Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer.

BACKGROUND: Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer. METHODS: A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis. RESULTS: In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival. CONCLUSIONS: Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.

Ultrasensitive amplification-free detection of circulating miRNA via droplet-based processing of SERS tag-miRNA-magnetic nanoparticle sandwich nanocomplexes on a paper-based electrowetting-on-dielectric platform.

MicroRNAs (miRNAs) have emerged as a promising class of biomarkers for early detection of various cancers, including ovarian cancer. However, quantifying miRNAs in human blood samples is challenging owing to the issues of sensitivity and specificity. In this study, hsa-miR-200a-3p of the miR-200a sub-family, which is a biomarker of ovarian cancer, was used as the analyte to demonstrate the analytical capability of an integrated biosensing platform using an extremely sensitive surface-enhanced Raman scattering (SERS) nanotag-nanoaggregate-embedded beads (NAEBs), magnetic nanoparticles (MNPs), a pair of highly specific locked nucleic acid (LNA) probes, and a semi-automated paper-based electrowetting-on-dielectric (pEWOD) device to provide labor-less and thorough sample cleanup and recovery. A sandwich approach where NAEBs are modified by one LNA-1 probe and MNPs are modified by another LNA-2 probe was applied. Then, the target analyte miRNA-200a-3p was introduced to form a sandwich nanocomplex through hybridization with the pair of LNA probes. The pEWOD device was used to achieve short cleanup time and good recovery of the nanocomplex, bringing the total analysis time to less than 30 min. The detection limit of this approach can reach 0.26 fM through SERS detection. The versatility of this method without the need for RNA extraction from clinical samples is expected to have good potential in detecting other miRNAs.

Downregulation of Salt-Inducible Kinase 3 Enhances CCL24 Activation in the Placental Environment with Preeclampsia.

Preeclampsia (PE) remains one of the leading causes of maternal and perinatal morbidity and mortality. However, the exact pathophysiology of PE is still unclear. The recent widely accepted notion that successful pregnancy relies on maternal immunological adaptation is of utmost importance. Moreover, salt-inducible kinase 3 (SIK3) is an AMP-activated protein kinase-related kinase, and it has reported a novel regulator of energy and inflammation, and its expression related with some diseases. To explore whether SIK3 expression correlated with PE, we analyzed SIK3 gene expression and its association with PE through GEO datasets. We identified that SIK3 was significantly downregulated in PE across four datasets (p < 0.05), suggesting that SIK3 participated in the pathogenesis of PE. We initially demonstrated the significant downregulation of SIK3 in trophoblast cells of PE. SIK3 downregulation was positively correlated with the increased number of CD204(+) cells in in vivo and in vitro experiments. The increased number of CD204(+) cells could inhibit the migration and invasion of trophoblast cells. We then clarified the potential mechanism of PE with SIK3 downregulation: M2 skewing was triggered by trophoblast cells derived via the CCL24/CCR3 axis, leading to an increase in CD204(+) cells, a decrease in phagocytosis, and the production of IL-10 at the maternal-fetal interface of the placenta with PE. IL-10 further contributed to a reduction in the migration and invasion of trophoblast cells. It also established a feedback loop wherein trophoblast cells increased CCL24 production to maintain M2 dominance in the placental environments of PE.

Integrated Microfluidic System for Cell-Free DNA Extraction from Plasma for Mutant Gene Detection and Quantification.

Ovarian cancer (OvCa) is among the most severe gynecologic cancers, yet individuals may be asymptomatic during its early stages. Routine, early screening for genetic abnormalities associated with OvCa could improve prognoses, and this can be achieved by detecting mutant genes in cell-free DNA (cfDNA). Herein, we developed an integrated microfluidic chip (IMC) that could extract cfDNA from plasma and automatically detect and quantify mutations in the OvCa biomarker BRCA1. The cfDNA extraction module relied on a vortex-type micromixer to mix cfDNA with magnetic beads surface-coated with cfDNA probes and could isolate 76% of molecules from a 200 µL plasma sample in 45 min. The cfDNA quantification module, which comprised a micropump that evenly distributed 4.5 µL of purified cfDNA into the on-chip, allele-specific quantitative polymerase chain reaction (qPCR) zones, was capable of quantifying mutant genes within 90 min. By automating the cfDNA extraction and qPCR processes, this IMC could be used for clinical screening for OvCa-associated mutations.

