Synaptic dysfunction and abnormal processing of amyloid precursor protein (APP) are early pathological features in Alzheimer’s disease (AD). Recently, non-coding RNAs such as microRNAs (miRNAs) and ...circular RNAs (circRNAs) have been reported to contribute to the pathogenesis of AD. We found an age-dependent elevation of miR-138 in APP/PS1 (presenilin-1) mice. MiR-138 inhibited the expression of ADAM10 a disintegrin and metalloproteinase domain-containing protein 10, promoted amyloid beta (Aβ) production, and induced synaptic and learning/memory deficits in APP/PS1 mice, while its suppression alleviated the AD-like phenotype in these mice. Overexpression of sirtuin 1 (Sirt1), a target of miR-138, ameliorated the miR-138-induced inhibition of ADAM10 and elevation of Aβ
in vitro
. The circRNA HDAC9 (circHDAC9) was predicted to contain a miR-138 binding site in several databases. Its expression was inversely correlated with miR-138 in both Aβ-oligomer-treated N2a cells and APP/PS1 mice, and it co-localized with miR-138 in the cytoplasm of N2a cells. CircHDAC9 acted as a miR-138 sponge, decreasing miR-138 expression, and reversing the Sirt1 suppression and excessive Aβ production induced by miR-138
in vitro
. Moreover, circHDAC9 was decreased in the serum of both AD patients and individuals with mild cognitive impairment. These results suggest that the circHDAC9/miR-138/Sirt1 pathway mediates synaptic function and APP processing in AD, providing a potential therapeutic target for its treatment.
"A sheep, a sheep", is a recently popular mini game related to consumer goods. In terms of entertainment and classic gameplay, it cannot compare with many excellent works of the same type.With ...incomplete gameplay and superb operational methods, it has been lifted to a height that does not belong to it by netizens. This article attempts to discuss its viral marketing process and logic, as well as the industry causes and harms that cause this phenomenon, in order to decipher the key to the popularity of this phenomenal mini game.
The correct identification of pills is very important to ensure the safe administration of drugs to patients. Here, we use three current mainstream object detection models, namely RetinaNet, Single ...Shot Multi-Box Detector (SSD), and You Only Look Once v3(YOLO v3), to identify pills and compare the associated performance.
In this paper, we introduce the basic principles of three object detection models. We trained each algorithm on a pill image dataset and analyzed the performance of the three models to determine the best pill recognition model. The models were then used to detect difficult samples and we compared the results.
The mean average precision (MAP) of RetinaNet reached 82.89%, but the frames per second (FPS) is only one third of YOLO v3, which makes it difficult to achieve real-time performance. SSD does not perform as well on the indicators of MAP and FPS. Although the MAP of YOLO v3 is slightly lower than the others (80.69%), it has a significant advantage in terms of detection speed. YOLO v3 also performed better when tasked with hard sample detection, and therefore the model is more suitable for deployment in hospital equipment.
Our study reveals that object detection can be applied for real-time pill identification in a hospital pharmacy, and YOLO v3 exhibits an advantage in detection speed while maintaining a satisfactory MAP.
Myricetin: A review of the most recent research Song, Xiaominting; Tan, Lu; Wang, Miao ...
Biomedicine & pharmacotherapy,
February 2021, 2021-Feb, 2021-02-00, 20210201, 2021-02-01, Letnik:
134
Journal Article
Recenzirano
Odprti dostop
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•MYR has extensive antitumor effects and its mechanisms are distinct.•Other biological activities have been reported, as anti-inflammatory, cardio-cerebrovascular protection, etc.•The ...potential effects of MYR targeting SARS-CoV-2 M Pro or human ACE2, and future research prospects.
Myricetin(MYR) is a flavonoid compound widely found in many natural plants including bayberry. So far, MYR has been proven to have multiple biological functions and it is a natural compound with promising research and development prospects. This review comprehensively retrieved and collected the latest pharmacological abstracts on MYR, and discussed the potential molecular mechanisms of its effects. The results of our review indicated that MYR has a therapeutic effect on many diseases, including tumors of different types, inflammatory diseases, atherosclerosis, thrombosis, cerebral ischemia, diabetes, Alzheimer's disease and pathogenic microbial infections. Furthermore, it regulates the expression of Hippo, MAPK, GSK-3β, PI3K/AKT/mTOR, STAT3, TLR, IκB/NF-κB, Nrf2/HO-1, ACE, eNOS / NO, AChE and BrdU/NeuN. MYR also enhances the immunomodulatory functions, suppresses cytokine storms, improves cardiac dysfunction, possesses an antiviral potential, can be used as an adjuvant treatment against cancer, cardiovascular injury and nervous system diseases, and it may be a potential drug against COVID-19 and other viral infections. Generally, this article provides a theoretical basis for the clinical application of MYR and a reference for its further use.
