The application of organoids in colorectal diseases.

Intestinal organoids are a three-dimensional cell culture model derived from colon or pluripotent stem cells. Intestinal organoids constructed in vitro strongly mimic the colon epithelium in cell composition, tissue architecture, and specific functions, replicating the colon epithelium in an in vitro culture environment. As an emerging biomedical technology, organoid technology has unique advantages over traditional two-dimensional culture in preserving parental gene expression and mutation, cell function, and biological characteristics. It has shown great potential in the research and treatment of colorectal diseases. Organoid technology has been widely applied in research on colorectal topics, including intestinal tumors, inflammatory bowel disease, infectious diarrhea, and intestinal injury regeneration. This review focuses on the application of organoid technology in colorectal diseases, including the basic principles and preparation methods of organoids, and explores the pathogenesis of and personalized treatment plans for various colorectal diseases to provide a valuable reference for organoid technology development and application.

The involvement and application potential of exosomes in breast cancer immunotherapy.

Breast cancer has a high incidence and a heightened propensity for metastasis. The absence of precise targets for effective intervention makes it imperative to devise enhanced treatment strategies. Exosomes, characterized by a lipid bilayer and ranging in size from 30 to 150 nm, can be actively released by various cells, including those in tumors. Exosomes derived from distinct subsets of immune cells have been shown to modulate the immune microenvironment within tumors and influence breast cancer progression. In addition, tumor-derived exosomes have been shown to contribute to breast cancer development and progression and may become a new target for breast cancer immunotherapy. Tumor immunotherapy has become an option for managing tumors, and exosomes have become therapeutic vectors that can be used for various pathological conditions. Edited exosomes can be used as nanoscale drug delivery systems for breast cancer therapy, contributing to the remodeling of immunosuppressive tumor microenvironments and influencing the efficacy of immunotherapy. This review discusses the regulatory role of exosomes from different cells in breast cancer and the latest applications of exosomes as nanoscale drug delivery systems and immunotherapeutic agents in breast cancer, showing the development prospects of exosomes in the clinical treatment of breast cancer.

Mechanisms and therapeutic strategies of extracellular vesicles in cardiovascular diseases.

Cardiovascular disease (CVD) significantly impacts global society since it is the leading cause of death and disability worldwide, and extracellular vesicle (EV)-based therapies have been extensively investigated. EV delivery is involved in mediating the progression of CVDs and has great potential to be biomarker and therapeutic molecular carrier. Besides, EVs from stem cells and cardiac cells can effectively protect the heart from various pathologic conditions, and then serve as an alternative treatment for CVDs. Moreover, the research of using EVs as delivery carriers of therapeutic molecules, membrane engineering modification of EVs, or combining EVs with biomaterials further improves the application potential of EVs in clinical treatment. However, currently there are only a few articles summarizing the application of EVs in CVDs. This review provides an overview of the role of EVs in the pathogenesis and diagnosis of CVDs. It also focuses on how EVs promote the repair of myocardial injury and therapeutic methods of CVDs. In conclusion, it is of great significance to review the research on the application of EVs in the treatment of CVDs, which lays a foundation for further exploration of the role of EVs, and clarifies the prospect of EVs in the treatment of myocardial injury.

Common Allergens and Immune Responses Associated with Allergic Rhinitis in China.

Allergic rhinitis (AR) is a chronic allergic disease of the upper respiratory system that affects approximately 10-40% of the global population. Due to the large number of plant pollen allergens with obvious seasonal variations, AR is common in China. AR is primarily caused by the abnormal regulation of the immune system. Its pathophysiological mechanism involves a series of immune cells and immune mediators, including cytokines. The present review summarizes the common allergens in China and the complex pathophysiological mechanism of AR. Additionally, host allergen contact, signal transduction, immune cell activation, cytokine release, and a series of inflammatory reactions are described according to their sequence of occurrence.

Decreased acetylation of HDGF improves oviduct production in Rana dybowskii, Rana amurensis, and Rana huanrenensis.

