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1.
Cardiovasc Diabetol ; 23(1): 331, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39252021

RESUMEN

BACKGROUND: Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes. METHODS: The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests. RESULTS: We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX. CONCLUSION: These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis.


Asunto(s)
Apoptosis , Aterosclerosis , Movimiento Celular , Proliferación Celular , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Exosomas , Ratones Endogámicos C57BL , MicroARNs , Músculo Liso Vascular , Miocitos del Músculo Liso , Placa Aterosclerótica , Animales , MicroARNs/metabolismo , MicroARNs/genética , Exosomas/metabolismo , Exosomas/patología , Aterosclerosis/metabolismo , Aterosclerosis/patología , Aterosclerosis/genética , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Miocitos del Músculo Liso/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Músculo Liso Vascular/patología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Masculino , Transducción de Señal , Células Cultivadas , Obesidad/metabolismo , Obesidad/patología , Ratones Noqueados para ApoE , Células Endoteliales/metabolismo , Células Endoteliales/patología , Células Endoteliales/efectos de los fármacos , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/metabolismo , Enfermedades de la Aorta/genética , Becaplermina/farmacología , Becaplermina/metabolismo , Grasa Intraabdominal/metabolismo , Grasa Intraabdominal/patología , Ratones , Humanos
2.
J Nanobiotechnology ; 22(1): 361, 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38910236

RESUMEN

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.


Asunto(s)
Autofagia , Frío , Exosomas , Ratones Endogámicos C57BL , MicroARNs , Osteogénesis , Animales , Autofagia/efectos de los fármacos , Ratones , Exosomas/metabolismo , MicroARNs/metabolismo , MicroARNs/genética , Osteogénesis/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Osteoporosis/patología , Diferenciación Celular/efectos de los fármacos , Huesos/metabolismo , Femenino , Densidad Ósea , Sirolimus/farmacología
3.
BMC Musculoskelet Disord ; 25(1): 142, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38355528

RESUMEN

BACKGROUND: This study aims to compare the clinical outcomes and safety of a novel hand-held retractor system-assisted Wiltse TLIF with that P-TLIF and assess whether this hand-held retractor system assisted Wiltse TLIF can yield less paraspinal muscle injury. METHODS: 56 patients (P-TLIF: 26, Wiltse TLIF: 30) were included in this one year prospective controlled study. The operation time, intraoperative blood loss, postoperative drainage, mobilization time, and discharge time were recorded. The clinical outcomes were evaluated by ODI, VAS, JOA, and SF-36 scores (7 days, 3, 6, and 12 months after surgery). Paraspinal muscle injury was assessed by postoperative MRI (6 months after surgery). CK and C-reaction protein were measured pre and postoperatively, and CT or X-ray (one year postoperatively) was used to assess bony union/non-union. RESULTS: The Wiltse (study) group was associated with significantly less estimated blood loss (79.67 ± 28.59 ml vs 192.31 ± 59.48 ml, P = 0.000*), postoperative drainage (43.33 ± 27.89 ml vs 285.57 ± 123.05 ml, P = 0.000*), and shorter mobilization (4.1 ± 1.2 d vs. 3.0 ± 0.9 d, P < 0.05) and discharge times (7.7 ± 1.9 d vs. 6.1 ± 1.2 d, P = 0.002*) than the P-TLIF (control) group. Serum CK activity at 24 h postoperatively in the study group was significantly lower than in the control group (384.10 ± 141.99 U/L vs 532.76 ± 225.76 U/L, P = 0.018*). At 7 days after surgery, VAS (2.3 ± 0.6 vs 3.2 ± 0.7, P = 0.000*)and ODI scores (43.9 ± 11.9 vs 55.2 ± 12.9, P = 0.001*) were lower, while the JOA scores (18.4 ± 3.4 vs 16.3 ± 4.2, P = 0.041*) was higher in the control group than in the study group. Results observed at 3 months of follow-up were consistent with those at 7 days. After six months postoperatively, paraspinal muscle degeneration in the control group was more significant than in the study group (P = 0.008*). CONCLUSION: Our study showed that this novel hand-held retractor system assisted Wiltse approach TLIF can significantly reduce paraspinal muscle injury, postoperative drainage, and intraoperative blood loss, mobilization and discharge time, as well as yield better short-term outcomes compared to P-TLIF. TRIAL REGISTRATION: 25/09/2023 NCT06052579.