Hypobaric hypoxia in regions of high altitude may increase the risk of having sleep-disordered breathing (SDB). SDB at high altitude mainly refers to the SDB incurred in highlanders and lowlanders at ...a high altitude. At present, research on SDB at high altitude is mainly focused on these two groups of people. On the one hand, highlanders have SDB at a higher prevalence and greater severity than lowlanders do and highlanders have a prolonged duration of apnea when they travel to low-altitude regions. On the other hand, the severity of SDB increased in lowlanders when they travel to high altitude, represented mainly by an increase in central and hypopnea events. In terms of treatment, a substantial number of studies have shown that medication, including acetazolamide and dexamethasone, and nocturnal oxygen supplementation could improve SDB in lowlanders when they travel to high altitude. However, not much research has been done on the treatment of SDB in highlanders and it has only been reported that nocturnal
Oxidative stress is emerging as a crucial contributor to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD), but the molecular mechanisms underlying the disturbed redox ...homeostasis in cystic cells remain elusive. Here, we identified the impaired activity of the NRF2 (nuclear factor erythroid 2-related factor 2) antioxidant pathway as a driver of oxidative damage and ADPKD progression. Using a quantitative proteomic approach, together with biochemical analyses, we found that increased degradation of NRF2 protein suppressed the NRF2 antioxidant pathway in ADPKD mouse kidneys. In a cohort of patients with ADPKD, reactive oxygen species (ROS) frequently accumulated, and their production correlated negatively with NRF2 abundance and positively with disease severity. In an orthologous ADPKD mouse model, genetic deletion of
further increased ROS generation and promoted cyst growth, whereas pharmacological induction of NRF2 reduced ROS production and slowed cystogenesis and disease progression. Mechanistically, pharmacological induction of NRF2 remodeled enhancer landscapes and activated NRF2-bound enhancer-associated genes in ADPKD cells. The activation domain of NRF2 formed phase-separated condensates with MEDIATOR complex subunit MED16 in vitro, and optimal Mediator recruitment to genomic loci depended on NRF2 in vivo. Together, these findings indicate that NRF2 remodels enhancer landscapes and activates its target genes through a phase separation mechanism and that activation of NRF2 represents a promising strategy for restoring redox homeostasis and combatting ADPKD.
There is strong evidence that obesity is a risk factor for poor semen quality. However, the effects of multigenerational paternal obesity on the susceptibility to cadmium (a reproductive ...toxicant)-induced spermatogenesis disorders in offspring remain unknown. Here, we show that, in mice, spermatogenesis and retinoic acid levels become progressively lower as the number of generations exposed to a high-fat diet increase. Furthermore, exposing several generations of mice to a high fat diet results in a decrease in the expression of Wt1, a transcription factor upstream of the enzymes that synthesize retinoic acid. These effects can be rescued by injecting adeno-associated virus 9-Wt1 into the mouse testes of the offspring. Additionally, multigenerational paternal high-fat diet progressively increases METTL3 and Wt1 N6-methyladenosine levels in the testes of offspring mice. Mechanistically, treating the fathers with STM2457, a METTL3 inhibitor, restores obesity-reduced sperm count, and decreases Wt1 N6-methyladenosine level in the mouse testes of the offspring. A case-controlled study shows that human donors who are overweight or obese exhibit elevated N6-methyladenosine levels in sperm and decreased sperm concentration. Collectively, these results indicate that multigenerational paternal obesity enhances the susceptibility of the offspring to spermatogenesis disorders by increasing METTL3-mediated Wt1 N6-methyladenosine modification.
Ferroptosis is an iron‐dependent programmed cell death, which participates in the pathogenesis of spinal cord injury (SCI). Our previous study has revealed that Lipoxin A4 (LXA4) exerts a protective ...role in SCI. Here, we investigated whether LXA4 can protect SCI through inhibiting neuronal ferroptosis. We treated primary spinal cord neurons with Erastin (ferroptosis activator) to induce ferroptosis. Erastin treatment reduced cell viability and enhanced cell death of primary spinal cord neurons, which was rescued by ferrostatin‐1 (ferroptosis inhibitor). Moreover, Erastin repressed glutathione peroxidase 4 (GPX4) expression and the levels of glutathione and cysteine in primary spinal cord neurons. Erastin also enhanced the expression of ferroptosis biomarkers (PTGS2 and ACSL4) and the levels of reactive oxygen species (ROS) in primary spinal cord neurons. The influence conferred by Erastin was effectively abolished by LXA4 treatment. Furthermore, LXA4 enhanced the protein expression of p‐AKT, nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and haem‐oxygenase‐1 (HO‐1) in primary spinal cord neurons. LXA4‐mediated inhibition of ferroptosis of primary spinal cord neurons was prohibited by LY294002 (AKT inhibitor), brusatol (Nrf2 inhibitor) or zinc protoporphyrin (HO‐1 inhibitor). In conclusion, this work demonstrated that LXA4 exerted a neuroprotective effect in Erastin‐induced ferroptosis of primary spinal cord neurons by activating the Akt/Nrf2/HO‐1 signaling pathway. Thus, this work provides novel insights into the mechanisms of action of LXA4 in ferroptosis of primary spinal cord neurons and indicates that LXA4 may be a potential therapeutic agent for SCI.
