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Breast cancer is the most frequently diagnosed and fatal cancer among women worldwide. Dairy protein-derived peptides and dairy products are important parts of the daily human diet and have shown promising activities in suppressing the proliferation, migration, and invasion of breast cancer cells, both in vitro and in vivo . Most of the review literature employs meta-analysis methods to explore the association between dairy intake and breast cancer risk. However, there is a lack of comprehensive summary regarding the anti-breast cancer properties of dairy protein-derived peptides, dairy products, and dairy protein-based nanoparticles as well as their underlying mechanisms of action. Therefore, the present study discussed the breast cancer inhibitory effects and mechanisms of active peptides derived from various dairy protein sources. Additionally, the characteristics, anti-breast cancer activities and active components of several types of dairy products, including fermented milk, yogurt and cheeses, were summarized. Furthermore, the preparation methods and therapeutic effects of various dairy protein-containing nanoparticle delivery systems for breast cancer therapy were briefly described. Lastly, this work also provided an overview of what is currently known about the anti-breast cancer effects of dairy products in clinical studies. Our review will be of interest to the development of natural anticancer drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Yuan, Xiong, Zeng, Gan, Jiang and Xie.)

Introduction: Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the damage caused by the influenza virus A/PR/8/1934 (PR8), but its specific mechanism is unclear. Methods: Molecular biological methods, together with network pharmacology, were used to analyze the effects and underlying mechanism of QFPDD treatment on PR8-induced myocardial damage to obtain insights into the treatment of COVID-19-mediated myocardial damage. Results: Increased apoptosis and subcellular damage were observed in myocardial cells of mice infected by PR8. QFPDD treatment significantly inhibited the apoptosis and subcellular damage induced by the PR8 virus. The inflammatory factors IFN-β, TNF-α, and IL-18 were statistically increased in the myocardia of the mice infected by PR8, and the increase in inflammatory factors was prevented by QFPDD treatment. Furthermore, the expression levels or phosphorylation of necroptosis-related proteins RIPK1, RIPK3, and MLKL were abnormally elevated in the group of infected mice, while QFPDD restored the levels or phosphorylation of these proteins. Our study demonstrated that HIF-1α is a key target of QFPDD in the treatment of influenza virus-mediated injury. The HIF-α level was significantly increased by PR8 infection. Both the knockdown of HIF-1α and treatment of the myocardial cell with QFPDD significantly reversed the increased inflammatory factors during infection. Overexpression of HIF-1α reversed the inhibition effects of QFPDD on cytokine expression. Meanwhile, seven compounds from QFPDD may target HIF-1α. Conclusion: QFPDD can ameliorate influenza virus-mediated myocardial damage by reducing the degree of cell necroptosis and apoptosis, inhibiting inflammatory response and the expression of HIF-1α. Thus, our results provide new insights into the treatment of respiratory virus-mediated myocardial damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JC declared a shared affiliation with the authors JZ, NX, HL, XW, and YZ to the handling editor at the time of the review., (Copyright © 2024 Du, Zhao, Xie, Xie, Xu, Bao, Zhou, Liu, Wu, Hu, He, Xu and Zheng.)

Immune cells are essential for initiating and developing the fibrotic process by releasing cytokines and growth factors that activate fibroblasts and promote extracellular matrix deposition. Immunometabolism describes how metabolic alterations affect the function of immune cells and how inflammation and immune responses regulate systemic metabolism. The disturbed immune cell function and their interactions with other cells in the tissue microenvironment lead to the origin and advancement of fibrosis. Understanding the dysregulated metabolic alterations and interactions between fibroblasts and the immune cells is critical for providing new therapeutic targets for fibrosis. This review provides an overview of recent advances in the pathophysiology of fibrosis from the immunometabolism aspect, highlighting the altered metabolic pathways in critical immune cell populations and the impact of inflammation on fibroblast metabolism during the development of fibrosis. We also discuss how this knowledge could be leveraged to develop novel therapeutic strategies for treating fibrotic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Feng, Chen, Huang, Zhang, Zheng and Xie.)