The oviduct of female Rana dybowskii is a functional food and can be used as a component of Traditional Chinese medicine. The differentially expressed genes enriched was screened in cell growth of three Rana species. We quantitatively analyzed 4549 proteins using proteomic techniques, enriching the differentially expressed proteins of Rana for growth and signal transduction. The results showed that log2 expression of hepatoma-derived growth factor (HDGF) was increased. We further verified 5 specific differential genes (EIF4a, EIF4g, HDGF1, HDGF2 and SF1) and found that HDGF expression was increased in Rana dybowskii. Through acetylation modification analysis, we identified 1534 acetylation modification sites in 603 proteins, including HDGF, and found that HDGF acetylation expression was significantly reduced in Rana dybowskii. Our results suggest that HDGF is involved in the development of oviductus ranae, which is regulated by acetylation modification.

Clinical Efficacy and Safety of Tumor Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy for Ovarian Cancer.

Objective: To assess the clinical efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer. Methods: From April 2018 to November 2021, 66 patients with ovarian cancer were admitted to our hospital and randomly allocated to undergo intravenous chemotherapy following CRS (the observation group) or CRS with HIPEC (the experimental group) using a parallel randomized technique, with 33 cases in each group. Clinical effectiveness, intraoperative and postoperative recovery, VEGF level, T-lymphocyte subpopulation cell level, adverse events, and patient survival were all outcome metrics. Results: CRS plus HIPEC was associated with significantly higher clinical efficacy versus CRS alone (P < 0.05). The difference in the intraoperative bleeding and operative time between the two groups did not meet the statistical standard (P > 0.05). Patients in the experimental group experienced shorter postoperative chemotherapy and length of hospital stay than those in the observation group (P < 0.05). CRS plus HIPEC resulted in significantly lower levels of VEGFA, VEGFB, and VEGFC and higher levels of CD3+, CD4+, and CD3+/CD4+ than CRS alone (P < 0.05). The two groups of patients had a similar incidence of adverse events (P > 0.05). The experimental group showed a longer median survival (25 months) and a 1-year survival rate (79.55%) than the observation group (22 months, 49.56%) (log rank = 20.411, P < 0.05). A significantly lower 1-year recurrence rate was observed in the experimental group than in the observation group (P < 0.05). Conclusion: CRS plus HIPEC effectively improves the clinical efficacy of ovarian cancer patients, prolongs the survival of patients, and improves the level of VEGF and T-lymphocyte subpopulation cells, with a manageable safety. In addition, the treatment method can improve the therapeutic effect, reduce the toxic and side effects, and improve the immunity of the body, which is worthy of clinical promotion.

Remote sensing identification of green plastic cover in urban built-up areas.

Urban renewal can transform areas that are not adapted to modern urban life, allowing them to redevelop and flourish; however, the renewal process generates many new construction sites, producing environmentally harmful construction dust. The widespread use of urban green plastic cover (GPC) at construction sites and the development of high-resolution satellites have made it possible to extract the spatial distribution of construction sites and provide a basis for environmental protection authorities to protect against dust sources. Existing GPC extraction methods based on remote sensing images are either difficult to obtain the exact boundary of GPC or cannot provide corresponding algorithms according to different application scenarios. In order to determine the distribution of green plastic cover in the built-up area, this paper selects a variety of typical machine learning algorithms to classify the land cover of the test area image and selects K-nearest neighbor as the best machine learning algorithm through accuracy evaluation. Then multiple deep learning methods were used and the top networks with high overall scores were selected by comparing various aspects. Then these networks were used to predict the GPC of the test area image, and the accuracy evaluation results showed that the segmentation accuracy of deep learning was much higher than that of machine learning methods, but it took more time to predict. Therefore, combining different application scenarios, this paper gives the corresponding suggested methods for GPC extraction.

Advances of hydrogel combined with stem cells in promoting chronic wound healing.

