Zengtao Wei

Pulmonary sequestration is a rare pulmonary malformation, typically characterized by asymptomatic presentation or recurrent pulmonary infections, with chest pain and hemothorax being exceedingly rare occurrences. The rupture and hemorrhage of maternal pulmonary sequestration during pregnancy pose a life‐threatening condition that is challenging to diagnose. We present a case of a 37‐year‐old pregnant woman in her third trimester who presented with acute progressive hemothorax, a complication arising from maternal pulmonary sequestration. The patient experienced chest pain, which was followed by a decrease in blood pressure, albeit without a concomitant drop in blood oxygen saturation. Within a critical 24‐h window, an emergency cesarean section was performed, promptly followed by a right inferior lobectomy. Intraoperative diagnosis confirmed pulmonary sequestration. Fortunately, both the patient and the newborn had a favorable prognosis post‐surgery. The diagnosis of pulmonary sequestration in pregnancy is challenging and can present with non‐specific symptoms. Clinicians should maintain a high index of suspicion for pulmonary sequestration, especially in cases of unexplained chest pain or hemothorax during pregnancy. Timely surgical intervention can be life‐saving and is crucial for maternal and fetal well‐being.

Epithelial ovarian cancer is the deadliest gynecologic malignancy, characterized by high metastasis. Transforming growth factor‐β1 (TGF‐β1) drives epithelial‐ mesenchymal transformation (EMT), a key process in tumor metastasis. Tumor necrosis factor‐α‐induced protein 8 (TNFAIP8)‐like 2 (TIPE2) acts as a negative regulator of innate and adaptive immunity and involves in various cancers. However, its relationship with TGF‐β1 in ovarian cancer and its role in reversing TGF‐β1‐induced EMT remain unclear. This study examined TIPE2 mRNA and protein expression using quantitative RT‐PCR (qRT‐PCR), western blot and immunohistochemistry. The effects of TIPE2 overexpression and knockdown on the proliferation, migration and invasion of epithelial ovarian cancer cells were assessed through 5‐ethynyl‐2‐deoxyuridine, colony‐forming, transwell migration and invasion assays. The relationship between TIPE2 and TGF‐β1 was investigated using qRT‐PCR and enzyme‐linked immunosorbent assay, while the interaction between TIPE2 and Smad2 was identified via co‐immunoprecipitation. The results revealed that TIPE2 protein was significantly down‐regulated in epithelial ovarian cancer tissues and correlated with the pathological type of tumor, patients' age, tumor differentiation degree and FIGO stage. TIPE2 and TGF‐β1 appeared to play an opposite role to each other during the progression of human ovarian cancer cells. Furthermore, TIPE2 inhibited the metastasis and EMT of ovarian cancer cells by combining with Smad2 in vitro or in an intraperitoneal metastasis model. Consequently, these findings suggest that TIPE2 plays a crucial inhibitory role in ovarian cancer metastasis by modulating the TGF‐β1/Smad2/EMT signaling pathway and may serve as a potential target for ovarian cancer, providing important direction for future diagnostic and therapeutic strategies.

Ovarian cancer is the deadliest among all the gynecologic malignancies, and it is also a kind of highly metastatic disease. Transforming growth factor-β1 (TGF-β1) is a dominant driver of epithelial-mesenchymal transformation (EMT) and promotes the metastasis of tumor cells and therapy resistance. Tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TIPE2) is a negative regulator of innate and adaptive immunity. It also involves the occurrence and development of different tumors. However, the roles of TIPE2 in ovarian cancer and whether TIPE2 reverses TGF-β1-induced EMT in ovarian cancer cells remain unclear. The present study demonstrated that TIPE2 protein was significantly down-regulated in ovarian cancer tissues and related to tumor pathological types, patients’age, tumor differentiation degree, and FIGO stage of tumor. TIPE2 inhibited the metastasis and EMT of ovarian cancer cells by combining with Smad2 in vitro and intraperitoneal metastasis model and reversed TGF-β1-induced migration, invasion of ovarian cancer cells by targeting the Smad2-EMT signaling pathway. Moreover, we found that TIPE2 decreased the expression of TGF-β1 and TGF-β1 down-regulated the levels of TIPE2 in ovarian cancer cells. There is a negative relationship between TIPE2 and TGF-β1. In summary, our results suggest TIPE2 plays an important inhibitory role in the metastasis of ovarian cancer by affecting TGF-β1/Smad2/EMT signal pathway and acts as a potential target in the diagnosis and treatment of ovarian cancer.

