Field performance of 15 rain gardens in different cities in Taiwan.

Rain gardens are widely used for low impact development (LID) or as a nature-based solution (NbS). They help to reduce runoff, mitigate hot temperatures, create habitats for plants and insects, and beautify landscapes. Rain gardens are increasingly being established in urban areas. In Taiwan, the Ministry of Environment (MoE) initiated a rain garden project in Taipei city in 2018, and 15 rain gardens have since been constructed in different cities. These Taiwanese-style rain gardens contain an underground storage tank to collect the filtrated rainwater, which can be used for irrigation. Moreover, the 15 rain gardens are equipped with sensors to monitor temperature, rainfall, and underground water levels. The monitoring data were transmitted with Internet of Things (IoT) technology, enabling the capture and export of real-time values. The water retention, temperature mitigation, water quality, and ecological indices of the rain gardens were quantified using field data. The results from the young rain gardens (1-3 years) showed that nearly 100 % of the rainfall was retained onsite and did not flow out from the rain gardens; however, if the stored water was not used and the tanks were full, the rainwater from subsequent storms could not be stored, and the tanks overflowed. The surface temperatures of the rain garden and nearby impermeable pavement differed by an average of 2-4 °C. This difference exceeded 20 °C in summer at noon. The water in the underground storage tanks had very low levels of SS and BOD, with averages of 1.6 mg/L and 5.6 mg/L, respectively. However, the E. coli concentrations were high, and the average was 6283 CFU/100 mL; therefore, washing or drinking water is not recommended. The ecological indices, i.e., the Shannon and Simpson indices, demonstrated the good flora status of the rain gardens after one year. Although the weather differed by city, the performance of the rain gardens in terms of water retention, temperature mitigation, rainwater harvesting, and providing biological habitats was consistent. However, maintenance influences rain garden performance. If the stored water is not frequently used, the stored volume is reduced, and the stored water quality degrades.

Disparities in medical recommendations from AI-based chatbots across different countries/regions.

This study explores disparities and opportunities in healthcare information provided by AI chatbots. We focused on recommendations for adjuvant therapy in endometrial cancer, analyzing responses across four regions (Indonesia, Nigeria, Taiwan, USA) and three platforms (Bard, Bing, ChatGPT-3.5). Utilizing previously published cases, we asked identical questions to chatbots from each location within a 24-h window. Responses were evaluated in a double-blinded manner on relevance, clarity, depth, focus, and coherence by ten experts in endometrial cancer. Our analysis revealed significant variations across different countries/regions (p < 0.001). Interestingly, Bing's responses in Nigeria consistently outperformed others (p < 0.05), excelling in all evaluation criteria (p < 0.001). Bard also performed better in Nigeria compared to other regions (p < 0.05), consistently surpassing them across all categories (p < 0.001, with relevance reaching p < 0.01). Notably, Bard's overall scores were significantly higher than those of ChatGPT-3.5 and Bing in all locations (p < 0.001). These findings highlight disparities and opportunities in the quality of AI-powered healthcare information based on user location and platform. This emphasizes the necessity for more research and development to guarantee equal access to trustworthy medical information through AI technologies.

A novel long non-coding RNA MIR4500HG003 promotes tumor metastasis through miR-483-3p-MMP9 axis in triple-negative breast cancer.

Breast cancer (BC) is the most common cancer and the leading cause of cancer-related deaths in women worldwide. The 5-year survival rate is over 90% in BC patients, but once BC cells metastasis into distal organs, it is dramatically decreasing to less than 30%. Especially, triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. Understanding the underline mechanisms of TNBC metastasis is a critical issue. Non-coding RNAs, including of lncRNAs and microRNAs, are non-protein-coding transcripts and have been reported as important regulators in TNBC metastasis. However, the underline mechanisms for non-coding RNAs regulating TNBC metastasis remain largely unclear. Here, we found that lncRNA MIR4500HG003 was highly expressed in highly metastatic MDA-MB-231 TNBC cells and overexpression of MIR4500HG003 enhanced metastasis ability in vitro and in vivo and promoted MMP9 expression. Furthermore, we found MIR4500HG003 physically interacted with miR-483-3p and reporter assay showed miR-483-3p attenuated MMP9 expression. Importantly, endogenous high expressions of MIR4500HG003 were correlated with tumor recurrence in TNBC patients with tumor metastasis. Taken together, our findings suggested that MIR4500HG003 promotes metastasis of TNBC through miR-483-3p-MMP9 signaling axis and may be used as potential prognostic marker for TNBC patients.