Asunto(s)
Vértebras Lumbares , Fusión Vertebral , Humanos , Resultado del Tratamiento , Estudios Prospectivos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Pérdida de Sangre Quirúrgica , Estudios Retrospectivos
4.
J Nanobiotechnology ; 21(1): 315, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37667298

RESUMEN

Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFsHPi-Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFsHPi-Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFsHPi-Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFsmiR21M-Exos) significantly accelerate vascular calcification in CRF mice. In general, AFsHPi-Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment.


Asunto(s)
Exosomas , MicroARNs , Calcificación Vascular , Animales , Ratones , Células Endoteliales , Fibroblastos , Fósforo , MicroARNs/genética , Receptores de Proteínas Morfogenéticas Óseas
5.
J Nanobiotechnology ; 21(1): 226, 2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37461031

RESUMEN

Medial arterial calcification (MAC), a systemic vascular disease different from atherosclerosis, is associated with an increased incidence of cardiovascular events. Several studies have demonstrated that ambient temperature is one of the most important factors affecting cardiovascular events. However, there has been limited research on the effect of different ambient temperatures on MAC. In the present study, we showed that cold temperature exposure (CT) in mice slowed down the formation of vitamin D (VD)-induced vascular calcification compared with room temperature exposure (RT). To investigate the mechanism involved, we isolated plasma-derived exosomes from mice subjected to CT or RT for 30 days (CT-Exo or RT-Exo, respectively). Compared with RT-Exo, CT-Exo remarkably alleviated the calcification/senescence formation of vascular smooth muscle cells (VSMCs) and promoted autophagy by activating the phosphorylation of AMP-activated protein kinase (p-AMPK) and inhibiting phosphorylation of mammalian target of rapamycin (p-mTOR). At the same time, CT-Exo promoted autophagy in ß-glycerophosphate (ß-GP)-induced VSMCs. The number of autophagosomes and the expression of autophagy-related proteins ATG5 and LC3B increased, while the expression of p62 decreased. Based on a microRNA chip microarray assay and real-time polymerase chain reaction, miR-320a-3p was highly enriched in CT-Exo as well as thoracic aortic vessels in CT mice. miR-320a-3p downregulation in CT-Exo using AntagomiR-320a-3p inhibited autophagy and blunted its anti-calcification protective effect on VSMCs. Moreover, we identified that programmed cell death 4 (PDCD4) is a target of miR-320a-3p, and silencing PDCD4 increased autophagy and decreased calcification in VSMCs. Treatment with CT-Exo alleviated the formation of MAC in VD-treated mice, while these effects were partially reversed by GW4869. Furthermore, the anti-arterial calcification protective effects of CT-Exo were largely abolished by AntagomiR-320a-3p in VD-induced mice. In summary, we have highlighted that prolonged cold may be a good way to reduce the incidence of MAC. Specifically, miR-320a-3p from CT-Exo could protect against the initiation and progression of MAC via the AMPK/mTOR autophagy pathway.


