Effects of probiotic Bacillus as a substitute for antibiotics on antioxidant capacity and intestinal autophagy of piglets

The objective of this study was to evaluate effects of probiotic Bacillus amyloliquefaciens (Ba) as a substitute for antibiotics on growth performance, antioxidant ability and intestinal autophagy of piglets. Ninety piglets were divided into three groups: G1 (containing 150 mg/Kg aureomycin in the diet); G2 (containing 75 mg/Kg aureomycin and 1 × 10(8) cfu/Kg Ba in the diet); G3 (containing 2 × 10(8) cfu/Kg Ba in the diet without any antibiotics). Each treatment had three replications of ten pigs per pen. Results showed that Ba replacement significantly increased the daily weight gain of piglets. Moreover, improved antioxidant status in serum and jejunum was noted in Ba-fed groups as compared with aureomycin group. Increased gene expression of antioxidant enzymes and elevated nuclear factor erythroid 2 related factor 2 (Nrf2) in jejunum was also observed in Ba-fed groups. Besides, Ba replacement significantly decreased jejunal c-Jun N-terminal kinase (JNK) phosphorylation compared with antibiotic group. Western blotting results also revealed that replacing all antibiotics with Ba initiated autophagy in the jejunum as evidenced by increased microtubule-associated protein 1 light chain 3 II (LC3-II) abundance. Taken together, these results indicate that replacing aureomycin with Ba can improve growth performance and antioxidant status of piglets via increasing antioxidant capacity and intestinal autophagy, suggesting a good potential for Ba as an alternative to antibiotics in feed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13568-017-0353-x) contains supplementary material, which is available to authorized users

Bmal1 haploinsufficiency impairs fear memory and modulates neuroinflammation via the 5-HT2C receptor

BackgroundBMAL1, a key regulator of circadian rhythms, plays a multifaceted role in brain function. However, the complex interplay between BMAL1, memory, neuroinflammation, and neurotransmitter regulation remains poorly understood. To investigate these interactions, we conducted a study using BMAL1-haplodeficient mice (BMAL1+/−).MethodsWe exposed BMAL1+/− mice to behavioral assessments including cued fear conditioning, new objection recognition (NOR) test, and Y-maze test to evaluate BMAL1+/− haplodeficiency impact on memory. Furthermore, biochemical changes were analyzed through western blotting, and ELISA to explore further the mechanism of BMAL1+/− in memory, and neuroinflammation.ResultsWe found that BMAL1 haploinsufficiency led to deficits in cued fear learning and memory, while spatial memory and object recognition remained intact. Further analysis revealed dysregulated neurotransmitter levels and alterations in neurotransmitter-related proteins in the prefrontal cortex of BMAL1+/− mice. Pharmacological interventions targeting dopamine uptake or the 5-HT2C receptor demonstrated that inhibiting the 5-HT2C receptor could rescue fear learning and memory impairments in BMAL1+/− mice. Additionally, we observed downregulation of the inflammasome and neuroinflammation pathways in BMAL1+/− mice, which is validated by inflammation mediator lipopolysaccharide (LPS) administration.ConclusionThese findings highlight that BMAL1 haploinsufficiency leads to deficits in fear learning and memory, which are linked to alterations in neurotransmitters and receptors, particularly the 5-HT2C receptor. Targeting the 5-HT2C receptor may offer a potential therapeutic strategy for mitigating cognitive impairments associated with BMAL1 dysfunction

Targeted p53 on Small-Molecules-Induced Ferroptosis in Cancers

Ferroptosis is a type of programmed cell death characterized by the accumulation of lipid reactive oxygen species (L-ROS) driven by the oxidative degeneration of lipids in an iron-dependent manner. The mechanism by which lipid oxidative degradation drives ROS-ferroptosis involves metabolic dysfunctions that result in impaired intracellular metabolic processes and ROS production. Recent studies have found that p53 acts as a positive regulator of ferroptosis by promoting ROS production. p53 directly regulates the metabolic versatility of cells by favoring mitochondrial respiration, leading to ROS-mediated ferroptosis. In mild stress, p53 protects cell survival via eliminating ROS; additionally, in human colorectal cancer, p53 antagonizes ferroptosis by formation of the DPP4–p53 complex. In short, the mechanisms of p53-mediated ROS production underlying cellular response are poorly understood. In the context of recent research results, the indistinct roles of p53 on ROS-mediated ferroptosis are scrutinized to understand the mechanism underlying p53-mediated tumor suppression

