Vital osteocytes have been well known to function as an important orchestrator in the preservation of robustness and fidelity of the bone remodeling process. Nevertheless, some key pathological ...factors, such as sex steroid deficiency and excess glucocorticoids, and so on, are implicated in inducing a bulk of apoptotic osteocytes, subsequently resulting in resorption-related bone loss. As much, osteocyte apoptosis, under homeostatic conditions, is in an optimal state of balance tightly controlled by pro- and anti-apoptotic mechanism pathways. Importantly, there exist many essential signaling proteins in the process of osteocyte apoptosis, which has a crucial role in maintaining a homeostatic environment. While increasing in vitro and in vivo studies have established, in part, key signaling pathways and cross-talk mechanism on osteocyte apoptosis, intrinsic and complex mechanism underlying osteocyte apoptosis occurs in various states of pathologies remains ill-defined. In this review, we discuss not only essential pro- and anti-apoptotic signaling pathways and key biomarkers involved in these key mechanisms under different pathological agents, but also the pivotal role of apoptotic osteocytes in osteoclastogenesis-triggered bone loss, hopefully shedding new light on the attractive and proper actions of pharmacotherapeutics of targeting apoptosis and ensuing resorption-related bone diseases such as osteoporosis and fragility fractures.
Elevated temperature as a result of global climate warming, either in form of sudden heatwave (heat shock) or prolonged warming, has profound effects on the growth and development of plants. However, ...how plants differentially respond to these two forms of elevated temperatures is largely unknown. Here we have therefore performed a comprehensive comparison of multi-level responses of Arabidopsis leaves to heat shock and prolonged warming.
The plant responded to prolonged warming through decreased stomatal conductance, and to heat shock by increased transpiration. In carbon metabolism, the glycolysis pathway was enhanced while the tricarboxylic acid (TCA) cycle was inhibited under prolonged warming, and heat shock significantly limited the conversion of pyruvate into acetyl coenzyme A. The cellular concentration of hydrogen peroxide (H
O
) and the activities of antioxidant enzymes were increased under both conditions but exhibited a higher induction under heat shock. Interestingly, the transcription factors, class A1 heat shock factors (HSFA1s) and dehydration responsive element-binding proteins (DREBs), were up-regulated under heat shock, whereas with prolonged warming, other abiotic stress response pathways, especially basic leucine zipper factors (bZIPs) were up-regulated instead.
Our findings reveal that Arabidopsis exhibits different response patterns under heat shock versus prolonged warming, and plants employ distinctly different response strategies to combat these two types of thermal stress.
Abstract
Background
The innovative combination of all‐trans retinoic acid (ATRA) and arsenic trioxide (ATO) has established a new chapter of curative approach in acute promyelocytic leukemia (APL). ...The disease characteristics and prognostic influence of additional cytogenetic abnormalities (ACA) in APL with modern therapeutic strategy need to be elucidated.
Methods
In the present study, we retrospectively investigated disease features and prognostic power of ACA in 171 APL patients treated with ATRA‐ATO‐containing regimens.
Results
Patients with ACA had markedly decreased hemoglobin levels than that without ACA (
p
= 0.021). Risk stratification in the ACA group was significantly worse than that in the non‐ACA group (
p
= 0.032). With a median follow‐up period of 62.0 months, worse event‐free survival (EFS) was demonstrated in patients harboring ACA. Multivariate analysis showed that ACA was an independent adverse factor for EFS (
p
= 0.033). By further subgroup analysis, in CD34 and CD56 negative APL, patients harboring ACA had inferior EFS (
p
= 0.017;
p
= 0.037).
Conclusions
To sum up, ACA remains the independent prognostic value for EFS, we should build risk‐adapted therapeutic strategies in the long‐term management of APL when such abnormalities are detected.
Familial hyperkalemic hypertension (FHHt; also called pseudohypoaldosteronism type II) is a hereditary hypertensive disease which can be caused by mutations in four genes:
WNK1
with no lysine (K) 1,
...WNK4
,
Kelch-like3
(KLHL3), and
cullin3
(CUL3). Decreased KLHL3 expression was identified as being involved in the pathogenesis of FHHt caused by cullin 3 disease mutations. Recent studies have revealed an increased WNK4 and hence Na-Cl cotransporter (NCC) activity in the db/db mice, resulting from PKC-mediated KLHL3 phosphorylation, which impairs the degradation of its substrate, WNK4. However, whether WNK4 and NCC were activated in type 1 diabetes still remains unclear. We created streptozotocin-induced type 1 diabetic mice and revealed that renal WNK-oxidative stress response kinase-1/STE20/SPS1-related proline alanine–rich kinase (OSR1/SPAK)-NCC cascade was activated, whereas KLHL3 expression was markedly decreased and CUL3 was heavily neddylated. Moreover, decreased KLHL3 was reversed and WNK1 and WNK4 abundance increased by MLN4924, a neddylation inhibitor. In vitro, our study also showed decreased KLHL3 abundance without any significant change in phosphorylated KLHL3 under high glucose exposure. These results indicate that decreased KLHL3 likely plays a role in the pathogenesis of renal sodium reabsorption in hyperglycemic conditions.
