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MiRNA-21 is recognized as an important biological marker for the diagnosis, treatment, and prognosis of breast cancer. Here, we have created a nanochannel biosensor utilizing the duplex-specific nuclease (DSN) signal amplification strategy to achieve the detection of miRNAs. In this system, DNA as the capture probe was covalently immobilized on the surface of nanochannels, which hybridized with the target miRNA and forms RNA/DNA duplexes. DSN could cleave the probe DNA in RNA/DNA duplexes, recycling target miRNA, which may again hybridized with other DNA probes. After N cycles, most of the DNA probes had been cleaved, and the content of miRNA could be quantified by detecting changes in surface charge density. This biosensor can distinguish miR-21 from non-complementary miRNAs and one-base mismatched miRNAs, with reliable detection limits as low as 1 fM in PBS. In addition, we had successfully applied this method to analysis of total RNA samples in MCF-7 cells and HeLa cells, and the nanochannels had also shown excellent responsiveness and strong anti-interference ability. This new method is expected to contribute to miRNA detection in clinical diagnostics, providing a unique approach to detecting and distinguishing disease-associated molecules.
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AIMS: The evidence for joint and independent associations of low muscle mass and low muscle strength with diabetes is limited and mixed. The study aimed to determine the associations of muscle parameters (muscle mass, strength, quality, and sarcopenia) and sarcopenia obesity with diabetes, and the previously unstudied mediating effect of inflammation. MATERIALS AND METHODS: A total of 13,420 adults from the 2023 China National Health Survey (CNHS) and 5,380 adults from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) were included in this study. Muscle mass was determined using bioelectrical impedance analysis (BIA) in the CNHS, and whole-body dual X-ray absorptiometry (DXA) in the NHANES. Muscle strength was assessed using digital hand dynamometer. Multivariate logistic regression models were used to evaluate the associations of muscle parameters and sarcopenia obesity with diabetes. Inflammatory status was assessed using blood cell counts and two systemic inflammation indices (platelet-to-lymphocyte ratio (PLR) and system inflammation response index (SIRI)). Mediation analysis was conducted to examine inflammation's role in these associations. RESULTS: Low muscle mass and strength were independently related to diabetes. Low muscle quality was associated with elevated diabetes risk. Sarcopenia has a stronger association with diabetes compared to low muscle strength alone or mass alone (CNHS, odds ratio (OR) = 1.93, 95 % confidence interval (CI):1.64-2.27; NHANES, OR = 3.80, 95 %CI:2.58-5.58). Participants with sarcopenia obesity exhibit a higher risk of diabetes than those with obesity or sarcopenia alone (CNHS, OR = 2.21, 95 %CI:1.72-2.84; NHANES, OR = 6.06, 95 %CI:3.64-10.08). Associations between muscle parameters and diabetes were partially mediated by inflammation (mediation proportion: 1.99 %-36.64 %, P < 0.05). CONCLUSION: Low muscle mass and muscle strength are independently or jointly associated with diabetes, and inflammation might be a potential mechanism underlying this association. Furthermore, the synergistic effects of sarcopenia and obesity could significantly increase diabetes risk.