Asunto(s)
Aterosclerosis , MicroARNs , Ratones , Animales , Proteínas Quinasas Activadas por AMP/metabolismo , Antagomirs , Serina-Treonina Quinasas TOR , Autofagia , MicroARNs/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
6.
Small ; 18(21): e2201548, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35491513

RESUMEN

Adequately harvesting all excitons in a single molecule and inhibiting exciton losses caused by intermolecular interactions are two important factors for achieving high efficiencies thermally activated delayed fluorescence (TADF). One potential approach for optimizing these is to tune alignment of various excited state energy levels by using different doping concentrations. Unfortunately, emission efficiencies of most TADF emitters decrease rapidly with concentrations which limits the window for energy level tunning. In this work, by introducing a spiro group to increase steric hindrance of a TADF emitter (BPPXZ) with a phenoxazine and a dibenzo[a,c]phenazine, emission efficiency of the resulting molecule (BPSPXZ) is much less affected by concentration increase. This enables exploitation of the concentration effects to tune energy levels of its excited states for obtaining simultaneously small singlet-triplet energy offset and large spin-orbital coupling, leading to high-efficiency reverse intersystem crossing. With these merits, organic light-emitting diodes (OLEDs) using the BPSPXZ emitter from 5 to 60 wt% doping can all deliver EQE of over 20%. More importantly, record-high EQEs of 33.4% and 15.8% are respectively achieved in the optimized and nondoped conditions. This work proposes a strategy for developing red TADF emitters by optimizing the intermolecular interaction and energy level alignments to facilitate exciton utilization over wide doping concentrations.

7.
J Nanobiotechnology ; 20(1): 334, 2022 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-35842695

RESUMEN

The pathogenesis of vascular calcification in diabetic patients remains elusive. As an effective information transmitter, small extracellular vesicles (sEVs) carry abundant microRNAs (miRNAs) that regulate the physiological and pathological states of recipient cells. In the present study, significant up-regulation of miR-126-5p was observed in sEVs isolated from human umbilical vein endothelial cells (HUVECs) stimulated with advanced glycation end-products (A-EC/sEVs). Intriguingly, these sEVs suppressed the osteogenic differentiation of vascular smooth muscle cells (VSMCs) by targeting BMPR1B, which encodes the receptor for BMP, thereby blocking the smad1/5/9 signalling pathway. In addition, knocking down miR-126-5p in HUVECs significantly diminished the anti-calcification effect of A-EC/sEVs in a mouse model of type 2 diabetes. Overall, miR-126-5p is highly enriched in sEVs derived from AGEs stimulated HUVECs and can target BMPR1B to negatively regulate the trans-differentiation of VSMCs both in vitro and in vivo.


Asunto(s)
Diabetes Mellitus Tipo 2 , Vesículas Extracelulares , MicroARNs , Calcificación Vascular , Animales , Vesículas Extracelulares/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Ratones , MicroARNs/metabolismo , Osteogénesis , Calcificación Vascular/metabolismo , Calcificación Vascular/patología
8.
J Pineal Res ; 68(3): e12631, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31943334

RESUMEN

In the elderly with atherosclerosis, hypertension and diabetes, vascular calcification and ageing are ubiquitous. Melatonin (MT) has been demonstrated to impact the cardiovascular system. In this study, we have shown that MT alleviates vascular calcification and ageing, and the underlying mechanism involved. We found that both osteogenic differentiation and senescence of vascular smooth muscle cells (VSMCs) were attenuated by MT in a MT membrane receptor-dependent manner. Moreover, exosomes isolated from VSMCs or calcifying vascular smooth muscle cells (CVSMCs) treated with MT could be uptaken by VSMCs and attenuated the osteogenic differentiation and senescence of VSMCs or CVSMCs, respectively. Moreover, we used conditional medium from MT-treated VSMCs and Transwell assay to confirm exosomes secreted by MT-treated VSMCs attenuated the osteogenic differentiation and senescence of VSMCs through paracrine mechanism. We also found exosomal miR-204/miR-211 mediated the paracrine effect of exosomes secreted by VSMCs. A potential target of these two miRs was revealed to be BMP2. Furthermore, treatment of MT alleviated vascular calcification and ageing in 5/6-nephrectomy plus high-phosphate diet-treated (5/6 NTP) mice, while these effects were partially reversed by GW4869. Exosomes derived from MT-treated VSMCs were internalised into mouse artery detected by in vivo fluorescence image, and these exosomes reduced vascular calcification and ageing of 5/6 NTP mice, but both effects were largely abolished by inhibition of exosomal miR-204 or miR-211. In summary, our present study revealed that exosomes from MT-treated VSMCs could attenuate vascular calcification and ageing in a paracrine manner through an exosomal miR-204/miR-211.


