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BACKGROUND: Previous observational studies have indicated associations of physical activity (PA) and air pollution with mortality. A few studies have evaluated air pollution and PA interactions for health. Still, the trade-off between the harmful effects of air pollution exposure and the protective effects of PA remains controversial and unclear. OBJECTIVE: This study aimed to investigate the joint association of air pollution and PA with mortality risks. METHODS: This prospective cohort study included 322,092 participants from 2006 to 2010 and followed up to 2021 in the UK Biobank study. The concentrations of air pollutants (2006-2010), including particulate matter (PM) with diameters <=2.5â¯mm (PM2.5), <=10â¯mm (PM10), and between 2.5 and 10â¯mm (PM2.5-10), and nitrogen oxides (NO2 and NOx) were obtained. Information on PA measured by the International Physical Activity Questionnaire short form (2006-2010) and wrist-worn accelerometer (2013-2015) were collected. All-cause and cause-specific mortalities were recorded. Cox proportional hazard models were used to investigate the associations of air pollution exposure and PA with mortality risks. The additive and multiplicative interactions were also examined. RESULTS: During a mean follow-up of 11.83 years, 16629 deaths were recorded. Compared with participants reporting low PA, higher PA was negatively associated with all-cause [hazard ratio (HR), 0.74; 95% CI, 0.71-0.78], cancer (HR, 0.85; 95% CI, 0.80-0.90), CVD (HR, 0.79; 95% CI, 0.71-0.87), and respiratory disease-specific mortality (HR, 0.51; 95% CI, 0.44-0.60). Exposure to PM2.5 (HR, 1.05; 95% CI, 1.00-1.09) and NOx (HR, 1.06; 95% CI, 1.02-1.10) was connected with increased all-cause mortality risk, and significant PM2.5-associated elevated risks for CVD mortality and NOx-associated elevated risks for respiratory disease mortality were observed. No obvious interaction between PA and PM2.5 or NOx exposure was detected. CONCLUSIONS: Our study provides additional evidence that higher PA and lower air pollutant levels are independently connected with reduced mortality risk. The benefits of PA are not significantly affected by long-term air pollution exposure, indicating PA can be recommended to prevent mortality regardless of air pollution levels. Our findings highlight the importance of public health policies and interventions facilitating PA and reducing air pollution in reducing mortality risks and maximizing health benefits. Future investigation is urgently needed to identify these findings in areas with severe air pollution conditions.
Subject(s)
Air Pollutants , Air Pollution , Exercise , Particulate Matter , Humans , Prospective Studies , Air Pollution/adverse effects , Air Pollution/statistics & numerical data , Male , Middle Aged , United Kingdom , Female , Air Pollutants/analysis , Air Pollutants/adverse effects , Particulate Matter/analysis , Particulate Matter/adverse effects , Aged , Biological Specimen Banks , Mortality/trends , Risk Assessment , Environmental Exposure/statistics & numerical data , Environmental Exposure/adverse effects , Adult , Cardiovascular Diseases/mortality , Proportional Hazards Models , UK BiobankABSTRACT
Background: Changes to work-life balance has increased the incidence of cervical cancer among younger people. A minor ginseng saponin known as ginsenoside Rk1 can inhibit the growth and survival of human cancer cells; however, whether ginsenoside Rk1 inhibits HeLa cell proliferation is unknown. Methods and results: Ginsenoside Rk1 blocked HeLa cells in the G0/G1 phase in a dose-dependent manner and inhibited cell division and proliferation. Ginsenoside Rk1 markedly also activated the apoptotic signaling pathway via caspase 3, PARP, and caspase 6. In addition, ginsenoside Rk1 increased LC3B protein expression, indicating the promotion of the autophagy signaling pathway. Protein processing in the endoplasmic reticulum signaling pathway was downregulated in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, consistent with teal-time quantitative PCR and western blotting that showed YOD1, HSPA4L, DNAJC3, and HSP90AA1 expression levels were dramatically decreased in HeLa cells treated with ginsenoside Rk1, with YOD1 was the most significantly inhibited by ginsenoside Rk1 treatment. Conclusion: These findings indicate that the toxicity of ginsenoside Rk1 in HeLa cells can be explained by the inhibition of protein synthesis in the endoplasmic reticulum and enhanced apoptosis, with YOD1 acting as a potential target for cervical cancer treatment.
