Myeloid-Derived Suppressor Cells in Tumors: From Mechanisms to Antigen Specificity and Microenvironmental Regulation

Among the various immunological and non-immunological tumor-promoting activities of myeloid-derived suppressor cells (MDSCs), their immunosuppressive capacity remains a key hallmark. Effort in the past decade has provided us with a clearer view of the suppressive nature of MDSCs. More suppressive pathways have been identified, and their recognized targets have been expanded from T cells and natural killer (NK) cells to other immune cells. These novel mechanisms and targets afford MDSCs versatility in suppressing both innate and adaptive immunity. On the other hand, a better understanding of the regulation of their development and function has been unveiled. This intricate regulatory network, consisting of tumor cells, stromal cells, soluble mediators, and hostile physical conditions, reveals bi-directional crosstalk between MDSCs and the tumor microenvironment. In this article, we will review available information on how MDSCs exert their immunosuppressive function and how they are regulated in the tumor milieu. As MDSCs are a well-established obstacle to anti-tumor immunity, new insights in the potential synergistic combination of MDSC-targeted therapy and immunotherapy will be discussed

Cinnamaldehyde Exerts Its Antifungal Activity by Disrupting the Cell Wall Integrity of Geotrichum citri-aurantii

Our previous study showed that cinnamaldehyde (CA) significantly inhibited the mycelial growth of Geotrichum citri-aurantii, one of the main postharvest pathogens in citrus fruits. This study investigated the antifungal mechanism of CA against G. citri-aurantii. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images showed that CA treatment led to clear morphological changes in the cell walls and membranes of G. citri-aurantii. However, the membrane integrity, total lipids and ergosterol contents were not apparently affected by CA treatment. Notably, the extracellular alkaline phosphatase (AKP) activity was increased after CA treatment, suggesting impairment in cell wall permeability. A weakened fluorescence in the cell wall, a decrease in the chitin contents, and changes of ten genes involved in cell wall integrity were also observed. These results suggested that CA may exhibit its antifungal activity against G. citri-aurantii by interfering the build of cell wall and therefore lead to the damage of cell wall permeability and integrity

Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism

Berberine is known to improve glucose and lipid metabolism disorders, but the mechanism is still under investigation. In this paper, we explored the effects of berberine on the weight, glucose levels, lipid metabolism, and serum insulin of KKAy mice and investigated its possible glucose and lipid-regulating mechanism. We randomly divided KKAy mice into two groups: berberine group (treated with 250 mg/kg/d berberine) and control group. Fasting blood glucose (FBG), weight, total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), and fasting serum insulin were measured in both groups. The oral glucose tolerance test (OGTT) was performed. RT2 PCR array gene expression analysis was performed using skeletal muscle of KKAy mice. Our data demonstrated that berberine significantly decreased FBG, area under the curve (AUC), fasting serum insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR) index, TC, and TG, compared with those of control group. RT2 profiler PCR array analysis showed that berberine upregulated the expression of glucose transporter 4 (GLUT4), mitogen-activated protein kinase 14 (MAPK14), MAPK8(c-jun N-terminal kinase, JNK), peroxisome proliferator-activated receptor α (PPARα), uncoupling protein 2 (UCP2), and hepatic nuclear factor 4α(HNF4α), whereas it downregulated the expression of PPARγ, CCAAT/enhancer-binding protein (CEBP), PPARγ coactivator 1α(PGC 1α), and resistin. These results suggest that berberine moderates glucose and lipid metabolism through a multipathway mechanism that includes AMP-activated protein kinase-(AMPK-) p38 MAPK-GLUT4, JNK pathway, and PPARα pathway

Biphasic activation of PI3K/Akt and MAPK/Erk1/2 signaling pathways in bovine herpesvirus type 1 infection of MDBK cells

Many viruses have been known to control key cellular signaling pathways to facilitate the virus infection. The possible involvement of signaling pathways in bovine herpesvirus type 1 (BoHV-1) infection is unknown. This study indicated that infection of MDBK cells with BoHV-1 induced an early-stage transient and a late-stage sustained activation of both phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen activated protein kinases/extracellular signal-regulated kinase 1/2 (MAPK/Erk1/2) signaling pathways. Analysis with the stimulation of UV-irradiated virus indicated that the virus binding and/or entry process was enough to trigger the early phase activations, while the late phase activations were viral protein expression dependent. Biphasic activation of both pathways was suppressed by the selective inhibitor, Ly294002 for PI3K and U0126 for MAPK kinase (MEK1/2), respectively. Furthermore, treatment of MDBK cells with Ly294002 caused a 1.5-log reduction in virus titer, while U0126 had little effect on the virus production. In addition, the inhibition effect of Ly294002 mainly occurred at the post-entry stage of the virus replication cycle. This revealed for the first time that BoHV-1 actively induced both PI3K/Akt and MAPK/Erk1/2 signaling pathways, and the activation of PI3K was important for fully efficient replication, especially for the post-entry stage

Dispersion characteristics of double-corrugated rectangular waveguide for terahertz vacuum devices

An analytical study on the dispersion of the double-corrugated waveguide for THz vacuum devices is presented. The boundary element method (BEM) is introduced to improve the accuracy of the dispersion. The results are compared with the 3D electromagnetic simulations

ACP-DRL: an anticancer peptides recognition method based on deep representation learning

Cancer, a significant global public health issue, resulted in about 10 million deaths in 2022. Anticancer peptides (ACPs), as a category of bioactive peptides, have emerged as a focal point in clinical cancer research due to their potential to inhibit tumor cell proliferation with minimal side effects. However, the recognition of ACPs through wet-lab experiments still faces challenges of low efficiency and high cost. Our work proposes a recognition method for ACPs named ACP-DRL based on deep representation learning, to address the challenges associated with the recognition of ACPs in wet-lab experiments. ACP-DRL marks initial exploration of integrating protein language models into ACPs recognition, employing in-domain further pre-training to enhance the development of deep representation learning. Simultaneously, it employs bidirectional long short-term memory networks to extract amino acid features from sequences. Consequently, ACP-DRL eliminates constraints on sequence length and the dependence on manual features, showcasing remarkable competitiveness in comparison with existing methods