Search Results (2,485)

Aim: The main purpose of the present study was to investigate the carrier rate of Aggregatibacter actinomycetemcomitans and its JP2 genotype in a cohort of 200 Western Australians diagnosed with periodontitis. Materials and Methods: In this descriptive cross-sectional study, 220 consecutive patients with periodontitis, aged 18 years and older, were recruited to a specialist periodontal practice in Perth City. Every patient included in this study contributed three different intra-oral samples. Periodontal, radiographical, and microbiological assessments were performed. The samples were analysed using a polymerase chain reaction for the detection of Aggregatibacter actinomycetemcomitans and its JP2 genotype using the primers and conditions described previously. A Chi-square test and logistic regression analysis were performed to evaluate the results. Results: The prevalence of Aggregatibacter actinomycetemcomitans was 28.18%. The carrier rates of A. actinomycetemcomitans in the unstimulated saliva, cheek swabs, and pooled subgingival plaque samples were 21.80%, 19.50%, and 17.70%, respectively. There was a significant correlation between the severe form of periodontitis (stage IV, grade C) and younger age (p = 0.004), positive family history of periodontitis (p < 0.001), oral hygiene method (p < 0.001), and irregular dental visit attendance (p < 0.001). The binary logistic regression analysis revealed that having severe periodontitis risk increased almost three times in those who were young (OR: 2.812) and came from a family with a history of periodontal disease (OR: 3.194). However, the risk of severe periodontitis was five times higher in those patients with tooth loss due to periodontal disease (OR: 5.071). The highly leukotoxic JP2 genotype of Aggregatibacter actinomycetemcomitans was not detected. Conclusions: This study of a Western Australian cohort confirmed the low presence of Aggregatibacter actinomycetemcomitans and the complete absence of its JP2 genotype. Young age, family history of periodontal disease, lack of flossing, irregular dental visits, and tooth loss due to periodontitis were identified as potential risk factors for periodontitis stage IV, grade C in this cohort. Full article

Objectives: Alzheimer’s disease (AD) is a devastating neurodegenerative disorder with a complex aetiology. The aims of this study were to investigate the relationship between vitamin B supplementation and AD risk and to explore the potential mediating effect of the gut microbiota in this relationship. Methods: We employed a Mendelian randomisation analysis to examine the association between different vitamin B supplementation modalities (vitamin B₆, folic acid, B₁₂, and vitamin B complex tablets) and AD risk. Univariate Mendelian randomisation with inverse-variance weighting was used. Additionally, mediation analyses were conducted to identify the potential mediating effects of 119 known bacterial genera. Results: The univariate Mendelian randomisation analyses showed no significant direct associations between individual vitamin B supplements or vitamin B complex tablets and AD risk. However, several gut bacterial genera were significantly associated with AD risk. Lachnospiraceae (NK4A136 group), Paraprevotella, Slackia, and Bifidobacterium were associated with reduced AD risk, while Defluviitaleaceae (UCG011), Desulfovibrio, Eubacterium ventriosum group, and Ruminococcaceae UCG-003 were associated with increased AD risk. The mediation analysis revealed that Lachnospiraceae (NK4A136 group), Defluviitaleaceae (UCG011), and Bifidobacterium fully mediated the causal relationships between vitamin B₁₂, B₆, and B complex supplementation, respectively, and AD risk. Conclusions: This study provides evidence suggesting that certain gut microbiota genera are significantly associated with AD risk and may mediate the relationship between vitamin B supplementation and AD risk. These findings offer new insights into the variable effectiveness of B vitamins in treating neurodegenerative diseases and suggest potential new strategies for AD treatment and prevention. Full article