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Inflamación , Fuerza Muscular , Músculo Esquelético , Encuestas Nutricionales , Sarcopenia , Humanos , Masculino , Femenino , China/epidemiología , Inflamación/fisiopatología , Inflamación/epidemiología , Persona de Mediana Edad , Sarcopenia/epidemiología , Sarcopenia/fisiopatología , Sarcopenia/patología , Adulto , Fuerza Muscular/fisiología , Estados Unidos/epidemiología , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Diabetes Mellitus/epidemiología , Diabetes Mellitus/fisiopatología , Obesidad/epidemiología , Obesidad/fisiopatología , Obesidad/complicaciones , Anciano , Absorciometría de FotónRESUMEN
BACKGROUND: Multimorbidity is common, particularly among elderly people. Restructuring health service systems to better manage this public health issue requires knowledge regarding disease prevalence and patterns. We quantified the epidemiology characteristics of multimorbidity among adults in China to inform policy-making and resource allocation. METHODS: We searched 10 databases for studies (January 2000-October 2023) reporting primary epidemiological multimorbidity data for adults in China. We included observational studies; we excluded duplicate publications and studies investigating a single comorbidity pattern, focused on specific population categories, using medical insurance reimbursement data, and with unclear/incomplete data. We assessed risk of bias using the STROBE checklist and estimated heterogeneity among studies. The prevalence was pooled using the random-effects method and sample size as weight. FINDINGS: Of 13,998 records retrieved, 67 studies (30 in English, 37 in Chinese) were included. The prevalence (95% confidence interval) of multimorbidity was 25.4% (15.1%, 35.7%) among Chinese adults. Among 42 studies reporting age-specific prevalence, multimorbidity prevalence increased rapidly with age: 3.3% (0%, 15.2%) for age 18-29 years, 5.9% (0%, 12.9%) for 30-44 years, 17.6% (6.1%, 29.1%) for 45-59 years, 32.4% (16.1%, 48.7%) for 60-69 years, 38.5% (23.6%, 53.4%) for 70-79 years, and 40.2% (20.8%, 59.6%) for age ≥ 80 years. Overall prevalence of multimorbidity has increased in recent years, with regional disparity. The most common patterns included hypertension with hearing impairment (10.4% [95% CI: 4.3%, 16.5%]), dyslipidemia (8.9% [4.1%, 13.6%]), and diabetes (8.7% [3.7%, 13.8%]). CONCLUSION: Multimorbidity was present nearly one in four Chinese adults, with hypertensive diseases and other comorbidities being the most-observed pattern; the prevalence increased rapidly with increased age. There is huge variation in the prevalence of multimorbidity across China. Coordinated, comprehensive strategies are urgently needed to control the ongoing impact of multimorbidity.
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Diabetes Mellitus , Hipertensión , Humanos , China/epidemiología , Enfermedad Crónica , Comorbilidad , Diabetes Mellitus/epidemiología , Hipertensión/epidemiología , Multimorbilidad , PrevalenciaRESUMEN
Objective: Traditional Chinese medicine Polygonum cuspidatum (PC) has significant effects on reducing pain. In this study, we investigated the analgesic effects of the alcohol extract of PC on three types of inflammatory pain and explored its mechanism. Methods: Potential targets for the analgesic effects of the main active components of PC alcohol extract were screened by network pharmacology and molecular docking. Three different inflammatory pain mouse models (acetic acid twisting, formalin foot swelling, and xylene ear swelling) were used to study the analgesic effects of PC. The expression of latent signaling pathways in L4-6 spinal cord tissues in formalin foot swelling mice was evaluated using real-time qPCR (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) analyses. Results: Network pharmacology analysis shows that PC analgesic mechanism is related to the MAPK/ERK signaling pathway. The five main active components of PC have good docking ability with JNK and p38. PC alcohol extract significantly reduced the pain behavior and alleviated inflammatory reactions in three mouse models, inhibited the mRNA and protein phosphorylation levels of JNK, ERK, p38, and CREB in spinal cord tissues. Conclusion: PC alcohol extract can inhibit inflammation and alleviate pain, which is related to its inhibition of the MAPK/ERK signaling pathway in spinal cord. Thus, PC alcohol extract is a promising candidate for pain treatment.
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Fallopia japonica , Ratas , Ratones , Animales , Fallopia japonica/química , Ratas Sprague-Dawley , Simulación del Acoplamiento Molecular , Dolor/tratamiento farmacológico , Transducción de Señal , Analgésicos/farmacología , Analgésicos/uso terapéutico , Etanol , Inflamación/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Modelos Animales de Enfermedad , Formaldehído/farmacologíaRESUMEN
Although cigarette smoking (CS) and low back pain (LBP) are common worldwide, their correlations and the mechanisms of action remain unclear. We have shown that excessive activation of mast cells (MCs) and their proteases play key roles in CS-associated diseases, like asthma, chronic obstructive pulmonary disease (COPD), blood coagulation, and lung cancer. Previous studies have also shown that MCs and their proteases induce degenerative musculoskeletal disease. By using a custom-designed smoke-exposure mouse system, we demonstrated that CS results in intervertebral disc (IVD) degeneration and release of MC-restricted tetramer tryptases (TTs) in the IVDs. TTs were found to regulate the expression of methyltransferase 14 (METTL14) at the epigenetic level by inducing N6-methyladenosine (m6A) deposition in the 3' untranslated region (UTR) of the transcript that encodes dishevelled-axin (DIX) domain-containing 1 (DIXDC1). That reaction increases the mRNA stability and expression of Dixdc1. DIXDC1 functionally interacts with disrupted in schizophrenia 1 (DISC1) to accelerate the degeneration and senescence of nucleus pulposus (NP) cells by activating a canonical Wnt pathway. Our study demonstrates the association between CS, MC-derived TTs, and LBP. These findings raise the possibility that METTL14-medicated DIXDC1 m6A modification could serve as a potential therapeutic target to block the development of degeneration of the NP in LBP patients.
