Assessing the impact of Medical Education's Innovation & Entrepreneurship Program in China.

OBJECTIVE: A growing number of clinical undergraduates are chosen to enter institutions for higher education biotechnology and industry workforce, though most need more laboratory experience training and business practice. Innovation and Entrepreneurship Program (I&E Program) can benefit from biological experiment and commercialization training largely absent from standard clinical medical educational curricula. Our study investigates the impact and status of the I&E Program in enhancing medical students' research and entrepreneurial abilities and provides recommendations for improving this program. METHODS: A cross-sectional study was applied by delivering a questionnaire to survey medical students from Central South University who participated in the I&E Program. The questionnaire consisted of three parts: basic information, the impact of the I&E Program on medical students' research and entrepreneurial abilities, and attitudes and recommendations regarding the I&E Program. RESULTS: Many students participating in the I&E Program have received competition awards and improved their academic experience, article writing, and application patents. Their research-related abilities have been enhanced, including in-lab techniques, theoretical research skills, data analysis knowledge, clinical research skills, experimental research skills, entrepreneurship, data analysis ability, teamwork, and communication. While 73.93% of students express satisfaction with the I&E Program, there are still several areas of improvement, including more robust practical components, increased support, and enhanced teamwork. CONCLUSION: The scale of the I&E Program is rapidly expanding to address scientific research or business skills needed by college students in the new era. However, more programs still need to be discontinued during their further study. The I&E Program significantly enhances research abilities and fosters confidence in their study. This analysis emphasizes the importance of research-oriented and interdisciplinary education for students' holistic development in medical schools compared with formal medical education.

Prepubertal exposure to polycyclic aromatic hydrocarbons are associated with early pubertal development onset in boys: A longitudinal study.

OBJECTIVE: To investigate the effects of polycyclic aromatic hydrocarbons(PAHs) on puberty in boys. METHODS: 695 subjects were selected from four primary schools in Chongqing, China. 675 urine samples from these boys were collected four PAH metabolites: 1-hydroxypyrene, 2-hydroxynaphthoic, 2-hydroxyfluorene, and 9-hydroxyphenanthrene. Pubertal development of 695 boys was assessed at follow-up visits starting in December 2015 and occurring every six months thereafter until now, data used in this article ending in June 2021. A total of 12 follow-up visits were performed. Cox proportional hazards regression models were used to analyze the relationship between PAH metabolite concentrations and indicators of pubertal timing. RESULTS: The mean age at puberty onset of testicular volume, facial hair, pubic hair, first ejaculation, and axillary hair in boys was 11.66, 12.43, 12.51, 12.72 and 13.70 years, respectively. Cox proportional hazards regression models showed that boys with moderate level of 1-OHPyr exposure was associated with earlier testicular development (hazard ratio [HR] = 1.276, 95% confidence interval [CI]: 1.006-1.619), with moderate level of 2-OHNap were at higher risk of early testicular development (HR = 1.273, 95% CI: 1.002-1.617) and early axillary hair development (HR = 1.355, 95% CI: 1.040-1.764), with moderate level of 2-OHFlu was associated with earlier pubic hair development (HR = 1.256, 95% CI: 1.001-1.577), with high level of 9-OHPhe were at higher risk of early fisrt ejaculation (HR = 1.333, 95% CI: 1.005-1.767) and early facial hair development (HR = 1.393, 95% CI: 1.059-1.831). CONCLUSION: Prepubertal exposure to PAHs may be associated with earlier pubertal development in boys.

Tumor­suppressive effects of Smad­ubiquitination regulator 2 in papillary thyroid carcinoma.