Protein lipoylation: mitochondria, cuproptosis, and beyond.

Protein lipoylation, a crucial post-translational modification (PTM), plays a pivotal role in mitochondrial function and emerges as a key player in cell death through cuproptosis. This novel copper-driven cell death pathway is activated by excessive copper ions binding to lipoylated mitochondrial proteins, disrupting energy production and causing lethal protein aggregation and cell death. The intricate relationship among protein lipoylation, cellular energy metabolism, and cuproptosis offers a promising avenue for regulating essential cellular functions. This review focuses on the mechanisms of lipoylation and its significant impact on cell metabolism and cuproptosis, emphasizing the key genes involved and their implications for human diseases. It offers valuable insights into targeting dysregulated cellular metabolism for therapeutic purposes.

Relationship Between Rectal Swab and Tissue Samples in Mucosa-associated Microbiota in Patients With Inflammatory Bowel Disease.

BACKGROUND: Gut mucosa-associated microbiota is more closely correlated with disease phenotypes than fecal microbiota; however sampling via tissue biopsy is more invasive and uncomfortable. Rectal swab may be a suitable substitute for tissue biopsy, but its effectiveness is controversial. This study aimed to evaluate differences in the microbiota at these sites in patients with inflammatory bowel disease (IBD). METHODS: Inflammatory bowel disease patients and a control group were enrolled when surveillance colonoscopy was scheduled. Samples of colon biopsy tissues, rectal swabs during colonoscopy, and feces before bowel preparation were collected to analyze microbial composition. To explore the short-term effects of bowel preparation on swab microbiota, prepreparation swab samples were also collected from 27 IBD patients. RESULTS: A total of 33 Crohn's disease, 54 ulcerative colitis, and 21 non-IBD patients were enrolled. In beta diversity analysis, fecal microbiota clearly differed from swab and tissue microbiota in the 3 disease groups. The swab microbiota was closer to, but still different from, the tissue microbiota. Consistently, we identified that swab samples differed more in abundant genera from feces than from tissue. Beta diversity analysis did not reveal a difference in swab microbiota before and after bowel preparation, but the genus composition of most individuals varied markedly. CONCLUSIONS: Swab microbiota more closely resembled tissue microbiota relative to fecal microbiota, but there were still differences. Bowel preparation did not alter the overall swab microbiota in the short term but markedly changed the microbial composition in most patients.

Fucoidan Enhances Cisplatin-induced Effects on SCC-25 Human Oral Cancer Cells by Inhibiting the PI3K/AKT Pathway.

BACKGROUND/AIM: Cisplatin is a drug for treating oral cancer. However, several previous studies indicate that oral cancer cells can develop resistance to cisplatin, which may result in a poor prognosis for patients with oral cancer. Fucoidan, a natural health product extracted from brown seaweed, has anticancer abilities against various types of cancer cell. This study evaluated whether fucoidan can enhance the sensitivity of oral cancer cells to cisplatin and explored the underlying mechanism. MATERIALS AND METHODS: SCC-25 cells were used in the present study and treated with 0.3125 mg/ml fucoidan, 12.5 µg/ml cisplatin, or 0.3125 mg/ml fucoidan plus 12.5 µg/ml cisplatin for 48 h, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, enzyme-linked immunosorbent, and immunoblotting assays were performed to evaluate cell survival, cytokeratin-18 fragment release, and expression of markers of apoptosis and autophagy, respectively. RESULTS: Cotreatment with fucoidan enhanced cisplatin-induced reduction of SCC-25 cell survival compared to cisplatin alone. In addition, cotreatment also increased the expression of apoptosis markers, including activated caspase-8, activated caspase-9, activated caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP), but did not increase the expression of the two autophagy markers studied, beclin and autophagy-related 12-autophagy-related 5 conjugate. Fucoidan significantly inhibited cisplatin-induced AKT serine/threonine kinase 1 activation, which promoted PARP cleavage, caspase-3 activation, and cytokeratin-18 fragment expression in SCC-25 cells. CONCLUSION: Fucoidan promoted cisplatin-induced effects by inhibiting phosphatidylinositol 4,5 bisphosphate 3 kinase/AKT serine/threonine kinase 1 activation induced by cisplatin. The results of this study may provide a basis for the possible application of the combination of fucoidan and cisplatin in the clinical treatment of oral cancer in the future to improve the prognosis of patients with oral cancer.