Isolation and Quantification of Methylated Cell-Free DNA in Plasma on an Integrated Microfluidic System.

Methylated cell-free DNA (cfDNA) has been deemed a promising biomarker for ovarian cancer (OvCa) prognosis and therapy selection. However, exploring the methylation profiles of tumor suppressor genes in cfDNA remains a challenge due to their extremely low concentrations and complicated protocols, as well as methodological constraints. In this study, an integrated microfluidic system was developed to automatically (1) capture methylated cfDNA in plasma by magnetic beads coated with the methyl-CpG-binding domain and (2) quantify the methylation level of tumor suppressor genes by on-chip quantitative polymerase chain reaction (qPCR). For capturing methylated cfDNA from a very small amount of plasma, samples along with beads were mixed in a new micromixer to enhance the capture rate. With a high capture rate (72%) and a limit of quantification of 0.1 pg/µL (3 orders of magnitude lower than that of the benchtop method), the compact system could detect the methylated cfDNA from only 20 µL of plasma sample in 2 h. Furthermore, the dynamic range, from 0.1 to 2000 pg/µL of methylated cfDNA, spans the physiological range in plasma, signifying that this device has great potential for personalized medicine in OvCa.

Maternal Th17/Treg Cytokines and Small Extracellular Vesicles in Plasma as Potential Biomarkers for Preeclampsia.

Preeclampsia is one of the most serious pregnancy complications. It may be caused by immunological changes in the early placental microenvironment. The contents of small EVs may serve as biomarkers of pregnancy complications. Evidence suggests that the balance between T helper 17 (Th17) and regulatory T (Treg) cells are critical for preventing preeclampsia. The study recruited 39 pregnant women with preeclampsia and 127 healthy pregnant women. We assessed the levels of both Th17 and Treg cytokines (IL-10, IL-17, IL-21, IL-22, and TGF-ß) in their plasma and small EVs. We found significant differences in the levels of all cytokines in the plasma between the two groups during the second trimester. We also observed significant differences between the two groups in the levels of EV-encapsulated cytokines IL-21, IL-22, and TGF-ß, as well as in total small EVs, during the second trimester. The ROC analysis showed that the classification efficiency (AUC) of TGF-ß in small EVs was 0.81. TGF-ß had the best discriminant ability of all the single EV biomarkers tested, the cross-validation of the accuracy was 0.89. Th17 and Treg cytokines in plasma and small EVs may contribute to maternal immune activation and clarify the potential mechanisms of small EVs and cytokines in preeclampsia.

Psychometric evaluation of a Chinese version of Lymphoedema Functioning, Disability and Health Questionnaire for Lower Limb Lymphoedema in women with gynaecological cancer surgery.

The prevalence of lower limb lymphoedema and its impact in gynaecological cancer patients is underestimated. However, a valid and reliable scale to measure lower leg lymphoedema in Taiwan has not been available. The purpose of the study was to translate the English version of Lymphoedema Functioning, Disability and Health Questionnaire for Lower Limb Lymphoedema into a Chinese version (Lymph-ICF-LL-C), and evaluate the psychometric properties of the Lymph-ICF-LL-C in Taiwanese women with gynaecological cancer surgery. A total of 170 women with gynaecological cancer surgery were recruited to examine the Lymph-ICF-LL-C. The Lymph-ICF-LL-C shows satisfactory internal consistency (Cronbach's alphas ≥ 0.84) and stability test-retest reliability (Intraclass correlation coefficient ≥0.55-0.90) at a 2-week interval. Exploratory factor analysis showed that 68.53% of the total variance was explained by a five-factor solution. The concurrent validity of the Lymph-ICF-LL-C was evidenced by a significant correlation with a fatigue scale (r = 0.46, p < 0.01) and with the bilateral difference of lower limb circumference (r = 0.24-0.36, all p < 0.01). The Lymph-ICF-LL-C can be used for assessing the life impact of lower limb lymphoedema, allowing appropriate interventions to prevent further deterioration and complications.