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Degeneración del Disco Intervertebral , Núcleo Pulposo , Ratones , Animales , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/metabolismo , Triptasas/metabolismo , Triptasas/uso terapéutico , Núcleo Pulposo/metabolismo , Vía de Señalización Wnt , Fumar , Péptidos y Proteínas de Señalización Intracelular/metabolismoRESUMEN
Background: Variations in the prevalence and pattern of multimorbidity might be attributable to lifestyle and environmental factors. This study was performed to determine the prevalence of common chronic diseases and to reveal multimorbidity patterns among adults in Guangdong province with Chaoshan, Hakka, and island cultures. Methods: We used data collected at the baseline survey (April-May 2021) of the Diverse Life-Course Cohort study and included 5,655 participants aged ≥20 years. Multimorbidity was defined as the presence of two or more of the 14 chronic diseases collected by self-reports, physical examinations, and blood tests. Multimorbidity patterns were explored by association rule mining (ARM). Results: Overall, 40.69% of participants had multimorbidity, and the prevalence among coastland (42.37%) and mountain residents (40.36%) was higher than that among island residents (37.97%). The prevalence of multimorbidity increased rapidly with higher age groups and showed an inflection point at 50 years, beyond which >50% of the middle-aged and older adults had multimorbidity. The proportion of people with two chronic diseases accounted for most cases of multimorbidity, and the strongest association was found between hyperuricemia and gout (lift of 3.26). The most prevalent multimorbidity pattern was dyslipidemia and hyperuricemia in the coastland areas and dyslipidemia combined with hypertension in the mountain and island areas. Furthermore, the most common triad combination consisted of cardiovascular diseases, gout, and hyperuricemia, which was verified in the mountain and coastal areas. Conclusion: These observations of multimorbidity patterns, including the most frequent multimorbidity and associations, will help healthcare providers develop healthcare plans that improve the effectiveness of multimorbidity management.
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Gota , Hiperuricemia , Persona de Mediana Edad , Humanos , Anciano , Multimorbilidad , Estudios de Cohortes , Prevalencia , Hiperuricemia/epidemiología , Enfermedad Crónica , China/epidemiologíaRESUMEN
Background: Studies comparing the effects of different sizes and concentrations of ambient particulate matter (PM) on pulmonary function in different regions and sexes remain sparse. Objectives: To investigate the associations of different sizes and levels of long-term ambient PM exposure with pulmonary function among people of different sexes in typical areas of South and North China. Methods: In 2021, a total of 1,592 participants aged 20-73 years were recruited to participate in the pulmonary function test from the baseline survey of the Diverse Life-Course Cohort (DLCC) in typical areas of Guangdong Province and Hebei Province. The three-year (2018-2020) average ambient PM concentrations were assessed from the ChinaHighPM1 dataset, ChinaHighPM2.5 dataset and ChinaHighPM10 dataset. Mean differences in pulmonary function were used in multilevel models for different regions and sexes. Results: We discovered significant associations of ambient PM exposure with reduced forced vital capacity (FVC) and increased forced expiratory volume in 1 s/forced vital capacity ratio (FEV1/FVC) among men and lower levels of FEV1 and FVC among women, such that a 5-µg/m3 concentration increase in PM1, PM2.5, and PM10 was associated with decreases in FVC of 122.1 ml (95% confidence interval (CI): 30.8, 213.4), 54.6 ml (95% CI: 15.8, 93.3) and 42.9 ml (95% CI: 12.7, 73.1) and increases in FEV1/FVC of 2.2% (95% CI: 0.6, 3.9), 1.1% (95% CI: 0.4, 1.9) and 0.9% (95% CI: 0.3, 1.5) among men and decreases in FEV1 of 51.1 ml (95% CI: 9.7, 92.4), 21.6 ml (95% CI: 4.3, 38.9) and 16.7 ml (95% CI: 3.3, 30.1) and in FVC of 77.8 ml (95% CI: 10.0, 145.6), 38.7 ml (95% CI: 9.0, 68.5) and 31.1 ml (95% CI: 8.1, 54.1) among women in Hebei Province. There was no association between ambient PM and pulmonary function in Guangdong Province. Conclusion: Long-term exposure to different sizes and concentrations of ambient PM were associated with FEV1 and FVC among men and women differently. The impact of ambient PM on FVC should be of greater concerned.