Design strategies of tumor-targeted delivery systems based on 2D nanomaterials

Conventional chemotherapy and radiotherapy are nonselective and nonspecific for cell killing, causing serious side effects and threatening the lives of patients. It is of great significance to develop more accurate tumor-targeting therapeutic strategies. Nanotechnology is in a leading position to provide new treatment options for cancer, and it has great potential for selective targeted therapy and controlled drug release. 2D nanomaterials (2D NMs) have broad application prospects in the field of tumor-targeted delivery systems due to their special structure-based functions and excellent optical, electrical, and thermal properties. This review emphasizes the design strategies of tumor-targeted delivery systems based on 2D NMs from three aspects: passive targeting, active targeting, and tumor-microenvironment targeting, in order to promote the rational application of 2D NMs in clinical practice.This work was supported by the Guangdong Basic and Applied Basic Research Foundation (Nos. 2021A1515110657 and 2022A1515010056), Shenzhen Science and Technology Program (Grant No. RCBS20210609104513023), National Natural Science Foundation of China (No. 81922037), and Shanghai Biomedical Science and Technology Support Project (No. 19441903600)

Current status and future prospects of molecular imaging in targeting the tumor immune microenvironment

Molecular imaging technologies have significantly transformed cancer research and clinical practice, offering valuable tools for visualizing and understanding the complex tumor immune microenvironment. These technologies allow for the non-invasive examination of key components within the tumor immune microenvironment, including immune cells, cytokines, and stromal cells, providing crucial insights into tumor biology and treatment responses. This paper reviews the latest advancements in molecular imaging, with a focus on its applications in assessing interactions within the tumor immune microenvironment. Additionally, the challenges faced by molecular imaging technologies are discussed, such as the need for highly sensitive and specific imaging agents, issues with data integration, and difficulties in clinical translation. The future outlook emphasizes the potential of molecular imaging to enhance personalized cancer treatment through the integration of artificial intelligence and the development of novel imaging probes. Addressing these challenges is essential to fully realizing the potential of molecular imaging in improving cancer diagnosis, treatment, and patient outcomes

Glycyrrhizic Acid Promotes M1 Macrophage Polarization in Murine Bone Marrow-Derived Macrophages Associated with the Activation of JNK and NF- κ

The roots and rhizomes of Glycyrrhiza species (licorice) have been widely used as natural sweeteners and herbal medicines. The aim of this study is to investigate the effect of glycyrrhizic acid (GA) from licorice on macrophage polarization. Both phenotypic and functional activities of murine bone marrow-derived macrophages (BMDMs) treated by GA were assessed. Our results showed that GA obviously increased the cell surface expression of CD80, CD86, and MHCII molecules. Meanwhile, GA upregulated the expression of CCR7 and the production of TNF-α, IL-12, IL-6, and NO (the markers of classically activated (M1) macrophages), whereas it downregulated the expression of MR, Ym1, and Arg1 (the markers of alternatively activated (M2) macrophage). The functional tests showed that GA dramatically enhanced the uptake of FITC-dextran and E. coli K88 by BMDMs and decreased the intracellular survival of E. coli K88 and S. typhimurium. Moreover, we demonstrated that JNK and NF-κB activation are required for GA-induced NO and M1-related cytokines production, while ERK1/2 pathway exhibits a regulatory effect via induction of IL-10. Together, these findings indicated that GA promoted polarization of M1 macrophages and enhanced its phagocytosis and bactericidal capacity. The results expanded our knowledge about the role of GA in macrophage polarization