Wounds can be divided into two categories, acute and chronic. Acute wounds heal through the normal wound healing process. However, chronic wounds take longer to heal, leading to inflammation, pain, serious complications, and an economic burden of treatment costs. In addition, diabetes and burns are common causes of chronic wounds that are difficult to treat. The rapid and thorough treatment of chronic wounds, including diabetes wounds and burns, represents a significant unmet medical need. Wound dressings play an essential role in chronic wound treatment. Various biomaterials for wound healing have been developed. Among these, hydrogels are widely used as wound care materials due to their good biocompatibility, moisturizing effect, adhesion, and ductility. Wound healing is a complex process influenced by multiple factors and regulatory mechanisms in which stem cells play an important role. With the deepening of stem cell and regenerative medicine research, chronic wound treatment using stem cells has become an important field in medical research. More importantly, the combination of stem cells and stem cell derivatives with hydrogel is an attractive research topic in hydrogel preparation that offers great potential in chronic wound treatment. This review will illustrate the development and application of advanced stem cell therapy-based hydrogels in chronic wound healing, especially in diabetic wounds and burns.

Interferon and interferon-stimulated genes in HBV treatment.

Human hepatitis B virus (HBV) is a small enveloped DNA virus with a complex life cycle. It is the causative agent of acute and chronic hepatitis. HBV can resist immune system responses and often causes persistent chronic infections. HBV is the leading cause of liver cancer and cirrhosis. Interferons (IFNs) are cytokines with antiviral, immunomodulatory, and antitumor properties. IFNs are glycoproteins with a strong antiviral activity that plays an important role in adaptive and innate immune responses. They are classified into three categories (type I, II, and III) based on the structure of their cell-surface receptors. As an effective drug for controlling chronic viral infections, Type I IFNs are approved to be clinically used for the treatment of HBV infection. The therapeutic effect of interferon will be enhanced when combined with other drugs. IFNs play a biological function by inducing the expression of hundreds of IFN-stimulated genes (ISGs) in the host cells, which are responsible for the inhibiting of HBV replication, transcription, and other important processes. Animal models of HBV, such as chimpanzees, are also important tools for studying IFN treatment and ISG regulation. In the present review, we summarized the recent progress in IFN-HBV treatment and focused on its mechanism through the interaction between HBV and ISGs.

Effect of femtosecond laser ablate ultra-fine microgrooves on surface properties of dental zirconia materials.

OBJECTIVES: Zirconia is an important dental implant material, yet it surfaces milling method is still under investigation. To explore the feasibility of laser etching in processing fine micro grooves on the surface of zirconia and to observe fine micro groove structure' influence on mouse embryonic osteoblasts, the survey was conducted. METHODS: 31 zirconia discs were made and polished to mirror surface. Then, they were divided into 3 groups: the mirror group, the femtosecond laser ablated microgroove group and the air blasted + acid etched group. Then, the surface properties of zirconia discs were analyzed by Scanning Electron Microscope/Energy Dispersive Spectrometer (SEM/EDS), X-Ray Diffraction (XRD), Atomic Force Microscope (AFM), water contact angle test and micro-Vickers hardness test. The biocompatibility of each machined zirconia was tested by cell proliferation test and SEM analyze of cell morphology. Then, the effect of these surface treatment to MC-3T3-E1's osteogenic differentiation was evaluated by Q-PCR test. RESULTS: SEM image showed that the femtosecond laser is a reliable method for forming regular-arranged microgrooves with pitch width of around 5 µm. EDS and XRD indicated that there were stable and purified tetragonal crystal system on the laser-roughened surface. AFM suggested that laser machining generated rougher surface (Ra) (271.7 ± 67.2 nm) than other groups. Furthermore, the contact angle showed laser ablated grooves induced anisotropic wetting. The micro-Vickers hardness test ascertained that laser-ablation strengthened zirconia surface. In vitro experiment showed that MC-3T3-E1 grown along the long axis of microgrooves on the first day. Besides, Real time PCR implied that osteogenesis-related gene expression OPN and ALP was much higher than the rest groups. SIGNIFICANCE: Femtosecond laser is able to machine zirconia with ultra-fine microgrooves (around 2.5 µm). These structures promoted MC-3T3-E1 cell to line along the microstructure and differentiate into osteogenic cells. Thus, femtosecond laser might be a potential processing options for zirconia micro-texturing.

The role of major immune cells in myocardial infarction.