Smad-ubiquitination regulator 2 (SMURF2) functions as a homolog of E6AP carboxyl terminus-type E3 ubiquitin ligase to regulate cell cycle progression and tumor growth factor expression. SMURF2 has been revealed to function as a tumor suppressor in a number of cancers; however, its function in papillary thyroid carcinoma (PTC) remains largely unknown. Therefore, the aim of the present study was to investigate the function of SMURF2 in PTC. Reverse transcription-quantitative PCR and western blotting were used to detect cellular expression of SMURF2 in vitro. After increasing or inhibiting the expression of SMURF2, MTT was used to detect the effect on tumor cell proliferation and Transwell assays were used to detect the effect on tumor cell migration and invasion. Finally, ELISA was used to detect the effects on glucose and glutamine metabolism in tumor cells and the findings revealed that SMURF2 was downregulated in PTC tissues. Moreover, SMURF2 inhibited the proliferation, invasion and migration of PTC cells, and promoted their apoptosis. Finally, SMURF2 inhibited cell glycolysis and glutaminolysis and affected metabolism in the PTC cell line, TPC-1. Thus, the findings of the present study suggest that SMURF2 may be a potential target in the treatment of PTC.

Ultramicroporous Tröger's Base Framework Membranes for pH-Neutral Aqueous Organic Redox Flow Batteries.

Processable polymers of intrinsic microporosity (PIMs) are emerging as promising candidates for next-generation ion exchange membranes (IEMs). However, especially with high ion exchange capacity (IEC), IEMs derived from PIMs suffer from severe swelling, thus, resulting in decreased selectivity. To solve this problem, we report ultramicroporous polymer framework membranes constructed with rigid Tröger's Base network chains, which are fabricated via an organic sol-gel process. These membranes demonstrate excellent antiswelling, with swelling ratios below 4.5% at a high IEC of 2.09 mmol g-1, outperforming currently reported PIM membranes. The rigid ultramicropore confinement and charged modification of pore channels endow membranes with both very high size-exclusion selectivity and competitive ion conductivity. The membranes thus enable the efficient and stable operation of pH-neutral aqueous organic redox flow batteries (AORFBs). This work presents the advantages of polymer framework materials as IEMs and calls for increasing attention to extending their varieties and utilization in other applications.

PI3Kδ Mediates Fibrosis by Patient-Derived Vitreous.

The epithelial-mesenchymal transition (EMT) is a fundamental process in developing fibrotic diseases, including forming epiretinal membranes (ERMs). ERMs can result in irreversible vision loss. Previous research has demonstrated that vitreous (VIT) derived from patients with proliferative diabetic retinopathy can stimulate angiogenesis through the Axl/PI3K/Akt pathway. Building upon this knowledge, we aimed to explore the influence of VIT from patients with macular membranes in ARPE-19 cells. Our findings reveal that patient-derived VIT from individuals with macular membranes promotes EMT and phosphoinositide 3-kinase-delta (PI3Kδ) expression in ARPE-19 cells. To elucidate the function of PI3Kδ in the ERM, we conducted experiments involving the knockout of p110δ, a key subunit of PI3Kδ, and observed that its absence hinders EMT induced by patient-derived VIT. Moreover, p110δ depletion reduces cell proliferation and migration in ARPE-19 cells. Remarkably, these effects were further corroborated by applying the p110δ inhibitor idelalisib, which blocks fibrosis in the laser-induced fibrosis model. Collectively, our results propose that p110δ plays a critical role in the progression of ERMs. Consequently, targeting p110δ emerges as a promising therapeutic approach for mitigating fibrosis. These findings contribute to a better understanding of the underlying mechanisms involved in ERM formation and highlight the potential for p110δ-directed antifibrotic therapy in retinal diseases.

Enhanced Downstream Processing for a Cell-Based Avian Influenza (H5N1) Vaccine.

H5N1 highly pathogenic avian influenza virus (HPAIV) infections pose a significant threat to human health, with a mortality rate of around 50%. Limited global approval of H5N1 HPAIV vaccines, excluding China, prompted the need to address safety concerns related to MDCK cell tumorigenicity. Our objective was to improve vaccine safety by minimizing residual DNA and host cell protein (HCP). We developed a downstream processing method for the cell-based H5N1 HPAIV vaccine, employing CaptoTM Core 700, a multimodal resin, for polishing. Hydrophobic-interaction chromatography (HIC) with polypropylene glycol as a functional group facilitated the reversible binding of virus particles for capture. Following the two-step chromatographic process, virus recovery reached 68.16%. Additionally, HCP and DNA levels were reduced to 2112.60 ng/mL and 6.4 ng/mL, respectively. Western blot, high-performance liquid chromatography (HPLC), and transmission electron microscopy (TEM) confirmed the presence of the required antigen with a spherical shape and appropriate particle size. Overall, our presented two-step downstream process demonstrates potential as an efficient and cost-effective platform technology for cell-based influenza (H5N1 HPAIV) vaccines.