What nature has to offer: Opportunities for immuno-oncology.

Recent rapid development of cancer therapy has come about with the paradigm shift from the traditional goal of targeting cancer cells themselves, to reprograming the immune tumor microenvironment. Accumulating evidence shows that compounds that target epigenetic regulation, called epidrugs, play a crucial role in mediating the immunogenicity of cancer cells and in reshaping antitumor immunity. A large body of literature has recognized natural compounds as epigenetic modulators for their immunomodulatory effects and anticancer potential. Unifying our understanding of the role of these biologically active compounds in immuno-oncology may open new avenues for more effective cancer therapies. In this review, we explore how natural compounds modulate the epigenetic machinery to shape antitumor immune response, highlighting the promise offered by the Mother Nature that could be exploited therapeutically to improve outcomes for cancer patients.

Serum Starvation Induces Matrix Metalloproteinase 9 Expression in Nasopharyngeal Carcinoma Cells Through the ERK-AP1 Pathway In Vitro.

BACKGROUND/AIM: Although clinical medicine has significantly progressed in treating nasopharyngeal carcinoma (NPC) in recent years, many patients still have poor prognoses due to distant metastasis. It is still relatively unclear why NPC has a highly metastatic ability. Especially whether the tumor microenvironment affects the invasion and metastasis of NPC still needs to be cleared. In this study, serum starvation was used to simulate nutrient deficiency in the tumor microenvironment to explore whether nutrient deficiency affects the malignancy of NPC cells. MATERIALS AND METHODS: Semiquantitative reverse transcription-polymerase chain reaction, ELISA, immunoblotting assay, reporter gene assay, and Matrigel invasion assay were carried out. RESULTS: Under serum starvation, NPC cells could induce the mRNA expression and protein secretion of matrix metalloproteinase 9 (MMP9). The ERK-AP1 pathway was activated under serum starvation in NPC cells, resulting in the expression of MMP9. In contrast, treatment with an MMP9 inhibitor or an MMP9 siRNA inhibited serum starvation-induced invasion. CONCLUSION: Serum starvation could up-regulate MMP9 expression in NPC cells, contributing to NPC invasion. Therefore, serum starvation may promote malignancy of NPC cells but also support MMP9 as a potential therapeutic target to prevent NPC cell invasion and metastasis.

High incidence of trigger finger after carpal tunnel release: a systematic review and meta-analysis.

INTRODUCTION: Trigger finger (TF) often occurs after carpal tunnel release (CTR), but the mechanism and outcomes remain inconsistent. This study evaluated the incidence of TF after CTR and its related risk factors. MATERIALS AND METHODS: ​PubMed, Embase, and Scopus databases were searched up to 27 August 2022, with the following keywords: "carpal tunnel release" and "trigger finger". Studies with complete data on the incidence of TF after CTR and published full text. The primary outcome was the association between CTR and the subsequent occurrence of the TF and to calculate the pooled incidence of post-CTR TF. The secondary outcomes included the potential risk factors among patients with and without post-CTR TF as well as the prevalence of the post-CTR TF on the affected digits. RESULTS: Ten studies with total 10,399 participants in 9 studies and 875 operated hands in one article were included for meta-analysis. CTR significantly increases the risk of following TF occurrence (odds ratio=2.67; 95% CI 2.344-3.043; P <0.001). The pooled incidence of TF development after CTR was 7.7%. Women were more likely to develop a TF after CTR surgery (odds ratio=2.02; 95% CI 1.054-3.873; P =0.034). Finally, the thumb was the most susceptible fingers, followed by middle and ring fingers. CONCLUSIONS: High incidence of TF comes after CTR, and women were more susceptible than man. Clinicians were suggested to notice the potential risk of TF after CTR in clinical practice. LEVEL OF EVIDENCE: Level III, meta-analysis.

Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer.