Asunto(s)
Melatonina/farmacología , MicroARNs/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Calcificación Vascular/metabolismo , Envejecimiento , Animales , Diferenciación Celular/efectos de los fármacos , Exosomas/química , Exosomas/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , Músculo Liso Vascular/fisiopatología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Calcificación Vascular/fisiopatología
9.
Int J Syst Evol Microbiol ; 69(1): 63-67, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30403583

RESUMEN

A Gram-stain-negative, facultatively anaerobic, motile bacterial strain, designated gBX10-1-2T, was isolated from symptomatic bark of Populus×euramericana canker in China. Phylogenetic analysis based on its 16S rRNA gene sequence showed that the novel isolate belonged to the genus Brenneria, and shared the highest sequence similarity to Brenneria nigrifluens LMG 2694T (98.3 %). In the phylogenetic trees based on the four housekeeping genes sequences, the novel strain formed a separate branch different from B. nigrifluens LMG 2694T, indicating that the novel strain should be classified as a novel species. The genome sequence-derived average nucleotide identity (ANI) values between the novel isolate and B. nigrifluens LMG 2694T, Brenneria roseaesubsp. roseae FRB 222T and Brenneria roseaesubsp. americana FRB 223T were less than 85 %, lower than the proposed species boundary ANI cut-off value (95-96 %). The DNA G+C content was 56.2 mol%, and the main fatty acids were C16 : 0, C16 : 1ω7c, C18 : 1ω7c and C17 : 0cyclo. Based on the phenotypic and genotypic characteristics, strain gBX10-1-2T represents a novel species of genus Brenneria, for which the name Brenneria corticis sp. nov. is proposed. The type strain is gBX10-1-2T (=CFCC 11842T=KCTC 42840T).


Asunto(s)
Enterobacteriaceae/clasificación , Filogenia , Corteza de la Planta/microbiología , Enfermedades de las Plantas/microbiología , Populus/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Enterobacteriaceae/aislamiento & purificación , Ácidos Grasos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
11.
J Nurs Manag ; 27(8): 1614-1619, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31424580

RESUMEN

AIM: To explore and improve nursing care for infants after enterostomy. METHODS: A total of 483 infants who underwent enterostomy from January 2014 to January 2019 were enrolled in this study. RESULTS: During hospitalization and follow-up, there were 30 infants with peripheral skin complications, including 15 cases of allergic dermatitis, 13 cases of faecal dermatitis and two cases of avulsion injury. CONCLUSION: Without proper and effective nursing care, the peripheral skin complications of enterostomy-related can easily develop. Therefore, careful postoperative care and effective family follow-up and guidance are essential after discharge, and using WeChat to follow-up can provide timely and effective follow-up and guidance to patients. IMPLICATIONS FOR NURSING MANAGEMENT: This study summarizes the experience of nursing care for infants over a 5-year period. Nurses must provide sound care for infants after enterostomy, timely and effectively address complications, guide nursing care performed by family members and strengthen follow-up through the WeChat online support group to reduce the occurrence of complications.


Asunto(s)
Enterostomía/enfermería , Atención de Enfermería/métodos , Complicaciones Posoperatorias/enfermería , China/epidemiología , Enterostomía/efectos adversos , Femenino , Humanos , Lactante , Masculino , Complicaciones Posoperatorias/epidemiología , Periodo Posoperatorio , Estudios Retrospectivos , Cicatrización de Heridas
13.
Int J Syst Evol Microbiol ; 67(9): 3633-3638, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28875909