Myocardial infarction (MI) is a cardiovascular disease (CVD) with high morbidity and mortality worldwide, often leading to adverse cardiac remodeling and heart failure, which is a serious threat to human life and health. The immune system makes an important contribution to the maintenance of normal cardiac function. In the disease process of MI, necrotic cardiomyocytes release signals that activate nonspecific immunity and trigger the action of specific immunity. Complex immune cells play an important role in all stages of MI progression by removing necrotic cardiomyocytes and tissue and promoting the healing of damaged tissue cells. With the development of biomaterials, cardiac patches have become an emerging method of repairing MI, and the development of engineered cardiac patches through the construction of multiple animal models of MI can help treat MI. This review introduces immune cells involved in the development of MI, summarizes the commonly used animal models of MI and the newly developed cardiac patch, so as to provide scientific reference for the accurate diagnosis and effective treatment of MI.

Angiogenic Aptamer-Modified Tetrahedral Framework Nucleic Acid Promotes Angiogenesis In Vitro and In Vivo.

In a search for a solution to large-area soft and hard tissue defects, whether or not tissue regeneration or tissue-substitutes transplantation is used, the problems with angiogenesis need to be solved urgently. Thus, a new and efficient proangiogenic approach is needed. Nanoengineering systems have been considered one of the most promising approaches. In this study, we modify the tetrahedral framework nucleic acid (tFNA) for the first time with two different angiogenic DNA aptamers to form aptamer-tFNA nanostructures, tFNA-Apt02 and tFNA-AptVEGF, and the effects of them on angiogenesis both in vitro and in vivo are investigated. We develop new nanomaterials for enhancing angiogenesis to solve the problem of tissue engineering vascularization and ischemic diseases. The results of our study confirm that tFNA-Apt02 and tFNA-AptVEGF has a stronger ability to accelerate endothelial cell proliferation and migration, tubule formation, spheroid sprouting, and angiogenesis in vivo. We first demonstrate that the engineered novel tFNA-Apt02 and tFNA-AptVEGF have promoting effects on angiogenesis both in vitro and in vivo and provide a theoretical basis and opportunity for their application in tissues engineering vascularization and ischemic diseases.

Chrysin Induced Cell Apoptosis Through H19/let-7a/COPB2 Axis in Gastric Cancer Cells and Inhibited Tumor Growth.

BACKGROUND: Chrysin is a natural flavone that is present in honey and has exhibited anti-tumor properties. It has been widely studied as a therapeutic agent for the treatment of various types of cancers. The objectives of this present study were to elucidate how chrysin regulates non-coding RNA expression to exert anti-tumor effects in gastric cancer cells. METHODS: Through the use of RNA sequencing, we investigated the differential expression of mRNAs in gastric cancer cells treated with chrysin. Furthermore, COPB2, H19 and let-7a overexpression and knockdown were conducted. Other features, including cell growth, apoptosis, migration and invasion, were also analyzed. Knockout of the COPB2 gene was generated using the CRISPR/Cas9 system for tumor growth analysis in vivo. RESULTS: Our results identified COPB2 as a differentially expressed mRNA that is down-regulated following treatment with chrysin. Moreover, the results showed that chrysin can induce cellular apoptosis and inhibit cell migration and invasion. To further determine the underlying mechanism of COPB2 expression, we investigated the expression of the long non-coding RNA (lncRNA) H19 and microRNA let-7a. Our results showed that treatment with chrysin significantly increased let-7a expression and reduced the expression of H19 and COPB2. In addition, our results demonstrated that reduced expression of COPB2 markedly promotes cell apoptosis. Finally, in vivo data suggested that COPB2 expression is related to tumor growth. CONCLUSIONS: This study suggests that chrysin exhibited anti-tumor effects through a H19/let-7a/COPB2 axis.

Enhanced Penetrability of a Tetrahedral Framework Nucleic Acid by Modification with iRGD for DOX-Targeted Delivery to Triple-Negative Breast Cancer.

