Polygonatum sibiricum polysaccharides protect against knee osteoarthritis by inhibiting the TLR2/NF-κB signaling pathway in vivo and in vitro.

Polygonatum sibiricum polysaccharides (PSP), the primary constituent of Polygonatum sibiricum, have been shown to exhibit a wide range of pharmacological effects, but their impact on osteoarthritis (OA) remains unclear. The objective of this study was to investigate the protective effects of PSP against OA and to elucidate its underlying molecular mechanism. In our in vitro experiments, PSP not only inhibited the IL-1ß-induced inflammatory responses and the nuclear factor kappa-B (NF-κB) signaling pathway in chondrocytes but also regulated the cartilage matrix metabolism. In addition, we detected 394 significantly differentially expressed genes through RNA-seq analysis on PSP-intervened chondrocytes, and the toll-like receptor 2 (TLR2) was identified as the most important feature by functional network analysis and qRT-PCR. It was also revealed that PSP treatment significantly reversed the IL-1-induced up-regulation of TLR2 expression in chondrocytes, while TLR2 overexpression partially inhibited the regulatory effects of PSP on inflammation, NF-κB signaling pathway and matrix metabolism. In our in vivo experiments, PSP treatment alleviated the development of destabilization of medial meniscus (DMM)-induced OA in mouse knee joints, inhibited the DMM-induced activation of the TLR2/NF-κB signaling pathway in mouse knee joint cartilage, and reduced the serum levels of inflammatory cytokines. In conclusion, PSP exerts its anti-inflammatory, matrix synthesis-promoting and matrix catabolism-suppressing effects in knee OA by inhibiting the TLR2/NF-κB signaling pathway, suggesting that PSP may be potentially targeted as a novel all-natural, low-toxicity drug for OA prevention and treatment.

Methyl protodioscin reduces c-Myc to ameliorate diabetes mellitus erectile dysfunction via downregulation of AKAP12.

BACKGROUND: Diabetes mellitus erectile dysfunction (DMED) is one of common complications of diabetes. We aimed to investigate the potential efficacy of methyl protodioscin (MPD) in DMED and explored the underlying mechanism. METHODS: Diabetic mice were induced by streptozotocin, while vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were stimulated with high glucose. MPD was administrated in vitro and in vivo to verify its efficacy on DMED. The interaction of c-Myc and AKAP12 was determined by luciferase reporter assay and chromatin immunoprecipitation assay. RESULTS: c-Myc and AKAP12 were upregulated in penile tissues in DMED mice. In high glucose-stimulated VSMCs or VECs, MPD intervention enhanced cell viability, inhibited apoptosis, decreased c-Myc and AKAP12, as well as elevated p-eNOS Ser1177. MPD-induced apoptosis inhibition, AKAP12 reduction and p-eNOSSer1177 elevation were reversed by AKAP12 overexpression. c-Myc functioned as a positive regulator of AKAP12. Overexpression of c-Myc reversed the effects induced by MPD in vitro, which was neutralized by AKAP12 silencing. MPD ameliorated erectile function in diabetic mice via inhibiting AKAP12. CONCLUSIONS: MPD improved erectile dysfunction in streptozotocin-caused diabetic mice by regulating c-Myc/AKAP12 pathway, indicating that MPD could be developed as a promising natural agent for the treatment of DMED.

SPARC: a potential target for functional nanomaterials and drugs.

Secreted protein acidic and rich in cysteine (SPARC), also termed osteonectin or BM-40, is a matricellular protein which regulates cell adhesion, extracellular matrix production, growth factor activity, and cell cycle. Although SPARC does not perform a structural function, it, however, modulates interactions between cells and the surrounding extracellular matrix due to its anti-proliferative and anti-adhesion properties. The overexpression of SPARC at sites, including injury, regeneration, obesity, cancer, and inflammation, reveals its application as a prospective target and therapeutic indicator in the treatment and assessment of disease. This article comprehensively summarizes the mechanism of SPARC overexpression in inflammation and tumors as well as the latest research progress of functional nanomaterials in the therapy of rheumatoid arthritis and tumors by manipulating SPARC as a new target. This article provides ideas for using functional nanomaterials to treat inflammatory diseases through the SPARC target. The purpose of this article is to provide a reference for ongoing disease research based on SPARC-targeted therapy.

Testosterone attenuates senile cavernous fibrosis by regulating TGFßR1 and galectin-1 signaling pathways through miR-22-3p.