Currently, the survival rate for breast cancer is more than 90%, but once the cancer cells metastasize to distal organs, the survival rate is dramatically reduced, to less than 30%. Triple-negative breast cancer accounts for 15-20% of all breast cancers. Triple-negative breast cancer (TNBC) is associated with poor prognostic and diagnostic outcomes due to the limiting therapeutic strategies, relative to non-TNBC breast cancers. Therefore, the development of targeted therapy for TNBC metastasis remains an urgent issue. In this study, high Carboxyl-terminal modulator protein (CTMP) is significantly associated with recurrence and disease-free survival rate in TNBC patients. Overexpression of CTMP promotes migration and invasion abilities in BT549 cells. Down-regulating of CTMP expression inhibits migration and invasion abilities in MDA-MB-231 cells. In vivo inoculation of high-CTMP cells enhances distant metastasis in mice. The metastasis incidence rate is decreased in mice injected with CTMP-downregulating MDA-MB-231 cells. Gene expression microarray analysis indicates the Akt-dependent pathway is significantly enhanced in CTMP overexpressing cells compared to the parental cells. Blocking Akt activation via Akt inhibitor treatment or co-expression of the dominant-negative form of Akt proteins successfully abolishes the CTMP mediating invasion in TNBC cells. Our findings suggest that CTMP is a potential diagnostic marker for recurrence and poor disease-free survival in TNBC patients. CTMP promotes TNBC metastasis via the Akt-activation-dependent pathway.

Studying the Roles of the Renin-Angiotensin System in Accelerating the Disease of High-Fat-Diet-Induced Diabetic Nephropathy in a db/db and ACE2 Double-Gene-Knockout Mouse Model.

Diabetic nephropathy (DN) is a crucial metabolic health problem. The renin-angiotensin system (RAS) is well known to play an important role in DN. Abnormal RAS activity can cause the over-accumulation of angiotensin II (Ang II). Angiotensin-converting enzyme inhibitor (ACEI) administration has been proposed as a therapy, but previous studies have also indicated that chymase, the enzyme that hydrolyzes angiotensin I to Ang II in an ACE-independent pathway, may play an important role in the progression of DN. Therefore, this study established a model of severe DN progression in a db/db and ACE2 KO mouse model (db and ACE2 double-gene-knockout mice) to explore the roles of RAS factors in DNA and changes in their activity after short-term (only 4 weeks) feeding of a high-fat diet (HFD) to 8-week-old mice. The results indicate that FD-fed db/db and ACE2 KO mice fed an HFD represent a good model for investigating the role of RAS in DN. An HFD promotes the activation of MAPK, including p-JNK and p-p38, as well as the RAS signaling pathway, leading to renal damage in mice. Blocking Ang II/AT1R could alleviate the progression of DN after administration of ACEI or chymase inhibitor (CI). Both ACE and chymase are highly involved in Ang II generation in HFD-induced DN; therefore, ACEI and CI are potential treatments for DN.

PRMT1 is an important factor for medulloblastoma cell proliferation and survival.

Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number of brain tumors, but the role of PRMT1 in medulloblastoma, the most common malignant pediatric brain tumor, remains unexplored. By examining the publicly available databases of pediatric brain tumor collection, we found that PRMT1 was predominantly expressed in medulloblastomas across all the pediatric brain tumors and that the high-level expression of PRMT1 correlated with poor survival of medulloblastoma patients. To determine the role of PRMT1 in medulloblastoma cells, we established an inducible knockdown system and demonstrated that PRMT1 depletion decreased medulloblastoma cell proliferation and induced cell apoptosis. Furthermore, the diamidine compounds, previously shown to exhibit selective PRMT1 inhibition, suppressed medulloblastoma cell viability in a dose-dependent manner. Finally, we observed induction of medulloblastoma cell apoptosis by the potent diamidine compounds at low micromolar concentrations. Together, our results suggest that PRMT1 could be an actionable therapeutic target in medulloblastoma.

Concurrent Chemoradiotherapy-Driven Cell Plasticity by miR-200 Family Implicates the Therapeutic Response of Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common and fatal malignancy with an increasing incidence worldwide. Over the past decade, concurrent chemoradiotherapy (CCRT) with or without surgery is an emerging therapeutic approach for locally advanced ESCC. Unfortunately, many patients exhibit poor response or develop acquired resistance to CCRT. Once resistance occurs, the overall survival rate drops down rapidly and without proper further treatment options, poses a critical clinical challenge for ESCC therapy. Here, we utilized lab-created CCRT-resistant cells as a preclinical study model to investigate the association of chemoradioresistantresistance with miRNA-mediated cell plasticity alteration, and to determine whether reversing EMT status can re-sensitize refractory cancer cells to CCRT response. During the CCRT treatment course, refractory cancer cells adopted the conversion of epithelial to mesenchymal phenotype; additionally, miR-200 family members were found significantly down-regulated in CCRT resistance cells by miRNA microarray screening. Down-regulated miR-200 family in CCRT resistance cells suppressed E-cadherin expression through snail and slug, and accompany with an increase in N-cadherin. Rescuing expressions of miR-200 family members in CCRT resistance cells, particularly in miR-200b and miR-200c, could convert cells to epithelial phenotype by increasing E-cadherin expression and sensitize cells to CCRT treatment. Conversely, the suppression of miR-200b and miR-200c in ESCC cells attenuated E-cadherin, and that converted cells to mesenchymal type by elevating N-cadherin expression, and impaired cell sensitivity to CCRT treatment. Moreover, the results of ESCC specimens staining established the clinical relevance that higher N-cadherin expression levels associate with the poor CCRT response outcome in ESCC patients. Conclusively, miR-200b and miR-200c can modulate the conversion of epithelial-mesenchymal phenotype in ESCC, and thereby altering the response of cells to CCRT treatment. Targeting epithelial-mesenchymal conversion in acquired CCRT resistance may be a potential therapeutic option for ESCC patients.

