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CD147, a glycosylated transmembrane protein in the immunoglobulin superfamily, is overexpressed on the surfaces of various tumor cells and promotes cancer cell proliferation, invasion, and metastasis. Nanobodies, characterized by small sizes, high affinities and specificities, and low immunogenicities, are promising diagnostic and therapeutic tools. However, there are few reports on nanobodies that specifically target CD147. In this work, a specific anti-CD147 nanobody has been successfully identified using phage display technology. The tumor target and antitumor effects have also been detected in different CD147-positive tumors in in vitro and in vivo assays, respectively. Meanwhile, it has a synergistic effect for inhibiting 4T1-bearing mice through conjugating doxorubicin. It may afford new strategies for cancer therapies.

Nasopharyngeal carcinoma (NPC) is a respiratory malignant epithelial carcinoma. Research has indicated that bactericidal/permeability-increasing fold-containing protein B1 (BPIFB1), mostly secreted by nasopharyngeal epithelia, is dysregulated in patients with NPC. This study aimed to explore the effects of BPIFB1 inviability, proliferation, apoptosis and its molecular mechanism. To confirm the effects of BPIFB1 on NPC cells, BPIFB1 was overexpressed or silenced in NPC-KT cells after being transfected with BPIFB1 or siBPIFB1 plasmids. The results showed that BPIFB1 overexpression could induce apoptosis and DNA damage in NPC-KT cells, and silenced BPIFB1 had the opposite effects. BPIFB1 overexpression can inhibit the cell cycle by being arrested at the G0/G1 phase and by regulating the MEK/ERK signaling pathway. MEK inhibitor U0126 was used to confirm the effects of BPIFB1 on the MEK/ERK pathway, and U0126 can inverse the effects of siBPIFB1. Additionally, BPIFB1 can enhance the anti-proliferative effect of chemotherapy drugs on NPC-KT cells. All the results indicated that BPIFB1 could be a potential target for the treatment of NPC.

Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From the 14th to 28th days, the mice were maintained free of gentamicin treatment. Immunohistochemistry labeling was employed to trace RIBEYE, a major presynaptic componment of ribbon synapses. RIBEYE/CtBP2 expression levels were assessed and compared with hearing threshold shifts. Auditory function was assessed by auditory brainstem responses. The stereocilia of outer hair cells (OHCs) and IHCs was examined by scanning electron microscopy (SEM). Results Hearing thresholds were elevated with peak hearing loss observed on the 7th day after gentamicin exposure, followed by improvement after the 7th day. RIBEYE/CtBP2 expression directly correlated with observed hearing threshold shifts. Strikingly, we did not see any obvious changes in stereocilia in both OHCs and IHCs until the 28th day. Mild changes in stereocilia were only observed in OHCs on the 28th day. Conclusions These findings indicate that presynapse cochlear ribbons, rather than stereocilia, may be sensitive to aminoglycoside ototoxic exposure in mice cochleae. A pattern of RIBEYE/CtBP2 expression changes seems to parallel hearing threshold shifts and suggests presynaptic response properties to lower dosage of aminoglycoside ototoxic stimuli.