Ferroptosis is closely associated with the pathogenesis of spinal cord injury. Erastin induced ferroptosis of primary spinal cord neurons, which was effectively abolished by Lipoxin A4 (LXA4) treatment. LXA4 exerted a neuroprotective effect in Erastin‐induced ferroptosis of primary spinal cord neurons by activating the Akt/nuclear factor (erythroid‐derived 2)‐like 2/haem‐oxygenase‐1 signaling pathway. Thus, LXA4 may be a potential therapeutic agent for spinal cord injury.
The increasing global prevalence of antibiotic resistance genes (ARGs) in the environment is attributed to anthropogenic activities, particularly the misuse of antimicrobial drugs in human care and ...animal production. In the present study, we first examined Arctic/sub-Arctic (polar) sediments for the abundance and diversity of 30 ARGs against sulfonamide, tetracycline, aminoglycoside, quinolone, macrolide, and β-lactam antibiotics. Polar sediment ARGs were detected by qPCR at relatively low levels (10−9 to 10−5 copies/16S rRNA gene copies) compared to the reference sites, which were heavily impacted regions of China (the Haihe River, the Tianjin Water Park water and the Qilihai Wetland water, at 10−8 to 10−2 copies/16S rRNA gene copies). A human mitochondrial gene target, Hmt, was first used to aid in the identification of ARGs associated with anthropogenic activities, being relatively persistent, in high copy number and a human-specific molecular marker. Hmt was consistently present in easily quantifiable amounts in the polar sediment samples, indicating their relationship with human-impact, and it was also positively correlated with the relative abundance of ARGs and to the concentrations of modern-day antibiotics. Phylogenetic analyses of resistance sequences from both the Arctic marine sediments and a major database of human pathogens indicated that the ARGs in polar region were the result of a mix of human influence and natural origins. To our knowledge, this is the first study to show that ARGs in Arctic marine sediments appear to be a mixture of both natural origins and recent human influence. This study provides a significant reference regarding the global reach of antibiotic resistance, which is associated with anthropogenic activities.
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•Polar sediment ARGs were detected by qPCR at relatively low levels.•ARGs in polar sediments were from human source and natural origin.•Hmt was positively correlated to both ARGs and modern-day antibiotics.•Hmt gene is a promising molecular marker to indicate anthropogenic activities.
Cadmium (Cd), is a well-known reproductive toxicant. The impacts of paternal Cd exposure on offspring glucose and lipid metabolism remain unclear, despite the abundance of adverse reports following ...early exposure from the mother. Here, we assessed paternally acquired metabolic derailment using a mouse model. LC-MS/MS, transcriptomics and molecular experimental techniques were subsequently applied in this study to explore the potential mechanism. We found that paternal Cd exposure caused glucose intolerance, lower insulin sensitivity and abnormal hepatic glycogen storage in adult female offspring, but not in males. LC-MS/MS data showed that hepatic phospholipids accumulation was also only observed in adult female offspring after paternal Cd exposure. Gene expression data showed that the level of insulin signaling and lipid transport-related genes was decreased in Cd-treated adult female offspring livers. Meanwhile, AHR, a transcription factor that combines with phospholipids to promote insulin resistance, was increased in Cd-treated adult female offspring livers. In addition, the escalation of the afore-mentioned lipid metabolites in the liver occurred as early as fetal stages in the female pups following paternal Cd exposure, suggesting the potential for these lipid species to be selected as early markers of disease for metabolic derailment later in life. Altogether, paternal Cd exposure causes offspring glucose metabolism disorder and phospholipids accumulation in a sex-dependent manner. This study provides a theoretical framework for future understanding of paternal-originated metabolic diseases.
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•Paternal Cd impairs glucose metabolism in adult female offspring.•Paternal Cd enhances hepatic phospholipids in adult female offspring.•Paternal Cd reduces phospholipid transport-related mRNAs in offspring livers.•Paternal Cd persistently elevated six phospholipids in fetal and adult female livers.
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