Photoacoustic imaging (PAI) is a rapidly developing emerging non-invasive biomedical imaging technique that combines the strong contrast from optical absorption imaging and the high resolution from ...acoustic imaging. Abnormal biological tissues (such as tumors and inflammation) generate different levels of thermal expansion after absorbing optical energy, producing distinct acoustic signals from normal tissues. This technique can detect small tissue lesions in biological tissues and has demonstrated significant potential for applications in tumor research, melanoma detection, and cardiovascular disease diagnosis. During the process of collecting photoacoustic signals in a PAI system, various factors can influence the signals, such as absorption, scattering, and attenuation in biological tissues. A single ultrasound transducer cannot provide sufficient information to reconstruct high-precision photoacoustic images. To obtain more accurate and clear image reconstruction results, PAI systems typically use a large number of ultrasound transducers to collect multi-channel signals from different angles and positions, thereby acquiring more information about the photoacoustic signals. Therefore, to reconstruct high-quality photoacoustic images, PAI systems require a significant number of measurement signals, which can result in substantial hardware and time costs. Compressed sensing is an algorithm that breaks through the Nyquist sampling theorem and can reconstruct the original signal with a small number of measurement signals. PAI based on compressed sensing has made breakthroughs over the past decade, enabling the reconstruction of low artifacts and high-quality images with a small number of photoacoustic measurement signals, improving time efficiency, and reducing hardware costs. This article provides a detailed introduction to PAI based on compressed sensing, such as the physical transmission model-based compressed sensing method, two-stage reconstruction-based compressed sensing method, and single-pixel camera-based compressed sensing method. Challenges and future perspectives of compressed sensing-based PAI are also discussed.
The glutathione (GSH) system is considered to be one of the most powerful endogenous antioxidant systems in the cardiovascular system due to its key contribution to detoxifying xenobiotics and ...scavenging overreactive oxygen species (ROS). Numerous investigations have suggested that disruption of the GSH system is a critical element in the pathogenesis of myocardial injury. Meanwhile, a newly proposed type of cell death, ferroptosis, has been demonstrated to be closely related to the GSH system, which affects the process and outcome of myocardial injury. Moreover, in facing various pathological challenges, the mammalian heart, which possesses high levels of mitochondria and weak antioxidant capacity, is susceptible to oxidant production and oxidative damage. Therefore, targeted enhancement of the GSH system along with prevention of ferroptosis in the myocardium is a promising therapeutic strategy. In this review, we first systematically describe the physiological functions and anabolism of the GSH system, as well as its effects on cardiac injury. Then, we discuss the relationship between the GSH system and ferroptosis in myocardial injury. Moreover, a comprehensive summary of the activation strategies of the GSH system is presented, where we mainly identify several promising herbal monomers, which may provide valuable guidelines for the exploration of new therapeutic approaches.
Rheumatoid arthritis (RA) is a chronicautoimmune disease, marked by joint swelling and pain, articular synovial hyperplasia, as well as cartilage and bone destruction. Triptolide (TP) is an ...anti-inflammatory molecule but its use to treat RA is limited due to poor solubility and extremely high toxicity. In this study, by encapsulating TP into a star-shaped amphiphilic block copolymer, POSS-PCL-b-PDMAEMA, we engineered a pH-sensitive TP-loaded nanomedicine (TP@NPs) to simultaneously reduce the toxicity of TP and improve its therapeutic efficacy. TP@NPs shows a uniform spherical structure with a hydrodynamic diameter of ~92 nm and notable pH-responsiveness. In vitro TP@NPs showed reduced cytotoxicity and cell apoptosis of treated RAW264.7 cells compared to free TP. And in vivo intravenous injection of indocyanine green-labeled NPs into a collagen-induced arthritis model in mice showed that the engineered compound had potent pharmacokinetic and pharmacodynamic profiles, while exhibiting significant cartilage-protective and anti-inflammatory effects with a better efficacy and neglible systemic toxicity even at an ultralow dose compared to free TP. These results suggest that TP@NPs may be a safe and effective therapy for RA and other autoimmune diseases.
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Rheumatoid arthritis (RA) is a chronic autoimmune disorder, characterized by an increased number of M1-like macrophages in the joints. Polyphyllin I (PPI), one of the main components in the Rhizoma ...of Paris polyphyllin, displays a selective inhibitory effect on various tumor cells. Here we sought to investigate the anti-rheumatoid arthritis effects and mechanisms of PPI on macrophages
and
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, primary bone marrow-derived macrophages (BMMs) and peritoneal elucidated macrophages (PEMs) were stimulated by lipopolysaccharide (LPS) and Interferon (IFN)-γ and then treated with PPI. We determined the degree of activation of IKKα/β and p65, two key mediators of the NF-κB-mediated inflammatory pathway, by measuring their phosphorylated forms by Western blot. The p65 nuclear localization was detected by immunofluorescent staining. Further, a NF-κB-linked luciferase reporter plasmid, as well as those expressing key mediators of the Toll-like receptor 4 pathway, such as myeloid differentiation primary response 88 (MYD88), interleukin-1 receptor (IL-1R) associated kinase (IRAK)-1, TNF receptor associated factors (TRAF)-6, Transforming growth factor-b-activated kinase 1 (TAK1) and p65, were used to identify the mechanism by which PPI achieves its inhibitory effects on macrophage-mediated inflammation. Moreover, a NF-κB inhibitor, p65-targeted siRNAs, and a p65 plasmid were further used to validate the anti-inflammatory mechanism of PPI.