Nora's lesion of the distal ulna: a case report.

Nora's lesion, also known as bizarre parosteal osteochondromatous proliferation (BPOP), is a very rare benign lesion with few published cases. BPOP is more common in adults during the second to third decades of life, and usually occurs on the hands and feet. Radiologically, it appears as a calcified mass attached to the bone cortex that grows rapidly and that recurs easily following resection. Aggressive features on imaging and confusing histopathological findings usually result in misdiagnosis or mistreatment. Herein, we present a case of a rare bony tumour involving the distal ulna presenting as a painless growing mass. An excisional biopsy with clear margins was performed without disturbing the ulnar nerve and arteries. There was no recurrent mass or calcified lesion 1 year after surgery. Based on its rarity and difficult diagnosis, BPOP should be considered in the differential diagnosis of a painless mass in the distal ulnar region. Careful follow-up after surgery is essential, even without lesion recurrence.

MiR-211 determines brain metastasis specificity through SOX11/NGN2 axis in triple-negative breast cancer.

Brian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood-brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.

Downregulation of STK4 promotes colon cancer invasion/migration through blocking ß-catenin degradation.

Mammalian STE20-like kinase 1 (MST1/STK4/KRS2) encodes a serine/threonine kinase that is the mammalian homolog of Drosophila Hippo. STK4 plays an important role in controlling cell growth, apoptosis, and organ size. STK4 has been studied in many cancers with previous studies indicating an involvement in colon cancer lymph node metastasis and highlighting its potential as a diagnostic marker for colon cancer. However, the role of STK4 defect in promoting colon cancer progression is still understudied. Here, we found that STK4 was significantly downregulated in colon cancer and was associated with distal metastasis and poor survival. Furthermore, STK4 knockdown enhanced sphere formation and metastasis in vitro and promoted tumor development in vivo. We found that STK4 colocalized with ß-catenin and directly phosphorylated ß-catenin resulting in its degradation via the ubiquitin-mediated pathway. This may suggest that STK4 knockdown causes ß-catenin phosphorylation failure and subsequently ß-catenin accumulation, consequently leading to anchorage-independent growth and metastasis in colon cancer. Our results support that STK4 may act as a potential candidate for the assessment of ß-catenin-mediated colon cancer prognosis.

High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in Asia and demonstrates poor survival rates following a therapeutic regimen. METHODS: Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and treatment failure in cancers. Therefore, identification and characterization of CSCs may help to improve clinical outcomes for ESCC patients. Tumor sphere formation assay are performed to isolate cancer stem-like ESCC cells. QRT-PCR, tumor initiation, metastasis, CCRT treatment are used to evaluate ESCC cells' stemness properties in vitro and in vivo. RESULTS: The authors' data demonstrates that cancer stem-like ESCC cells harbored stemness characteristics including self-renewal, differentiation, and transdifferentiation, and possess tumor initiation, metastasis, and treatment inefficiency properties. For the identification of useful biomarkers of cancer stem-like ESCC cells, the authors further identified that CLDN4 was upregulated in cancer stem-like ESCC cells when compared with bulk cancer cells. High-CLDN4 cells harbored stemness and cisplatin/concurrent chemoradiation therapy (CCRT) resistance properties and a high level of CLDN4 was correlated with poor prognosis and poor CCRT response in ESCC patients. Importantly, thiamine tetrahydrofurfuryl disulfide (TTFD) decreased CLDN4 and attenuated stemness in ESCC cells, and TTFD combined with CCRT improved CCRT response in vivo. CONCLUSIONS: CLDN4 was suggested as prognostic and a CCRT response indicator for ESCC patients. TTFD combined with CCRT has potential to improve ESCC patient's clinical outcomes in the future.

