Renal fibrosis is a common pathological process that occurs with diverse etiologies in chronic kidney disease. However, its regulatory mechanisms have not yet been fully elucidated. Ferroptosis is a ...form of non-apoptotic regulated cell death driven by iron-dependent lipid peroxidation. It is currently unknown whether ferroptosis is initiated during unilateral ureteral obstruction (UUO)-induced renal fibrosis and its role has not been determined. In this study, we demonstrated that ureteral obstruction induced ferroptosis in renal tubular epithelial cells (TECs) in vivo. The ferroptosis inhibitor liproxstatin-1 (Lip-1) reduced iron deposition, cell death, lipid peroxidation, and inhibited the downregulation of GPX4 expression induced by UUO, ultimately inhibiting ferroptosis in TECs. We found that Lip-1 significantly attenuated UUO-induced morphological and pathological changes and collagen deposition of renal fibrosis in mice. In addition, Lip-1 attenuated the expression of profibrotic factors in the UUO model. In vitro, we used RSL3 treatment and knocked down of GPX4 level by RNAi in HK2 cells to induce ferroptosis. Our results indicated HK2 cells secreted various profibrotic factors during ferroptosis. Lip-1 was able to inhibit ferroptosis and thereby inhibit the secretion of the profibrotic factors during the process. Incubation of kidney fibroblasts with culture medium from RSL3-induced HK2 cells promoted fibroblast proliferation and activation, whereas Lip-1 impeded the profibrotic effects. Our study found that Lip-1 may relieve renal fibrosis by inhibiting ferroptosis in TECs. Mechanistically, Lip-1 could reduce the activation of surrounding fibroblasts by inhibiting the paracrine of profibrotic factors in HK2 cells. Lip-1 may potentially be used as a therapeutic approach for the treatment of UUO-induced renal fibrosis.
Transcatheter arterial chemoembolization (TACE) is the primary local treatment for patients with unresectable hepatocellular carcinoma (HCC). Numerous studies have demonstrated the pivotal role of ...circular RNAs (circRNAs) in TACE efficacy. This study aimed to investigate the function of circular RNA DNAH14 (circDNAH14) in TACE for HCC and to elucidate its molecular mechanisms. To simulate hypoxia conditions experienced during TACE, HCC cells were treated with cobalt chloride. The expression levels of circDNAH14, microRNA-508-3p (miR-508-3p), and Prothymosin Alpha (PTMA) were modulated via transfection for knockdown or overexpression. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, flow cytometry, and Transwell assays, along with epithelial-mesenchymal transition (EMT) evaluations, were employed to assess cell proliferation, apoptosis, invasion, migration, and EMT. The results indicated that hypoxia treatment downregulated the expression of circDNAH14 and PTMA while upregulating miR-508-3p. Such treatment suppressed HCC cell proliferation, invasion, migration, and EMT, and induced apoptosis. Knockdown of circDNAH14 or PTMA intensified the suppressive effects of hypoxia on the malignant behaviors of HCC cells. Conversely, upregulation of miR-508-3p or PTMA mitigated the effects of circDNAH14 overexpression and knockdown, respectively. Mechanistically, circDNAH14 was found to competitively bind to miR-508-3p, thereby regulating PTMA expression. In vivo, nude mouse xenograft experiments demonstrated that circDNAH14 knockdown augmented the hypoxia-induced suppression of HCC tumor growth. In conclusion, circDNAH14 mitigates the suppressive effects of hypoxia on HCC, both in vitro and in vivo, by competitively binding to miR-508-3p and regulating PTMA expression.
To explore the influences of digital media use on the core symptoms, emotional state, life events, learning motivation, executive function (EF) and family environment of children and adolescents ...diagnosed with attention deficit hyperactivity disorder (ADHD) during the novel coronavirus disease 2019 (COVID-19) pandemic.
A total of 192 participants aged 8-16 years who met the diagnostic criteria for ADHD were included in the study. Children scoring higher than predetermined cut-off point in self-rating questionnaires for problematic mobile phone use (SQPMPU) or Young's internet addiction test (IAT), were defined as ADHD with problematic digital media use (PDMU), otherwise were defined as ADHD without PDMU. The differences between the two groups in ADHD symptoms, EF, anxiety and depression, stress from life events, learning motivation and family environment were compared respectively.
