVs released from STCs on CRC progression in vitro and in vivo. Quantitative proteomic analysis was applied to identify protein cargo inside EVs secreted from STCs. Immunoprecipitation and mass spectrometer identification were utilized to explore the binding partners of SERPINE1. The interaction of SERPINE1 with p65 was verified by co-immunoprecipitation, and their co-localization was confirmed by immunofluorescence. RESULTS: Chemotherapeutic agents and irradiation could potently induce senescence in CRC cells in vitro and in human CRC tissues. The more significant elevation of p16 and p21 expression in patients after anti-cancer treatment displayed shorter disease-free survival (DFS) for LARC or progression-free survival (PFS) for mCRC. We observed that compared to non-STCs, STCs released an increased number of EVs enriched in SERPINE1, which further promoted the progression of recipient cancer cells. Targeting SERPINE1 with a specific inhibitor, tiplaxtinin, markedly attenuated the tumor-promoting effect of STCs-derived EVs. Additionally, the patients with greater increment of SERPINE1 expression after anti-cancer treatment had shorter DFS for LARC or PFS for mCRC. Mechanistically, SERPINE1 bound to p65, promoting its nuclear translocation and subsequently activating the NF-κB signaling pathway. CONCLUSIONS: We provide the in vivo evidence of the clinical prognostic implications of therapy-induced senescence. Our results revealed that STCs were responsible for CRC progression by producing large amounts of EVs enriched in SERPINE1. These findings further confirm the crucial role of therapy-induced senescence in tumor progression and offer a potential therapeutic strategy for CRC treatment.


Asunto(s)
Neoplasias Colorrectales , Vesículas Extracelulares , Neoplasias del Recto , Humanos , FN-kappa B/metabolismo , Proteómica , Transducción de Señal , Vesículas Extracelulares/metabolismo , Neoplasias del Recto/metabolismo , Senescencia Celular , Neoplasias Colorrectales/patología , Inhibidor 1 de Activador Plasminogénico/metabolismo , Inhibidor 1 de Activador Plasminogénico/farmacología
11.
Int J Rheum Dis ; 27(3): e15128, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38509724

RESUMEN

BACKGROUND: Epidemiological and observational studies have indicated an association between Sjögren's syndrome (SS) and Parkinson's disease (PD). However, consistent conclusions have not been reached due to various limitations. In order to determine whether SS and PD are causally related, we conducted a Mendelian randomization study (MR) with two samples. METHODS: Data for SS derived from the FinnGen consortium's R9 release (2495 cases and 365 533 controls). Moreover, data for PD were acquired from the publicly available GWAS of European ancestry, which involved 33 674 cases and 449 056 controls. The inverse variance weighted, along with four other effective methodologies, were employed to comprehensively infer the causal relationships between SS and PD. To assess the estimation's robustness, a number of sensitivity studies were performed. To determine the probability of reverse causality, we performed a reverse MR analysis. RESULTS: There was no evidence of a significant causal effect of SS on PD risks based on the MR [odds ratio (OR) = 1.03; 95% confidence interval (CI) = 0.95-1.11; p = .45]. Similarly, no evidence supported the causal effects of PD on SS (OR = 0.92; 95% CI = 0.81-1.04; p = .20). These findings held up under rigorous sensitivity analysis. CONCLUSIONS: MR bidirectional analysis did not reveal any cause-and-effect relationship between SS and PD, or vice versa. Further study of the mechanisms that may underlie the probable causal association between SS and PD is needed.


Asunto(s)
Enfermedad de Parkinson , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/epidemiología , Síndrome de Sjögren/genética , Análisis de la Aleatorización Mendeliana , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/genética , Causalidad , Oportunidad Relativa , Estudio de Asociación del Genoma Completo
12.
Chem Commun (Camb) ; 60(32): 4322-4325, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38535993

RESUMEN

Here, we synthesized a series of cholesteryl-based compounds, whose phases and their transformation can be modulated by temperature and the chain length of the fluoroalkyl moieties. To our knowledge, this is the first time that the phase transition could be modulated with perfluoroalkyl tail engineering in organic single-component ferroelectric crystals.