Background/Objectives: The aim of this study was to determine the assessment of the percentage of NK and NKT-like cells expressing Toll-like receptors (TLR-2, TLR-3, TLR-4, and TLR-9) in patients with gastric cancer (GC) compared with healthy volunteers (HV) and to investigate differences according to cancer subtype. We also assessed TLR gene expression by RT-qPCR to assess whether TLRs could be diagnostic and prognostic biomarkers. Methods: The study included 86 patients with histologically confirmed gastric cancer and 30 healthy volunteers. Peripheral blood samples were collected from the participants, and TLR expression on NK and NKT-like cells was assessed by flow cytometry and RT-qPCR. The expression of TLR2, TLR3, TLR4, and TLR9 genes was assessed using genetic material derived from NK and NKT-like cells sourced from PBMC. The obtained results were statistically analyzed using Mann–Whitney U and Kruskal–Wallis tests, and the predictive ability of variables was assessed using ROC curve analysis. Results: A significantly higher expression of TLR receptors (TLR-2, TLR-3, TLR-4, and TLR-9) was found in patients with gastric cancer compared to healthy volunteers (p < 0.05). TLR expression also differed depending on the cancer subtype, and higher expression was observed in more advanced GC subtypes. RT-qPCR analysis showed significantly increased expression of TLR genes in the group of GC patients. ROC curves indicate a high ability of TLRs to differentiate between GC patients and healthy individuals. Conclusions: The expression of TLRs on NK and NKT-like cells is clearly increased in patients with gastric cancer, especially in more advanced subtypes of the tumor. The results suggest that TLRs could potentially be used as diagnostic and prognostic biomarkers and represent potential targets for immune therapies in GC. However, further studies are needed to determine the functional role of TLRs in disease progression and the possibility of their use in personalized treatment. Full article

The wheat–maize rotation system in the North China Plain (NCP) has a large amount of crop straw. However, improper crop straw management and blind fertilization lead to nutrient imbalance and accelerated nutrient loss from the soil, ultimately leading to nutrient deficiency affecting the wheat–maize rotation system. In order to explore the effects of nutrient deficiency on the yield and nutrient use efficiency of wheat and maize, the experiment was conducted in a randomized complete block design consisting of five treatments with three replicates for each treatment: (1) a potassium fertilizer deficiency and appropriate nitrogen and phosphate fertilizer treatment (NP); (2) a phosphate fertilizer deficiency and appropriate nitrogen and potassium fertilizer treatment (NK); (3) a nitrogen fertilizer deficiency and appropriate phosphate and potassium fertilizer treatment (PK); (4) an adequate nitrogen, phosphorus, and potassium fertilizer treatment (NPK); and (5) a no-fertilizer treatment (CK). The results showed that, compared with CK, the yields of wheat and maize treated with NPK were increased by 21.5% and 27.5%, respectively, and the accumulation of the dry matter of the wheat and maize was increased by 42.5% and 57.3%. In all the deficiency treatments, the NK treatment performed better in terms of yield compared to the NP and PK treatments, while the NP treatment demonstrated a greater increase in dry matter accumulation. The NPK treatment significantly improved the nitrogen use efficiency (NUE) and nitrogen harvest index (NHI) of the wheat and maize, which resulted in higher nitrogen accumulation in the NPK treatment, and the NP treatment was the best among the other nutrient deficiency treatments. The inorganic nitrogen content showed a similar trend. In conclusion, nutrient deficiency can severely restrict crop growth. Nitrogen deficiency can significantly reduce crop yields. Phosphorus deficiency had a greater impact than potassium deficiency in terms of nutrient absorption and accumulation. Therefore, nitrogen fertilizer application should be emphasized in crop rotation systems, with moderate increases in phosphorus fertilizer application. This practice can effectively improve the nutrient deficiency under the wheat and maize rotation system in the NCP and complete a rational fertilization system. Full article

In B-cell malignancies, the overexpression of MYC is associated with poor prognosis, but its mechanism underlying resistance to immunochemotherapy remains less clear. In further investigations of this issue, we show here that the pharmacological inhibition of MYC in various lymphoma and multiple myeloma cell lines, as well as patient-derived primary tumor cells, enhances their susceptibility to NK cell-mediated cytotoxicity induced by conventional antibodies targeting CD20 (rituximab) and CD38 (daratumumab), as well as T cell-mediated cytotoxicity induced by the CD19-targeting bispecific T-cell engager blinatumomab. This was associated with upregulation of the target antigen only for rituximab, suggesting additional escape mechanisms. To investigate these mechanisms, we targeted the MYC gene in OCI-LY18 cells using CRISPR-Cas9 gene-editing technology. CRISPR-Cas9-mediated MYC targeting not only upregulated CD20 but also triggered broader apoptotic pathways, upregulating pro-apoptotic PUMA and downregulating anti-apoptotic proteins BCL-2, XIAP, survivin and MCL-1, thereby rendering tumor cells more prone to apoptosis, a key tumor-lysis mechanism employed by T-cells and NK-cells. Moreover, MYC downregulation boosted T-cell activation and cytokine release in response to blinatumomab, revealing a MYC-mediated T-cell suppression mechanism. In conclusion, MYC overexpressing tumor cells mitigated the efficacy of therapeutic antibodies through several non-overlapping mechanisms. Given the challenges associated with direct MYC inhibition due to toxicity, successful modulation of MYC-mediated immune evasion mechanisms may improve the outcome of immunotherapeutic approaches in B-cell malignancies. Full article