, PPI (1 mg/kg) was administered intragastrically one time a day for 7 weeks starting on the 42nd day after the first immunization with collagen in a collagen-induced arthritis (CIA) mouse model. Micro-computed Tomography scanning, histological examination, F4/80 and iNOS double immunofluorescent staining and CD4 immunohistochemical staining were performed to determine the effect of PPI treatment on joint structure and inflammation in this model.
PPI reduced the inflammatory cytokines production of PEMs stimulated by LPS/IFN-γ, inhibited the phosphorylation of IKKα/β and p65, and prevented p65 nuclear localization. The NF-κB luciferase assay showed that the target of PPI was closely related to the NF-κB pathway. Moreover, NF-κB inhibition, siRNA-mediated knockdown of p65, and p65 overexpression eliminated PPI's inhibitory effect. In addition, PPI attenuated the bone erosion and synovitis, as well as M1-like macrophage and T cell infiltration, in the ankle joint of the CIA model.
PPI demonstrated effective amelioration of synovial inflammation in the ankle joint of CIA mice while suppressing NF-κB-mediated production of pro-inflammatory effectors in activated macrophages.
Postmenopausal osteoporosis (POP) is quite prevalent and many new drugs are under development to obtain better therapeutic outcomes. Oleanolic acid (OA) has been reported to prevent bone loss in ...ovariectomized (OVX) rats by stimulating osteoblastogenesis. One previous study has demonstrated that acetate of OA suppressed lipopolysaccharides (LPS)-induced bone loss in mice. However, the role of OA in the receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis is still not elucidated. Here we show that OA dose-dependently inhibits RANKL-mediated osteoclastogenesis and the formation of functional osteoclasts without impairing the viability and osteoclastic potential in bone marrow macrophages (BMMs). Moreover, OA administration attenuates bone loss in OVX mice by inhibiting osteoclast’s densities. Mechanistically, OA does not affect RANKL-induced activation of the NF-кB, JNK, p38, ERK and Akt pathways, but inhibits the expression of the nuclear factor of activated T-cells c1(NFATc1) and c-Fos. Moreover, OA significantly suppresses the expression of RANKL-activated osteoclast genes encoding matrix metalloproteinase 9 (MMP9), Cathepsin K(Ctsk), tartrate-resistant acid phosphatase (TRAP) and carbonic anhydrase II (Car2). This work has elucidated the molecular mechanism of OA in RANKL-mediated osteoclastogenesis and revealed the promising potential of OA to be further developed as a new drug to prevent and treat POP.
Primary osteoporosis (POP), which is caused by unbalanced bone remodeling, leads to significant economic and societal burdens globally. Gushukang (GSK) granule serves as one commonly used ...prescription for POP in Traditional Chinese Medicine (TCM). The present study aimed to clarify the exact roles of GSK in bone remodeling with in vivo and in vitro assays. Here we showed that GSK prevented bone loss and the alternations of osteoporotic bone parameters as well as the decreased density of osteoclast in ovariectomized (OVX) mice. GSK inhibited receptor activator for nuclear factor-κ B Ligand (RANKL)-activated osteoclastogenesis in bone marrow macrophages (BMMs). At the molecular levels, GSK inhibited the expression of nuclear factor of activated T cells cytoplasm 1(NFATc1) and c-Fos, two master regulators of osteoclastogenesis. GSK also inhibited bone resorbed genetic expression of matrix metalloproteinase 9 (MMP9), cathepsin K (Ctsk), TRAP and carbonic anhydrase II (Car2). Meanwhile, GSK stimulated osteoblastogenesis from bone primary mesenchymal stem cells (MSCs) and enhanced the expression of Osteirx, and Runx2. GSK also stimulated the expression of Col-1, Osteocalcein and alkaline phosphatase (ALP). Our investigation established the systemic bone protective effects of GSK by suppressing osteoclastogenesis and stimulating osteoblastogenesis and laid bases for new drugs discovery in treating POP.