13.
Sci Total Environ ; 926: 172031, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38552985

RESUMEN

Long-term deposition of atmospheric radioactive iodine-129 (129I) is important for assessing the impact of human nuclear activities (HNAs), but still not well understood in East Asia. In this study, we quantitatively reconstructed the deposition history of airborne 129I using varved sediment from Sihailongwan Maar Lake (SHLW) in northeast China. Our results revealed significant increases in 129I concentrations and 129I/127I atomic ratios since the 1950s, indicating the influence of HNAs on the environment and marking the onset of the Anthropocene. The variation of 129I in the investigated site can be primarily attributed to the global fallout of ANWT as well as nuclear fuel reprocessing in Europe, Russia and the USA. Notably, neither the Chernobyl nor the Fukushima nuclear accidents have had any discernable impact on the SHLW Lake. Over the past 170 years (1846-2021), the reconstructed fluxes indicate a rapid increase in 129I deposition from the early 1950s until the 1970s followed by dramatic changes thereafter. The measured 129I fluxes range between (1.26-349) × 109 atoms m-2 yr-1 in the SHLW Lake, which are consistent with similar latitude zones across East Asia, but differ significantly from those observed in high-elevation glaciers within the Northern Hemisphere due to prevailing atmospheric circulation patterns. The total 129I inventory was calculated to be 11.9 × 1012 atoms m-2, with natural and anthropogenic 129I accounting for 2.86 % and 97.1 %, respectively, suggesting an overwhelming artificial contribution. The reconstructed fluxes and inventory of atmospheric 129I deposition quantitatively distinguish the natural and artificial contributions, and provide a novel insight into the historical environmental impact of HNAs in East Asia and the characteristics of the Anthropocene.

14.
Chem Biol Interact ; 393: 110955, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38492842

RESUMEN

Aucubin (AU), an iridoid glycoside extracted from Eucommia ulmoides, exerts anti-osteoporotic effects by promoting osteogenesis, as reported in previous studies. Here, we investigated the effects of AU under mechanical stretch stress. MC3T3-E1 cells were treated with dexamethasone (DEX) in vitro and subjected to mechanical stretch stress to establish an osteoporotic orthodontic force cell model. AU treatment increased the mRNA and protein expressions of BMP2, OPN, RUNX2, COL-1 and other osteogenic differentiation factors in MC3T3-E1 cells. Furthermore, we established an in vivo orthodontic tooth movement (OTM) model of osteoporosis. Serum parameter detection of ALP concentration, radiography of the femur, hematoxylin-eosin (HE) staining, and micro-CT of the maxilla confirmed that AU could partially reverse the damage induced by DEX. Immunohistochemical (IHC) analysis showed that AU increased the expression of COL-1, OCN, and OPN on the tension side of the periodontium. In conclusion, AU treatment promotes osteogenic differentiation under mechanical stretch stress and positively affects bone remodeling during OTM in DEX-induced osteoporosis.


Asunto(s)
Glucósidos Iridoides , Osteogénesis , Osteoporosis , Humanos , Técnicas de Movimiento Dental , Ligamento Periodontal , Diferenciación Celular , Osteoporosis/tratamiento farmacológico
16.
BMC Public Health ; 24(1): 774, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38475821

RESUMEN

BACKGROUND: Lithuania, a Baltic country in the European Union, can be characterized by high alcohol consumption and attributable burden. The aim of this contribution is to estimate the mortality burden due to alcohol use for the past two decades based on different relative risk functions, identify trends, and analyse the associations of alcohol-attributable burden with alcohol control policies and life expectancy. METHODS: The standard methodology used by the World Health Organization for estimating alcohol-attributable mortality was employed to generate mortality rates for alcohol-attributable mortality, standardized for Lithuania's 2021 population distribution. Joinpoint analysis, T-tests, correlations, and regression analyses including meta-regressions were used to describe trends and associations. RESULTS: Age-standardized alcohol-attributable mortality was high in Lithuania during the two decades between 2001 and 2021, irrespective of which relative risks were used for the estimates. Overall, there was a downward trend, mainly in males, which was associated with four years of intensive implementation of alcohol control policies in 2008, 2009, 2017, and 2018. For the remaining years, the rates of alcohol-attributable mortality were stagnant. Among males, the correlations between alcohol-attributable mortality and life expectancy were 0.90 and 0.76 for Russian and global relative risks respectively, and regression analyses indicated a significant association between changes in alcohol-attributable mortality and life expectancy, after controlling for gross domestic product. CONCLUSIONS: Male mortality and life expectancy in Lithuania were closely linked to alcohol-attributable mortality and markedly associated with strong alcohol control policies. Further implementation of such policies is predicted to lead to further improvements in life expectancy.


Asunto(s)
Consumo de Bebidas Alcohólicas , Esperanza de Vida , Humanos , Masculino , Lituania/epidemiología , Riesgo , Política Pública
17.
Artículo en Inglés | MEDLINE | ID: mdl-38497748

RESUMEN

Aims: Endothelial cells are the critical targets of injury in diabetic nephropathy (DN), and endothelial cell lesions contribute to the disease progression. Neurite outgrowth inhibitor B (Nogo-B), an endoplasmic reticulum (ER)-resident protein, plays a pivotal role in vascular remodeling after injury, and maintains the structure and function of the ER. Yet, the role of Nogo-B in the regulation of ER stress and endothelial cell injury remains largely unknown. Herein, we tested the hypothesis that Nogo-B activates ER stress-mediated autophagy and protects endothelial cells in DN. Results: The level of Nogo-B was decreased in glomerular endothelial cells in biopsy specimens from DN patients. In vivo and in vitro studies have shown that silencing Nogo-B activated ER stress signaling, and affected the expression of autophagy-related marker early growth response 1 and microtubule-associated protein light chain 3 (LC3) in endothelial cells in hyperglycemic condition. Conclusion and Innovation: These results denote that Nogo-B contributes to ER stress-mediated autophagy and protects endothelial cells in DN, providing new evidence for understanding the role of ER stress-mediated autophagy in endothelial cells of DN.