Drug targets regulate systemic metabolism and provide new horizons to treat nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH), is the advanced stage of nonalcoholic fatty liver disease (NAFLD) with rapidly rising global prevalence. It is featured with severe hepatocyte apoptosis, inflammation and hepatic lipogenesis. The drugs directly targeting the processes of steatosis, inflammation and fibrosis are currently under clinical investigation. Nevertheless, the long-term ineffectiveness and remarkable adverse effects are well documented, and new concepts are required to tackle with the root causes of NASH progression. We critically assess the recently validated drug targets that regulate the systemic metabolism to ameliorate NASH. Thermogenesis promoted by mitochondrial uncouplers restores systemic energy expenditure. Furthermore, regulation of mitochondrial proteases and proteins that are pivotal for intracellular metabolic homeostasis normalize mitochondrial function. Secreted proteins also improve systemic metabolism, and NASH is ameliorated by agonizing receptors of secreted proteins with small molecules. We analyze the drug design, the advantages and shortcomings of these novel drug candidates. Meanwhile, the structural modification of current NASH therapeutics significantly increased their selectivity, efficacy and safety. Furthermore, the arising CRISPR-Cas9 screen strategy on liver organoids has enabled the identification of new genes that mediate lipid metabolism, which may serve as promising drug targets. In summary, this article discusses the in-depth novel mechanisms and the multidisciplinary approaches, and they provide new horizons to treat NASH.

SCD1 is the critical signaling hub to mediate metabolic diseases: Mechanism and the development of its inhibitors.

Metabolic diseases, featured with dysregulated energy homeostasis, have become major global health challenges. Patients with metabolic diseases have high probability to manifest multiple complications in lipid metabolism, e.g. obesity, insulin resistance and fatty liver. Therefore, targeting the hub genes in lipid metabolism may systemically ameliorate the metabolic diseases, along with the complications. Stearoyl-CoA desaturase 1(SCD1) is a key enzyme that desaturates the saturated fatty acids (SFAs) derived from de novo lipogenesis or diet to generate monounsaturated fatty acids (MUFAs). SCD1 maintains the metabolic and tissue homeostasis by responding to, and integrating the multiple layers of endogenous stimuli, which is mediated by the synthesized MUFAs. It critically regulates a myriad of physiological processes, including energy homeostasis, development, autophagy, tumorigenesis and inflammation. Aberrant transcriptional and epigenetic activation of SCD1 regulates AMPK/ACC, SIRT1/PGC1α, NcDase/Wnt, etc, and causes aberrant lipid accumulation, thereby promoting the progression of obesity, non-alcoholic fatty liver, diabetes and cancer. This review critically assesses the integrative mechanisms of the (patho)physiological functions of SCD1 in metabolic homeostasis, inflammation and autophagy. For translational perspective, potent SCD1 inhibitors have been developed to treat various types of cancer. We thus discuss the multidisciplinary advances that greatly accelerate the development of SCD1 new inhibitors. In conclusion, besides cancer treatment, SCD1 may serve as the promising target to combat multiple metabolic complications simultaneously.