When compared with ADHD group without PDMU, the group with PDMU showed significant worse symptoms of inattention, oppositional defiant, behavior and emotional problems by Swanson, Nolan, and Pelham Rating Scale (SNAP), more self-reported anxiety by screening child anxiety-related emotional disorders (SCARED) and depression by depression self-rating scale for children (DSRSC), more severe EF deficits by behavior rating scale of executive function (BRIEF), more stress from life events by adolescent self-rating life events checklist (ASLEC), lower learning motivation by students learning motivation scale (SLMS), and more impairment on cohesion by Chinese version of family environment scale (FES-CV). The ADHD with PDMU group spent significantly more time on both video game and social media with significantly less time spend on physical exercise as compared to the ADHD without PDMU group.
The ADHD children with PDMU suffered from more severe core symptoms, negative emotions, EF deficits, damage on family environment, pressure from life events, and a lower motivation to learn. Supervision of digital media usage, especially video game and social media, along with increased physical exercise, is essential to the management of core symptoms and associated problems encountered with ADHD.
Suicide risk is greatly increased in depression. Detection of those at risk is clinically important. Hence, this study aimed to evaluate the prevalence and identify independent risk factors ...associated with suicidal ideation (SI) in a widespread symptomatology within and outside DSM framework.
This study was part of the National Survey on Symptomatology of Depression (NSSD) which was designed to investigate the magnitude of symptoms of current major depressive episode in China. Stepwise multivariable logistic regression was performed to examine the independent risk factors for SI, including variables that are statistically significant in univariate analysis. Receiver operating characteristic (ROC) was used to evaluate the performance of the regression model.
A total of 3275 patients (1293 males and 1982 females) were included in our analysis. Of these, 1750 patients (53.4%) had SI. Independent risk predictors included crying (P = 0.000; odds ratio = 1.827), helplessness (P = 0.000; odds ratio = 1.514), worthlessness (P = 0.001; odds ratio = 1.359), hopelessness (P = 0.000; odds ratio = 1.805), unusually restless (P = 0.005; odds ratio = 1.276), self-harm (P = 0.000; odds ratio = 3.385), mood-incongruent psychosis (P = 0.000; odds ratio = 2.782), feeling losing control of oneself (P = 0.009; odds ratio = 1.352), hypersomnia (P = 0.000; odds ratio = 1.805), sensory system complaints (P = 0.000; odds ratio = 1.546), derealization (P = 0.006; odds ratio = 1.580), guilt (P = 0.002; odds ratio = 1.332), suicidal attempts (P = 0.000; odds ratio = 2.841), male gender (P = 0.001; odds ratio = 0.756), the total course of depression (P = 0.010; odds ratio = 1.003) in the regression model. In addition, the areas under the curve of the ROC and the accuracy for the regression model were 0.80 and 0.76, respectively.
This study provided an effective risk model for SI in MDD and indicated that all these factors in our model allow better the employment of preventative measures.
Randall’s plaques (RP) are well established as precursor lesions of idiopathic calcium oxalate (CaOx) stones, and the process of biomineralization driven by osteogenic-like cells has been highlighted ...in RP formation, but the mechanism is poorly understood. Given the inhibitory role of α-Klotho (KL), an aging suppressor protein with high expression in kidneys, in ectopic calcification and the close association between
KL
gene polymorphisms and urolithiasis susceptibility, we determined the potential role of KL in RP formation. This study found that both soluble KL (s-KL) and transmembrane KL (m-KL) were downregulated, and that s-KL but not m-KL was inversely correlated with upregulation of osteogenic markers in RP tissues. Additionally, s-KL expression was markedly suppressed in human renal interstitial fibroblasts (hRIFs) and slightly suppressed in HK-2 cells after osteogenic induction, intriguingly, which was echoed to the greater osteogenic capability of hRIFs than HK-2 cells. Further investigations showed the inhibitory effect of s-KL on hRIF osteogenic differentiation in vitro and in vivo. Moreover, coculture with recombinant human KL (r-KL) or HK-2 cells suppressed osteogenic differentiation of hRIFs, and this effect was abolished by coculture with
KL
-silenced HK-2 cells or the β-catenin agonist SKL2001. Mechanistically, s-KL inactivated the Wnt–β-catenin pathway by directly binding to Wnt2 and upregulating SFRP1. Further investigations identified activation of the Wnt–β-catenin pathway and downregulation of SFRP1 and DKK1 in RP tissues. In summary, this study identified s-KL deficiency as a pathological feature of RP and revealed that s-KL released from HK-2 cells inhibited osteogenic differentiation of hRIFs by inactivating the Wnt–β-catenin pathway, not only providing in-depth insight into the role of s-KL in renal interstitial biomineralization but also shedding new light on the interaction of renal tubular epithelial cells with interstitial cells to clarify RP formation.
