Effectiveness of topical corticosteroids on the prevention of acute radiation dermatitis in patients with breast cancer: An updated systematic review and meta-analysis.

Objectives: To evaluate the effect of topical corticosteroids (TCS) in preventing acute radiation dermatitis in patients with breast cancer. Methods: An updated systematic review and meta-analysis were conducted following the preferred reporting items for systematic reviews and meta-analyses. Randomized controlled trials (RCTs) in six English databases (PubMed, Web of Science, Scopus, CINAHL, Cochrane Library, Embase), three Chinese databases (Sinomed, China National Knowledge Infrastructure, Cqvip), and two clinical trial registration platforms (CHICTR, Clinicaltrials.gov) were systematically searched from inception to 1 February 2024. Results: Thirteen RCTs were included, with 1172 patients in this updated review. Meta-analysis showed that TCS reduced the rate of moist desquamation (OR = 0.31; 95% CI = [0.22, 0.44]; P < 0.01), the incidence of Radiation Therapy Oncology Group ratings of grade 2 or higher (OR = 0.22; 95% CI = [0.14, 0.32]; P < 0.01), the incidence of Common Terminology Criteria for Adverse Events ratings of grade 2 or higher (OR = 0.56; 95% CI = [0.37, 0.84]; P < 0.01), the mean score of radiation dermatitis (SMD = -0.46; 95% CI = [-0.59, -0.34]; P < 0.01), skin erythema and hyperpigmentation readings, and improved subjective symptoms. Conclusions: TCS can effectively prevent acute radiation dermatitis in patients with breast cancer. Systematic review registration: Prospero (CRD42024507890).

Liquid biopsy biomarkers to guide immunotherapy in breast cancer.

Immune checkpoint inhibitors (ICIs) therapy has emerged as a promising treatment strategy for breast cancer (BC). However, current reliance on immunohistochemical (IHC) detection of PD-L1 expression alone has limited predictive capability, resulting in suboptimal efficacy of ICIs for some BC patients. Hence, developing novel predictive biomarkers is indispensable to enhance patient selection for immunotherapy. In this context, utilizing liquid biopsy (LB) can provide supplementary or alternative value to PD-L1 IHC testing for identifying patients most likely to benefit from immunotherapy and exhibit favorable responses. This review discusses the predictive and prognostic value of LB in breast cancer immunotherapy, as well as its limitations and future directions. We aim to promote the individualization and precision of immunotherapy in BC by elucidating the role of LB in clinical practice.

DeepDetect: Deep Learning of Peptide Detectability Enhanced by Peptide Digestibility and Its Application to DIA Library Reduction.

In tandem mass spectrometry-based proteomics, proteins are digested into peptides by specific protease(s), but generally only a fraction of peptides can be detected. To characterize detectable proteotypic peptides, we have developed a series of methods to predict peptide digestibility and detectability. Here, we propose a bidirectional long short-term memory (BiLSTM)-based algorithm, named DeepDetect, for the prediction of peptide detectability enhanced by peptide digestibility. Compared with existing algorithms, DeepDetect is featured by its improved prediction accuracy for a wide range of commonly used proteases, covering trypsin, ArgC, chymotrypsin, GluC, LysC, AspN, LysN, and LysargiNase. On 11 test data sets from E. coli, yeast, mouse, and human samples, DeepDetect achieved higher prediction accuracies than PepFormer, a state-of-the-art deep-learning-based peptide detectability prediction algorithm. The results further demonstrated that peptide digestibility can substantially enhance the performance of peptide detectability predictors. As an application, DeepDetect was used to reduce the in silico predicted spectral libraries in data-independent acquisition mass spectrometry data analysis. Experiments using DIA-NN software showed that DeepDetect can significantly accelerate the library search without loss of peptide and protein identification sensitivity.

The Role of N6-Methyladenosine in Inflammatory Diseases.

N6-Methyladenosine (m6A) is the most abundant epigenetic RNA modification in eukaryotes, regulating RNA metabolism (export, stability, translation, and decay) in cells through changes in the activity of writers, erasers, and readers and ultimately affecting human life or disease processes. Inflammation is a response to infection and injury in various diseases and has therefore attracted significant attention. Currently, extensive evidence indicates that m6A plays an essential role in inflammation. In this review, we focus on the mechanisms of m6A in inflammatory autoimmune diseases, metabolic disorder, cardio-cerebrovascular diseases, cancer, and pathogen-induced inflammation, as well as its possible role as targets for clinical diagnosis and treatment.