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Contaminantes Atmosféricos , Material Particulado , Masculino , Humanos , Femenino , Material Particulado/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/efectos adversos , Pulmón , China/epidemiologíaRESUMEN
The 5-year survival rate of non-small cell lung cancer (NSCLC) patients is very low. MicroRNAs (miRNAs) are involved in the occurrence of NSCLC. miR-122-5p interacts with wild-type p53 (wtp53), and wtp53 affects tumor growth by inhibiting the mevalonate (MVA) pathway. Therefore, this study aimed to evaluate the role of these factors in NSCLC. The role of miR-122-5p and p53 was established in samples from NSCLC patients, and human NSCLC cells A549 using the miR-122-5p inhibitor, miR-122-5p mimic, and si-p53. Our results showed that inhibiting miR-122-5p expression led to the activation of p53. This inhibited the progression of the MVA pathway in the NSCLC cells A549, hindered cell proliferation and migration, and promoted apoptosis. miR-122-5p was negatively correlated with p53 expression in p53 wild-type NSCLC patients. The expression of key genes in the MVA pathway in tumors of p53 wild-type NSCLC patients was not always higher than the corresponding normal tissues. The malignancy of NSCLC was positively correlated with the high expression of the key genes in the MVA pathway. Therefore, miR-122-5p regulated NSCLC by targeting p53, providing potential molecular targets for developing targeted drugs.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Ácido Mevalónico , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Línea Celular TumoralRESUMEN
Objectives: The aim of this study was to explore spousal similarities in cardiovascular risk factors in northern China. Methods: We conducted a cross-sectional study of married couples from Beijing, Hebei, Gansu, and Qinghai provinces between 2015 and 2019. A total of 2,020 couples were included in the final analyses. The spousal similarities for metabolic indicators and cardiovascular risk factors (including lifestyle factors and cardiometabolic diseases) were evaluated using Spearman's correlation and logistic regression analyses, respectively. Results: All metabolic indicators showed positive spousal correlations (p < 0.001), with the strongest for fasting blood glucose (r = 0.30) and the lowest for high-density lipoprotein cholesterol (r = 0.08). Significant husband-wife associations were observed for several cardiovascular risk factors except for hypertension in multivariable models, with the strongest association for physical inactivity (odds ratios with 95% confidence intervals of 3.59 [2.85, 4.52] and 3.54 [2.82, 4.46] for husbands and wives, respectively). In addition, the interaction of age with spousal overweight/obesity status was statistically significant, and the association was stronger in people ≥50 years. Conclusion: There were spousal similarities in cardiovascular risk factors. The finding may have public health implications that targeted screening and interventions for spouses of people with cardiovascular risk factors.