Longitudinal psychosocial adjustment of women to human papillomavirus infection.

AIM: The aim of this study was to examine the psychosocial adjustment trajectory, focusing on psychological distress, sexual relationships and healthcare information, and factors which have an impact on adjustment on receiving a positive diagnosis of human papillomavirus infection. BACKGROUND: Human papillomavirus is a common sexually transmitted infection in females. To date, knowledge of the longitudinal psychosocial response to the diagnosis of human papillomavirus is limited. DESIGN: A prospective longitudinal design was conducted with a convenience sample. METHODS: Women aged 20-65 years old were followed at one, 6 and 12 months after a diagnosis of HPV. Participants completed measures of initial emotional distress and followed up psychosocial adjustment. A mixed-effects model was applied to analyse the longitudinal changes in psychosocial adjustment. RESULTS: Seventy human papillomavirus positive women participated in the study with nearly 20% of the women reporting emotional distress during their first visit. Mixed-effects model analyses showed that a trajectory of psychosocial adjustment in healthcare orientation, sexual relationship and psychosocial distress occur from one to 6 months after HPV diagnosis. However, a declining trend from 6 to 12 months was significant in healthcare orientation. Initial emotional distress was associated with changes in psychological adjustment. CONCLUSIONS: Psychosocial adjustment to human papillomavirus was worse at 1 month compared with 6 and 12 months after diagnosis. Healthcare providers should offer health information and psychosocial support to women according to their disease progression.

The store-operated Ca(2+) entry-mediated signaling is important for cancer spread.

Tumor cell migration and invasion are essential steps in the metastatic cascade that has great impact on patient outcomes. Spatial and temporal organization of Ca(2+) signaling regulates the multiple aspects of migration machinery, including cytoskeletal reorganization, traction force generation, and focal adhesion dynamics. Stromal interaction molecules (STIM) and Orai proteins, recently identified as critical constituents of store-operated Ca(2+) entry (SOCE), have been implicated in cancer cell migration and tumor metastasis. The clinical significance of STIM proteins and Orai Ca(2+) channels in tumor progression and their diagnostic and prognostic potentials have also been demonstrated in different types of cancers. Here we review the recent advances in understanding the important roles and regulatory mechanisms of STIM/Orai-mediated SOCE in cancer spread. The clinical implications and the emergence as a selective target for cancer therapeutics are also discussed. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen.

Phellinus linteus extract induces autophagy and synergizes with 5-fluorouracil to inhibit breast cancer cell growth.

Phellinus linteus (PL) is a medicinal mushroom due to its several biological properties, including anticancer activity. However, the mechanisms of its anticancer effect remain to be elucidated. We evaluated the inhibitory effects of the ethanolic extract from the PL combined with 5-FU on MDA-MB-231 breast cancer cell line and to determine the mechanism of cell death. Individually, PL extract and 5-FU significantly inhibited the proliferation of MDA-MB-231 cells in a dose-dependent manner. PL extract (30 mg/mL) in combination with 5-FU (10 µg/mL) synergistically inhibited MDA-MB-231 cells by 1.8-fold. PL did not induce apoptosis, as demonstrated by the DNA fragmentation assay, the sub-G1 population, and staining with annexin V-FITC and propidium iodide. The exposure of MDA-MB-231 cells to PL extracts resulted in several confirmed characteristics of autophagy, including the appearance of autophagic vacuoles revealed by monodansylcadaverine staining, the formation of acidic vesicular organelles, autophagosome membrane association of microtubule-associated protein light chain 3 (LC3) characterized by cleavage of LC3 and its punctuate redistribution, and ultrastructural observation of autophagic vacuoles by transmission electron microscopy. We concluded that PL extracts synergized with low doses of 5-FU to inhibit triple-negative breast cancer cell growth and demonstrated that PL extract can induce autophagy-related cell death.