Abstract Background Routine coagulation tests are not widely accepted diagnostic criteria of trauma-induced hypercoagulopathy (TIH) due to insensitivity. Lymphatic vessels drain approximately 10% of ...the interstitial fluid into the lymphatic system and form lymph. Subjective The purpose of this study was to identify the potential lymph biomarkers for TIH. Methods Eighteen male Sprague-Dawley rats were randomly assigned to the sham (non-fractured rats with sham surgery and vehicle treatment), the VEH (fractured rats with vehicle treatment) and the CLO (fractured rats with clopidogrel treatment) group. Thoracic duct lymph was obtained to perform proteomics and untargeted metabolomics. Results A total of 1207 proteins and 16,695 metabolites were identified. The top 5 GO terms of lymph proteomics indicated that oxidative stress and innate immunity were closely associated with TIH and antithrombotic therapy. The top 5 GO terms of lymph metabolomics showed that homocystine and lysophosphatidylcholine were the differential expressed metabolites (DEMs) between the sham and VEH groups, while cholic acid, docosahexaenoic acid, N1-Methyl-2-pyridone-5-carboxamide, isoleucine and testosterone are the DEMs between the VEH and CLO group. Conclusions This study presents the first proteomic and metabolomic profiling of lymph after TIH and antithrombotic therapy, and predicts the possible lymph biomarkers for TIH.
Osteosarcoma is a most common highly malignant bone tumor in children and adolescents. Polyphyllin I (PPI) is an ethanol extraction from Paris polyphylla Smith var.yunnanensis (Franch.) Hand.-Mazz, ...which belongs to antipyretic-detoxicate family and has been used as a natural medicine in the treatment of infectious disease and cancer in China for centuries. The proteasome activity inhibitory and anti-osteosarcoma effects of PPI have not been known. Here we found PPI exhibited a selective inhibitory effect on proteasomal chymotrypsin (CT)-like activity, both in purified human proteasome and in cultured osteosarcoma cellular proteasome, and caused an accumulation of ubiquitinated proteins. PPI also inhibited viability, proliferation, migration, and invasion of MG-63, Saos-2, and U-2 OS osteosarcoma cells and resulted in S phase arrest and apoptosis. Furthermore, we explored the molecular targets involved. Exposure of osteosarcoma cells to PPI caused an inactivation of the intrinsic nuclear factor κB (NF-κB) and activation of unfolded protein response (UPR)/endoplasmic reticulum (ER) stress signaling cascade in osteosarcoma cells, followed by down-regulation of anti-apoptotic proteins, with up-regulation of pro-apoptotic proteins. We also demonstrated down-regulation of c-Myc, Cyclin B1, Cyclin D1, and CDK1, which are involved in the cell cycle and growth. Finally, we identified down-regulation of Vimentin, Snail, Slug, and up-regulation of E-cadherin, which are integral proteins involved in epithelial–mesenchymal transition (EMT). Taken together, our data provide insights into the mechanism underlying the anticancer activity of PPI in human osteosarcoma cells.
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Maximum likelihood (ML) is the best estimator asymptotically as the number of training samples approaches infinity. This paper deduces an adaptive algorithm for blind signal processing problem based ...on gradient optimization criterion. A parametric density model is introduced through a parameterized generalized distribution family in ML framework. After specifying a limited number of parameters, the density of specific original signal can be approximated automatically by the constructed density function. Consequently, signal separation can be conducted without any prior information about the probability density of the desired original signal. Simulations on classical biomedical signals confirm the performance of the deduced technique.
Abstract
Background
Macrophages and inflammatory cytokines play important roles in bone fracture healing. However, the expression patterns of macrophages and inflammatory cytokines during fracture ...healing under the condition of postmenopausal osteoporosis have not been fully revealed.
Methods
Tibia transverse fracture was established 12 weeks after ovariectomy or sham operation in 16-week old female mice. Tibias were harvested before fracture or 1, 3, 5, 7, 14, 21, 28 days after fracture for radiological and histological examinations. M1/M2 inflammatory macrophages, osteal macrophages and gene expressions of tumor necrosis factor-α, interleukin-6, interleukin-1β and macrophage conversion related molecules in the fracture haematoma or callus were also detected.
Results
The processes of fracture healing, especially the phases of endochondral ossification and callus remodeling, were delayed in ovariectomized mice. The expressions of tumor necrosis factor-α and interleukin-6, but not interleukin-1β, in the fracture haematoma or callus were disturbed. Expressions of tumor necrosis factor-α were decreased at 1, 14 and 21 days post-fracture (DPF), and were increased at 3, 5 and 7 DPF. Interleukin-6 expressions at 1, 3 and 21 DPF were significantly increased. We found the decreases in M1 and M2 macrophages at 1 DPF of the initial inflammatory stage. M2 macrophages at 14 DPF of the middle stage and osteal macrophages at 14, 21 and 28 DPF of the middle and late stages of fracture healing were also reduced in ovariectomized mice.
Conclusions
The expressions of macrophages and inflammatory cytokines were impaired in ovariectomized mice, which might contribute partially to poor fracture healing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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