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Enfermedades Cardiovasculares , Humanos , Persona de Mediana Edad , Factores de Riesgo , Estudios Transversales , Enfermedades Cardiovasculares/epidemiología , Obesidad , Esposos , Factores de Riesgo de Enfermedad Cardiaca , China/epidemiologíaRESUMEN
Both O-linked ß-N-acetylglucosaminylation (O-GlcNAcylation) and endoplasmic reticulum-phagy (ER-phagy) are well-characterized conserved adaptive regulatory mechanisms that maintain cellular homeostasis and function in response to various stress conditions. Abnormalities in O-GlcNAcylation and ER-phagy have been documented in a wide variety of human pathologies. However, whether O-GlcNAcylation or ER-phagy is involved in the pathogenesis of intervertebral disc degeneration (IDD) is largely unknown. In this study, we investigated the function of O-GlcNAcylation and ER-phagy and the related underlying mechanisms in IDD. We found that the expression profiles of O-GlcNAcylation and O-GlcNAc transferase (OGT) were notably increased in degenerated NP tissues and nutrient-deprived nucleus pulposus (NP) cells. By modulating the O-GlcNAc level through genetic manipulation and specific pharmacological intervention, we revealed that increasing O-GlcNAcylation abundance substantially enhanced cell function and facilitated cell survival under nutrient deprivation (ND) conditions. Moreover, FAM134B-mediated ER-phagy activation was regulated by O-GlcNAcylation, and suppression of ER-phagy by FAM134B knockdown considerably counteracted the protective effects of amplified O-GlcNAcylation. Mechanistically, FAM134B was determined to be a potential target of OGT, and O-GlcNAcylation of FAM134B notably reduced FAM134B ubiquitination-mediated degradation. Correspondingly, the protection conferred by modulating O-GlcNAcylation homeostasis was verified in a rat IDD model. Our data demonstrated that OGT directly associates with and stabilizes FAM134B and subsequently enhances FAM134B-mediated ER-phagy to enhance the adaptive capability of cells in response to nutrient deficiency. These findings may provide a new option for O-GlcNAcylation-based therapeutics in IDD prevention.
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Degeneración del Disco Intervertebral , Animales , Autofagia , Retículo Endoplásmico/metabolismo , Humanos , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/metabolismo , N-Acetilglucosaminiltransferasas/genética , N-Acetilglucosaminiltransferasas/metabolismo , RatasRESUMEN
The Diverse Life-Course Cohort (DLCC) is a large-scale prospective study including around 130,000 participants in mainland China. The primary aims of DLCC include contributing to knowledge on noncommunicable chronic disease determinants, particularly cardiometabolic diseases, and exploring the long-term effect of ambient air pollutants or other environmental risk factors on health among all-age populations. The cohort consists of several sub-populations that cover the whole life-course and diverse resources: from premarital to adolescents, adults from workplace and communities ranged from 18 to 93 years old. Baseline assessment (2017-2021) included face-to-face standardized questionnaire interview and measurements to assess social and biological factors of health. Blood samples were collected from each participant (except for children younger than 6) to establish the biobank. DLCC consists of two visits. Visit 1 was conducted from 2017, and 114850 individuals from one of the world-class urban agglomerations: Beijing, Tianjin, and Hebei area were recruited. By the end of 2021, at least one follow-up was carried out, with an overall follow-up rate of 92.33%. In 2021, we initiated Visit 2, newly recruited 9,866 adults from Guangdong province (South China) and Hebei province (Central China), with research focuses on the comparations on ambient pollution hazards and other unique dietary or environmental risks for health. The baseline survey of Visit 2 was finished in July 2021. DLCC is still ongoing with a long-term follow-up design, and not limited by the current funding period. With reliable data and the well-established biobank which consists of over 120,000 individuals' blood samples, DLCC will provide invaluable resources for scientific research.
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Contaminantes Atmosféricos , Contaminación del Aire , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Niño , China/epidemiología , Estudios de Cohortes , Monitoreo del Ambiente/métodos , Humanos , Persona de Mediana Edad , Material Particulado , Estudios Prospectivos , Adulto JovenRESUMEN
The present study explored the differences in active ingredients and in vitro anti-inflammatory effects of the decoction pieces by integrated processing(IPDP) and traditional processing(TPDP) of Polygoni Cuspidati Rhizoma et Radix(PCRER).The content of polydatin, resveratrol, emodin-8-O-ß-D-glucoside, emodin, and physcion in IPDP and TPDP was determined by high-performance liquid chromatography(HPLC).The inflammation model was induced by lipopolysaccharide(LPS) in RAW264.7 cells.The mRNA levels of inflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) in 60% ethanol extracts of IPDP and TPDP of different concentrations(5 and 10 µg·mL~(-1)) were determined by PCR.The results showed that the content of polydatin and emodin-8-O-ß-D-glucoside in IPDP was significantly higher than that in TPDP, while the content of resveratrol, emodin, and physcion was higher in TPDP.The anti-inflammatory results showed that ethanol extracts of IPDP of different concentrations(5 and 10 µg·mL~(-1)) significantly inhibited the increase in the mRNA levels of IL-1ß and TNF-α induced by LPS, whereas TPDP only had a significant inhibitory effect on IL-1ß.This study preliminarily showed that the total content of five active ingredients in IPDP was higher than that in TPDP, and IPDP was superior to TPDP in anti-inflammatory activity in vitro, which provided an experimental basis for the production and application of IPDP.