Objective: To understand the level of knowledge about inhaler devices among medical staff. Methods: This study evaluated the knowledge of inhalation therapy and the use of inhaler devices among nurses in China. We administered a new self-designed online questionnaire to 1,831 nurses. The questionnaire comprised 11 questions, including the storage location of inhaler devices, steps involved in using inhaler devices, and common errors when using various devices. Results: Among the 1,831 participants, 816(44.57%), 122(6.66%), and 893(48.77%) nurses worked in community, secondary, and tertiary hospitals, respectively. Adequate knowledge of inhaler devices was demonstrated by 20.10%, 8.20%, and 13.10% of nurses working in community, secondary, and tertiary hospitals, respectively. Of the nurses working in community hospitals, 27.70% knew the key points for using inhalers compared to 15.57% in secondary hospitals and 23.18% in tertiary hospitals ( p < 0.01). Only 9.50%-26.00% of participants chose correct answers to the 9 questions about the use of inhalers. The accuracy rate of the responses was generally low, and the highest accuracy rate was 26.00%. Conclusion: Knowledge of inhalation therapy was better among nurses working in community hospitals than among those working in high-level hospitals. This is because of the clearer division of work and higher workload in high-level hospitals. Overall, nurses' knowledge of inhalation therapy is low. Furthermore, knowledge about inhaler devices should be strengthened among nurses in Chinese hospitals. It is necessary to create training opportunities for nurses in China to increase their awareness and knowledge regarding the management of chronic respiratory diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xie, Zheng, Yang, Li and Ye.)

Two-dimensional (2D) tumor model has always poorly predicted drug response of animal model due to the lack of recapitulation of tumor microenvironment. Establishing a biomimetic, controllable, and cost-effective three-dimensional (3D) model and large-scale validation of its in vivo predictivity has shown promise in bridging the gap between the 2D tumor model and animal model. Here, we established a matrigel-based 3D micro-tumor model on an array chip for large-scale anticancer drug evaluation. Compared with the 2D tumor model, the 3D tumor model on the chip showed spheroid morphology, slower proliferation kinetics, and comparable reproducibility. Next, the results of the chemotherapeutic evaluation from 18 drugs against 27 cancer cell lines showed 17.6% of drug resistance on the 3D tumor model. Moreover, the evaluation results of targeted drugs showed expected sensitivity and higher specificity on the 3D tumor model compared with the 2D model. Finally, the evaluation results on the 3D tumor model were more consistent with the in vivo cell-derived xenograft model, and excluded 95% false-positive results from the 2D model. Overall, the matrigel-based 3D micro-tumor model on the array chip provides a promising tool to accelerate anticancer drug discovery., Competing Interests: XA and PT are scientific advisors in Beijing Daxiang Biotech. RX and PL are current employees in Beijing Daxiang Biotech. LJ, NX, and WG are current employees in WuXi AppTec (Shanghai) Co., Ltd., (Copyright © 2022 Xiao, Jin, Xie, Luo, Gao, Tu and Ai.)

Selective serotonin reuptake inhibitors (SSRIs) are widely used for a variety of diseases, and their impact on semen quality is unclear. We performed a systematic search in PubMed and Embase, and after a strict screening, we included 4 studies with a total of 222 male participants. In result, SSRIs reduced normal sperm morphology (95% CI [-16.29, -3.77], p = 0.002), sperm concentration (95%CI [-43.88, -4.18], p = 0.02), sperm motility (95%CI [-23.46, -0.47], p = 0.04) and sperm DNA fragmentation index (DFI) (95% CI [6.66,21.93], p = 0.0002), without a statistically significant effect on semen volume (95%CI [-0.75,0.65], p = 0.89). Moreover, the impact on both sperm morphology and sperm concentration were observed within the 3-month period of SSRIs use. In general, our meta-analysis showed that SSRIs have a negative effect on semen quality. More larger, randomized, well-controlled clinical studies should be conducted to support our conclusion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, He, Zhou, Zhao, Lin, Huang, Xie, Yue and Tang.)

Cancer is the leading cause of death and one of the greatest barriers to increased life expectancy worldwide. Currently, chemotherapy with synthetic drugs remains one of the predominant ways for cancer treatment, which may lead to drug resistance and normal organ damage. Increasing researches have suggested that apoptosis, a type of programmed cell death, is a promising way for cancer therapy. Furthermore, natural products are important sources for finding new drugs with high availability, low cost and low toxicity. As a well-known isoquinoline alkaloid, accumulating evidence has revealed that berberine (BBR) exerts potential pro-apoptotic effects on multiple cancers, including breast, lung, liver, gastric, colorectal, pancreatic, and ovarian cancers. The related potential signal pathways are AMP-activated protein kinase, mitogen-activated protein kinase, and protein kinase B pathways. In this review, we provide a timely and comprehensive summary of the detailed molecular mechanisms of BBR in treating three types of cancer (breast, lung and liver cancer) by inducing apoptosis. Furthermore, we also discuss the existing challenges and strategies to improve BBR's bioavailability. Hopefully, this review provides valuable information for the comprehension of BBR in treating three types of cancer and highlight the pro-apoptotic effects of BBR, which would be beneficial for the further development of this natural compound as an effective clinical drug for treating cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Xie, Chai, Nie, Liu, Liu, Yang, Su and Zhang.)

Methicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant pathogen threatening human health and safety. Biofilms are an important cause of its drug resistance and pathogenicity. Inhibition and elimination of biofilms is an important strategy for the treatment of MRSA infection. Andrographolide sulfonate (AS) is an active component of the traditional herbal medicine Andrographis paniculata . This study aims to explore the inhibitory effect and corresponding mechanisms of AS on MRSA and its biofilms. Three doses of AS (6.25, 12.5, and 25 mg/ml) were introduced to MRSA with biofilms. In vitro antibacterial testing and morphological observation were used to confirm the inhibitory effect of AS on MRSA with biofilms. Real-time PCR and metabonomics were used to explore the underlying mechanisms of the effect by studying the expression of biofilm-related genes and endogenous metabolites. AS displayed significant anti-MRSA activity, and its minimum inhibitory concentration was 50 μg/ml. Also, AS inhibited biofilms and improved biofilm permeability. The mechanisms are mediated by the inhibition of the expression of genes, such as quorum sensing system regulatory genes ( agrD and sarA ), microbial surface components-recognizing adhesion matrix genes ( clfA and fnbB ), intercellular adhesion genes ( icaA , icaD, and PIA ), and a gene related to cellular eDNA release ( cidA ), and the downregulation of five biofilm-related metabolites, including anthranilic acid, D -lactic acid, kynurenine, L -homocitrulline, and sebacic acid. This study provided valuable evidence for the activity of AS against MRSA and its biofilms and extended the methods to combat MRSA infection., Competing Interests: LL and NX were employed by Qingfeng Pharmaceutical Co. Ltd, Ganzhou, Jiangxi Province. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Wen, Bao, Cheng, Mahmood, Yang, Chen, Lv, Li, Yi, Xie, Lu and Tan.)

Hypertrophic scars formed after burns remain a challenge in clinical practice. Development of effective scar therapies relies on validated animal models that mimic human hypertrophic scars. A consistent porcine full-thickness burn hypertrophic scar model has yet to be developed. We have previously reported that Shikonin induces apoptosis and reduces collagen production in hypertrophic scar fibroblasts in vitro and may therefore hold potential as a novel scar remediation therapy. In this study, we aimed to validate the potential of Shikonin on scar remediation in vivo . A novel porcine hypertrophic scar model was created after full-thickness burn wounds, and the effect of Shikonin on scar remediation was investigated. Clinical scar assessments, histology, and immunohistochemistry were used to evaluate scar appearance, morphology, and protein expression. Eight weeks after scar formation, clinical scar assessment indicated that the score of hypertrophic scars treated with Shikonin was significantly lower than that of the control group. Hypertrophic scars treated with Shikonin appeared flat, pink, and pliable. In addition, histological analysis indicated that hypertrophic scars treated with Shikonin exhibited reduced thickness of the epidermis and dermis, thin and even epithelial layers, reduced numbers of keratinocytes, uniform distribution of fibroblasts, and a parallel and loose arrangement of collagen fibers in the dermis. Moreover, immunohistochemical analysis indicated that Shikonin inhibited the expression of p63, cytokeratin 10, alpha-smooth muscle actin, transforming growth factor-beta 1, and collagen I, which play important roles in hypertrophic scar formation. Based on these results, we conclude that Shikonin has potential as a novel scar therapy.

Macrophages are abundant in the tumor microenvironment where they adopt a pro-tumor phenotype following alternative polarization induced by paracrine factors from cancer and stromal cells. In contrast, classically activated macrophages have tumoricidal activities, such that the polarization of tumor-associated macrophages has become a novel therapeutic target. Toll-like receptor 4 engagement promotes classical activation of macrophages, and recent literature suggests TLR4 agonism to prevent metastasis and promote survival in experimental metastasis models. A growing number of studies indicate that TLR4 can respond to opioids, including the opioid receptor-inactive morphine metabolite morphine-3-glucuronide (M3G). We measured the activation of TLR4 in a reporter cell line exogenously expressing TLR4 and TLR4 co-receptors, and confirmed that M3G weakly but significantly activates TLR4. We hypothesized that M3G would promote the expression of classical activation signature genes in macrophages in vitro . We exposed mouse and human macrophage cell lines to M3G or the TLR4 activator lipopolysaccharide (LPS), alone or in combination with interferon gamma (IFN-γ). The classical macrophage activation markers tested were iNOS, CD86, IL-6, or TNF-α in RAW 264.7 cells and IL-6, IL-12, IL-23, TNF-α, CXCL10, and CXCL11 in THP1 cells. Our results show that despite exhibiting TLR4-activation ability, M3G does not elicit the expression of classical activation markers in LPS-responsive macrophages.