Poor penetrability and nonselective distribution of chemotherapeutic drugs are the main obstacles for chemotherapy for triple-negative breast cancer (TNBC). In our work, we developed a DNA-based drug delivery system to surmount these barriers. In addition, a tetrahedral framework nucleic acid (tFNA) was employed to load doxorubicin (DOX) with iRGD decoration to form a novel nanoparticle (tFNA/DOX@iRGD). The RGD sequence and the CendR motif in iRGD are used in tumor targeting and tissue penetration, respectively. Based on the sustained serum stability and pH-sensitive release behavior of DOX, tFNA/DOX@iRGD exhibited superiority for biomedical application. Moreover, tFNA/DOX@iRGD showed excellent deep penetration and drug accumulation in three-dimensional (3D) multicellular tumor spheroids compared to DOX and tFNA/DOX. Additionally, the therapeutic effect was verified in a 4T1 subcutaneous tumor model, and the complexes displayed a superior antitumor and antiangiogenic efficiency with fewer collateral damages. Therefore, these findings suggested that tFNA/DOX@iRGD might be a more effective pattern for drug delivery and TNBC therapy.

Characteristics of TCM Constitution and Related Biomarkers for Mild Cognitive Impairment.

INTRODUCTION: The incidence of Alzheimer's disease is on the rise, early detection of cognitive impairment of the elderly is very important. In traditional Chinese medicine, constitution is related to the susceptibility of the human body to diseases. Based on the theory of constitution of traditional Chinese medicine (TCM), the human population can be classified into 9 constitutions. However, little is known about the characteristics of medical constitution and related biomarkers in subjects with mild cognitive impairment (MCI). METHODS: We measured the TCM Constitution of 214 subjects by using the Constitution in Chinese Medicine Questionnaire (CCMQ). MMSE and MoCA were used to assess cognitive function. The subjects were divided into mild cognitive impairment group (MCI, n = 152) and normal control group (NC, n = 62). The levels of serum Hcy and serum/urine 8-iso-PGF 2α were determined. RESULTS: 1) It was found that there was a significant difference in constitution types between MCI and NC. There were significant differences in MMSE and MoCA score, serum Hcy and serum/urine 8-iso-PGF 2a levels between the two groups. 2) In logistic regression analysis, the variables with statistical significance were TCM Constitution of Yang-Deficient, Phlegm-Dampness, Blood-Stasis and abnormal increase of Hcy (OR>1). 3) The MoCA scores had a positive correlation with the MMSE. A statistically significant inverse association was found between serum Hcy, blood and urine 8-iso-PGF 2a and scores of cognitive assessment in MCI. CONCLUSION: Constitution types (Yang-Deficient, Phlegm-Dampness and Blood-Stasis) and abnormal serum Hcy elevation can be used as risk factors for MCI. MoCA scores can serve to detect MCI at early stage. Serum/urine 8-iso-PGF 2α has a certain relationship with MCI. Higher levels of serum/urine 8-iso-PGF 2α are more likely to be associated with MCI risk.

Synthesis and Antitumor Application of Antiangiogenetic Gold Nanoclusters.

Conventional antiangiogenetic inhibitors suffered from poor delivery problems that result in unsatisfactory antitumor treatment efficacy. Although the liposomes or nanomaterial-based delivery systems can improve the therapeutic efficacy of antiangiogenic molecules, the assembly process is far too complex. Herein, a nanomaterial or a new nanodrug that could work without the help of a carrier and could be easily synthesized is needed. Au nanoclusters (AuNCs) are a kind of ideal nanostructures that could spontaneously enter into the cell and could be synthesized by a relatively easy one-pot method. Here, changing the traditional ligand glutathione (GSH) into an anti-Flt1 peptide (AF) has enriched the newly synthesized AF@AuNCs with targeted antiangiogenic properties. Based on the specific binding between AF and vascular endothelial growth factor receptor 1 (VEGFR1), the interaction between VEGFR1 and its ligands could be blocked. Furthermore, the expression of VEGFR2 could be downregulated. Compared with pure AF peptide- and GSH-participated AuNCs (GSH@AuNCs), AF@AuNCs were more effective in inhibiting both tube formation and migration of the endothelial cells in vitro. Furthermore, the in vivo chick embryo chorioallantoic membrane (CAM) experiment and antitumor experiment were conducted to further verify the enhanced antiangiogenesis and tumor inhibition effect of AF@AuNCs. Our findings provide promising evidence of a carrier-free nanodrug for tumors and other vascular hyperproliferative diseases.