RESUMEN

Two Gram-stain-negative, facultatively anaerobic, motile bacterial strains isolated from symptomatic bark of Populus × euramericana canker in China were investigated using a polyphasic approach, including 16S rRNA gene sequencing, multilocus sequence analysis, and biochemical and physiological assays. 16S rRNA gene sequencing indicated that these strains belonged to the genus Brenneria, family Pectobacteriaceae, and had the highest sequence similarity with Brenneria populi CFCC 11963T (98 %). DNA-DNA hybridization experiments revealed DNA-DNA relatedness values of 72.1-78.2 % between the new isolates and strains of B. populi, revealing that these strains belonged to the same species. The 16S rRNA gene sequencing and multilocus sequence analysis suggested that the two novel strains and those of B. populi are phylogenetically closely related but form two clearly separated subgroups. Based on the data, the two novel isolates represent a subspecies of B. populi for which the name B. populi subsp. brevivirga subsp. nov. is proposed with D8-10-4-5T (=CFCC 11935T=KCTC 42841T) as the type strain, with the automatic creation of B. populi subsp. populi subsp. nov. (type strain D9-5T=CFCC 11963T=KCTC 42088T).


Asunto(s)
Enterobacteriaceae/clasificación , Filogenia , Corteza de la Planta/microbiología , Enfermedades de las Plantas/microbiología , Populus/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Enterobacteriaceae/genética , Enterobacteriaceae/aislamiento & purificación , Tipificación de Secuencias Multilocus , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
14.
World J Clin Cases ; 12(4): 729-736, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38322673

RESUMEN

BACKGROUND: Sepsis, as a non-limiting host infection disease, can be accompanied by serious complications such as organ failure, which seriously threatens patient quality of life. AIM: To investigate the effect of early stepwise cardiopulmonary rehabilitation on cardiopulmonary function and quality of life in patients evacuated from mechanical ventilation with sepsis. METHODS: A total of 80 patients with sepsis who were hospitalized in our hospital from January 2021 to January 2022 were selected and divided into the observation group (n = 40) and the control group (n = 40) according to the random number table method. The observation group was treated with early stepwise cardiopulmonary rehabilitation, and the control group was treated with a conventional treatment regimen. Cardiac function indexes (central venous pressure, cardiac troponin I, B-type brain natriuretic peptide), lung function indicators (diaphragmatic mobility, changes in central venous oxygen saturation, oxygenation index), and quality of life (Quality of Life Evaluation Scale) were compared between the two groups after treatment. RESULTS: After treatment, the central venous pressure, diaphragm mobility, central venous oxygen saturation, oxygenation index, and Quality of Life Evaluation Scale scores in the observation group were higher than those in the control group, and the differences were statistically significant (P < 0.05). The observation group was less than that of the control group for other parameters, and the differences were statistically significant (P < 0.05). CONCLUSION: Early stepwise cardiopulmonary rehabilitation can effectively enhance cardiac and pulmonary function and improve the quality of life in patients evacuated from mechanical ventilation with sepsis.

15.
Obes Rev ; 25(6): e13740, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38571458

RESUMEN

Exosomes are extracellular vesicles, measuring 40-160 nm in diameter, that are released by many cell types and tissues, including adipose tissue. Exosomes are critical mediators of intercellular communication and their contents are complex and diverse. In recent years, accumulating evidence has proved that multiple adipose tissue-derived exosomal noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in the pathogenesis of diverse metabolic diseases, such as obesity. In this narrative review, we focus on the adipose tissue-derived exosomal ncRNAs, especially exosomal miRNAs, and their dysregulation in multiple types of metabolic diseases. A deeper understanding of the role of adipose tissue-derived exosomal ncRNAs may help provide new diagnostic and treatment methods for metabolic diseases.