Direct degradation and stabilization of proteins: New horizons in treatment of nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is featured with excessive hepatic lipid accumulation and its global prevalence is soaring. Nonalcoholic steatohepatitis (NASH), the severe systemic inflammatory subtype of NAFLD, is tightly associated with metabolic comorbidities, and the hepatocytes manifest severe inflammation and ballooning. Currently the therapeutic options for treating NASH are limited. Potent small molecules specifically intervene with the signaling pathways that promote pathogenesis of NASH. Nevertheless they have obvious adverse effects and show long-term ineffectiveness in clinical trials. It poses the fundamental question to efficiently and safely inhibit the pathogenic processes. Targeted protein degradation (TPD) belongs to the direct degradation strategies and is a burgeoning strategy. It utilizes the small molecules to bind to the target proteins and recruit the endogenous proteasome, lysosome and autophagosome-mediated degradation machineries. They effectively and specifically degrade the target proteins. It has exhibited promising therapeutic effects in treatment of cancer, neurodegenerative diseases and other diseases in a catalytic manner at low doses. We critically discuss the principles of multiple direct degradation strategies, especially PROTAC and ATTEC. We extensively analyze their emerging application in degradation of excessive pathogenic proteins and lipid droplets, which promote the progression of NASH. Moreover, we discuss the opposite strategy that utilizes the small molecules to recruit deubiquinases to stabilize the NASH/MASH-suppressing proteins. Their advantages, limitations, as well as the solutions to address the limitations have been analyzed. In summary, the innovative direct degradation strategies provide new insights into design of next-generation therapeutics to combat NASH with optimal safety paradigm and efficiency.

Ion channels regulate energy homeostasis and the progression of metabolic disorders: Novel mechanisms and pharmacology of their modulators.

The progression of metabolic diseases, featured by dysregulated metabolic signaling pathways, is orchestrated by numerous signaling networks. Among the regulators, ion channels transport ions across the membranes and trigger downstream signaling transduction. They critically regulate energy homeostasis and pathogenesis of metabolic diseases and are potential therapeutic targets for treating metabolic disorders. Ion channel blockers have been used to treat diabetes for decades by stimulating insulin secretion, yet with hypoglycemia and other adverse effects. It calls for deeper understanding of the largely elusive regulatory mechanisms, which facilitates the identification of new therapeutic targets and safe drugs against ion channels. In the article, we critically assess the two principal regulatory mechanisms, protein-channel interaction and post-translational modification on the activities of ion channels to modulate energy homeostasis and metabolic disorders through multiple novel mechanisms. Moreover, we discuss the multidisciplinary methods that provide the tools for elucidation of the regulatory mechanisms mediating metabolic disorders by ion channels. In terms of translational perspective, the mechanistic analysis of recently validated ion channels that regulate insulin resistance, body weight control, and adverse effects of current ion channel antagonists are discussed in details. Their small molecule modulators serve as promising new drug candidates to combat metabolic disorders.

Phosphoinositide 3-kinase as a therapeutic target in angiogenic disease.

Phosphoinositide 3-kinases (PI3Ks) generate lipids that control multitudinous intracellular cell signaling events which participate in cell survival and proliferation. In addition, PI3K signaling also contributes to metabolism, immunity, angiogenesis and cardiovascular homeostasis, and many diseases. The diverse actions of PI3K stem from the existence of their various isoforms and a variety of protein effectors. Hence, PI3K isoform-specific inhibitors have already achieved a wonderful effect on treating cancer. Herein, we summarize the molecular mechanism of PI3K inhibitors in preventing the permeability of vessels and neovascularization. Additionally, we briefly illustrate how PI3K signaling modulates blood vessel growth and discuss the different roles that PI3K isoforms play in angiogenesis.

Nintedanib inhibits normal human vitreous-induced epithelial-mesenchymal transition in human retinal pigment epithelial cells.

