Advances in immune regulation of the G protein-coupled estrogen receptor.

Estrogen and related receptors have been shown to have a significant impact on human development, reproduction, metabolism and immune regulation and to play a critical role in tumor development and treatment. Traditionally, the nuclear estrogen receptors (nERs) ERα and ERß have been thought to be involved in mediating the estrogenic effects. However, our group and others have previously demonstrated that the G protein-coupled estrogen receptor (GPER) is the third independent ER, and estrogen signaling mediated by GPER is known to play an important role in normal physiology and a variety of abnormal diseases. Interestingly, recent studies have progressively revealed GPER involvement in the maintenance of the normal immune system, abnormal immune diseases, and inflammatory lesions, which may be of significant clinical value primarily in the immunotherapy of tumors. In this article, we review current advances in GPER-related immunomodulators and provide a theoretical basis and potential clinical targets to ameliorate immune-related diseases and immunotherapy for tumors.

Exploring genetic associations of Crohn's disease and ulcerative colitis with extraintestinal cancers in European and East Asian populations.

Background: Previous studies have reported associations of Crohn's disease (CD) and ulcerative colitis (UC) with the risks of extraintestinal cancers, but the causality remains unclear. Methods: Using genetic variations robustly associated with CD and UC extracted from genome-wide association studies (GWAS) as instrumental variables. Nine types of extraintestinal cancers of European and Asian populations were selected as outcomes. We used the inverse variance weighted method as the primary approach for two-sample Mendelian randomization analysis. Sensitivity analyses were carried out to evaluate the reliability of our findings. Results: In the European population, we found that CD showed a potential causal relationship with pancreatic cancer (OR: 1.1042; 95% CI: 1.0087-1.2088; P=0.0318). Meanwhile, both CD (outliers excluded: OR: 1.0208; 95% CI: 1.0079-1.0339; P=0.0015) and UC (outliers excluded: OR: 1.0220; 95% CI: 1.0051-1.0393; P=0.0108) were associated with a slight increase in breast cancer risk. Additionally, UC exhibited a potential causal effect on cervical cancer (outliers excluded: OR: 1.1091; 95% CI: 1.0286-1.1960; P=0.0071). In the East Asian population, CD had significant causal effects on pancreatic cancer (OR: 1.1876; 95% CI: 1.0741-1.3132; P=0.0008) and breast cancer (outliers excluded: OR: 0.9452; 95% CI: 0.9096-0.9822; P=0.0040). For UC, it exhibited significant causal associations with gastric cancer (OR: 1.1240; 95% CI: 1.0624-1.1891; P=4.7359×10-5), bile duct cancer (OR: 1.3107; 95% CI: 1.0983-1.5641; P=0.0027), hepatocellular carcinoma (OR: 1.2365; 95% CI: 1.1235-1.3608; P=1.4007×10-5) and cervical cancer (OR: 1.3941; 95% CI: 1.1708-1.6599; P=0.0002), as well as a potential causal effect on lung cancer (outliers excluded: OR: 1.1313; 95% CI: 1.0280-1.2449; P=0.0116). Conclusions: Our study provided evidence that genetically predicted CD may be a risk factor for pancreatic and breast cancers in the European population, and for pancreatic cancer in the East Asian population. Regarding UC, it may be a risk factor for cervical and breast cancers in Europeans, and for gastric, bile duct, hepatocellular, lung, and cervical cancers in East Asians. Therefore, patients with CD and UC need to emphasize screening and prevention of site-specific extraintestinal cancers.

Visualization of breast cancer-related protein synthesis from the perspective of bibliometric analysis.

Breast cancer, as a daunting global health threat, has driven an exponential growth in related research activity in recent decades. An area of research of paramount importance is protein synthesis, and the analysis of specific proteins inextricably linked to breast cancer. In this article, we undertake a bibliometric analysis of the literature on breast cancer and protein synthesis, aiming to provide crucial insights into this esoteric realm of investigation. Our approach was to scour the Web of Science database, between 2003 and 2022, for articles containing the keywords "breast cancer" and "protein synthesis" in their title, abstract, or keywords. We deployed bibliometric analysis software, exploring a range of measures such as publication output, citation counts, co-citation analysis, and keyword analysis. Our search yielded 2998 articles that met our inclusion criteria. The number of publications in this area has steadily increased, with a significant rise observed after 2003. Most of the articles were published in oncology or biology-related journals, with the most publications in Journal of Biological Chemistry, Cancer Research, Proceedings of the National Academy of Sciences of the United States of America, and Oncogene. Keyword analysis revealed that "breast cancer," "expression," "cancer," "protein," and "translation" were the most commonly researched topics. In conclusion, our bibliometric analysis of breast cancer and related protein synthesis literature underscores the burgeoning interest in this research. The focus of the research is primarily on the relationship between protein expression in breast cancer and the development and treatment of tumors. These studies have been instrumental in the diagnosis and treatment of breast cancer. Sustained research in this area will yield essential insights into the biology of breast cancer and the genesis of cutting-edge therapies.