This paper examines the relationship between a technology shock and employment, considering price, wage rigidities, and heterogeneous agents. To explore this relationship, we utilized a Dynamic Stochastic General Equilibrium (DSGE) model, incorporating households with varying savings rates. For empirical validation, we conducted a Structural Vector Autoregression (SVAR) analysis using data from two economies with distinct savings patterns—the United States and China. This approach allowed us to assess the impact of technology shocks on employment dynamics across different savings environments. Under these conditions, we observe that the effect of technology on aggregate employment is initially positive. Still, it gradually decreases in the mid-term, eventually switching to a negative impact before slowly recovering to equilibrium. The reason for this phenomenon depends on (i) the magnitude of fluctuations in price and wage, precisely, which variable’s fluctuations have a greater magnitude, and (ii) which effect, between income effect and substitute effect, is preferred by restricted and unrestricted households. Due to (i), real wages change, and because of (ii), households make different labor supply decisions, leading to fluctuations in employment in response to technology shocks. Full article

Understanding natural killer (NK) cell functionality is essential in developing more effective immunotherapeutic strategies that can enhance patient outcomes, especially in the context of cancer treatment. This review provides a comprehensive overview of both traditional and novel techniques for evaluating NK cell functionality, focusing on multiparameter assays and spatial methods that illuminate NK cell interactions within their microenvironment. We discuss the significance of standardized assays for assessing NK cell function across various research and clinical settings, including cancer immunotherapy, infectious diseases, and transplantation. Key factors influencing NK cell functionality include the origin of the sample, target–effector ratios, the functional state of NK cells, and the impact of pre-treatment conditions and their natural aging effect on NK cell activity. By emphasizing the importance of selecting a suitable technique for reliable measurements, especially for longitudinal monitoring, this review aims to give an overview on techniques to measure NK cell functionality in vitro and show the interaction with their microenvironment cells by spatial imaging. Ultimately, our understanding of NK cell functionality could be critical to biomarker development, drug design, and understanding of disease progression in the field of oncology or infectious disease. Full article

Natural killer (NK) cells are innate lymphocytes that can rapidly mount a response to their targets by employing diverse mechanisms. Due to their functional attributes, NK cells have been implicated in anti-viral and anti-tumour immune responses. Although traditionally known to mount non-specific, rapid immune responses, in recent years, the notion of memory NK cells with adaptive features has gained more recognition. Memory NK cells emerge in response to different stimuli, such as viral antigens and specific cytokine combinations. They form distinct populations, accompanied by transcriptional, epigenetic and metabolic reprogramming, resulting in unique phenotypic and functional attributes. Several clinical trials are testing the efficacy of memory NK cells due to their enhanced functionality, bioenergetic profile and persistence in vivo. The therapeutic potential of NK cells is being harnessed in viral infections, with wider applications in the cancer field. In this review, we summarise the current state of research on the generation of memory NK cells, along with their clinical applications in viral infection and cancer. Full article

The objective of this study was to explore the rumen fermentation characteristics, bacterial diversity, community composition, and metabolite profiles of rice straw from three distinct varieties. Straws from two hybrid rice varieties, Lingliangyou 268 (L268) and Yueyou 9113 (Y9113), and one inbred rice variety, Zhongzao 39 (Z39), were selected for a 72 h in vitro rumen fermentation test. The fermentation products were analyzed for rumen fermentation characteristics, bacterial community, and rumen metabolomics. The results showed that Y9113 had higher total gas and methane production, greater dry matter digestibility, and higher concentrations of ammonium nitrogen and volatile fatty acids compared to Z39 (p < 0.05). The variety of rice straw did not affect the richness or diversity of the rumen bacterial community (p > 0.05). However, the relative abundances of Verrucomicrobiota, Euryarchaeota, Elusimicrobiota, Probable genus 10, Lachnospiraceae AC2044 group, WCHB1-41, and VadinBE97 were higher in Z39 than in Y9113, while the opposite was observed for Saccharofermentans, UCG-010, and NK4A214 group (p < 0.05). Both principal coordinates analysis (PCoA) and partial least squares discrimination analysis (PLS-DA) revealed clear distinctions in the rumen bacterial communities between Y9113 and Z39. Metabolomic analysis identified eighteen differential metabolites among L268, Z39, and Y9113, with six showing strong correlations with the rumen microbiota. These findings suggest that the feed value of rice straw is influenced by the variety under the same cultivation conditions, due to nutritional disparities that subsequently affect the rumen microbial community and metabolite profiles. This study offers valuable data and insights for the strategic resource utilization of rice straw from different varieties in the livestock industry. Full article

