Differential expressions of TGF-β1, HIF-1, VEGF, α-SMA and E-cadherin in renal tissues of a neonatal rat model of hydronephrosis

Purpose: To investigate the differential expressions of transforming growth factor-β1 (TGF-β1), hypoxia inductive factor-1 (HIF-1), vascular endothelial growth factor (VEGF), α-smooth muscle protein (α-SMA) and E-cadherin in renal tissues of neonatal rat model of hydronephrosis.Methods: The neonatal rats (90) were randomly divided into sham group and model group. The rats in the model group were further divided into two subgroups: week 1 and week 12 after relief of obstruction, with 30 rats in each group. Six rats were taken from each group for the determination of renal histopathological changes. Levels of TGF-β1, HIF-1, VEGF, α-SMA and E-cadherin in renal tissues were compared for different pathological grades and at different time points of obstruction relief.Results: With increase in Elder grade, the concentrations of TGF-β1, HIF-1, VEGF and α-SMA in renal tissues of hydronephrosis neonatal rats were gradually increased, while the expression level of Ecadherin gradually decreased (p < 0.05). However, the concentrations of TGF-β1, HIF-1, VEGF and α-SMA in renal tissues were significantly reduced, while the expression level of E-adherin was upregulated with time after relief of obstruction (p < 0.05).Conclusion: These findings are of great significance in determining the degree of kidney injury and recovery, and for the development of drugs for the treatment of renal injury

The effect of anti-VEGF drugs (bevacizumab and aflibercept) on the survival of patients with metastatic colorectal cancer (mCRC)

Significant progression has been achieved in the treatment of metastatic colorectal cancer (mCRC) in recent years. This has been partly attributed to successfully incorporating new drugs into combination chemotherapy. In addition to the traditional cytotoxic chemotherapeutic agents, molecularly targeted agents began to play an important role in the treatment of advanced solid tumors. To date, two classes of molecularly targeted agents have been approved for treatment of patients with mCRC: (1) antivascular endothelial growth factor (anti-VEGF) agents (such as bevacizumab and aflibercept) and (2) antiendothelial cell growth factor receptor (anti-EGFR) agents (such as cetuximab and panitumumab). Aflibercept is a new member of anti-VEGF agents which has demonstrated efficacy for treatment of mCRC. With the commencement of clinical trials and basic research into aflibercept, more data from the bedside and the bench have been obtained. This review will outline the application of anti-VEGF agents by reviewing clinic experiences of bevacizumab and aflibercept, and try to add perspectives on the use of anti-VEGF agents in mCRC

Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation

BackgroundNeuroinflammation is an important factor causing numerous neurodegenerative pathologies. Inflammation can lead to abnormal neuronal structure and function and even death, followed by cognitive dysfunction. There is growing evidence that chlorogenic acid has anti-inflammatory effects and immunomodulatory activity.PurposeThe aim of this study was to elucidate the potential targets and molecular mechanisms of chlorogenic acid in the treatment of neuroinflammation.MethodsWe used the lipopolysaccharide-induced neuroinflammation mouse model and the lipopolysaccharide-stimulated BV-2 cells in vitro model. Behavioral scores and experiments were used to assess cognitive dysfunction in mice. HE staining and immunohistochemistry were used to assess neuronal damage in the mouse brain. Immunofluorescence detected microglia polarization in mouse brain. Western blot and flow cytometry detected the polarization of BV-2 cells. The migration of BV-2 cells was detected by wound healing assay and transwell assay. Potential targets for chlorogenic acid to exert protective effects were predicted by network pharmacology. These targets were then validated using molecular docking and experiments.ResultsThe results of in vivo experiments showed that chlorogenic acid had an obvious ameliorating effect on neuroinflammation-induced cognitive dysfunction. We found that chlorogenic acid was able to inhibit BV-2 cells M1 polarization and promote BV-2 cells M2 polarization in vitro while also inhibiting the abnormal migration of BV-2 cells. Based on the network pharmacology results, we identified the TNF signaling pathway as a key signaling pathway in which chlorogenic acid exerts anti-neuroinflammatory effects. Among them, Akt1, TNF, MMP9, PTGS2, MAPK1, MAPK14, and RELA are the core targets for chlorogenic acid to function.ConclusionChlorogenic acid can inhibit microglial polarization toward the M1 phenotype and improve neuroinflammation-induced cognitive dysfunction in mice by modulating these key targets in the TNF signaling pathway

Assessment of a Novel VEGF Targeted Agent Using Patient-Derived Tumor Tissue Xenograft Models of Colon Carcinoma with Lymphatic and Hepatic Metastases

