Smad3-mediated upregulation of miR-21 promotes renal fibrosis

TGF-β/Smad signaling plays a role in fibrogenesis, but therapies targeting TGF-β are ineffective in treating renal fibrosis. Here, we explored the therapeutic potential of targeting TGF-β-induced microRNA in the progression of renal fibrosis. Microarray analysis and real-time PCR revealed upregulation of miR-21 in tubular epithelial cells (TECs) in response to TGF-β. Lack of Smad3, but not lack of Smad2, prevented cells from upregulating miR-21 in response to TGF-β. In addition, Smad3-deficient mice were protected from upregulation of miR-21 and fibrosis in the unilateral ureteral obstruction model. In contrast, conditional knockout of Smad2 enhanced miR-21 expression and renal fibrosis. Furthermore, ultrasound-microbubble- mediated gene transfer of a miR-21-knockdown plasmid halted the progression of renal fibrosis in established obstructive nephropathy. In conclusion, these data demonstrate that Smad3, but not Smad2, signaling increases expression of miR-21, which promotes renal fibrosis. Inhibition of miR-21 may be a therapeutic approach to suppress renal fibrosis. Copyright © 2011 by the American Society of Nephrology.link_to_subscribed_fulltex

MicroRNA-29b inhibits diabetic nephropathy in db/db mice

Inflammation and its consequent fibrosis are two main features of diabetic nephropathy (DN), but target therapy on these processes for DN remains yet ineffective. We report here that miR-29b is a novel therapeutic agent capable of inhibiting progressive renal inflammation and fibrosis in type 2 diabetes in db/db mice. Under diabetic conditions, miR-29b was largely downregulated in response to advanced glycation end (AGE) product, which was associated with upregulation of collagen matrix in mesangial cells via the transforming growth factor-β (TGF-β)/Smad3-dependent mechanism. These pathological changes were reversed by overexpressing miR-29b, but enhanced by knocking-down miR-29b. Similarly, loss of renal miR-29b was associated with progressive diabetic kidney injury, including microalbuminuria, renal fibrosis, and inflammation. Restored renal miR-29b by the ultrasound-based gene therapy was capable of attenuating diabetic kidney disease. Further studies revealed that inhibition of Sp1 expression, TGF-β/Smad3-dependent renal fibrosis, NF-κB-driven renal inflammation, and T-bet/Th1-mediated immune response may be mechanisms associated with miR-29b treatment in db/db mice. In conclusion, miR-29b may play a protective role in diabetic kidney disease and may have therapeutic potential for diabetic kidney complication. © The American Society of Gene & Cell Therapy.link_to_subscribed_fulltex

The psychological distress and coping styles in the early stages of the 2019 coronavirus disease (COVID-19) epidemic in the general mainland Chinese population: A web-based survey

As the epidemic outbreak of 2019 coronavirus disease (COVID-19), general population may experience psychological distress. Evidence has suggested that negative coping styles may be related to subsequent mental illness. Therefore, we investigate the general population’s psychological distress and coping styles in the early stages of the COVID-19 outbreak. A cross-sectional battery of surveys was conducted from February 1–4, 2020. The Kessler 6 psychological distress scale, the simplified coping style questionnaire and a general information questionnaire were administered on-line to a convenience sample of 1599 in China. A multiple linear regression analysis was performed to identify the influence factors of psychological distress. General population’s psychological distress were significant differences based on age, marriage, epidemic contact characteristics, concern with media reports, and perceived impacts of the epidemic outbreak (all p <0.001) except gender (p = 0.316). The population with younger age (F = 102.04), unmarried (t = 15.28), with history of visiting Wuhan in the past month (t = -40.86), with history of epidemics occurring in the community (t = -10.25), more concern with media reports (F = 21.84), perceived more impacts of the epidemic outbreak (changes over living situations, F = 331.71; emotional control, F = 1863.07; epidemic-related dreams, F = 1642.78) and negative coping style (t = 37.41) had higher level of psychological distress. Multivariate analysis found that marriage, epidemic contact characteristics, perceived impacts of the epidemic and coping style were the influence factors of psychological distress (all p <0.001). Epidemic of COVID-19 caused high level of psychological distress. The general mainland Chinese population with unmarried, history of visiting Wuhan in the past month, perceived more impacts of the epidemic and negative coping style had higher level of psychological distress in the early stages of COVID-19 epidemic. Psychological interventions should be implemented early, especially for those general population with such characteristics

RY10-4 Inhibits the Proliferation of Human Hepatocellular Cancer HepG2 Cells by Inducing Apoptosis In Vitro and In Vivo.

This study aimed to investigate the anti-tumor activity of RY10-4, a small molecular that was designed and synthesized based on the structure of protoapigenone. A previous screening study showed that RY10-4 possessed anti-proliferative effects against HepG2 human hepatocellular carcinoma cells. However, the full range of RY10-4 anti-cancer effects on liver tumors and the underlying mechanisms have not been identified. Herein, employing flow cytometry, and Western blot analysis, we demonstrate that RY10-4 can induce cell cycle arrest, intracellular reactive oxygen species (ROS) production and apoptosis in HepG2 cells. In HepG2 cell xenograft tumor model, RY10-4 significantly inhibited the growth of tumors and induced apoptosis in tumor cells, with little side effects. Moreover, RY10-4 caused the suppression of STAT3 activation, which may be involved the apoptosis induction. In addition, RY10-4 inhibited the proliferation of Hep3B and HuH-7 human hepatocellular carcinoma cells in a concentration-dependent manner. Taken together, our results suggest that RY10-4 has a great potential to develop as chemotherapeutic agent for liver cancer

CRTransSar: A Visual Transformer Based on Contextual Joint Representation Learning for SAR Ship Detection