A simple mesoporous silica Nanoparticle-based aptamers SERS sensor for the detection of acetamiprid.

In this study, we developed a novel, rapid, simple, and sensitive nano sensor based on the controlled release of 4-Aminothiophenol (4-ATP) signal molecules from aptamers (Apts) modified aminated mesoporous silica nanoparticles (MSNs-NH2) for the quantitative detection of acetamiprid (ACE). Firstly, we synthesized the positively charged MSNs-NH2 by one-pot method, then loaded 4-ATP signal molecules into the pore, and finally electrostatically adsorbed the Apts onto the MSNs-NH2, which acts as a gate to control the release of signal molecules. When ACE is added to the system, ACE preferentially and specifically binds to Apts, so the gate opens and 4-ATP signal molecules are released from the pore. Meanwhile, the silver-loaded mesoporous silica nanoparticles (Ag@SiO2) were prepared by one-pot method as surface-enhanced Raman spectroscopy (SERS) substrate to amplify the signal. The intensity of 4-ATP signal molecules at 1433 cm-1 position was observed to has a linear relationship with the concentration of ACE by SERS detection. Under the optimized detection conditions, a linear correlation was observed in the range of 5-60 ng/mL (R2 = 0.99749), and the limit of detection (LOD) was 2.66 ng/mL. The method has high sensitivity, good selectivity and reproducibility, and can be used for actual sample analysis with the recovery rate of 96.24-103.6 %. This study provides a reference for the rapid and convenient detection of ACE in agricultural products.

N6-Methyladenosine-Modified circRNA in the Bovine Mammary Epithelial Cells Injured by Staphylococcus aureus and Escherichia coli.

Mastitis is a common disease that hinders the development of dairy industry and animal husbandry. It leads to the abuse of antibiotics and the emergence of super drug-resistant bacteria, and poses a great threat to human food health and safety. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) are the most common pathogens of mastitis in dairy cows and usually cause subclinical or clinical mastitis. CircRNAs and N6-methyladenosine (m6A) play important roles in immunological diseases. However, the mechanisms by which m6A modifies circRNA in bovine mammary epithelial cells remain poorly understood. The aim of our study was to investigate m6A-modified circRNAs in bovine mammary epithelial cells (MAC-T cells) injured by S. aureus and E. coli. The profile of m6A-modified circRNA showed a total of 1,599 m6A peaks within 1,035 circRNAs in the control group, 35 peaks within 32 circRNAs in the S. aureus group, and 1,016 peaks within 728 circRNAs in the E. coli group. Compared with the control group, 67 peaks within 63 circRNAs were significantly different in the S. aureus group, and 192 peaks within 137 circRNAs were significantly different in the E. coli group. Furthermore, we found the source genes of these differentially m6A-modified circRNAs in the S. aureus and E. coli groups with similar functions according to GO and KEGG analyses, which were mainly associated with cell injury, such as inflammation, apoptosis, and autophagy. CircRNA-miRNA-mRNA interaction networks predicted the potential circRNA regulation mechanism in S. aureus- and E. coli-induced cell injury. We found that the mRNAs in the networks, such as BCL2, MIF, and TNFAIP8L2, greatly participated in the MAPK, WNT, and inflammation pathways. This is the first report on m6A-modified circRNA regulation of cells under S. aureus and E. coli treatment, and sheds new light on potential mechanisms and targets from the perspective of epigenetic modification in mastitis and other inflammatory diseases.

Mesenchymal Stem Cells-derived Exosomes Ameliorate Lupus by Inducing M2 Macrophage Polarization and Regulatory T Cell Expansion in MRL/lpr Mice.