Pulmonary vein (PV) isolation has become the mainstay acute procedural end point for paroxysmal atrial fibrillation (AF) ablation.
To examine the incidence of conduction recovery in the PVs in ...patients without clinical recurrence of AF after paroxysmal AF ablation.
From August 2008 to March 2011, 392 patients with drug-refractory PAF underwent catheter ablation in our center, a wide area circumferential ablation approach guided with a circular mapping catheter was performed with the intended endpoint of entrance block in all PVs. 276 (70.4%) of them were free from recurrence at one year follow-up, and 32 of them were enrolled to assess the incidence of PV reconnection. Forty-three patients with clinical recurrence after ablation were analyzed for comparison. The regions of gap were mapped and characterized in all of the reconnected PVs.
Among patients without recurrence, recovery of PV conduction was observed in 29 of 32 (90.6%) patients: 10/32 (31.2%) reconnection in 4 veins, 7/32 (21.9%) in 3 veins, 10/32 (31.2%) in 2 veins, and 2/32 (6.2%) in 1 vein. No anatomic propensity was seen because reconnection was evenly distributed throughout all veins (left superior pulmonary vein 21, left inferior pulmonary vein 20, right superior pulmonary vein 19, and right inferior pulmonary vein 23). When compared to patients with recurrence, no significant differences were seen in the proportion of patients with reconnection (P = 1.0) or in left atrium-PV intervals (73.4 ± 43.3 ms vs 61.9 ± 31.8 ms; P > .05).
A high incidence of PV reconnection was similarly observed in patients with and without recurrence of AF, suggesting that sustained PV isolation may not be required for freedom from clinical recurrence of AF.
Earwigs (Dermaptera), such as Forficula auricularia L., are important euryphagous predators for a wide variety of prey and can markedly influence the populations of orchard pests. Most previous ...studies on earwig feeding behaviour have not used adult beetles of the prey species; few researchers have focused on prey preference in earwigs. Some fragments of beetle exoskeleton and an earwig adult, Anisolabella marginalis (Dohrn), were found in the same cage, where adults of ambrosia beetle, Euwallacea interjectus (Blandford), were emerging from the logs of a fig tree infected with Ceratocystis canker (fig wilt disease). Thus, A. marginalis was suspected of being a predator of E. interjectus. To shed light on this issue, in the laboratory, we set up a test arena and observed and recorded behavioural interactions between A. marginalis and E. interjectus. E. interjectus was collected from the logs of fig trees and reared on an artificial diet, along with six different ambrosia beetle species, which were collected from a trap (baited with ethanol) and a fallen maple tree. A series of laboratory experiments demonstrated that A. marginalis is actually a predator of E. interjectus and other species of ambrosia beetle, indicating its a potential for use in effective pest control in the field. The predators frequently consume and tend to select their prey depending on prey size, rather than sex and beetle species. Furthermore, earwigs have alternative predatory strategies for dealing with seven different species, although they use their forceps to cut the body of most tested beetles.
The present study demonstrated for the first time that SNORA70E, which belongs to box H/ACA small nucleolar noncoding RNAs (snoRNAs) who could bind and induce pseudouridylation of RNAs, was ...significantly elevated in ovarian cancer tissues and was an unfavourable prognostic factor of ovarian cancer. The over‐expression of SNORA70E showed increased cell proliferation, invasion and migration in vitro and induced tumour growth in vivo. Further research found that SNORA70E regulates RAS‐Related Protein 1B (RAP1B) mRNA through pseudouracil modification by combing with the pyrimidine synthase Dyskerin Pseudouridine Synthase 1 (DKC1) and increase RAP1B protein level. What's more, the silencing of DKC1/RAP1B in SNORA70E overexpression cells both inhibited cell proliferation, migration and invasion through reducing β‐catenin, PI3K, AKT1, mTOR, and MMP9 protein levels. Besides, RNA‐Seq results revealed that SNORA70E regulates the alternative splicing of PARP‐1 binding protein (PARPBP), leading to the 4th exon‐skipping in PARPBP‐88, forming a new transcript PARPBP‐15, which promoted cell invasion, migration and proliferation. Finally, ASO‐mediated silencing of SNORA70E could inhibit ovarian cancer cell proliferation, invasion, migration ability in vitro and inhibit tumorigenicity in vivo. In conclusion, SNORA70E promotes the occurrence and development of ovarian cancer through pseudouridylation modification of RAP1B and alternative splicing of PARPBP. Our results demonstrated that SNORA70E may be a new diagnostic and therapeutic target for ovarian cancer.