Asunto(s)
Tejido Adiposo , Exosomas , Enfermedades Metabólicas , ARN no Traducido , Humanos , Exosomas/metabolismo , Enfermedades Metabólicas/genética , Enfermedades Metabólicas/metabolismo , Tejido Adiposo/metabolismo , ARN no Traducido/genética , ARN no Traducido/metabolismo , ARN Largo no Codificante/metabolismo , ARN Largo no Codificante/fisiología , Animales
16.
J Bone Miner Res ; 39(7): 942-955, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38624186

RESUMEN

The correlation between socio-economic status (SES) and bone-related diseases garners increasing attention, prompting a bidirectional Mendelian randomization (MR) analysis in this study. Genetic data on SES indicators (average total household income before tax, years of schooling completed, and Townsend Deprivation Index at recruitment), femoral neck bone mineral density (FN-BMD), heel bone mineral density (eBMD), osteoporosis, and five different sites of fractures (spine, femur, lower leg-ankle, foot, and wrist-hand fractures) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates, complemented by alternative MR techniques, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Furthermore, sensitivity analyses and multivariable MR were performed to enhance the robustness of our findings. Higher educational attainment exhibited associations with increased eBMD (ß: .06, 95% confidence interval [CI]: 0.01-0.10, P = 7.24 × 10-3), and reduced risks of osteoporosis (OR: 0.78, 95% CI: 0.65-0.94, P = 8.49 × 10-3), spine fracture (OR: 0.76, 95% CI: 0.66-0.88, P = 2.94 × 10-4), femur fracture (OR: 0.78, 95% CI: 0.67-0.91, P = 1.33 × 10-3), lower leg-ankle fracture (OR: 0.79, 95% CI: 0.70-0.88, P = 2.05 × 10-5), foot fracture (OR: 0.78, 95% CI: 0.66-0.93, P = 5.92 × 10-3), and wrist-hand fracture (OR: 0.83, 95% CI: 0.73-0.95, P = 7.15 × 10-3). Material deprivation appeared to increase the risk of spine fracture (OR: 2.63, 95% CI: 1.43-4.85, P = 1.91 × 10-3). A higher FN-BMD level positively affected increased household income (ß: .03, 95% CI: 0.01-0.04, P = 6.78 × 10-3). All these estimates were adjusted for body mass index, type 2 diabetes, smoking initiation, and frequency of alcohol intake. The MR analyses show that higher educational levels is associated with higher eBMD, reduced risk of osteoporosis and fractures, while material deprivation is positively related to spine fracture. Enhanced FN-BMD correlates with increased household income. These findings provide valuable insights for health guideline formulation and policy development.


We conducted stratified analyses to explore the causal links between socio-economic status and osteoporosis and various fractures and observed that education significantly reduced the risk of osteoporosis and lower eBMD. It also lowered the risks of fractures of spine, femur, lower leg-ankle, foot, and wrist-hand, while material deprivation exhibited positive associations with spine fracture risk. Bidirectional MR analysis showed that an elevated score of FN-BMD was associated with a higher income level. Our study shows the importance of conducting routine BMD estimations and osteoporosis screening, to enhance knowledge and awareness among individuals to promote bone health and prevent fractures.


Asunto(s)
Fracturas Óseas , Análisis de la Aleatorización Mendeliana , Osteoporosis , Clase Social , Humanos , Osteoporosis/genética , Osteoporosis/epidemiología , Femenino , Masculino , Fracturas Óseas/genética , Fracturas Óseas/epidemiología , Población Blanca/genética , Densidad Ósea/genética , Persona de Mediana Edad , Europa (Continente)/epidemiología , Estudio de Asociación del Genoma Completo
17.
Bioact Mater ; 42: 52-67, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39280584

RESUMEN

Vascular calcification and vascular ageing are "silent" diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N6-methyladenosine (m6A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m6A methylation.