Studies suggest that the dynamic changes in cellular response might correlate with disease severity and outcomes in SARS-CoV-2 patients. The study aimed to investigate the dynamic changes of lymphocyte subsets in patients with COVID-19. In this regard, 53 patients with COVID-19 were prospectively included, classified as mild, moderate, and severe. The peripheral lymphocyte profiles (LyT, LyB, and NK cells), as well as CD4+/CD8+, CD3+/CD19+, CD3+/NK and CD19+/NK ratios, and their dynamic changes during hospitalization and correlation with disease severity and outcome were assessed. We found significant differences in CD3+ lymphocytes between severity groups (p < 0.0001), with significantly decreased CD3+CD4+ and CD3+CD8+ in patients with severe disease (p < 0.0001 and p = 0.048, respectively). Lower CD3+/CD19+ and CD3+/NK ratios among patients with severe disease (p = 0.019 and p = 0.010, respectively) were found. The dynamic changes of lymphocyte subsets showed a significant reduction in NK cells (%) and a significant increase in CD3+CD4+ and CD3+CD8+ cells in patients with moderate and severe disease. The ROC analysis on the relationship between CD3+ cells and fatal outcome yielded an AUC of 0.723 (95% CI 0.583–0.837; p = 0.007), while after addition of age and SpO₂, ferritin and NLR, the AUC significantly improved to 0.927 (95%CI 0.811–0.983), p < 0.001 with a sensitivity of 90.9% (95% CI 58.7–99.8%) and specificity of 85.7% (95% CI 69.7–95.2%). The absolute number of CD3+ lymphocytes might independently predict fatal outcomes in COVID-19 patients and T-lymphocyte subset evaluation in high-risk patients might be useful in estimating disease progression. Full article

There exists a long-standing research interest to understand the molecular and signaling interactions between tumor cells and the innate and adaptive immune cells such as dendritic cells, macrophages, NK cells, and B and T cells that occur in the tumor microenvironment (TME) [...] Full article

Infection of hepatitis B (HBV) patients with hepatitis D (HDV) can cause the most severe form of viral hepatitis, leading to liver fibrosis, liver failure, and hepatocellular carcinoma. HDV relies on simultaneous infection with HBV for the generation of infectious viral particles. The innate immune response, which is weakly induced in HBV infection, becomes strongly activated upon HDV co-infection. In HBV/HDV co-infection, the immune system comprises a cell-intrinsic strong IFN response, which leads to the induction of interferon-stimulated genes (ISGs), the local activation of liver-resident innate immune cells, and additional immune cell recruitment from the blood. Efficient innate immune responses are indispensable for successful viral control and spontaneous viral clearance. Despite this fact, innate immune cell activation can also contribute to adaptive immune cell inhibition and accelerate liver damage in HBV/HDV infection. While the intrinsic IFN response in HDV-infected cells is well characterized, far less is known about the cellular innate immune cell compartment. In this review, we summarize HBV/HDV replication characteristics and decipher the role of innate immune cell subsets in the anti-viral response in HBV/HDV infections. We further review the impact of epigenetic and metabolic changes in infected heptatocytes on the innate anti-viral response. Moreover, we discuss the potential of exploiting the innate immune response for improving vaccination strategies and treatment options, which is also discussed in this review. Full article

Background/Objectives: An inappropriate intake of dietary fats can disrupt the homeostasis of intestinal microbiota, affect the host’s metabolic status, and increase the risk of chronic diseases. The impact of dietary fat types on the composition and metabolic functionality of the intestinal microbiota has become a research focus over recent years. The objective of this study was to explore the effects of regular peanut oil (PO) and high-oleic-acid peanut oil (HOPO) on the composition and metabolic function of the intestinal microbiota. Methods: A dietary intervention test was conducted on SD rats fed a high-fat/high-fructose (HFF) diet. The composition and metabolic functionality of the intestinal microbiota of the experimental rats were investigated by 16S rRNA gene sequencing and fecal metabolomics. Results: Compared with saturated fat, PO and HOPO enhanced the diversity of intestinal microbiota in HFF diet-fed rats. Compared with PO, HOPO significantly increased the relative abundance of Lachnospiraceae_NK4A136_group and Harryflintia (p < 0.05), which are able to generate butyrate and acetate. Compared with saturated fat, 318 and 271 fecal biomarkers were identified in PO and HOPO groups, respectively. In contrast, 68 fecal biomarkers were identified between the PO and HOPO groups. The inhibition of harmful proteolytic fermentation in the colon may represent the main regulatory mechanism. With regard to metabolic status, HOPO provided better control of body weight and insulin sensitivity than PO. Conclusions: Compared with saturated fat, peanut oils better regulated the composition and metabolic function of the intestinal microbiota. In addition, HOPO exhibited better regulatory effects than PO. Full article