Impact of management on the prognosis of pure uterine papillary serous cancer - a Taiwanese Gynecologic Oncology Group (TGOG) study.

OBJECTIVE: To investigate the clinical and pathological characteristics and the management of uterine papillary serous carcinoma (UPSC) in relation to patients' outcomes. METHODS: Clinicopathological data and the management of patients treated between 1991 and 2010 at 11 member hospitals of the Taiwanese Gynecologic Oncology Group (TGOG) were retrospectively reviewed. The Kaplan-Meier method was used to generate survival curves, and factors predictive of outcome were compared using the log-rank test and Cox regression analysis. RESULTS: A total of 119 pure UPSC patients were recruited. Stages I, II, III, and IV were identified in 34.5%, 2.5%, 36.1%, and 26.9% of the patients, respectively. The recurrence rate was 20.5% in FIGO stage I/II disease and 55.2% in FIGO stage III/IV disease. The 5-year overall survival rates for the patients with stage I, II, III, and IV disease were 92.0%, 66.7%, 34.2%, and 17.3%, respectively. Multivariate analysis showed that tumor stage (stage III/IV hazard ratio [HR] 8.65, 95% confidence interval [CI] 3.00-24.9) and optimal cytoreduction (HR 0.40, 95% CI 0.22-0.73) independently influenced the overall survival rate of UPSC patients. In addition, optimal cytoreduction (HR 0.36, 95% CI 0.17-0.78) and the combination of chemotherapy and radiation (HR 0.11, 95% CI 0.04-0.37) improved the overall survival of the advanced stage (FIGO stage III/IV) UPSC patients. CONCLUSIONS: UPSC represents an aggressive subtype of endometrial cancer commonly accompanied by extra-uterine disease. Comprehensive surgical staging with cytoreductive surgery is mandatory and beneficial for UPSC patients. Systemic chemotherapy combined with radiation should be considered as an adjuvant therapy for advanced stage UPSC patients.

Prognostic factors and treatment outcomes for patients with surgically staged uterine clear cell carcinoma focusing on the early stage: A Taiwanese Gynecologic Oncology Group study.

OBJECTIVE: The aim of this study was to investigate the clinical and pathological characteristics of uterine clear cell carcinoma (UCCC) and the treatment of this disease in relation to patient outcomes. METHODS: The clinicopathological data for and the management of all patients with UCCC who presented between 1991 and 2010 at 11 member hospitals of the Taiwanese Gynecologic Oncology Group (TGOG) were retrospectively reviewed. RESULTS: There were no significant differences in 5-year overall survival (OS) rates between patients with pure UCCC (n=100) and non-pure UCCC (n=53) at the same surgical stage, with OS rates of 92.6%, and 87.7% for stage I; 83.3% and 83.3% for stage II; 64.0% and 67.8% for stage III; and 16.7% and 0% for stage IV (n=1), respectively. Tumor stage and age independently influenced the OS rate of UCCC. For the patients with early stage UCCC, the adjuvant therapy modality was the only significant prognostic factor for recurrence-free survival. The patients with early stage UCCC who received adjuvant therapy had excellent 5-year recurrence-free survival and OS rates compared to those who received radiotherapy (100% vs. 74%, p=0.01; 100% vs. 72%, p=0.03). CONCLUSIONS: The 5-year survival rates of patients with pure UCCC and non-pure UCCC were similar. The prognosis for surgical staging of patients with stage I/II UCCC was encouraging. Postoperative adjuvant platinum-based chemotherapy is recommended for patients with early stage UCCC who are at a high risk of recurrence.