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N6-methyladenosine (m6A) is considered as the most common and important internal transcript modification in several diseases like type 2 diabetes, schizophrenia and especially cancer. As a main target of m6A methylation, long non-coding RNAs (lncRNAs) have been proved to regulate cellular processes at various levels, including epigenetic modification, transcriptional, post-transcriptional, translational and post-translational regulation. Recently, accumulating evidence suggests that m6A-modified lncRNAs greatly participate in the tumorigenesis of cancers. In this review, we systematically summarized the biogenesis of m6A-modified lncRNAs and the identified m6A-lncRNAs in a variety of cancers, as well as their potential diagnostic and therapeutic applications as biomarkers and therapeutic targets, hoping to shed light on the novel strategies for cancer treatment.
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MiRNAs are a group of non-coding RNA molecules that function in mRNA translational inhibition via base-pairing with complementary sequences in target mRNA. In oncology, miRNAs have raised great attention due to their aberrant expression and pivotal roles in the pathogenesis of multiple malignancies including osteosarcoma. MiRNAs can be transported by exosome, the nano-extracellular vesicle with a diameter of 30-150 nm. Recently, a growing number of studies have demonstrated that exosomal miRNAs play a critical role in tumor initiation and progression, by exerting multiple biological functions including metastasis, angiogenesis, drug resistance and immunosuppression. In this review, we aim to depict the biogenesis of exosomal miRNAs and summarize the potential diagnostic and therapeutic functions of exosomal miRNAs in osteosarcoma.
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With the development of technology, drugs are being developed for different purposes. Thus, the rate of drug injury considerably increased worldwide. Liver is the largest detoxification organ in the human body, but it is also the organ most vulnerable to drug damage. Ginsenoside Rg1 has been reported to have an extensive protective effect on liver injury. However, no evident results showed whether ginsenoside Rh1 could improve the injury caused by drugs. Therefore, this paper aimed to explore the protective effect in a mouse model with liver injury. Mice administered with acetaminophen (APAP) were used as the negative group, while those administered with Rg1 (10, 20, and 30 mg/kg) and Rh1 (10, 20, and 30 mg/kg) were used as the prevention groups. Results indicated that the treatments increased the levels of GSH and SOD remarkably and decreased that of MDA. In addition, the expression levels of GOT and GPT was remarkably reduced compared with the negative group. Inflammatory agents TNF-α, IL-6, and IL-1ß were also decreased by the treatments. Meanwhile, Rg1 and Rh1 not only prevented the expression of Bax but also promoted Bcl-2 levels in mice. All results suggested that ginsenoside Rg1 and ginsenoside Rh1 exerted a preventive effect on APAP-induced liver injury in mice. PRACTICAL APPLICATIONS: With the increasing number of patients suffering from drug-induced liver injury, it is urgent to find alternative natural plant drugs to treat liver injury. This paper focuses on the protective effects of Ginsenoside Rg1 and ginsenoside Rh1 on acetaminophen (APAP) induced liver injury. From the previous studies, we found that there is no sufficient evidence to show that ginsenoside Rh1 has protective effect on liver injury. In this paper, the detection of oxidative stress indicators, liver histopathological analysis and immunoprotein analysis show that both ginsenoside Rg1 and ginsenoside Rh1 have preventive effect on liver injury caused by APAP, which provides a reference for the follow-up experimental research.
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Nano-hydroxyapatite (nano-HA) has attracted substantial attention in the field of regenerative medicine. Endothelial cell (EC)-mesenchymal stem cell (MSC) interactions are necessary for bone reconstruction, but the manner in which nano-HA interacts in this process remains unknown. Herein, we investigated the cytotoxicity and osteoinductive effects of HA nanoparticles (HANPs) on MSCs using an indirect co-culture model mediated by ECs and highlighted the underlying mechanisms. It was found that at a subcytotoxic dose, HANPs increased the viability and expression of osteoblast genes, as well as mineralized nodules and alkaline phosphatase production of MSCs. These phenomena relied on HIF-1α secreted by ECs, which triggered the ERK1/2 signaling cascade. In addition, a two-stage cell-lineage mathematical model was established to quantitatively analyze the impact of HIF-1α on the osteogenic differentiation of MSCs. It demonstrated that HIF-1α exerted a dose-dependent stimulatory effect on the osteogenic differentiation rate of MSCs up to 1500 pg/mL, which was in agreement with the above results. Our data implied that cooperative interactions between HANPs, ECs, and MSCs likely serve to stimulate bone regeneration. Furthermore, the two-stage cell-lineage model is helpful in vitro system for assessing the potential influence of effector molecules in bone tissue engineering.