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Medicamentos Herbarios Chinos , Emodina , Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Emodina/farmacología , Etanol , Lipopolisacáridos , ARN Mensajero/genética , Resveratrol/farmacología , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Osteoclasts and osteoblasts play a major role in bone tissue homeostasis. The homeostasis and integrity of bone tissue are maintained by ensuring a balance between osteoclastic and osteogenic activities. The remodeling of bone tissue is a continuous ongoing process. Osteoclasts mainly play a role in bone resorption, whereas osteoblasts are mainly involved in bone remodeling processes, such as bone cell formation, mineralization, and secretion. These cell types balance and restrict each other to maintain bone tissue metabolism. Bone tissue is very sensitive to mechanical stress stimulation. Unloading and loading of mechanical stress are closely related to the differentiation and formation of osteoclasts and bone resorption function as well as the differentiation and formation of osteoblasts and bone formation function. Consequently, mechanical stress exerts an important influence on the bone microenvironment and bone metabolism. This review focuses on the effects of different forms of mechanical stress stimulation (including gravity, continuously compressive pressure, tensile strain, and fluid shear stress) on osteoclast and osteoblast function and expression mechanism. This article highlights the involvement of osteoclasts and osteoblasts in activating different mechanical transduction pathways and reports changings in their differentiation, formation, and functional mechanism induced by the application of different types of mechanical stress to bone tissue. This review could provide new ideas for further microscopic studies of bone health, disease, and tissue damage reconstruction.
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Osteoporosis can be caused by a multitude of factors and is defined by a decrease in bone density and mass caused by the destruction of bone microstructure, resulting in increased bone brittleness. Thus, it is a systemic bone disease in which patients are prone to fracture. The role of ferroptosis in the pathogenesis of osteoporosis has become a topic of growing interest. In this review, we discuss the cell morphology, basic mechanisms of ferroptosis, the relationship between ferroptosis and osteoclasts and osteoblasts, as well as the relationship between ferroptosis and diabetic osteoporosis, steroid-induced osteoporosis, and postmenopausal osteoporosis. Emerging biomedical research has provided new insights into the roles of ferroptosis and osteoporosis, such as in cellular function, signaling pathways, drug inhibition, and gene silencing. The pathophysiology and mechanism of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and immune regulation. Studies using animal models of osteoporosis in vivo and cell models in vitro will help clarify the relationship between ferroptosis and osteoporosis and provide research ideas for the elucidation of new mechanisms and development of new technologies and new drugs for the treatment of osteoporosis in the future.
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Ferroptosis/genética , Osteoporosis/genética , Animales , Femenino , HumanosRESUMEN
Although degeneration of the nucleus pulposus (NP) is a major contributor to intervertebral disc degeneration (IVDD) and low back pain, the underlying molecular complexity and cellular heterogeneity remain poorly understood. Here, a comprehensive single-cell resolution transcript landscape of human NP is reported. Six novel human NP cells (NPCs) populations are identified by their distinct molecular signatures. The potential functional differences among NPC subpopulations are analyzed. Predictive transcripts, transcriptional factors, and signal pathways with respect to degeneration grades are explored. It is reported that fibroNPCs is the subpopulation for end-stage degeneration. CD90+NPCs are observed to be progenitor cells in degenerative NP tissues. NP-infiltrating immune cells comprise a previously unrecognized diversity of cell types, including granulocytic myeloid-derived suppressor cells (G-MDSCs). Integrin αM (CD11b) and oxidized low density lipoprotein receptor 1 (OLR1) as surface markers of NP-derived G-MDSCs are uncovered. The G-MDSCs are found to be enriched in mildly degenerated (grade II and III) NP tissues compared to severely degenerated (grade IV and V) NP tissues. Their immunosuppressive function and alleviation effects on NPCs' matrix degradation are revealed in vitro. Collectively, this study reveals the NPC-type complexity and phenotypic characteristics in NP, thereby providing new insights and clues for IVDD treatment.