Tight junction protein cingulin variant is associated with cancer susceptibility by overexpressed IQGAP1 and Rac1-dependent epithelial-mesenchymal transition.

BACKGROUND: Cingulin (CGN) is a pivotal cytoskeletal adaptor protein located at tight junctions. This study investigates the link between CGN mutation and increased cancer susceptibility through genetic and mechanistic analyses and proposes a potential targeted therapeutic approach. METHODS: In a high-cancer-density family without known pathogenic variants, we performed tumor-targeted and germline whole-genome sequencing to identify novel cancer-associated variants. Subsequently, these variants were validated in a 222 cancer patient cohort, and CGN c.3560C > T was identified as a potential cancer-risk allele. Both wild-type (WT) (c.3560C > C) and variant (c.3560C > T) were transfected into cancer cell lines and incorporated into orthotopic xenograft mice model for evaluating their effects on cancer progression. Western blot, immunofluorescence analysis, migration and invasion assays, two-dimensional gel electrophoresis with mass spectrometry, immunoprecipitation assays, and siRNA applications were used to explore the biological consequence of CGN c.3560C > T. RESULTS: In cancer cell lines and orthotopic animal models, CGN c.3560C > T enhanced tumor progression with reduced sensitivity to oxaliplatin compared to the CGN WT. The variant induced downregulation of epithelial marker, upregulation of mesenchymal marker and transcription factor, which converged to initiate epithelial-mesenchymal transition (EMT). Proteomic analysis was conducted to investigate the elements driving EMT in CGN c.3560C > T. This exploration unveiled overexpression of IQGAP1 induced by the variant, contrasting the levels observed in CGN WT. Immunoprecipitation assay confirmed a direct interaction between CGN and IQGAP1. IQGAP1 functions as a regulator of multiple GTPases, particularly the Rho family. This overexpressed IQGAP1 was consistently associated with the activation of Rac1, as evidenced by the analysis of the cancer cell line and clinical sample harboring CGN c.3560C > T. Notably, activated Rac1 was suppressed following the downregulation of IQGAP1 by siRNA. Treatment with NSC23766, a selective inhibitor for Rac1-GEF interaction, resulted in the inactivation of Rac1. This intervention mitigated the EMT program in cancer cells carrying CGN c.3560C > T. Consistently, xenograft tumors with WT CGN showed no sensitivity to NSC23766 treatment, but NSC23766 demonstrated the capacity to attenuate tumor growth harboring c.3560C > T. CONCLUSIONS: CGN c.3560C > T leads to IQGAP1 overexpression, subsequently triggering Rac1-dependent EMT. Targeting activated Rac1 is a strategy to impede the advancement of cancers carrying this specific variant.

Impact of Antenatal SARS-CoV-2 Exposure on SARS-CoV-2 Neutralization Potency.

A pregnancy booster dose significantly reduces the risk and severity of COVID-19, and it is widely recommended. A prospective cohort study was conducted to compare the transplacental passage of maternal antibodies from vaccination or infection during three trimesters against both the vaccine-targeted Wuhan strain and the Omicron strain of SARS-CoV-2. Maternal-infant dyads from vaccinated mothers were collected between 6 June 2022 and 20 September 2022. We analyzed 38 maternal-infant dyads from mothers who had been infected with COVID-19 and 37 from mothers without any previous infection. Pregnant women who received their last COVID-19 vaccine dose in the third trimester exhibited the highest anti-spike protein antibody levels and neutralizing potency against both the Wuhan strain and Omicron BA.2 variant in their maternal and cord plasma. Both second- and third-trimester vaccination could lead to a higher level of neutralization against the Wuhan and Omicron strains. COVID-19 infection had a negative effect on the transplacental transfer ratio of SARS-CoV-2 antibodies. A booster dose during the second or third trimester is encouraged for the maximum transplacental transfer of humoral protection against COVID-19 for infants.