Erythromycin loaded by tetrahedral framework nucleic acids are more antimicrobial sensitive against Escherichia coli (E. coli).

Erythromycin is a commonly used broad-spectrum antibiotic, but resistance to this antibiotic makes its use less effective. Considerable efforts, beside finding alternatives, are needed to enhance its antimicrobial effect and stability against bacteria. Tetrahedral framework nucleic acids (tFNAs), a novel delivery vehicle with a three-dimensional nanostructure, have been studied as a carrying platform of antineoplastic drugs. In this study, the use of tFNAs in delivering erythromycin into Escherichia coli (E. coli) was investigated for the first time. The tFNAs vehicle increased the bacterial uptake of erythromycin and promoted membrane destabilization. Moreover, it increased the permeability of the bacterial cell wall, and reduced drug resistance by improving the movement of the drug across the membrane. The tFNAs-based delivery system enhanced the effects of erythromycin against E. coli. It may therefore provide an effective delivery vehicle for erythromycin in targeting antibiotic-resistant bacteria with thick cell wall.

The Role and Application of Exosomes in Gastric and Colorectal Cancer.

Gastric cancer and colorectal cancer are malignant tumors found in the human gastrointestinal tract. Bidirectional communication between tumor cells and their microenvironment can be realized through the transmission of exosomes-small, cell-derived vesicles containing complex RNA and proteins. Exosomes play an important role in the proliferation, metastasis, immune response, and drug resistance of cancer cells. In this review, we focus on the role and application of exosomes in gastric and colorectal cancer. We also summarize the role of exosomes secreted by different types of cells in tumor development and as drug carriers in cancer treatment.

Generation of a pHSPA6 gene-based multifunctional live cell sensor.

Biosensors utilizing intact live cells can report responses to certain stimuli rapidly and sensitively and have attracted a great deal of attention. The expression pattern of HSPA6, a little studied HSPA family member, has contributed to the development of multifunctional and intelligent whole-cell sensors. Herein, a new pHSPA6-based EGFP fluorescent reporter cell line was designed and developed via a CRISPR/Cas9-mediated knock-in strategy. The fluorescent reporter cell line has a precise EGFP integration site and gene copy number, and no selectable marker genes were introduced during the selection processes. Stimulation experiments with HSPA6-specific stressors indicated that EGFP fluorescent reporter cells could rapidly and effectively convert stress signals into EGFP fluorescent signals. Furthermore, cell proliferation and gene expression pattern analysis showed that the fluorescent reporter cells grew well and that both the integrated EGFP gene and the pHSPA6 gene were expressed rapidly and sensitively in response to stimulation. This study provides a new strategy for the construction of a cell model for HSPA6 expression/interaction and an intelligent live cell sensor, which can potentially be applied to numerous fields, such as those focusing on cellular models of HSPA6 signaling cascades, biomaterials, food security, environmental assessment, and drug screening.

Tetrahedral Framework Nucleic Acids Loading Ampicillin Improve the Drug Susceptibility against Methicillin-Resistant Staphylococcus aureus.

The overuse of antibiotics has led to the emergence of multidrug-resistant pathogens. There is an urgent need to develop alternative therapeutic strategies to reduce mortality and morbidity related to drug-resistant bacterial infections. Self-synthesized tetrahedral framework nucleic acids (tFNAs) are used as the drug loading platform to deliver ampicillin to combat methicillin-resistant Staphylococcus aureus (MRSA) infection. The results of average dimension, zeta potential, transmission electron microscopy, and ultraviolet spectrophotometry showed that tFNAs-ampicillin combined with a sufficient encapsulation rate and good stability. tFNAs-ampicillin had a better affinity to MRSA than free ampicillin because it had a better uptake by MRSA cells. Additionally, tFNAs-ampicillin had a better antibacterial effect and lower levels of resistance development than free ampicillin. The downregulation of genes related to bacterial cell wall synthesis (murA and murZ) and upregulation of a gene related to antibiotic sensibility (PBP2) were responsible for the enhanced killing effect of tFNAs-ampicillin against MRSA.