Background
Atrial esophageal fistula (AEF) is a lethal complication that can occur post atrial fibrillation (AF) ablation. Esophageal injury (EI) is likely to be the initial lesion leading to AEF. ...Endoscopic examination is the gold standard for a diagnosis of EI but extensive endoscopic screening is invasive and costly. This study was conducted to determine whether fecal calprotectin (Fcal), a marker of inflammation throughout the intestinal tract, may be associated with the existence of esophageal injury.
Methods
This diagnostic study was conducted in a cohort of 166 patients with symptomatic AF undergoing radiofrequency catheter ablation from May 2020 to June 2021. Fcal tests were performed 1–7 days after ablation. All patients underwent endoscopic ultrasonography 1 or 2 days after ablation.
Results
The levels of Fcal were significantly different between the EI and non‐EI groups (404.9 µg/g (IQR 129.6–723.6) vs. 40.4 µg/g (IQR 15.0–246.2), p < .001). Analysis of ROC curves revealed that a Fcal level of 125 µg/g might be the optimal cut‐off value for a diagnosis of EI, giving a 78.8% sensitivity and a 65.4% specificity. The negative predictive value of Fcal was 100% for ulcerated EI.
Conclusions
The level of Fcal is associated with EI post AF catheter ablation. 125 µg/g might be the optimal cut‐off value for a diagnosis of EI. Negative Fcal could predict the absence of ulcerated EI, which could be considered a precursor to AEF.
This study investigated the molecular mechanism by which sodium butyrate (NaB) causes oxidative stress damage induced by lipopolysaccharide (LPS) on cow mammary epithelial cells (MAC‐T). We found ...that NaB significantly increased the activities of antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, catalase, peroxidase, and total antioxidant capacity and decreased the reactive oxygen species production in LPS‐induced MAC‐T cells. NaB attenuated protein damage and reduced apoptosis in LPS‐induced MAC‐T cells. The messenger RNA (mRNA) levels of caspase‐3, caspase‐9, and Bax decreased, while the Bcl‐2 mRNA level increased in LPS‐induced MAC‐T cells treated with NaB. Our results showed that NaB treatment increased the phosphoinositide 3‐kinase (PI3K) and phospho‐AKT (P‐AKT) protein levels, whereas it decreased the Bax, caspase‐3, and caspase‐9 protein levels in LPS‐induced MAC‐T cells. However, the increase in PI3K and P‐AKT protein levels and the decrease in Bax, caspase‐3, and caspase‐9 protein levels induced by NaB treatment were reversed when the cells were pretreated with LY294002 (PI3K inhibitor). These results indicate that NaB ameliorates LPS‐induced oxidative damage by increasing antioxidative enzyme activities and ameliorating protein damage in MAC‐T cells. In addition, NaB decreased apoptosis by inhibiting caspase‐3, caspase‐9, and Bax protein levels, and this action was mainly achieved via activation of the PI3K/AKT signaling pathways in LPS‐induced MAC‐T cells. These results provide substantial information for NaB as a chemical supplement to treat oxidative stress and its related diseases in ruminants.
In this study, we found that sodium butyrate (NaB) could ameliorate lipopolysaccharide (LPS)‐induced oxidative damage and apoptosis in cow mammary epithelial cells (MAC‐T). We think that this interesting chemical (NaB) could be used in the future to treat mastitis. More important, NaB can be obtained very easily and cost effectively. NaB and agriculture are combined to solve problems in agricultural production. NaB can be used as a feed additive to feed ruminants.
Titanium dioxide/zinc oxide/chitosan nanocomposite thin films (TiO₂/ZnO/chitosan NTFs) were prepared by entrapping zinc ions and nanosized TiO₂ in chitosan thin films under mild conditions. The ...structure, thermal property, and surface morphology of TiO₂/ZnO/chitosan NTFs were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and high-resolution transmission electron microscopy (HRTEM). The photocatalytic activity of TiO₂/ZnO/chitosan NTFs was evaluated by photocatalytic decolorization of methyl orange in aqueous solution as a model pollutant under simulated solar irradiation. The HRTEM results revealed that well-dispersed and uniform TiO₂/ZnO nanocomposite with diameters of 5–15nm were embedded in chitosan films. The TiO₂/ZnO/chitosan NTFs exhibited high photocatalytic activity under simulated solar irradiation. After 4h of irradiation by simulated solar light, over 97% of methyl orange solution (15mgL⁻¹) was decolorized with 0.5gL⁻¹ of the photocatalyst. The TiO₂/ZnO/chitosan NTFs could be reused, which meant that the adsorption-photocatalytic decolorization process could be operated at a relatively low cost. Since this process does not require the addition of hydrogen peroxide and uses solar light, it can be developed as an economically feasible and environmentally friendly method to decolorize or treat dye wastewater using sunlight.
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