Programmed cell death 4 (PDCD4) is regarded as an important tumor suppressor that is lowly expressed or deleted in numerous human types of cancer, including ovarian and endometrial cancer. Tripartite motif‑containing 27 (TRIM27) is closely related to the occurrence and development of tumors and is highly expressed in numerous types of cancer such as ovarian and endometrial cancer. PDCD4 can be degraded through ubiquitination, while TRIM27 has the E3 ubiquitin ligase activity. However, whether TRIM27 may regulate the expression of PDCD4 by ubiquitination effect remains unclear. In the present study, the expression of PDCD4 and TRIM27 in different ovarian and endometrial cancer cell lines was detected by reverse transcription‑quantitative PCR (RT‑qPCR), western blotting and immunocytochemistry. The impact of TRIM27 overexpression and knockdown on PDCD4 expression and the effective mechanism of TRIM27 regulating PDCD4 expression were also investigated in vitro by RT‑qPCR, western blotting, co‑immunoprecipitation assay, Transwell migration and Matrigel invasion assays. The results showed that the expression of TRIM27 and PDCD4 had a negative association at the protein level, and the distribution of TRIM27 and PDCD4 proteins had a phenomenon of co‑localization in different ovarian and endometrial cancer cell lines. TRIM27 promoted the degradation of PDCD4 through the ubiquitin‑proteasome pathway. To sum up, TRIM27 could increase the migration and invasion of ovarian and endometrial cancer cells by promoting the ubiquitination and degradation of PDCD4. The present findings may provide a new target for the treatment of ovarian and endometrial cancer.

STUDY QUESTION: Do changes in tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TIPE2) levels in endometrium of patients with adenomyosis alter the proliferation, migration and invasion ability of endometrial cells? SUMMARY ANSWER: TIPE2 expression levels were low in eutopic and ectopic endometrium of adenomyosis patients, and TIPE2 inhibited the migration and invasion of endometrial cells, mainly by targeting β-catenin, to reverse the epithelial-mesenchymal transition (EMT). WHAT IS KNOWN ALREADY: Adenomyosis is a benign disease, but it has some pathophysiological characteristics similar to the malignant tumor. TIPE2 is a novel negative immune regulatory molecule, and it also participates in the development of malignant tumors. STUDY DESIGN, SIZE, DURATION: Control endometrium (n = 48 women with non-endometrial diseases) and eutopic/ectopic endometrium from patients with adenomyosis (n = 50), human endometrial cancer cell lines, and primary endometrial cells from the eutopic endometrium of adenomyosis patients were used in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: The expression level of TIPE2 mRNA and protein in the eutopic/ectopic endometrial tissues of adenomyosis patients and control endometrium was determined by quantitative RT-PCR (qRT-PCR), western blot and immunohistochemistry. The effects of TIPE2 overexpression and knockdown on the proliferation, migration and invasion of endometrial cell lines and primary adenomyotic endometrial cells were determined using a cell counting kit-8, 5-ethynyl-2′-deoxyuridine assay, colony-forming assay, transwell migration assay and matrigel invasion assay. The expression of EMT-related markers and signal molecules was detected by western blot. The interaction between TIPE2 and β-catenin was detected by co-immunoprecipitation and laser confocal microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: The mRNA and protein expression levels of TIPE2 in the eutopic and ectopic endometrial tissues of adenomyosis patients were significantly downregulated compared with the control endometrium (P ˂ 0.01). TIPE2 could bind to β-catenin and inhibit the nuclear translocation of β-catenin, downregulate the expression of stromal cell markers, upregulate the expression of glandular epithelial cell markers, decrease the occurrence of epithelial-mesenchymal transition (EMT) and suppress the migration and invasion of endometrial cells (P ˂ 0.01). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, the experiments were performed only in eutopic and ectopic endometrial tissues, endometrial cancer cell lines and primary adenomyotic endometrial cells. A mouse model of adenomyosis will be constructed to detect the effects of TIPE2 in vivo. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest that TIPE2 is involved in the development of adenomyosis, which provides a potential new diagnostic and therapeutic strategy for the treatment of adenomyosis. STUDY FUNDINGS/COMPETING INTEREST(S): This present study was supported by grants from the National Natural Science Foundation of China (81471437, 81771554), Natural Science Foundation of Shandong (ZR2018MH013), Science and technology development plan provided by Health and Family Planning Committee in Shandong (2014-25). The authors declare that they have no conflicts of interest.

Programmed cell death 4 (PDCD4) has been identified as a tumor-suppressor gene that inhibits neoplastic transformation, tumor progression, and protein translation. It has been reported that multiple factors participate in the regulation of PDCD4 mRNA and protein. The endometrium is regulated by changing concentrations of ovarian hormones, such as estrogen and progesterone, and shows periodical changes. However, whether ovarian hormones regulate PDCD4 expression remains unclear. This study aimed to explore the effect and mechanism of estrogen or progesterone on PDCD4 mRNA and protein expression in human endometrial cancer cells. The expression of PDCD4 mRNA and protein in Ishikawa and HEC-1-A cells was detected by quantitative real-time PCR and western blot analysis. The signaling pathway-related proteins were detected by western blot analysis. The results showed that PDCD4 mRNA levels exhibited no significant changes after treatment with estrogen or progesterone in both Ishikawa and HEC-1-A cell lines. Estrogen also had no obvious effect on PDCD4 protein expression. However, progesterone effectively decreased the expression of PDCD4 protein and the PI3K/AKT pathway may be involved in the downregulation of PDCD4 protein induced by progesterone. These results suggest that the downregulation of PDCD4 induced by progesterone affects the therapeutic efficacy of progesterone in human endometrial cancer or endometriosis, which may have important implications for progesterone treatment in the clinic.