Evaluating the Immune Response of a Nanoemulsion Adjuvant Vaccine Against Methicillin-Resistant Staphylococcus aureus (MRSA) Infection.

Nanoemulsion adjuvant vaccines have attracted extensive attention because of their small particle size, high thermal stability, and ability to induce validly immune responses. However, establishing a series of comprehensive protocols to evaluate the immune response of a novel nanoemulsion adjuvant vaccine is vital. Therefore, this article features a rigorous procedure to determine the physicochemical characteristics of a vaccine (by transmission electron microscopy [TEM], atomic force microscopy [AFM], and dynamic light scattering [DLS]), the stability of the vaccine antigen and system (by a high-speed centrifuge test, a thermodynamic stability test, SDS-PAGE, and western blot), and the specific immune response (IgG1, IgG2a, and IgG2b). Using this approach, researchers can evaluate accurately the protective effect of a novel nanoemulsion adjuvant vaccine in a lethal MRSA252 mouse model. With these protocols, the most promising nanoemulsion vaccine adjuvant in terms of effective adjuvant potential can be identified. In addition, the methods can help optimize novel vaccines for future development.

Visualization of the relationship between fungi and cancer from the perspective of bibliometric analysis.

The relationship between cancer and microorganisms has been extensively studied, with bacteria receiving more attention than fungi. However, fungi have been shown to play a significant role in cancer development and progression. Understanding the underlying mechanisms is crucial for identifying new avenues in prevention and treatment. To evaluate the current state of research on fungi and cancer, we conducted a comprehensive bibliometric analysis. Using the Web of Science Core Collection database, we searched for English-language articles published between 1998 and 2022. Analyzing the resulting publication data, we identified trends, patterns, and research gaps. Our analysis encompassed co-authorship networks, citation analysis, and keyword co-occurrence analysis. With 8283 publications identified, averaging 331.32 publications per year, our findings highlight China, the United States, India, Japan, and Germany as the top contributing countries. The Chinese Academy of Sciences, Sun Yat-Sen University, and University of São Paulo emerged as the most productive institutions. Key themes in the literature included "cancer," "cytotoxicity," "apoptosis," "metabolites," and "fungus." Recent trends indicate increased interest in keywords such as "green synthesis," "molecular docking," "anticancer activity," "antibacterial," "anticancer," and "silver nanoparticles." Our study provides a comprehensive assessment of the current research landscape in the field of fungi and cancer, offering insights into collaborative networks, research directions, and emerging hotspots. The growing publication rate demonstrates the rising interest in the topic, while identifying leading countries, institutions, and research themes serves as a valuable resource for researchers, policymakers, and funders interested in supporting investigations on fungi-derived compounds as potential anti-cancer agents.

Recent advance in phytonanomedicine and mineral nanomedicine delivery system of the treatment for acute myeloid leukemia.

Acute myeloid leukemia (AML) is an invasive hematopoietic malignancy caused by excessive proliferation of myeloblasts. Classical chemotherapies and cell transplantation therapies have remarkable efficacy in AML treatment; however, 30-40% of patients relapsed or had refractory disease. The resistance of AML is closely related to its inherent cytogenetics or various gene mutations. Recently, phytonanomedicine are found to be effective against resistant AML cells and have become a research focus for nanotechnology development to improve their properties, such as increasing solubility, improving absorption, enhancing bioavailability, and maintaining sustained release and targeting. These novel phytonanomedicine and mineral nanomedicine, including nanocrystals, nanoemulsion, nanoparticles, nanoliposome, and nanomicelles, offer many advantages, such as flexible dosages or forms, multiple routes of administration, and curative effects. Therefore, we reviewed the application and progress of phytomedicine in AML treatment and discussed the limitations and future prospects. This review may provide a solid reference to guide future research on AML treatment.

Appraising the causal association between Crohn's disease and breast cancer: a Mendelian randomization study.