Previous studies have implicated that the transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) effectively alleviates systemic lupus erythematosus (SLE) primarily due to immunomodulatory effects. However, little is known about the role of hUC-MSC-derived exosomes in SLE. This study is carried out to investigate the modifying effects of hUC-MSC-exosomes on the differentiation and function of immune cells in SLE. hUC-MSC-derived exosomes were extracted from the cultural supernatant of hUC-MSCs by ultrahigh speed centrifugation. Quantitative real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and flow cytometry were performed to estimate the effect of hUC-MSC-derived exosomes on macrophage and regulatory T cell (Treg) polarization. In vivo, hUC-MSC-exosomes were injected intravenously into 28-week-old MRL/lpr mice. We had found that exosomes derived from hUC-MSC restrained the proliferation and inflammation of macrophages in vitro. Besides, MSC-exosomes inhibited CD68+M1 and HLA-DR+M1 but promoted CD206+M2 and CD163+M2 in vitro. Moreover, MRL/lpr mice administrated by intravenous injection of MSC-exosomes had less infiltration of CD14+CD11c+M1 cells but more CD14+CD163+M2 cells as well as Tregs in spleens compared with those in MRL/lpr mice treated by PBS. Additionally, MSC-exosomes could alleviate nephritis, liver and lung injuries of MRL/lpr mice. The survival of lupus mice could be improved after MSC-exosome treatment. This study has suggested that MSC-derived exosomes exert anti-inflammatory and immunomodulatory effects in SLE. MSC-exosomes ameliorate nephritis and other key organ injuries by inducing M2 macrophages and Tregs polarization. As natural nanocarriers, MSC-exosomes may serve as a promising cell-free therapeutic strategy for SLE.Abbreviations: SLE: Systemic lupus erythematosus; hUC-MSCs: Human umbilical cord mesenchymal stem cells; MSCs: Mesenchymal stem cells; qRT-PCR: Quantitative real-time polymerase chain reaction; ELISA: Enzyme-linked immunosorbent assay; Tregs: Regulatory cells; TNF-α: Tumor necrosis factor alfa; IL: Interleukin; COVID-19: Coronavirus disease 2019; pTHP-1: PMA-induced THP-1 macrophages; TEM: Transmission electron microscopy; LPS: Lipopolysaccharide; EVs: Extracellular vesicles; TRAF1: Tumor necrosis factor receptor-associated factor 1; IRAK1: Interferon-α-interleukin-1 receptor-associated kinase 1; NF-κB: Nuclear factor-κB; BLyS: B lymphocyte stimulator; APRIL: A proliferation-inducing ligand.

Mechanism and effects of STING-IFN-I pathway on nociception: A narrative review.

Since the discovery of STING in 2008, numerous studies have investigated its functions in immunity, inflammation, and cancer. STING activates downstream molecules including IFN-I, NLRP3, and NF-κB. The STING-IFN-I pathway plays a vital role in nociception. After receiving the upstream signal, STING is activated and induces the expression of IFN-I, and after paracrine and autocrine signaling, IFN-I binds to IFN receptors. Subsequently, the activity of ion channels is inhibited by TYK2, which induces an acute antinociceptive effect. JAK activates PIK3 and MAPK-MNK-eIF4E pathways, which sensitize nociceptors in the peripheral nervous system. In the mid-late stage, the STING-IFN-I pathway activates STAT, increases pro-inflammatory and anti-inflammatory cytokines, inhibits ER-phagy, and promotes microglial M1-polarization in the central nervous system, leading to central sensitization. Thus, the STING-IFN-I pathway may exert complex effects on nociception at various stages, and these effects require further comprehensive elucidation. Therefore, in this review, we systematically summarized the mechanisms of the STING-IFN-I pathway and discussed its function in nociception.

Immunomodulatory Effect of MSCs and MSCs-Derived Extracellular Vesicles in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a common autoimmune connective tissue disease with unclear etiology and pathogenesis. Mesenchymal stem cell (MSC) and MSC derived extracellular vesicles (EVs) play important roles in regulating innate and adaptive immunity, which are involved in many physiological and pathological processes and contribute to the immune homeostasis in SLE. The effects of MSCs and EVs on SLE have been drawing more and more attention during the past few years. This article reviews the immunomodulatory effects and underlying mechanisms of MSC/MSC-EVs in SLE, which provides novel insight into understanding SLE pathogenesis and guiding the biological therapy.

Genome-Wide Analysis of LncRNA in Bovine Mammary Epithelial Cell Injuries Induced by Escherichia Coli and Staphylococcus Aureus.