Endometriosis (EM) is a kind of estrogen-dependent disease in reproductive-age women. Ovarian EM is the most common type. Although EM is a benign disease, it shares many similar features with cancers. Programmed cell death 4 (PDCD4), a newly identified tumor suppressor, plays an important role in inhibiting tumorigenesis and tumor progression at the transcriptional and translational levels. To explore the roles of PDCD4 in EM, we detected the expression of PDCD4 in control endometrium and eutopic/ectopic endometrium of ovarian EM patients, and analyzed the effects of PDCD4 on the biological behaviors of endometrial cell lines and primary endometrial cells. The results demonstrated that PDCD4 was downregulated in eutopic and ectopic endometrium of EM patients compared with control endometrium. PDCD4 effectively inhibited the proliferation and colony-forming ability of endometrial cells maybe by inhibiting cell autophagy. In addition, PDCD4 also suppressed the migration and invasion ability of endometrial cells, the mechanism may be related to NF-κB/MMP2/MMP9 signal pathway. Taken together, these results suggest that PDCD4 could be involved in the pathogenesis of EM, and provide a novel approach to target the aberrant PDCD4 expression in EM.

Programmed cell death 4 (PDCD4), as a novel tumor suppressor, serves important roles in the pathogenesis of tumors. The expression of PDCD4 is downregulated or lost in various human tumors. However, the expression of PDCD4 in endometrial cancer and the clinicopathological significance remain unclear. The aim of the present study was to investigate the expression of PDCD4 in endometrioid endometrial carcinoma (EEC) and the association with clinicopathological parameters. The expression of PDCD4 in EEC tissues and control endometrium was detected by reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry. PDCD4 expression was also investigated in control endometrial glandular epithelial cells and the endometrial cancer KLE cell line by immunocytochemistry, and the association between PDCD4 expression and clinicopathological parameters of patients with EEC was analyzed. The results demonstrated that PDCD4‑positive staining was mainly located in the cytoplasm of endometrial glandular epithelial cells and EEC cells. The staining index of PDCD4 in the proliferative phase was significantly increased compared with that in the secretory phase of control endometrium (P<0.001). There was significantly decreased PDCD4 expression in grade (G) 2/3 EEC tissues compared with the proliferative phase of control endometrium (P<0.001). PDCD4 expression was significantly associated with tumor grade. The PDCD4 levels in G1 EEC tissues were higher compared with the G2/3 EEC group (P<0.01). The results indicated that PDCD4 is associated with the histological grade of EEC, and that PDCD4 may be a valuable indicator of the degree of tumor malignancy in patients with EEC.

Missed abortion is a special form of spontaneous abortion and its incidence shows a rising trend. Immunological factor is one of the most common reasons. Tumor suppressor gene programmed cell death 4 (PDCD4) also participates in some immune-mediated inflammation, such as atherosclerosis, and so on, but the role of PDCD4 in missed abortion remains unclear. Here, the expression of PDCD4 was detected in decidual and chorionic tissues, as well as peripheral blood mononuclear cells from patients with missed abortion and healthy controls using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry. The expression of cytokines was also detected in decidual tissues using qRT-PCR. The levels of serum estradiol and progesterone were measured by radioimmunoassay. In addition, the correlations of PDCD4 expression with cytokines and hormones were analyzed. The results demonstrated that PDCD4 expression was reduced in decidual tissues from the missed abortion group compared with the control group. The levels of tumor necrosis factor α were significantly higher in decidual tissues of missed abortion patients than those in normal controls. We also found serum estradiol and progesterone levels were significantly lower in the missed abortion group than those in the control group, and serum progesterone level was inversely related to PDCD4 messenger RNA level. The data suggested that reduced PDCD4 expression may be involved in the occurrence of missed abortion. This may facilitate the potential development of novel diagnostic and therapeutic strategies for the treatment of missed abortion.

Missed abortion is a common occurrence for otherwise healthy women. Immunological factor is one of the most important reasons. Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) is a novel negative immune regulator related to several human diseases. However, the expression level and clinical significance of TIPE2 in missed abortion remain unclear. The expression of TIPE2 mRNA and protein in decidua and chorion from 36 missed abortion patients and 36 healthy controls was detected using quantitative real-time PCR, western blot and immunohistochemistry. In addition, serum TNF-ɑ and IL-10 levels were measured using flow cytometry. Serum estradiol and progesterone levels were measured by radioimmunoassay test. The correlations of TIPE2 protein levels with TNF-ɑ, IL-10, estradiol and progesterone were further analyzed. TIPE2 protein levels were significantly lower in decidual tissues of missed abortion patients than those in healthy controls. The patients with missed abortion had significantly higher levels of serum TNF-ɑ, and lower levels of serum IL-10, estradiol and progesterone compared with healthy controls. The TIPE2 protein levels were positively related to serum IL-10 levels. Our data indicate TIPE2 could play important roles in maintaining the maternal-fetal tolerance and decreased TIPE2 expression in the decidua may be related to the development of missed abortion.