•Chinese patients with first-episode major depressive disorder have a high risk to elicit suicidal ideation.•No gender difference in the incidence of suicidal ideation were found in present ...study.•Patients with more somatic symptoms would have the higher risk of suicidal ideation.•Younger patients were more likely to express suicidal thoughts.•Somatic symptoms like pre-verbal physical complaints, sensory system complaints, other pain conditions, late insomnia, hypersomnia, weight loss, hyposexuality were strongly associated with current SI in first-episode Chinese major depression.
Somatic symptoms are prevalent in patients with major depressive disorder (MDD) and often associated with a high risk of suicide. However, which somatic symptoms display as significant risk factors for suicidal ideation (SI) is still poorly understood in MDD.
Two thousand and seventeen Chinese patients with first-episode MDD from the National Survey on Symptomatology of Depression were included in this study. A doctor-rating assessment questionnaire was constructed to evaluate depression related somatic symptoms, and stepwise logistic regression analysis was performed to explore the relationship between somatic symptoms and SI.
Our results showed a high prevalence of current SI in first-episode MDD (50.87%), while no significant gender differences (53.32% vs. 49.26%, P = 0.076) were observed. In addition, patients who have more somatic symptoms would be at the higher risk to elicit SI, and stepwise logistic regression analysis indicated that age (β = -0.020, P < 0.001), Pre-verbal physical complaints (β = 0.356, P = 0.001), Sensory system complaints (β = 0.707, P = 0.000), Other pain conditions (β = 0.434, P < 0.001), Late insomnia (β = 0.267, P = 0.008), Hypersomnia (β = 0.936, P < 0.001), Weight loss (β = 0.272, P = 0.006), Hyposexuality (β = 0.513, P = P < 0.001) were strongly associated with current SI in first-episode Chinese major depression.
Somatic symptoms are strongly associated with SI in first-episode MDD. It is suggestive for clinicians to show concerns for patients' somatic symptoms in practice.
Renal interstitial fibrosis (RIF) considered the primary irreversible cause of chronic kidney disease. Recently, accumulating studies demonstrated that lncRNAs play an important role in the ...pathogenesis of RIF. However, the underlying exact mechanism of lncRNA MALAT1 in RIF remains barely known. Here, the aim of our study was to investigate the dysregulate expression of lncRNA MALAT1 in TGF-β1 treated HK2/NRK-49F cells and unilateral ureteral obstruction (UUO) mice model, defining its effects on HK2/NRK-49F cells and UUO mice fibrosis process through the miR-124-3p/ITGB1 signaling axis. It was found that lncRNA MALAT1 and ITGB1 was significantly overexpression, while miR-124-3p was downregulated in HK2/NRK-49F cells induced by TGF-β1 and in UUO mice model. Moreover, knockdown of lncRNA MALAT1 remarkably downregulated the proteins level of fibrosis-related markers, ITGB1, and upregulated the expression of epithelial marker E-cadherin. Consistently, mechanistic studies showed that miR-124-3p can directly binds to lncRNA MALAT1 and ITGB1. And the protect effect of Len-sh-MALAT1 on fibrosis related protein levels could be partially reversed by co-transfected with inhibitor-miR-124-3p. Moreover, the expression trend of LncRNA MALAT1/miR-124-3p/ITGB1 in renal tissues of patients with obstructive nephropathy (ON) was consistent with the results of cell and animal experiments. Taken together, these results indicated that lncRNA MALAT1 could promote RIF process in vitro and in vivo via the miR-124-3p/ITGB1 signaling pathway. These findings suggest a new regulatory pathway involving lncRNA MALAT1, which probably serves as a potential therapeutic target for RIF.