Escherichia coli and Staphylococcus aureus are two common pathogenic microorganisms that cause mastitis in dairy cows. They can cause clinical mastitis and subclinical mastitis. In recent studies, lncRNAs have been found to play an important role in the immune responses triggered by microbial inducers. However, the actions of lncRNAs in bovine mastitis remain unclear. The purpose of this study was to investigate the effects of bovine mammary epithelial cell injuries induced by treatment with E. coli and S. aureus, and to explore the lncRNA profile on cell injuries. The lncRNA transcriptome analysis showed a total of 2597 lncRNAs. There were 2234 lncRNAs differentially expressed in the E. coli group and 2334 in the S. aureus group. Moreover, we found that the E. coli and S. aureus groups of maternal genes targeted signaling pathways with similar functions according to KEGG and GO analyses. Two lncRNA-miRNA-mRNA interaction networks were constructed in order to predict the potential molecular mechanisms of regulation in the cell injuries. We believe that this is the first report demonstrating the dysregulation of lncRNAs in cells upon E. coli and S. aureus infections, suggesting that they have the potential to become important diagnostic markers and to provide novel insights into controlling and preventing mastitis.

Preparation of peppermint oil nanoemulsions: Investigation of stability, antibacterial mechanism and apoptosis effects.

Peppermint oil (PO) is one of the most popular and widely used essential oils. However, due to volatile and poor water solubility of volatile oil, its application in the fields of medicine and food is limited. In order to solve this problem, the high speed shearing technology was used to prepare the nanoemulsion from PO. By using a series of characterization methods, such as turbiscan scanning spectrum, dynamic light scattering (DLS), confocal laser scanning microscope (CLSM), the best nanoemulsion formula was identified as PO 10 %, surfactant 8 % (Tween-60: EL-20 = 3:1) and deionized water 82 % (w/w). The inhibition strength of nanoemulsion on bacteria was evaluated by detecting the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) treated with peppermint oil nanoemulsion (PON) and observing the morphology of bacteria with biological scanning electron microscope (SEM). The results showed that PON had strong inhibitory effect on E. coli. At the concentration range of 0.02 µg/µL-0.2 µg/µL, the apoptosis rate of BEAS-2B cells was less than 10 % compared with control cells. All in all, the PON prepared under this formula is stable, which provides a reference for further exploration of essential oil as natural antibacterial materials in the future.

Novel lncRNA UPLA1 mediates tumorigenesis and prognosis in lung adenocarcinoma.

With the development of molecular biotechnology and sequencing techniques, long non-coding RNAs (lncRNAs) have been shown to play a vital role in a variety of cancers including lung cancer. In our previous study, we used RNA sequencing and high-content screening proliferation screening data to identify lncRNAs that were significantly associated with tumour biological functions such as LINC01426. Herein, based on previous work, we report a novel lncRNA UPLA1 (upregulation promoting LUAD-associated transcript-1), which has not been explored or reported in any previous studies. Our results showed that UPLA1 is highly expressed and regulates important biological functions in lung adenocarcinoma. In vitro experiments revealed that UPLA1 promoted the migration, invasion, and proliferation abilities, and is related to cell cycle arrest, in lung adenocarcinoma cells. Moreover, the upregulation of UPLA1 significantly improved the growth of tumours in vivo. We identified that UPLA1 was mainly located in the nucleus using fluorescence in situ hybridisation, and that it promoted Wnt/ß-catenin signalling by binding to desmoplakin using RNA pulldown assay and mass spectrometry. Additionally, luciferase reporter assay revealed that YY1 is the transcription factor of UPLA1 and suppressed the expression of UPLA1 as a transcriptional inhibitor. This finding provides important evidence regarding the two roles of YY1 in cancer. Furthermore, in situ hybridisation assay results showed that UPLA1 was closely related to the prognosis and tumour, node, metastasis (TNM) stage of lung adenocarcinoma. In summary, our results suggest that the novel lncRNA UPLA1 promotes the progression of lung adenocarcinoma and may be used as a prognostic marker, and thus, has considerable clinical significance.

Exosomal miR-548c-5p Regulates Colorectal Cancer Cell Growth and Invasion Through HIF1A/CDC42 Axis.