18.
Huan Jing Ke Xue ; 44(3): 1678-1685, 2023 Mar 08.
Artículo en Zh | MEDLINE | ID: mdl-36922228

RESUMEN

Secondary copper smelting is an important source of heavy metal emission. Flue gas samples were collected from different stages in secondary copper smelters to study the emission characteristics and control of particulate matters (PM) and heavy metals such as Cd, Cr, As, Pb, Sn, and Sb. The mass concentrations of heavy metals in flue gas and fly ash were determined using inductively coupled plasma-mass spectrometry. The emission factors of heavy metals were estimated. The results showed that the mass concentrations of heavy metals and PM in the flue gas were high in the cooling stage. After passing through a series of air pollution control devices, such as a bag filter and adsorption tower, the heavy metals and PM were simultaneously removed with a removal efficiency of 80%-99%. The concentration order of heavy metals in the stack gas from different anode furnace stages followed feeding-fusion>oxidation≈deoxidization. In general, the mass concentrations of heavy metals and PM in the stack gas could meet the industry emission standards. The average emission factors of As, Pb, Cr, Sn, Sb, and Cd were 2.6×103, 2.4×103, 2.7×103, 5.6×102, 34.1, and 9.8 mg·t-1, respectively. This could provide data support for estimating the annual emission amounts of heavy metals from the secondary copper industry and establishing the emission inventories. The fly ash contained high concentrations of Cu and Zn, which can be recycled as raw materials for recycling the valuable metals.

19.
Pancreas ; 52(2): e151-e162, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37523607

RESUMEN

OBJECTIVES: This study aimed to develop a liver metastasis-related gene prognostic index (LMPI) for pancreatic ductal adenocarcinoma prognosis and therapy. METHODS: The Cancer Genome Atlas data set was used to identify liver metastasis-related hub genes via weighted gene coexpression network analysis. The core genes were identified to construct an LMPI by using the Cox regression method. An immune cell abundance identifier was applied to determine the immune cell abundance. RESULTS: A total of 78 hub liver metastasis-related genes in the black module were significantly enriched in complement and coagulation cascades, fat digestion and absorption, and the PPAR signaling pathway. Then, an LMPI was constructed on the basis of the 5 prognostic genes (MOGAT3, ASGR1, TRPM8, SGSM1, and LOC101927851). Patients with higher LMPI scores had poor overall survival, more co-occurring or mutually exclusive pairs of driver gene mutations, and less benefit from immunotherapy than patients with lower LMPI scores. In addition, a high correlation was also found between LMPI scores and immune infiltration, such as CD4 naive, CD8 T, cytotoxic T, T helper 2, follicular helper T, and natural killer cells. CONCLUSIONS: The core genes of the LMPI developed may be independent factors for predicting prognosis, immune characteristics, and immunotherapy efficacy in pancreatic ductal adenocarcinoma.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Pronóstico , Receptor de Asialoglicoproteína , Neoplasias Pancreáticas
20.
Signal Transduct Target Ther ; 8(1): 98, 2023 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-36864020

RESUMEN

Epigenetics regulates gene expression and has been confirmed to play a critical role in a variety of metabolic diseases, such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), osteoporosis, gout, hyperthyroidism, hypothyroidism and others. The term 'epigenetics' was firstly proposed in 1942 and with the development of technologies, the exploration of epigenetics has made great progresses. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, and noncoding RNA (ncRNA), which exert different effects on metabolic diseases. Genetic and non-genetic factors, including ageing, diet, and exercise, interact with epigenetics and jointly affect the formation of a phenotype. Understanding epigenetics could be applied to diagnosing and treating metabolic diseases in the clinic, including epigenetic biomarkers, epigenetic drugs, and epigenetic editing. In this review, we introduce the brief history of epigenetics as well as the milestone events since the proposal of the term 'epigenetics'. Moreover, we summarise the research methods of epigenetics and introduce four main general mechanisms of epigenetic modulation. Furthermore, we summarise epigenetic mechanisms in metabolic diseases and introduce the interaction between epigenetics and genetic or non-genetic factors. Finally, we introduce the clinical trials and applications of epigenetics in metabolic diseases.


Asunto(s)
Epigénesis Genética , Enfermedades Metabólicas , Humanos , Epigénesis Genética/genética , Enfermedades Metabólicas/genética , Metilación de ADN/genética , Ensamble y Desensamble de Cromatina
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