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BACKGROUND: Residual ridge resorption impairs patients' satisfaction with complete denture (CD) treatment, but influence of bone resorption on the aesthetic rehabilitation of edentulous patients still remains unclear due to insufficient quantitative investigations. OBJECTIVES: To quantitatively evaluate the effects of residual ridge resorption on facial aesthetic reconstruction in elderly edentulous patients. METHODS: According to radiological examination, a total of 19 edentulous subjects were categorised into two groups, atrophic patients (APs) and non-atrophic patients (NAPs). Before CD treatment and 3 months after treatment, patients were asked to complete the Orofacial Esthetic Scale (OES). The changes in facial appearance were measured by 3D stereophotogrammetry, and the facial parameters of two groups were compared. RESULTS: The patient's subjective satisfaction of oro-facial aesthetics and 3D objective assessment of facial appearance improved after CD treatment. Subnasale-gnathion (Sn-Gn) significantly increased from 60.13 ± 3.91 mm to 62.27 ± 3.82 mm. After rehabilitation, glabella-subnasale (G-Sn)/Sn-Gn, nasolabial (Cm-Sn-Ls) and mentolabial (Li-Sm-Pg) significantly decreased and were closer to normal values. Moreover, the subtraction value between G-Sn/Sn-Gn and normal value before treatment of APs and NAPs was 14.47 ± 8.04% and 6.94 ± 3.69%, respectively (P = .026), while after treatment, the values decreased to 10.61 ± 6.33% and 3.86 ± 2.31% (P = .013), respectively. CONCLUSION: The increased volume of lips and cheeks played an important role in the facial aesthetic reconstruction of edentulous patients. NAPs tended to have more attractive faces after CD treatment, as their facial profile parameters (G-Sn/Sn-Gn and Cm-Sn-Ls) were closer to normal Chinese with well-balanced faces.
Subject(s)
Mouth, Edentulous , Tooth , Aged , Denture, Complete , Esthetics, Dental , Humans , PhotogrammetryABSTRACT
Diabetic bone defects may exhibit impaired endochondral ossification (ECO) leading to delayed bone repair. AdipoRon, a receptor agonist of adiponectin polymers, can ameliorate diabetes and related complications, as well as overcome the disadvantages of the unstable structure of artificial adiponectin polymers. Here, the effects of AdipoRon on the survival and differentiation of chondrocytes in a diabetic environment were explored focusing on related mechanisms in gene and protein levels. In vivo, AdipoRon was applied to diet-induced-obesity (DIO) mice, a model of obesity and type 2 diabetes, with femoral fracture. Sequential histological evaluations and micro-CT were examined for further verification. We found that AdipoRon could ameliorate cell viability, apoptosis, and reactive oxygen species (ROS) production and promote mRNA expression of chondrogenic markers and cartilaginous matrix production of ATDC5 cells in high glucose medium via activating ERK1/2 pathway. Additionally, DIO mice with intragastric AdipoRon administration had more neocartilage and accelerated new bone formation. These data suggest that AdipoRon could stimulate bone regeneration via ECO in diabetes.
Subject(s)
Bone Regeneration/drug effects , Bone and Bones/drug effects , Cell Differentiation/drug effects , Chondrocytes/drug effects , Fracture Healing/drug effects , Fractures, Bone/drug therapy , Piperidines/pharmacology , Animals , Apoptosis/drug effects , Cartilage/drug effects , Cell Line , Chondrogenesis/drug effects , Diabetes Mellitus, Type 2/complications , Fractures, Bone/etiology , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Osteogenesis/drug effectsABSTRACT
The development of testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) has made it possible for patients with non-obstructive azoospermia to have their own children. However, sperm retrieval by conventional TESE succeeds but in a subset of patients and, therefore, how to improve the success rate of sperm retrieval is becoming a focus of research. Recent studies suggest that microdissection TESE, although with its limitations, has obvious advantages over traditional sperm retrieval methods. This article presents an overview on the characteristics, predictive factors, sperm retrieval rate, post-operative complications, and improvement of microdissection TESE.