The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents

Development of a Pneumatically Actuated Quadruped Robot Using Soft–Rigid Hybrid Rotary Joints

Inspired by musculoskeletal systems in nature, this paper presents a pneumatically actuated quadruped robot which utilizes two soft–rigid hybrid rotary joints in each of the four two-degrees of freedom (DoF) planar legs. We first introduce the mechanical design of the rotary joint and the integrated quadruped robot with minimized onboard electronic components. Based on the unique design of the rotary joint, a joint-level PID-based controller was adopted to control the angular displacement of the hip and knee joints of the quadruped robot. Typical gait patterns for legged locomotion, including the walking and trotting gaits, were investigated and designed. Proof-of-concept prototypes of the rotary joint and the quadruped robot were built and tested. The experimental results demonstrated that the rotary joint generated a maximum torque of 5.83 Nm and the quadruped robot was capable of locomotion, achieving a trotting gait of 187.5 mm/s with a frequency of 1.25 Hz and a walking gait of 12.8 mm/s with a gait cycle of 7.84 s. This study reveals that, compared to soft-legged robots, the quadruped robot has a simplified analytical model for motion control, size scalability and high movement speeds, thereby exhibiting significant potential for applications in extreme environments

Underwater Turbid Media Stokes-Based Polarimetric Recovery

Underwater optical imaging for information acquisition has always been an innovative and crucial research direction. Unlike imaging in the air medium, the underwater optical environment is more intricate. From an optical perspective, natural factors such as turbulence and suspended particles in the water cause issues like light scattering and attenuation, leading to color distortion, loss of details, decreased contrast, and overall blurriness. These challenges significantly impact the acquisition of underwater image information, rendering subsequent algorithms reliant on such data unable to function properly. Therefore, this paper proposes a method for underwater image restoration using Stokes linearly polarized light, specifically tailored to the challenges of underwater complex optical imaging environments. This method effectively utilizes linear polarization information and designs a system that uses the information of the first few frames to calculate the enhanced images of the later frames. By doing so, it achieves real-time underwater Stokes linear polarized imaging while minimizing human interference during the imaging process. Furthermore, the paper provides a comprehensive analysis of the deficiencies observed during the testing of the method and proposes improvement perspectives, along with offering insights into potential future research directions

The disulfidptosis-related signature predicts prognosis and immune features in glioma patients

Abstract Glioma is the most common primary malignant tumor in the central nervous system. Disulfidptosis is a recently identified programmed cell death in tumor cells overexpressing SLC7A11 under glucose starvation. Clinical prognostic significance of disulfidptosis has been reported in several tumors, and in this study, we explored the correlation of disulfidptosis with clinical prognosis, immune cell infiltration, and immunotherapy response in glioma. A total of 1592 glioma patients were included in this study, including 691 glioma patients from The Cancer Genomic Atlas (TCGA), 300 patients with from the Chinese Glioma Genomic Atlas (CGGA) array, 325 patients from CGGA sequencing, and 276 patients from Gene Expression Omnibus (GEO) GSE16011. R software (V4.2.2) and several R packages were applied to develop the risk score model and correlation calculation and visualization. Three disulfidptosis-related genes, LRPPRC, RPN1, and GYS1, were screened out and applied to establish the risk score model. Low-risk patients exhibit favorable prognosis, and the disulfidptosis-related signature significantly correlated with clinicopathological properties, molecular subtypes, and immunosuppressive microenvironment of glioma patients. We developed a disulfidptosis-related risk model to predict the prognosis and immune features in glioma patients, and this risk model may be applied as an independent prognostic factor for glioma

Modulating barriers of tumor microenvironment through nanocarrier systems for improved cancer immunotherapy: a review of current status and future perspective

Cancer immunotherapy suppresses and destroys tumors by re-activating and sustaining the tumor-immune process, and thus improving the immune response of the body to the tumor. Immunotherapeutic strategies are showing promising results in pre-clinical and clinical trials, however, tumor microenvironment (TME) is extremely immunosuppressive. Thus, their translation from labs to clinics still faces issues. Recently, nanomaterial-based strategies have been developed to modulate the TME for robust immunotherapeutic responses. The combination of nanotechnology with immunotherapy potentiates the effectiveness of immunotherapy by increasing delivery and retention, and by reducing immunomodulation toxicity. This review aims to highlight the barriers offered by TME for hindering the efficiency of immunotherapy for cancer treatment. Next, we highlight various nano-carriers based strategies for modulating those barriers for achieving better therapeutic efficacy of cancer immunotherapy with higher safety. This review will add to the body of scientific knowledge and will be a good reference material for academia and industries