Ovarian cancer is the deadliest gynecologic cancer. Although human epidermal growth factor receptor-2 (HER2) overexpression, a poor prognostic molecular marker in ovarian cancer, is found in almost 30% of ovarian cancer cases, there are no established therapies for HER2-overexpressing ovarian cancer. In this study, we investigated the efficacy of combined samfenet, a biosimilar compound of trastuzumab, and natural killer (NK) cells in preclinical model of HER2-overexpressing ovarian cancer. Firstly, we screened the HER2 expression in three ovarian cancer cell lines and eight ovarian cancer patient-derived tumor xenograft (PDTX) samples. Then, immunohistochemistry and silver in situ hybridization (SISH) were performed following clinical criteria. HER2-overexpressing cells exhibited the highest sensitivity to samfenet compared with low-HER2-expressing cells. In addition, the combination of samfenet with natural killer (NK) cells resulted in significantly enhanced sensitivity to HER2-overexpressing cells and showed a significant antitumor effect on PDTX mice compared with monotherapy. It is known that anti-HER2-humanized IgG1 monoclonal antibodies, including trastuzumab, induce antibody-dependent cellular cytotoxicity (ADCC). Consequently, the combination of samfenet with NK cells demonstrated NK cell-mediated ADCC, as confirmed using an in vitro NK cytotoxicity assay and in vivo antitumor efficacy. A transferase dUTP nick end labeling (TUNEL) assay using xenografted tumors further supported the ADCC effects based on the increase in the number of apoptotic cells in the combination group. Furthermore, high HER2 expression was associated with shorter progression-free survival and overall survival based on public mRNA expression data. In this study, we demonstrated that the combination of samfenet and NK cell therapy could be a promising treatment strategy for patients with HER2-overexpressing ovarian cancer, through ADCC effects. Therefore, this study supports a rationale for further clinical studies of the combination of samfenet and NK cells as a therapy for patients with HER2-overexpressing ovarian cancer. Full article

To determine the pivotal microorganisms affecting intramuscular fat (IMF) accumulation in Min pigs and to discern the extent of the influence exerted by various intestinal segments on IMF-related traits, we sequenced 16S rRNA from the contents of six intestinal segments from a high IMF group (Group H) and a low IMF group (Group L) of Min pigs weighing 90 ± 1 kg. We then compared their diversity and disparities in bacterial genera. Group H exhibited considerably higher α diversity in the jejunum and colon than Group L (p < 0.05). When 95% confidence levels were considered, the main β diversity components for the ileum, caecum, and colon within Groups H and L exhibited absolute segregation. Accordingly, 31 differentially abundant genera across Group H were pinpointed via LEfSe and the Wilcoxon test (p < 0.05) and subsequently scrutinised based on their distribution and abundance across distinct intestinal segments and their correlation with IMF phenotypes. The abundances of Terrisporobacter, Acetitomaculum, Bacteroides, Fibrobacter, Treponema, Akkermansia, Blautia, Clostridium sensu stricto 1, Turicibacter, Subdoligranulum, the [Eubacterium] siraeum group, and dgA 11 gut groups were positively correlated with IMF content (p < 0.05), whereas those of Bacillus, the Lachnospiraceae NK4A136 group, Streptococcus, Roseburia, Solobacterium, Veillonella, Lactobacillus, the Rikenellaceae RC9 gut group, Anaerovibrio, and the Lachnospiraceae AC2044 group were negatively associated with IMF content (p < 0.05). Employing PICRUSt2 for predicting intergenic metabolic pathways that differ among intestinal microbial communities revealed that within the 95% confidence interval the colonic microbiome was enriched with the most metabolic pathways, including those related to lipid metabolism. The diversity results, bacterial genus distributions, and metabolic pathway disparities revealed the colonic segment as an influential region for IMF deposition. Full article