18.
J Craniomaxillofac Surg ; 52(4): 503-513, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38383249

RESUMEN

This systematic review aimed to investigate the factors that may contribute to the development of OSA after orthognathic surgery in patients with skeletal class III. Electronic searches of PubMed, Embase, Web of Science, and Cochrane databases were conducted up to December 10, 2022. In total, 277 studies were retrieved and screened according to the inclusion and exclusion criteria, and 14 were finally selected. All studies were of medium quality (moderate risk of bias). The occurrence of OSA after orthognathic surgery in patients with class III skeletal relationships depends on surgical factors and patient self-factors. Surgical factors include surgery type, amount of maxillary and mandibular movement, and the patient's postoperative swelling. Patient self-factors include weight, age, gender, and hypertrophy of the soft palate, tonsils, and tongue. According to information in the 14 selected articles, the incidences of OSA after Le Fort I impaction and BSSO setback, BSSO setback, and Le Fort I advancement and BSSO setback were 19.2%, 8.57%, and 0.7%, respectively, mostly accompanied with greater amounts of mandibular recession. However, no clear evidence exists to confirm that orthognathic surgery is a causative factor for postoperative sleep breathing disorders in patients with mandibular prognathism. The wider upper airway in patients with class III skeletal might be the reason for the rare occurrence of OSA after surgery. In addition, obesity and advanced age may lead to sleep apnea after orthognathic surgery. Obese patients should be advised to lose weight preoperatively.


Asunto(s)
Maloclusión de Angle Clase III , Cirugía Ortognática , Procedimientos Quirúrgicos Ortognáticos , Apnea Obstructiva del Sueño , Humanos , Osteotomía Le Fort/efectos adversos , Apnea Obstructiva del Sueño/etiología , Maloclusión de Angle Clase III/cirugía , Mandíbula/cirugía , Procedimientos Quirúrgicos Ortognáticos/efectos adversos , Maxilar/cirugía , Cefalometría
19.
Water Res ; 252: 121180, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38301523

RESUMEN

This study proposes a sustainable approach for hard-to-treat wastewater using sintered activated carbon (SAC) both as an adsorption filter and as an electrode, allowing its simultaneous electrochemical regeneration. SAC improves the activated carbon (AC) particle contact and thus the conductivity, while maintaining optimal liquid flow. The process removed 87 % of total organic carbon (TOC) from real high-load (initial TOC of 1625 mg/L) pharmaceutical wastewater (PWW), generated during the manufacturing of azithromycin, in 5 h, without external input of chemicals other than catalytic amounts of Fe(II). Kinetic modelling indicated that adsorption was the dominant process, while concomitant electrochemical degradation of complex organics first converted them to short-chain acids, followed by their full mineralization. In-situ electrochemical regeneration of SAC, taking place at the same time as the treatment, is a key feature of our process, enhancing its performance and ensuring its stable operation over time, while eliminating cleaning downtimes altogether. The energy consumption of this innovative process was remarkably low at 8.0×10-3 kWh gTOC-1. This study highlights the potential of SAC for treating hard-to-treat effluents by concurrent adsorption and mineralization of organics.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Aguas Residuales , Eliminación de Residuos Líquidos , Carbón Orgánico , Adsorción , Contaminantes Químicos del Agua/análisis , Preparaciones Farmacéuticas
20.
Biofouling ; 40(1): 64-75, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38373897

RESUMEN

Aeromonas hydrophila, a Gram-negative zoonotic bacterium, causes high mortality in fish farming and immunocompromised patients. This study aimed to extract methyl gallate (MG) from the flowers of Camellia nitidissima Chi and evaluate its potential as a quorum sensing inhibitor (QSI) against Aeromonas hydrophila SHAe 115. MG reduced QS-associated virulence factors, including hemolysis, protease, and lipase, while impairing swimming motility and biofilm formation. Additionally, MG down-regulated positive regulatory genes (ahyR, fleQ) and up-regulated negative regulators (litR, fleN). This highlights MG's promise as a potent QSI for A. hydrophila SHAe 115, advancing strategies against infections in aquaculture and human health.


Asunto(s)
Biopelículas , Ácido Gálico/análogos & derivados , Percepción de Quorum , Animales , Humanos , Percepción de Quorum/genética , Virulencia/genética , Aeromonas hydrophila/genética , Factores de Virulencia/genética , Proteínas Bacterianas/genética
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