Erectile dysfunction (ED) is a major health problem affecting a large proportion of the general population. Testosterone also plays a key role in sexual dysfunction. In this study, we found that testosterone can inhibit cavernous fibrosis by affecting the expression of miR-22-3p, providing a new basis for research and treatment of ED. Old and young rats were used to study the effects of testosterone on cavernous fibrosis. Hematoxylin and eosin (HE) and Masson's staining were used to observe the cavernous tissue. A luciferase assay was used to analyze the relationship between the miR-22-3p, TGFßR1, and Galectin-1 signaling pathways. CCK-8 and flow cytometry were used to detect the proliferation and apoptosis rates of cavernosum smooth muscle cells (CSMCs) following testosterone intervention. Immunohistochemical analysis was performed to examine the positive rate of caspase 3 and Ki67. IF was used to analyze the expression of collagen IV, MMP2, and α-SMA. The levels of GnRH, tT, LH, and F-TESTO in old rats increased after testosterone intervention. miR-22-3p inhibits the expression of TGFßR1 and Galectin-1. The protein expression of TGFßR1, Galectin-1, SMAD2, and p-SMAD2 was reduced by testosterone. The expression levels of α-SMA, collagen I, collagen IV, FN, and MMP2 in the cavernous tissues of old rats treated with testosterone were significantly reduced. The levels of caspase 3 and collagen IV decreased, and the levels of MMP2, Ki67, and α-SMA increased. Testosterone and miR-22-3p inhibit CSMC apoptosis and promote cell proliferation. Testosterone promoted the expression of miR-22-3p to interfere with the expression of the cavernous TGFßR1 and Galectin-1 signaling pathways. Testosterone can reduce cavernous fibrosis during the treatment of functional ED.

DEPDC1B promotes colorectal cancer via facilitating cell proliferation and migration while inhibiting apoptosis.

Colorectal cancer (CRC) is a common malignant tumor with strong invasiveness. Given the reported involvement of DEP domain-containing protein 1B (DEPDC1B) in the progression of some cancers, its role in CRC was explored in this study. DEPDC1B expression in CRC was assessed based on database and tissue microarray (TMA). In addition, the knockdown and overexpression of DEPDC1B in CRC cell lines were constructed using small hairpin RNA (shRNA) interference. The biological function of DEPDC1B in CRC was evaluated in vitro and in vivo through loss/gain-of-function assays. The results demonstrated that DEPDC1B was highly expressed in CRC. Furthermore, DEPDC1B had the ability to promote CRC proliferation and migration coupled by cell apoptosis. In vivo results showed that DEPDC1B knockdown significantly inhibited the growth of xenograft tumors. Additionally, the results of antibody array indicated increased apoptosis-promoting proteins and decreased apoptosis-inhibiting proteins in DEPDC1B-knockdown CRC cells. In conclusion, DEPDC1B played a key driver role in CRC progression, and inhibition of its expression may be a potential target for precision medicine in CRC.

SPNet: a size-variant progressive network for aero-optical thermal radiation effects correction.

When an aircraft is flying at a high speed, the airflow meets the optical cover and is compressed, resulting in aero-optical thermal radiation effects that degrade image quality. In this paper, based on the inherent characteristic that the degrade level of the thermal radiation bias field remains consistent regardless of image size, a size-variant progressive aero-optical thermal radiation effects correction network (SPNet) is proposed. First, SPNet uses two sub-networks to progressively correct degraded image, first and second sub-networks are responsible for learning coarse and accurate thermal radiation bias fields respectively. Second, we introduce the multi-scale feature upsampling module (MFUM) to leverage the multi-scale information of the features and promote inter-channel information interaction. Third, we propose an adaptive feature fusion module (AFFM) to dynamically fuse features from different scales by assigning different weights. At last, a multi-head self-attention feature extraction module (MSFEM) is proposed to extract global information feature maps. Compared with state-of-the-art thermal radiation effects correction methods, experiments on both simulated and real degraded images demonstrate the performance of our proposed method.

Multi-scale thermal radiation effects correction via a fast surface fitting with Chebyshev polynomials.