Synthetic-aperture radar (SAR) image target detection is widely used in military, civilian and other fields. However, existing detection methods have low accuracy due to the limitations presented by the strong scattering of SAR image targets, unclear edge contour information, multiple scales, strong sparseness, background interference, and other characteristics. In response, for SAR target detection tasks, this paper combines the global contextual information perception of transformers and the local feature representation capabilities of convolutional neural networks (CNNs) to innovatively propose a visual transformer framework based on contextual joint-representation learning, referred to as CRTransSar. First, this paper introduces the latest Swin Transformer as the basic architecture. Next, it introduces the CNN’s local information capture and presents the design of a backbone, called CRbackbone, based on contextual joint representation learning, to extract richer contextual feature information while strengthening SAR target feature attributes. Furthermore, the design of a new cross-resolution attention-enhancement neck, called CAENeck, is presented to enhance the characterizability of multiscale SAR targets. The mAP of our method on the SSDD dataset attains 97.0% accuracy, reaching state-of-the-art levels. In addition, based on the HISEA-1 commercial SAR satellite, which has been launched into orbit and in whose development our research group participated, we released a larger-scale SAR multiclass target detection dataset, called SMCDD, which verifies the effectiveness of our method

MiR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes

Aims/hypothesis: As microRNA-21 (miR-21) plays a pathological role in fibrosis, we hypothesised that it may be a therapeutic target for diabetic nephropathy. Methods: Abundance of miR-21 was examined in diabetic kidneys from db/db mice. The therapeutic potential of miR-21 in diabetic kidney injury was examined in db/db mice by an ultrasound-microbubble-mediated miR-21 small hairpin RNA transfer. In addition, the role and mechanisms of miR-21 in diabetic renal injury were examined in vitro under diabetic conditions in rat mesangial and tubular epithelial cell lines by overexpressing or downregulating miR-21. Results: In db/db mice, a mouse model of type 2 diabetes, renal miR-21 at age 20 weeks was increased twofold compared with db/m + mice at the same age, and this increase was associated with the development of microalbuminuria and renal fibrosis and inflammation. More importantly, gene transfer of miR-21 knockdown plasmids into the diabetic kidneys of db/db mice at age 10 weeks significantly ameliorated microalbuminuria and renal fibrosis and inflammation at age 20 weeks, revealing a therapeutic potential for diabetic nephropathy by targeting miR-21. Overexpression of miR-21 in kidney cells enhanced, but knockdown of miR-21 suppressed, high-glucose-induced production of fibrotic and inflammatory markers. Targeting Smad7 may be a mechanism by which miR-21 regulates renal injury because knockdown of renal miR-21 restored Smad7 levels and suppressed activation of the TGF-β and NF-κB signalling pathways. Conclusions/interpretation: Inhibition of miR-21 might be an effective therapy for diabetic nephropathy. © 2012 Springer-Verlag Berlin Heidelberg.link_to_subscribed_fulltex

The anti-proliferative effects of RY10-4 on other hepatocellular carcinoma cells.

<p>(A) Hep3B or HuH-7 cells were treated with series concentrations of RY10-4, and cell growth inhibition ratio was determined by SRB assay. (B) Hep3B cells were treated with RY10-4, and the expressions of apoptosis-related proteins p53, Bcl-2 and Bax were analyzed by Western blot.</p

The molecular mechanisms of apoptosis induction by RY10-4 in HepG2 cells.

<p>(A) HepG2 cells were treated with indicated concentrations of RY10-4, and the expression of p-STAT3 and p21 was analyzed by Western blot. (B) HepG2 cells were treated with RY10-4 with or without IL-6 stimulation; expression of p-STAT3 and cyclin E was analyzed by Western blot. (C) HepG2 cells were treated with RY10-4 in the absence or presence of NAC pretreatment. The expression of p-STAT3 and p53 was analyzed by Western blot.</p

RY10-4 Inhibits the Proliferation of Human Hepatocellular Cancer HepG2 Cells by Inducing Apoptosis <i>In Vitro</i> and <i>In Vivo</i>

<div><p>This study aimed to investigate the anti-tumor activity of RY10-4, a small molecular that was designed and synthesized based on the structure of protoapigenone. A previous screening study showed that RY10-4 possessed anti-proliferative effects against HepG2 human hepatocellular carcinoma cells. However, the full range of RY10-4 anti-cancer effects on liver tumors and the underlying mechanisms have not been identified. Herein, employing flow cytometry, and Western blot analysis, we demonstrate that RY10-4 can induce cell cycle arrest, intracellular reactive oxygen species (ROS) production and apoptosis in HepG2 cells. In HepG2 cell xenograft tumor model, RY10-4 significantly inhibited the growth of tumors and induced apoptosis in tumor cells, with little side effects. Moreover, RY10-4 caused the suppression of STAT3 activation, which may be involved the apoptosis induction. In addition, RY10-4 inhibited the proliferation of Hep3B and HuH-7 human hepatocellular carcinoma cells in a concentration-dependent manner. Taken together, our results suggest that RY10-4 has a great potential to develop as chemotherapeutic agent for liver cancer.</p></div

RY10-4 induced apoptosis in HepG2 cells.

<p>(A) Cells were treated with indicated concentrations of RY10-4 for 24 h, and the nuclei were stained by Hoechst 33342. Arrows indicate condensed and fragmented nuclei. (B) Flow cytometry assay to detect apoptosis in HepG2 cells using Annexin V/PI staining. Representative flow cytometry profiles are shown. (C) The percentage of apoptotic cells, presented as mean ± SD of three independent experiments. (D) Expression of apoptosis-related proteins was analyzed by Western blot in HepG2 cells untreated or treated with RY10-4.</p