Pneumocephalus with Conscious Disturbance After Full Endoscopic Lumbar Diskectomy.

BACKGROUND: Pneumocephalus is a rare complication after an elective lumbar spine surgery. Full endoscopic lumbar diskectomy (FELD) is an evolving minimally invasive surgical procedure gaining its popularity in the past decade. Although seizure was recognized as a possible complication, organic injury to the central nervous system such as pneumocephalus has not yet been reported after FELD. CASE DESCRIPTION: A 63-year-old man with L3-4 intervertebral disk herniation received FELD via the transforaminal approach under general anesthesia. A small dural tear about 2 mm was encountered. After the operation, the patient was unable to recover from anesthesia and failed to be extubated due to tachypnea and generalized tonic-clonic seizures. Emergent brain computed tomography (CT) revealed pneumocephalus in the subdural and subarachnoid space. Pure oxygen was given, and hyperbaric oxygen therapy (HBO2) was arranged immediately. Fortunately, he started to regain his consciousness 8 hours after the operation and had full recovery of consciousness on the next day. Follow-up brain CT showed nearly complete resolution of the pneumocephalus. He had no neurologic deficits at final follow-up. CONCLUSIONS: This case report highlights the risk of pneumocephalus with conscious disturbance when a dural tear occurs during FELD under general anesthesia. FELD is safer when performed under local anesthesia because the patient is awake to report his discomfort and thus possible to prevent serious neurologic sequels. An emergent brain CT is critical to obtain a prompt diagnosis and HBO2 is probably helpful for resolving the mass effect caused by the pneumocephalus.

A novel long non-coding RNA linc-ZNF469-3 promotes lung metastasis through miR-574-5p-ZEB1 axis in triple negative breast cancer.

Triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. The major sites for TNBC metastasis include the lungs, brain, liver, and bone. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides and have been reported as important regulators in BC metastasis. However, the underlying mechanisms for lncRNAs regulating TNBC metastasis are not fully understood. Here we found that linc-ZNF469-3 was highly expressed in lung-metastatic LM2-4175 TNBC cells and overexpression of linc-ZNF469-3 enhanced invasion ability and stemness properties in vitro and lung metastasis in vivo. Furthermore, we found linc-ZNF469-3 physically interacted with miR-574-5p and overexpression of miR-574-5p attenuated ZEB1 expression. Importantly, endogenous high expressions of linc-ZNF469-3 and ZEB1 were correlated with tumor recurrence in TNBC patients with lung metastasis. Taken together, our findings suggested that linc-ZNF469-3 promotes lung metastasis of TNBC through miR-574-5p-ZEB1 signaling axis and may be used as potential prognostic marker for TNBC patients.

Hepatitis B virus surface gene pre-S2 mutant as a high-risk serum marker for hepatoma recurrence after curative hepatic resection.

Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S2 mutant large HBV surface antigen (LHBS) is highly associated with HCC. This study analyzed the expression of the large form of surface protein in tumors and evaluated the LHBS with mutations within the pre-S2 region as a high-risk recurrence marker in HCC patients after curative hepatic resection. By analyses using immunohistochemical staining (n = 12) and western blotting (n = 22), the HBV surface protein, which is mainly comprised of the major form of HBV surface antigen, was greatly diminished in the tumors. However, LHBS was not significantly decreased in tumorous regions, suggesting that LHBS maintains its expression in cancer development. A cohort of 175 patients with HBV-related HCC who underwent curative hepatic resection was analyzed for pre-S gene mutations using Pre-S Gene Chip. Results of the multivariate regression analysis showed that the serum pre-S2 mutant level and the American Joint Committee on Cancer stage were the two main independent high-risk factors for recurrence. A Cox proportional hazards analysis also revealed a prediction model, which indicated the recurrence-free survival rate along with the time after surgery; this was developed and further validated in an independent HCC cohort. Receiver operating characteristic curve analysis revealed that the model showed close sensitivities in the main and validation cohorts (area under the curve values, 0.741 and 0.704, respectively). Conclusion: Unlike the major HBV surface antigen, LHBS is mostly expressed in the tumorous regions of HBV-induced HCC, indicating that it plays a unique role in tumor progression; the relative level of pre-S2 mutant in serum is, independently of tumor stage, an important high-risk marker for HCC recurrence after primary hepatic resection. (Hepatology 2018).