In an uncooled infrared imaging system, thermal radiation effects are caused by the heat source from the target or the detection window, which affects the ability of target detection, tracking, and recognition seriously. To address this problem, a multi-scale correction method via a fast surface fitting with Chebyshev polynomials is proposed. A high-precision Chebyshev polynomial surface fitting is introduced into thermal radiation bias field estimation for the first time, to the best of our knowledge. The surface fitting in the gradient domain is added to the thermal radiation effects correction model as a regularization term, which overcomes the ill-posed matrix problem of high-order bivariate polynomials surface fitting, and achieves higher accuracy under the same order. Additionally, a multi-scale iterative strategy and vector representation are adopted to speed up the iterative optimization and surface fitting, respectively. Vector representation greatly reduces the number of basis function calls and achieves fast surface fitting. In addition, split Bregman optimization is used to solve the minimization problem of the correction model, which decomposes the multivariable optimization problem into multiple univariate optimization sub-problems. The experimental results of simulated and real degraded images demonstrate that our proposed method performs favorably against the state of the art in thermal radiation effects correction.

[Protective effects of rosiglitazone on hepatic ischemia reperfusion injury in rats].

OBJECTIVE: To explore the protective effect of rosiglitazone (RGZ) on hepatic ischemia reperfusion injury (HIRI) and the underlying mechanisms.
 Methods: A rat model of ischemia-reperfusion injury was established by clamping the left and middle lobe of liver with noninvasive vascular clamp. A total of 30 Sprague-Dawley rats were randomly divided into a sham group, an HIRI group, and a RGZ group (10 rats in each group). Two hours after reperfusion, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, lactate dehydrogenase (LDH) level, malondialdehyde (MDA) content and catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were examined. HE staining was used to observe liver pathological morphology. The liver peroxisome proliferators-activated receptor γ (PPAR-γ), p-PPAR-γ, nuclear factor related factor 2 (Nrf-2), antioxidant response element (ARE), heme oxygenase 1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were detected by Western blot.
 Results: Compared with the HIRI group, the levels of ALT, AST, LDH and MDA in the RGZ group were significantly decreased (all P<0.05), while the levels of Nrf-2, ARE, HO-1 and NQO-1 in the RGZ group were significantly increased. The hepatic swelling, necrosis and pathological damage were decreased (all P<0.05). In addition, there was no difference in the level of PPAR-γ between the 2 groups (P>0.05).
 Conclusion: PPAR-γ agonist RGZ can attenuate HIRI, which may be related to activating Nrf2/ARE signaling pathway and enhancement of antioxidant ability.

Performance of the fiber-optic low-coherent ground settlement sensor: From lab to field.

A fiber-optic low-coherent interferometry sensor was developed to measure the ground settlement (GS) in an accuracy of the micrometer. The sensor combined optical techniques with liquid-contained chambers that were hydraulically connected together at the bottom by using a water-filled tube. The liquid surface inside each chamber was at the same level initially. The optical interferometry was employed to read out the liquid level changes, which following the GS happened at the place where the chamber was put on and, thereby, the GS information was calculated. The laboratory effort had demonstrated its potential in the practical application. Here, the denoising algorithms on the measurement signal were carried out based on the specific environment to ensure the accuracy and stability of the system in field applications. After that, we extended this technique to the high-speed railway. The 5-days continuous measurement proved that the designed system could be applied to monitor the GS of the high-speed railway piers and approached an accuracy of ±70 µm in the field situation with a reference compensation sensor. So the performance of the sensor was suitable to the GS monitoring problem in the high-speed railway. There, the difficulties were to meet the monitoring requirement of both a large span in space and its quite tiny and slow changes.

Evaluation of vascular lesions using circulating endothelial cells in renal transplant patients.

OBJECTIVE: To investigate the correlation between circulating endothelial cells (CECs) and vascular lesions in renal allografts. METHODOLOGY: Sixty-two renal transplant patients were divided into four groups according to biopsy data. CECs were isolated from peripheral blood with anti-CD136-coated immunomagnetic Dynabeads and counted by microscopy during biopsy. CEC numbers were compared in each group, as well as the correlation between CECs and C4d and vascular changes in different groups. RESULT: CECs counts were higher in the acute rejection (AR) with endarteritis group than in the normal group (p < 0.01), acute tubular necrosis (ATN) group (p < 0.01) and chronic allograft nephropathy (CAN) group (p < 0.01), there were no difference among ATN, normal and CAN) group (p = 0.587). There was no difference among the normal group without hyaline, normal group with hyaline and CAN with hyaline group. An increasing CECs count was related to C4d-positive AR (p = 0.008; κ score = 0.519) and infiltration of inflammatory cells (p = 0.002, κ score = 0.573) in proximal tubule cells (PTCs). The CECs count decreased after intensive therapy in five patients (p = 0.001). CONCLUSION: Elevation of the CEC count in blood was related to endarteritis. Elevation of CEC count was related to C4d deposition and infiltration of inflammatory cells in PTCs.