PURPOSE: In this study, we aim to investigate the potential of nintedanib as a therapeutic approach to proliferative vitreoretinopathy (PVR), which is the leading cause of failure in retinal detachment repair. PVR is characterized by the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, and understanding the effects of nintedanib on EMT in the normal human vitreous (HV)-induced RPE cells is crucial. METHODS: Our research focuses on assessing the impact of nintedanib on HV-induced EMT in human retinal pigment epithelial (ARPE-19) cells in vitro. We employed various techniques, including quantitative real-time PCR (qPCR), western blot analysis, and immunofluorescence staining, to evaluate the mRNA and protein expression of EMT biomarkers in HV-induced ARPE-19 cells. Additionally, we measured the proliferation of RPE cells using cell counting, CCK-8, and Ki-67 assays. Migration was assessed through wound healing and transwell migration assays, while contraction was determined using a collagen gel contraction assay. Morphological changes were examined using phase-contrast microscopy. RESULTS: Our results demonstrate that nintedanib selectively attenuates the upregulation of mesenchymal markers in HV-induced ARPE-19 cells, at both the mRNA and protein levels. Furthermore, nintedanib effectively suppresses the HV-induced proliferation, migration, and contraction of ARPE-19 cells, while maintaining the cells' basal activity. These findings strongly suggest that nintedanib exhibits protective effects against EMT in ARPE-19 cells and could be a promising therapeutic option for PVR. CONCLUSIONS: By elucidating the anti-EMT effects of nintedanib in HV-induced RPE cells, our study highlights the potential of this oral triple tyrosine kinase inhibitor in the treatment of PVR. These findings contribute to the growing body of research aimed at developing novel strategies to prevent and manage PVR, ultimately improving the success rates of retinal detachment repair.

Ligand-independent activation of platelet-derived growth factor receptor ß promotes vitreous-induced contraction of retinal pigment epithelial cells.

BACKGROUND: Epiretinal membranes in patients with proliferative vitreoretinopathy (PVR) consist of extracellular matrix and a number of cell types including retinal pigment epithelial (RPE) cells and fibroblasts, whose contraction causes retinal detachment. In RPE cells depletion of platelet-derived growth factor (PDGF) receptor (PDGFR)ß suppresses vitreous-induced Akt activation, whereas in fibroblasts Akt activation through indirect activation of PDGFRα by growth factors outside the PDGF family (non-PDGFs) plays an essential role in experimental PVR. Whether non-PDGFs in the vitreous, however, were also able to activate PDGFRß in RPE cells remained elusive. METHODS: The CRISPR/Cas9 technology was utilized to edit a genomic PDGFRB locus in RPE cells derived from an epiretinal membrane (RPEM) from a patient with PVR, and a retroviral vector was used to express a truncated PDGFRß short of a PDGF-binding domain in the RPEM cells lacking PDGFRß. Western blot was employed to analyze expression of PDGFRß and α-smooth muscle actin, and signaling events (p-PDGFRß and p-Akt). Cellular assays (proliferation, migration and contraction) were also applied in this study. RESULTS: Expression of a truncated PDGFRß lacking a PDGF-binding domain in the RPEM cells whose PDGFRB gene has been silent using the CRISPR/Cas9 technology restores vitreous-induced Akt activation as well as cell proliferation, epithelial-mesenchymal transition, migration and contraction. In addition, we show that scavenging reactive oxygen species (ROS) with N-acetyl-cysteine and inhibiting Src family kinases (SFKs) with their specific inhibitor SU6656 blunt the vitreous-induced activation of the truncated PDGFRß and Akt as well as the cellular events related to the PVR pathogenesis. These discoveries suggest that in RPE cells PDGFRß can be activated indirectly by non-PDGFs in the vitreous via an intracellular pathway of ROS/SFKs to facilitate the development of PVR, thereby providing novel opportunities for PVR therapeutics. CONCLUSION: The data shown here will improve our understanding of the mechanism by which PDGFRß can be activated by non-PDGFs in the vitreous via an intracellular route of ROS/SFKs and provide a conceptual foundation for preventing PVR by inhibiting PDGFRß transactivation (ligand-independent activation).

Upregulation of ubiquitin carboxy­terminal hydrolase 47 (USP47) in papillary thyroid carcinoma ex vivo and reduction of tumor cell malignant behaviors after USP47 knockdown by stabilizing SATB1 expression in vitro.