Background: Previous research has indicated that there may be a link between Crohn's disease (CD) and breast cancer (BC), but the causality remains unclear. This study aimed to investigate the causal association between CD and BC using Mendelian randomization (MR) analysis. Methods: The summary data for CD (5,956 cases/14,927 controls) was obtained from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). And the summary data for BC (122,977 cases/105,974 controls) was extracted from the Breast Cancer Association Consortium (BCAC). Based on the estrogen receptor status, the cases were classified into two subtypes: estrogen receptor-positive (ER+) BC and estrogen receptor-negative (ER-) BC. We used the inverse variance weighted method as the primary approach for two-sample MR. MR-PRESSO method was used to rule out outliers. Heterogeneity and pleiotropy tests were carried out to improve the accuracy of results. Additionally, multivariable MR was conducted by adjusting for possible confounders to ensure the stability of the results. Results: The two-sample MR indicated that CD increased the risks of overall (OR: 1.020; 95% CI: 1.010-1.031; p=0.000106), ER+ (OR: 1.019; 95%CI: 1.006-1.034; p=0.006) and ER- BC (OR: 1.019; 95%CI: 1.000-1.037; p=0.046) after removal of outliers by MR-PRESSO. This result was reliable in the sensitivity analysis, including Cochran's Q and MR-Egger regression. In multivariate MR analyses, after adjusting for smoking and drinking separately or concurrently, the positive association between CD and the risks of overall and ER+ BC remained, but it disappeared in ER- BC. Furthermore, reverse MR analysis suggested that BC did not have a significant impact on CD risk. Conclusion: Our findings provide evidence for a possible positive association between CD and the risk of BC. However, further studies are needed to fully understand the underlying mechanisms and establish a stronger causal relationship.

In Vitro Cellular Activity Evaluation of the Nanoemulsion Vaccine Adjuvant Ophiopogonin D.

As a principal ingredient of vaccines, adjuvants can directly induce or enhance the powerful, widespread, innate, and adaptive immune responses associated with antigens. Ophiopogonin D (OP-D), a purified component extracted from the plant Ophiopogon japonicus, has been found to be useful as a vaccine adjuvant. The problems of the low solubility and toxicity of OP-D can be effectively overcome by using a low-energy emulsification method to prepare nanoemulsion ophiopogonin D (NOD). In this article, a series of in vitro protocols for cellular activity evaluation are examined. The cytotoxic effects of L929 were determined using a cell counting kit-8 assay. Then, the secreted cytokine levels and corresponding immune cell numbers after the stimulation and culture of splenocytes from immunized mice were detected by ELISA and ELISpot methods. In addition, the antigen uptake ability in bone marrow-derived dendritic cells (BMDCs), which were isolated from C57BL/6 mice and matured after incubation with GM-CSF plus IL-4, was observed by laser scanning confocal microscopy (CLSM). Importantly, macrophage activation was confirmed by measuring the levels of IL-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) cytokines by ELISA kits after coculturing peritoneal macrophages (PMs) from blank mice with the adjuvant for 24 h. It is hoped that this protocol will provide other researchers with direct and effective experimental approaches to evaluate the cellular response efficacies of novel vaccine adjuvants.

Preparation, Characteristics, Toxicity, and Efficacy Evaluation of the Nasal Self-assembled Nanoemulsion Tumor Vaccine In Vitro and In Vivo.

Epitope peptides have attracted widespread attention in the field of tumor vaccines because of their safety, high specificity, and convenient production; in particular, some MHC I-restricted epitopes can induce effective cytotoxic T lymphocyte activity to clear tumor cells. Additionally, nasal administration is an effective and safe delivery technique for tumor vaccines due to its convenience and improved patient compliance. However, epitope peptides are unsuitable for nasal delivery because of their poor immunogenicity and lack of delivery efficiency. Nanoemulsions (NEs) are thermodynamically stable systems that can be loaded with antigens and delivered directly to the nasal mucosal surface. Ile-Lys-Val-Ala-Val (IKVAV) is the core pentapeptide of laminin, an integrin-binding peptide expressed by human respiratory epithelial cells. In this study, an intranasal self-assembled epitope peptide NE tumor vaccine containing the synthetic peptide IKVAV-OVA257-264 (I-OVA) was prepared by a low-energy emulsification method. The combination of IKVAV and OVA257-264 can enhance antigen uptake by nasal mucosal epithelial cells. Here, we establish a protocol to study the physicochemical characteristics by transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic light scattering (DLS); stability in the presence of mucin protein; toxicity by examining the cell viability of BEAS-2B cells and the nasal and lung tissues of C57BL/6 mice; cellular uptake by confocal laser scanning microscopy (CLSM); release profiles by imaging small animals in vivo; and the protective and therapeutic effect of the vaccine by using an E.G7 tumor-bearing model. We anticipate that the protocol will provide technical and theoretical clues for the future development of novel T cell epitope peptide mucosal vaccines.

