A proinflammatory cytokine, interleukin 23 (IL-23), plays a role in tumor progression by inducing inflammation in the tumor microenvironment, although there is debate about its role in carcinogenesis. Direct effects of IL-23 on tumor cells have been reported rarely, and contradictory effects have been observed. Here, we studied such effects of IL-23 in lung cancer cells in vitro and in vivo and explored the underlying mechanism. We found IL-23 receptor expression in tissues from lung adenocarcinoma and small cell carcinoma but not in lung squamous cell carcinoma tissue. Interestingly, different concentrations of IL-23 had opposite effects in the same types of cells. We confirmed that the different effects could be explained by differences in binding to the IL-23 receptor (subunits IL-23r and IL-12Rβ1). Low concentrations of IL-23 promoted the proliferation of IL-23 receptor-positive A549 and SPCA-1 lung cancer cells by binding to IL-23r, whereas high concentrations of IL-23 inhibited proliferation of these cells by binding to both IL-23r and IL-12Rβ1. In contrast, IL-23 had no effect on IL-23 receptor-negative SK-MES-1 cells. IL-23 regulated the growth of human lung cancer cells through its effects on STAT3 expression and phosphorylation in a concentration-dependent way; the Ki-67 gene was involved in these processes. Our findings demonstrate for the first time that IL-23 affects the proliferation of IL-23 receptor-positive lung cancer cells and that this effect is dependent on the IL-23 concentration. This can explain at least part of the inconsistent reports on the role of IL-23 in the progression of carcinogenesis.

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Reactive oxygen species (ROS)-driven oxidative stress has been recognized as a critical inducer of cancer cell death in response to therapeutic agents. Our previous studies have demonstrated that zinc finger protein (ZNF)32 is key to cell survival upon oxidant stimulation. However, the mechanisms by which ZNF32 mediates cell death remain unclear. Here, we show that at moderate levels of ROS, Sp1 directly binds to two GC boxes within the ZNF32 promoter to activate ZNF32 transcription. Alternatively, at cytotoxic ROS concentrations, ZNF32 expression is repressed due to decreased binding activity of Sp1. ZNF32 overexpression maintains mitochondrial membrane potential and enhances the antioxidant capacity of cells to detoxify ROS, and these effects promote cell survival upon pro-oxidant agent treatment. Alternatively, ZNF32-deficient cells are more sensitive and vulnerable to oxidative stress-induced cell injury. Mechanistically, we demonstrate that complement 1q-binding protein (C1QBP) is a direct target gene of ZNF32 that inactivates the p38 MAPK pathway, thereby exerting the protective effects of ZNF32 on oxidative stress-induced apoptosis. Taken together, our findings indicate a novel mechanism by which the Sp1-ZNF32-C1QBP axis protects against oxidative stress and implicate a promising strategy that ZNF32 inhibition combined with pro-oxidant anticancer agents for hepatocellular carcinoma treatment.

Zfp637 is a recently identified zinc finger protein, and its functions remain largely unknown. Here, we innovatively demonstrate the effects of Zfp637 on the differentiation of mouse spermatogonia and on its downstream target gene SOX2 in vitro. Obesity has been recognized as a chronic inflammatory disease that leads to decreased sexual function and sexual development disorders. We observed higher levels of IL-6 in serum and testis homogenates from obese mice compared with control mice. We also demonstrated that high levels of IL-6 inhibited Zfp637 expression, and we elucidated the underlying mechanisms. SOCS3 overexpression and STAT3 phosphorylation inhibitor (AG490) were used to investigate the function of the SOCS3/STAT3 pathway during this process. Our results showed that exposure of mouse spermatogonial cells to high levels of IL-6 inhibited Zfp637 expression by increasing SOCS3 expression and inhibiting the phosphorylation of STAT3, further reducing cellular differentiation. Consistent with the in vitro results, we observed increasing expression levels of SOCS3 and SOX2, but a reduction of Zfp637 expression, in obese mouse testes. In conclusion, Zfp637 plays a crucial role in spermatogenesis by downregulating SOX2 expression, and IL-6 can decrease the expression of Zfp637 through the SOCS3/STAT3 signaling pathway.

Abstract. Splenogonadal fusion (SGF) is a rare congenital malformation. Since it lacks characteristic features, very few cases of SGF have been diagnosed preoperatively. Laparoscopy was effective in both diagnosing and surgically treating this condition. Herein, we reported left side SGF in a male patient who was diagnosed during laparoscopic exploration, and Fowler-Stephens orchidopexy was implemented at the same time. The patient was followed up for one year. At a 6-month follow-up, the left scrotum demonstrated swelling and the internal contents were hard. An ultrasound of this testicle indicated non-uniform, splenic-like organization. However, at the one-year follow-up, the volume of splenic-like organization was reduced but the testicular size did not exhibit further atrophy. IntroductionSplenogonadal fusion (SGF) is a rare congenital malformation. The condition was first described in 1883, but fewer than 200 cases have been reported to date (1). Only a few cases have been diagnosed preoperatively, which were typically regarded as cryptorchidism, testicular tumors or inguinal hernia, and accidentally determined to be SGF after exposure of the inguinal canal during surgery (2). This disease commonly leads to a preoperative misdiagnosis of testicular cancer, causing testes to be mistakenly removed in nearly a third of SGF cases (3,4). In order to avoid these errors, increased awareness of the diagnosis of and treatment for SGF therefore is required. In this case report, we summarize our experiences of treating SGF and review the literature to improve the understanding of this disease and provide helpful suggestions for future treatment strategies. Case reportA 4-year-old boy presented to the Department of Pediatric Surgery, West China Hospital of Sichuan University (Chengdu, China) with bilateral undescended testes from birth in April 2013. Physical examination indicated that the bilateral scrota were empty, the testes were also not present in the inguinal region, and the patient's penis was normal. An ultrasound confirmed that there were no testicular masses in the bilateral scrota and inguinal regions. In accordance with the above clinical findings, the patient was diagnosed with bilateral cryptorchidism, and therefore laparoscopic gonad exploration was performed. Complete abdominal exploration revealed gonad-like tissue connected with a smooth, fleshy, brown, cord-like structure beside the left colon, but left spermatic cord blood vessels were not observed. The cord-like structure was connected to the spleen (which was normal), and was approximately 5-6 cm long and 1.5 cm in diameter ( Fig. 1A and B). The spleen cord was cut off and the gonad-like tissues were pulled down into the scrotum through the inguinal canal (Fig. 1C-E). A small incision was made in the scrotum skin to expose the gonad-like tissue. A small piece of gonad-like tissue was harvested for pathological examination. The result of pathological examination demonstrated that the gonad-like tissue was a normal testis. As a result, the spleen c...