Aim
To explore the Chinese nurses’ current practices and challenges to trauma‐informed care (TIC) for accidentally injured patients, which can provide the way forward of improvement in the future.
...Design
A qualitative study.
Methods
Sixteen Chinese nurses who had experience working with accidentally injured patients were invited into the semi‐structured interviews. Following each interview, the dialogue was transcribed verbatim. Subsequently, we analysed the data in accordance with the principles of thematic analysis.
Results
Four common themes emerged from the analysis: (a) Awareness of patients’ psychological trauma; (b) Recognition of psychological trauma; (c) Response to psychological trauma; (d) Perceived barriers to implementing TIC. This research indicated an urgent need for interventions in the future, such as TIC education and training, time constraints, heavy workload, emotional exhaustion and mood self‐regulation, giving policy incentives, strengthening leadership support and internal cooperation. Identifying those factors of TIC practice among accidentally injured patients helps promote TIC development in hospitals.
Randall’s plaque (RP) serves as a nidus on which idiopathic calcium oxalate stones form. Renal interstitial mineralization may be the cause underlying RP, and recent studies demonstrated the ...similarities between the interstitial mineralization and ectopic calcification. The present study aimed to investigate whether human renal interstitial fibroblasts (hRIFs) could form calcification under osteogenic conditions, and whether long non-coding RNA H19 participated in regulating osteogenic differentiation of hRIFs through Wnt-β-catenin pathway. HRIFs were isolated and induced for osteogenic differentiation under osteogenic conditions. Runx2, OCN, alkaline phosphatase (ALP) activity, and the mineralized nodule formation were used to assess the osteogenic phenotype. Molecule expressions were determined by qRT-PCR, immunofluorescence staining, and western blot. The mineralized nodules were assessed by Alizarin red staining. Compared to the normal renal papillary tissue, Runx2, OCN, and H19 were significantly upregulated in RP. After hRIFs were induced with osteogenic medium, osteogenic markers (Runx2, OCN and ALP), β‐catenin and H19 were significantly upregulated, and the mineralized nodules are formed. Additionally, overexpression of H19 promoted the osteogenic phenotype of hRIFs and increased the expression of β‐catenin, whereas knock-down of H19 or XAV939 (inhibitor of Wnt-β‐catenin signaling pathway) significantly repressed the osteogenic phenotype of hRIFs and decreased the β‐catenin. Moreover, XAV939 was shown to abolish the osteogenic differentiation of hRIFs promoted by H19. The study demonstrated that ectopic calcification partly participated in the formation of RP, and H19 promoted osteogenic differentiation of hRIFs by activating Wnt-β-catenin pathway, which shed new light on the molecular mechanism of the RP formation.
Renal fibrosis (RF) is a pathological process that culminates in terminal renal failure in chronic kidney disease (CKD). Fibrosis contributes to progressive and irreversible decline in renal ...function. However, the molecular mechanisms involved in RF are complex and remain poorly understood. Long non-coding RNAs (lncRNAs) are a major type of non-coding RNAs, which significantly affect various disease processes, cellular homeostasis, and development through multiple mechanisms. Recent investigations have implicated aberrantly expressed lncRNA in RF development and progression, suggesting that lncRNAs play a crucial role in determining the clinical manifestation of RF. In this review, we comprehensively evaluated the recently published articles on lncRNAs in RF, discussed the potential application of lncRNAs as diagnostic and/or prognostic biomarkers, proposed therapeutic targets for treating RF-associated diseases and subsequent CKD transition, and highlight future research directions in the context of the role of lncRNAs in the development and treatment of RF.
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