Chronic salmon calcitonin exerts an antidepressant effect via modulating the p38 MAPK signaling pathway

Depression is a common recurrent psychiatric disorder with a high lifetime prevalence and suicide rate. At present, although several traditional clinical drugs such as fluoxetine and ketamine, are widely used, medications with a high efficiency and reduced side effects are of urgent need. Our group has recently reported that a single administration of salmon calcitonin (sCT) could ameliorate a depressive-like phenotype via the amylin signaling pathway in a mouse model established by chronic restraint stress (CRS). However, the molecular mechanism underlying the antidepressant effect needs to be addressed. In this study, we investigated the antidepressant potential of sCT applied chronically and its underlying mechanism. In addition, using transcriptomics, we found the MAPK signaling pathway was upregulated in the hippocampus of CRS-treated mice. Further phosphorylation levels of ERK/p38/JNK kinases were also enhanced, and sCT treatment was able only to downregulate the phosphorylation level of p38/JNK, with phosphorylated ERK level unaffected. Finally, we found that the antidepressant effect of sCT was blocked by p38 agonists rather than JNK agonists. These results provide a mechanistic explanation of the antidepressant effect of sCT, suggesting its potential for treating the depressive disorder in the clinic

Non-invasive monitoring of cardiac function through Ballistocardiogram: an algorithm integrating short-time Fourier transform and ensemble empirical mode decomposition

The Ballistocardiogram (BCG) is a vibration signal that is generated by the displacement of the entire body due to the injection of blood during each heartbeat. It has been extensively utilized to monitor heart rate. The morphological features of the BCG signal serve as effective indicators for the identification of atrial fibrillation and heart failure, holding great significance for BCG signal analysis. The IJK-complex identification allows for the estimation of inter-beat intervals (IBI) and enables a more detailed analysis of BCG amplitude and interval waves. This study presents a novel algorithm for identifying the IJK-complex in BCG signals, which is an improvement over most existing algorithms that only perform IBI estimation. The proposed algorithm employs a short-time Fourier transform and summation across frequencies to initially estimate the occurrence of the J wave using peak finding, followed by Ensemble Empirical Mode Decomposition and a regional search to precisely identify the J wave. The algorithm’s ability to detect the morphological features of BCG signals and estimate heart rates was validated through experiments conducted on 10 healthy subjects and 2 patients with coronary heart disease. In comparison to commonly used methods, the presented scheme ensures accurate heart rate estimation and exhibits superior capability in detecting BCG morphological features. This advancement holds significant value for future applications involving BCG signals

Effects of Probiotic Bacillus as an Alternative of Antibiotics on Digestive Enzymes Activity and Intestinal Integrity of Piglets

The previous study in our team found that supplementation of probiotic Bacillus amyloliquefaciens (Ba) instead of antibiotics promote growth performance of piglets. Hence, the present study was carried out to further demonstrate the effect of Ba replacement of antibiotics on digestive and absorption enzyme activity and intestinal microbiota population of piglets. A total of 90 piglets were selected and divided into three groups: G1 group was fed with basal diet supplemented with 150 mg/Kg aureomycin, G2 group was fed with 1 × 108 cfu/Kg Ba and half dose of aureomycin, G3 group was used the diet with 2 × 108cfu/Kg Ba replaced aureomycin. Each treatment had three replications of 10 pigs per pen. Results indicated that Ba replacement significantly increased the activities of amylase, disaccharides and Na+/K+-ATPase. And chymotrypsin activity in different section of intestine was dramatically enhanced in half replacement of aureomycin with Ba. Moreover, Ba replacement maintained the intestinal integrity with the significantly decreased activity of DAO compared with aureomycin group. Besides, supplementation with Ba increased the β-diversity of intestinal microbiota. Taken together, the current study indicated that diet supplementation with Ba instead of aureomycin increased the growth performance of piglets by improving the digestive and absorb enzyme activities, enhancing the intestinal integrity and regulating the population of intestinal micrbiota