BACKGROUND: Mounting evidence has implicated that exosomes-delivered noncoding RNAs are key regulators in carcinogenesis. The effect of miR-548c-5p has been elucidated in some cancers. However, the role of exosomal miR-548c-5p in colorectal cancer (CRC) is not fully understood. We aim to explore the function and mechanism of exosome-delivered miR-548c-5p in CRC. The altering effect of exosome-derived miR-548c-5p on the prognosis of CRC patients is also investigated by estimating overall survival and disease-free survival. MATERIALS AND METHODS: The expression of miR-548c-5p in exosomes is determined by real-time PCR. The proliferation and invasion of CRC cells are estimated by MTT, transwell assay and scratch test. The targeted gene of miR-548c-5p is investigated by luciferase reporter assay, real-time PCR, Western blot and chromosome immunoprecipitation (CHIP) assay. CRC cells are transplanted subcutaneously in BALB/c nude mice to estimate their growth in vivo. RESULTS: MiR-548c-5p derived from CRC cell exosomes inhibits the proliferation and invasion of CRC cells in vitro. Exosomal miR-548c-5p can also prevent from colorectal carcinogenesis in nude mice in vivo. HIF1A is documented to be a target of miR-548c-5p, and HIF1A can targetedly regulate CDC42 in CRC cells. Exosomal miR-548c-5p affects CRC cell growth, migration and invasion via miR-548c-5p/HIF1A/CDC42 axis. In addition, exosomal miR-548c-5p can be a predictive factor for CRC prognosis. CONCLUSION: Our study has suggested that exosomal miR-548c-5p can regulate CRC through HIF1A/CDC42 axis, which helps to understand CRC pathogenesis more clearly and identify novel therapeutic strategies for CRC patients.

CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis.

A number of circular RNAs (circRNAs) have been implicated in rheumatoid arthritis (RA) pathogenesis; however, little is known about their function and hidden molecular mechanism in immune and inflammation regulation. We investigated the role and the underlying mechanism of circRNA_09505 in RA in this study. Real-time PCR and fluorescence in situ hybridization (FISH) are adopted to estimate the quantitative expression and localization of circRNA_09505 in macrophages. The altering effect of circRNA_09505 on inflammation is investigated in vitro and in vivo by use of macrophage cell models and collagen-induced arthritis (CIA) mice. Luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) are used to confirm the circRNA_09505/miR-6089 ceRNA network predicted by bioinformatics analysis. Compared with controls, the expression of circRNA_09505 is upregulated in peripheral blood mononuclear cells (PBMCs) from patients with RA. The proliferation and cell cycle are significantly promoted when circRNA_09505 is upregulated in macrophages, whereas knockdown of circRNA_09505 inhibits macrophage proliferation and cell- cycle progression. Besides, circRNA_09505 can act as a miRNA sponge for miR-6089 in macrophages, and promote the production of TNF-α, IL-6, and IL-12 through ceRNA mechanism. Moreover, AKT1 is a direct target of miR-6089. CircRNA_09505 can promote AKT1 expression by acting as a miR-6089 sponge via IκBα/NF-κB signaling pathway in macrophages. Most interestingly, knockdown of circRNA_09505 significantly alleviates arthritis and inflammation in vivo in CIA mice. These data support the hypothesis that circRNA_09505 can function as a miR-6089 sponge and regulate inflammation via miR-6089/AKT1/NF-κB axis in CIA mice.

Role of mesenchymal stem cell derived extracellular vesicles in autoimmunity: A systematic review.

BACKGROUND: Mesenchymal stem cells (MSCs) have been reported to possess immune regulatory effects in innate and adaptive immune reactions. MSCs can mediate intercellular communications by releasing extracellular vesicles (EVs), which deliver functional molecules to targeted cells. MSC derived EVs (MSC-EVs) confer altering effects on many immune cells, including T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages. A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases. This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases. AIM: To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases. METHODS: Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language. The keywords, such as "MSCs," "EVs," "exosome," "autoimmunity," "tumor immunity," and "transplantation immunity," and Boolean operator "AND" and "NOT" coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases. Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded. RESULTS: A total of 96 articles were chosen for final reference lists. After analyzing those publications, we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells, like T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages, to regulate immune responses in innate immunity and adaptive immunity. Many validated EVs-delivered molecules have been identified as key biomarkers, such as proteins, lipids, and nucleotides. Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease. CONCLUSION: MSC-EVs play an equally important part in the differentiation, activation, and proliferation of immune cells, and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.