The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABA_A receptor (GABA_AR) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.

Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation.

Gliomas are one of the most common primary malignant tumours of the central nervous system (CNS), of which glioblastomas (GBMs) are the most common and destructive type. The glioma tumour microenvironment (TME) has unique characteristics, such as hypoxia, the blood-brain barrier (BBB), reactive oxygen species (ROS) and tumour neovascularization. Therefore, the traditional treatment effect is limited. As cellular oxidative metabolites, ROS not only promote the occurrence and development of gliomas but also affect immune cells in the immune microenvironment. In contrast, either too high or too low ROS levels are detrimental to the survival of glioma cells, which indicates the threshold of ROS. Therefore, an in-depth understanding of the mechanisms of ROS production and scavenging, the threshold of ROS, and the role of ROS in the glioma TME can provide new methods and strategies for glioma treatment. Current methods to increase ROS include photodynamic therapy (PDT), sonodynamic therapy (SDT), and chemodynamic therapy (CDT), etc., and methods to eliminate ROS include the ingestion of antioxidants. Increasing/scavenging ROS is potentially applicable treatment, and further studies will help to provide more effective strategies for glioma treatment.

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.

In our study, we determined the pattern of expression and biological roles of microRNA-20a (miR-20a) in diabetic kidney disease (DKD). The difference in the expression of miR-20a and proinflammatory genes (TNF-α, IL-6, and IL-1β) was measured across control, normal glucose (NG), and high glucose (HG) groups. Co-transfection miR-20a mimic and CXCL8 silence was used to assess the miR-20a/CXCL8 axis in the HG-induced HK-2 cell injury involved in DKD. miR-20a in HG group was significantly decreased, and a marked augmentation of inflammatory factor gene expression (TNF-α, IL-6, and IL-1β) in HK-2 cells was induced by HG. miR-20a over-expression enhanced cell proliferation, inhibited cell apoptosis, and suppressed the inflammatory response of HK-2 cells. CXCL8 knockdown strengthened the role of miR-20a. Our findings showed that miR-20a might be a significant regulator of HG-induced renal proximal tubular inflammatory injury mediating diabetic kidney disease through regulation of the expression of CXCL8 and the MEK/ERK pathway.