Aberrant ubiquitination contributes to cancer development, including thyroid carcinoma. The present study assessed the expression of ubiquitin carboxy-terminal hydrolase 47 (USP47) and underlying molecular events in the development of papillary thyroid carcinoma (PTC). The effects of USP47 on PTC cell invasion and migration were analyzed by Transwell assays, while. the effects of USP47 and SATB1on PTC cell gene expression and changes in tumor cell metabolism were assayed by reverse transcription-quantitative PCR, western bolt, or ELISA, respectively. The expression of USP47 mRNA and protein was upregulated in PTC tissue and associated with the PTC tumor size. Knockdown of USP47 expression in PTC cell lines (TPC-1 and K1), decreased the cell proliferation mobility and invasion capacities, whereas USP47 overexpression in these cell lines showed an inverse effect and promoted cell glycolysis and glutamine metabolism. Moreover, expression of special AT-rich sequence-binding protein-1 (SATB1) was high in PTC tissue and was associated with USP47 expression. SATB1 expression promoted tumor cell glycolysis and glutamine metabolism, while USP47 protein bound to and deubiquitinated SATB1 to increase its intracellular levels, thus promoting glycolysis and glutamine metabolism. USP47 promotion of PTC development may be due to its stabilization of SATB1 protein, suggesting that targeting the USP47/SATB1 signaling axis may serve as a therapeutic intervention for PTC.

Electric Control of Helicity-Dependent Photocurrent and Surface Polarity Detection on Two-Dimensional Bi2O2Se Nanosheets.

Bismuth oxyselenide (Bi2O2Se) is a two-dimensional (2D) layered semiconductor material with high electron Hall mobility and excellent environmental stability as well as strong spin-orbit interaction (SOI), which has attracted intense attention for application in spintronic and spin optoelectronic devices. However, a comprehensive study of spin photocurrent and its microscopic origin in Bi2O2Se is still missing. Here, the helicity-dependent photocurrent (HDPC) was investigated in Bi2O2Se nanosheets. By analyzing the dependence of HDPC on the angle of incidence, we find that the HDPC originates from surface states with Cs symmetry in Bi2O2Se, which can be attributed to the circular photogalvanic effect (CPGE) and circular photon drag effect (CPDE). It is revealed that the HDPC current almost changes linearly with the source-drain voltage. Furthermore, we demonstrate effective tuning of HDPC in Bi2O2Se by ionic liquid gating, indicating that the spin splitting of the surface electronic structure is effectively tuned. By analyzing the gate voltage dependence of HDPC, we can unambiguously identify the surface polarity and the surface electronic structure of Bi2O2Se. The large HDPC in Bi2O2Se nanosheets and its efficient electrical tuning demonstrate that 2D Bi2O2Se nanosheets may provide a good platform for opto-spintronics devices.

Emotional and Behavioral Changes in Preschool Firstborn Children During Transition to Siblinghood: A Mixed Methods Study.

Purpose: To help firstborn children in families expecting a second child navigate the role transition more smoothly, we investigated the emotional and behavioral changes of firstborn children during the transition to siblinghood (TTS) and the factors that contribute to these changes. Patients and Methods: From March to December 2019, a total of 97 firstborn children (Mage=3.00± 0.97, and female = 51) were included in the study through a questionnaire survey of their mothers, and two follow-up visits were conducted in Chongqing, China. Individual in-depth interviews were conducted with 14 mothers. Results: Both quantitative and qualitative results suggest that emotional and behavioral problems of firstborn children tend to increase during TTS, particularly in issues such as anxiety/depression, somatic complaints, withdrawal, sleep problems, attention problems, and aggressive behavior, as well as internalization problems, externalization problems and total problems in the quantitative study (P<0.05). A poor father-child relationship may increase emotional and behavioral problems in firstborn children (P=0.05). Further qualitative analysis found that younger age and outgoing personality of the firstborn child may improve the emotional and behavioral problems. Conclusion: The firstborn children did have more emotional and behavioral problems during TTS. But these problems can be regulated by family factors and their own characteristics.

Genome Editing Inhibits Retinal Angiogenesis in a Mouse Model of Oxygen-Induced Retinopathy.