A lipophilic chitosan-modified self-nanoemulsifying system influencing cellular membrane metabolism enhances antibacterial and anti-biofilm efficacy for multi-drug resistant Pseudomonas aeruginosa wound infection.

Wound infections, especially infections with multidrug-resistant bacteria, are a serious public health issue worldwide. In addition, the accumulation microbial biofilm of multidrug-resistant Pseudomonas aeruginosa increases the risk and physically obstruct its healing activity at the wound site. Therefore, the development of an eminent agent to control wound infection is urgently needed. Here, we report a novel chitosan (a natural biological macromolecule)-modified self-nanoemulsifying system (CSN) with lipophilic chlorhexidine acetate (CAA, a poorly water-soluble agent) that was designed and prepared using low-energy emulsification methods. We found that CSN displays better antibacterial efficacy, which occurs more quickly than its aqueous solution, in destroying the structure of the bacterial cell membrane and promoting the leakage of nucleic acids, proteins, K+, and Mg2+ from Pseudomonas aeruginosa cells. Importantly, CSN also accelerates skin wound healing after Pseudomonas aeruginosa infection by inhibiting biofilm formation and eradicating mature biofilms. Moreover, the proteomic results suggested that CSN altered membrane permeability and cellular membrane metabolism, allowing more drug molecules to enter the cytosol. Based on these results, this lipophilic self-nanoemulsifying system may be applied in the treatment of skin wounds caused by multidrug-resistant bacteria, especially Pseudomonas aeruginosa.

Nanomaterials in tuberculosis DNA vaccine delivery: historical perspective and current landscape.

Vaccinations, especially DNA vaccines that promote host immunity, are the most effective interventions for tuberculosis (TB) control. However, the vaccine delivery system exhibits a significant impact on the protective effects of the vaccine. Recently, effective nanomaterial-based delivery systems (including nanoparticles, nanogold, nanoliposomes, virus-like particles, and virus carriers) have been developed for DNA vaccines to control TB. This review highlights the historical development of various nanomaterial-based delivery systems for TB DNA vaccines, along with the emerging technologies. Nanomaterial-based vaccine delivery systems could enhance the efficacy of TB vaccination; therefore, this summary could guide nanomaterial selection for optimal and safe vaccine delivery, facilitating the design and development of highly effective TB vaccines.

Altitudinal patterns of plant diversity on the Jade Dragon Snow Mountain, southwestern China.

BACKGROUND: Understanding altitudinal patterns of biological diversity and their underlying mechanisms is critically important for biodiversity conservation in mountainous regions. The contribution of area to plant diversity patterns is widely acknowledged and may mask the effects of other determinant factors. In this context, it is important to examine altitudinal patterns of corrected taxon richness by eliminating the area effect. Here we adopt two methods to correct observed taxon richness: a power-law relationship between richness and area, hereafter "method 1"; and richness counted in equal-area altitudinal bands, hereafter "method 2". We compare these two methods on the Jade Dragon Snow Mountain, which is the nearest large-scale altitudinal gradient to the Equator in the Northern Hemisphere. RESULTS: We find that seed plant species richness, genus richness, family richness, and species richness of trees, shrubs, herbs and Groups I-III (species with elevational range size <150, between 150 and 500, and >500 m, respectively) display distinct hump-shaped patterns along the equal-elevation altitudinal gradient. The corrected taxon richness based on method 2 (TRcor2) also shows hump-shaped patterns for all plant groups, while the one based on method 1 (TRcor1) does not. As for the abiotic factors influencing the patterns, mean annual temperature, mean annual precipitation, and mid-domain effect explain a larger part of the variation in TRcor2 than in TRcor1. CONCLUSIONS: In conclusion, for biodiversity patterns on the Jade Dragon Snow Mountain, method 2 preserves the significant influences of abiotic factors to the greatest degree while eliminating the area effect. Our results thus reveal that although the classical method 1 has earned more attention and approval in previous research, method 2 can perform better under certain circumstances. We not only confirm the essential contribution of method 1 in community ecology, but also highlight the significant role of method 2 in eliminating the area effect, and call for more application of method 2 in further macroecological studies.