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Perfilación de la Expresión Génica/métodos , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/fisiopatología , Núcleo Pulposo/metabolismo , Células Madre/metabolismo , Femenino , Humanos , Disco Intervertebral/metabolismo , Masculino , Persona de Mediana Edad , Transducción de SeñalRESUMEN
Intervertebral disk (IVD) degeneration (IVDD) can cause various spinal degenerative diseases. Cumulative evidence has indicated that IVDD can result from inflammation, apoptosis, autophagy, biomechanical changes and other factors. Currently, lack of conservative treatment for degenerative spinal diseases leads to an urgent demand for clinically applicable medication to ameliorate the progression of IVDD. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol compound extracted from red wine or grapes, has shown protective effects on IVD, alleviating the progression of IVDD. Resveratrol has been demonstrated as a scavenger of free radicals both in vivo and in vitro. The antioxidant effects of resveratrol are likely attributed to its regulation on mitochondrial dysfunction or the elimination of reactive oxygen species. This review will summarize the mechanisms of the reactive oxygen species production and elaborate the mechanisms of resveratrol in retarding IVDD progression, providing a comprehensive understanding of the antioxidant effects of resveratrol in IVD.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Antioxidantes/uso terapéutico , Humanos , Degeneración del Disco Intervertebral/tratamiento farmacológico , Especies Reactivas de Oxígeno , Resveratrol/uso terapéuticoRESUMEN
Scutellariae Radix is a commonly used Chinese medicinal first recorded in the Shennong's Classic of Materia Medica. In the ancient books of traditional Chinese medicine(TCM), Scutellariae Radix is used in two specifications, solid one(Ziqin) and hollow one(Kuqin). In the current rules and regulations of Chinese medicine, Scutellariae Radix is used without the specific requirements for the specifications applied. To clarify the evolution of Scutellariae Radix specifications and analyze the current specifications of Scutellariae Radix pieces, the present study reviews the Scutellariae Radix from ancient literature, modern rules and regulations, and differences between Ziqin and Kuqin in composition, efficacy, and transformation mechanism. According to the research on ancient books, Kuqin is effective in clearing the fire of the upper energizer, and Ziqin in purging the heat of the lower energizer. Modern studies have revealed that Kuqin and Ziqin are significantly different in chemical components, and Ziqin and Kuqin target the colon and lung, respectively, which are consistent with the relevant records in ancient books. The review study suggests that the two specifications of Scutellariae Radix are reasonable since they can facilitate the precise treatment of Scutellariae Radix.
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Medicamentos Herbarios Chinos , Literatura Moderna , Materia Medica , Medicina Tradicional China , Scutellaria baicalensisRESUMEN
Compared with free miRNAs in blood, miRNAs in exosomes have higher abundance and stability. Therefore, miRNAs in exosomes can be regarded as an ideal tumor marker for early cancer diagnosis. Here, a peptide nucleic acid (PNA)-functionalized nanochannel biosensor for the ultrasensitive and specific detection of tumor exosomal miRNAs is proposed. After PNA was covalently bound to the inner surface of the nanochannels, the detection of tumor exosomal miRNAs was achieved by the charge changes on the surface of nanochannels before and after hybridization (PNA-miRNA). Due to the neutral characteristics of PNA, the efficiency of PNA-miRNA hybridization was improved by significantly reducing the background signal. This biosensor could not only specifically distinguish target miRNA-10b from single-base mismatched miRNA but also achieve a detection limit as low as 75 aM. Moreover, the biosensor was further used to detect exosomal miRNA-10b derived from pancreatic cancer cells and normal pancreatic cells. The results indicate that this biosensor could effectively distinguish pancreatic cancer tumor-derived exosomes from the normal control group, and the detection results show good consistency with those of the quantitative reverse-transcription polymerase chain reaction method. In addition, the biosensor was used to detect exosomal miRNA-10b in clinical plasma samples, and it was found that the content of exosomal miRNA-10b in cancer patients was generally higher than that of healthy individuals, proving that the method is expected to be applied for the early diagnosis of cancer.