This protocol describes a novel approach harnessing the technology of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9-based gene editing for treating retinal angiogenesis. In this system, adeno-associated virus (AAV)-mediated CRISPR/Cas9 was employed to edit the genome of vascular endothelial growth factor receptor (VEGFR)2 in retinal vascular endothelial cells in a mouse model of oxygen-induced retinopathy. The results showed that genome editing of VEGFR2 suppressed pathological retinal angiogenesis. This mouse model mimics a critical aspect of abnormal retinal angiogenesis in patients with neovascular diabetic retinopathy and retinopathy of prematurity, indicating genome editing has high potential for treating angiogenesis-associated retinopathies.

Relationship Between Infiltration of CD163+ TAMs, FoxP3+ Tregs, or CD66b+ TANs and Cell Differentiation in Colorectal Cancer Tissues.

BACKGROUND/AIMS: There are many studies on immune cell infiltration in colorectal cancer, including FoxP3+-regulatory T cells, CD66b+ tumorassociated neutrophils, and CD163+ tumor-associated macrophages. These studies mainly focus on the relationship between cell infiltration and tumor progression, prognosis, and so on, while the relationship between tumor cell differentiation and cell infiltration is poorly understood. We aimed to explore the relationship between cell infiltration and tumor cell differentiation. MATERIALS AND METHODS: The tissue microarray and immunohistochemistry were used to determine the infiltration of FoxP3+-regulatory T cells, CD66b+ tumor-associated neutrophils, and CD163+ tumor-associated macrophages in 673 colorectal cancer samples from the Second Affiliated Hospital, Wenzhou Medical University (2001-2009). Kruskal-Wallis test was used to assess the positive cell infiltration in colorectal cancer tissues with tumor cells of varying degrees of differentiation. RESULTS: The number of CD163+ tumor-associated macrophages, FoxP3+-regulatory T cells, and CD66b+ tumor-associated neutrophils in colorectal cancer tissues was different, and the level of CD163+ tumor-associated macrophages was the highest while the level of FoxP3+-regulatory T cells was the least. There were significant differences in the cell infiltration of colorectal cancer tissue cells with different levels of differentiation (P < .05). The highest infiltration of CD163+ tumor-associated macrophages (154.07 ± 6.95) and FoxP3+-regulatory T cells (20.14 ± 2.07) were in the poorly differentiated colorectal cancer tissues, while the higher infiltration of CD66b+ tumor-associated neutrophils was in the moderately or well-differentiated colorectal cancer tissues (36.70 ± 1.10 and 36.09 ± 1.06, respectively). CONCLUSION: Infiltration of CD163+ tumor-associated macrophages, FoxP3+-regulatory T cells, and CD66b+ tumor-associated neutrophils in colorectal cancer tissues may be related to the differentiation of tumor cells.

Nintedanib prevents TGF-ß2-induced epithelial-mesenchymal transition in retinal pigment epithelial cells.

Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a key fibrosis pathogenesis in proliferative vitreoretinopathy (PVR). However, few medicines can prevent proliferative membranes and cell proliferation in the clinic. Nintedanib, a tyrosine kinase inhibitor, has been shown to prevent fibrosis and be anti-inflammatory in multiple organ fibrosis. In our study, 0.1, 1, 10 µM nintedanib was added to 20 ng/mL transforming growth factor beta 2 (TGF-ß2)-induced EMT in ARPE-19 cells. Western blot and immunofluorescence assay showed that 1 µM nintedanib suppressed TGF-ß2-induced E-cadherin expression decreased and Fibronectin, N-cadherin, Vimentin, and α-SMA expression increased. Quantitative real-time PCR results showed that 1 µM nintedanib decreased TGF-ß2-induced increase in SNAI1, Vimentin, and Fibronectin expression and increased TGF-ß2-induced decrease in E-cadherin expression. In addition, the CCK-8 assay, wound healing assay, and collagen gel contraction assay also showed that 1 µM nintedanib ameliorated TGF-ß2-induced cell proliferation, migration, and contraction, respectively. These results suggested that nintedanib inhibits TGF-ß2-induced EMT in ARPE-19 cells, which may be a potential pharmacological treatment for PVR.