An integrated microfluidic platform for rapid tumor cell isolation, counting and molecular diagnosis.

Ovarian cancer is the second most common of the gynecological cancers in Taiwan. It is challenging to diagnose at an early stage when proper treatment is the most effective. It is well recognized that the detection of tumor cells (TCs) is critical for determining cancer growth stages and may provide important information for accurate diagnosis and even prognosis. In this study, a new microfluidic platform integrated with a moving-wall micro-incubator, a micro flow cytometer and a molecular diagnosis module performed automated identification of ovarian cancer cells. By efficiently mixing the cells and immunomagnetic beads coated with specific antibodies, the target TCs were successfully isolated from the clinical samples. Then counting of the target cells was achieved by a combination of the micro flow cytometer and an optical detection module and showed a counting accuracy as high as 92.5 %. Finally, cancer-associated genes were amplified and detected by the downstream molecular diagnosis module. The fluorescence intensity of specific genes (CD24 and HE4) associated with ovarian cancer was amplified by the molecular diagnosis module and the results were comparable to traditional slab-gel electrophoresis analysis, with a limit of detection around 10 TCs. This integrated microfluidic platform realized the concept of a "lab-on-a-chip" and had advantages which included automation, disposability, lower cost and rapid diagnosis and, therefore, may provide a promising approach for the fast and accurate detection of cancer cells.

Determinants of quality of life related to lower limb lymphedema in women with gynecological cancer surgery.

Objective: This study aimed to identify the predictors of quality of life (QoL) related to lower limb lymphedema among women who had undergone gynecological cancer surgery. Additionally, the association between fatigue and the QoL was examined. Methods: A cross-sectional design with a convenience sample was adopted. Participants included 200 women with lymphadenectomy following gynecological cancer surgery. Demographic data, QoL related to lower limb lymphedema, and fatigue symptoms were collected. Results: Of the 200 participants, 60 percent (n â€‹= â€‹120) reported a mild to severe impact on QoL related to lower limb lymphedema, with the main impact on the function of mobility and physical symptoms. Age less than 55 years (ߠ​= â€‹0.706, OR â€‹= â€‹2.027, P â€‹= â€‹0.017), a diagnosis of ovarian cancer (ߠ​= â€‹0.804, OR â€‹= â€‹2.235, P â€‹= â€‹0.048), undergoing chemotherapy (ߠ​= â€‹0.616, OR â€‹= â€‹1.854, P â€‹= â€‹0.046), time after surgery (ߠ​= â€‹-0.833, OR â€‹= â€‹0.435, P â€‹= â€‹0.05), and fatigue (ߠ​= â€‹0.055, OR â€‹= â€‹1.06, P â€‹< â€‹0.001) were independently associated with QoL related to lower limb lymphedema. Hierarchical multiple regression demonstrated that fatigue was significantly associated with QoL related to lower limb lymphedema after controlling for age, types of cancer, time after surgery, and chemotherapy. Fatigue explained 11% of the variance in the QoL. Conclusions: More than half of the women with gynecological cancer requiring lymphadenectomy experienced an impact on QoL related to lower limb lymphedema. Effective interventions are warranted to improve the QoL related to lower limb lymphedema among women with gynecological cancer, particularly those who present with fatigue.

Reversion of chemoresistance by endocannabinoid-induced ER stress and autophagy activation in ovarian cancer.

The difficulty of detection at an early stage and the ease of developing resistance to chemotherapy render ovarian cancer (OVC) difficult to cure. Although several novel cancer therapies have been developed recently, drug resistance remains a concern since chemotherapy remains as the most commonly used treatment for cancer patients. Therefore, there is an urgent need to reclaim potential combination treatments for OVC. So far, there have been several research targeting the endocannabinoid system (ECS) in cancer. Among the various cannabinoid-based drugs, endocannabinoids, which are lipid molecules generated in the body, have been reported to produce many anti-tumor effects; however, research investigating the anti-chemoresistance effect of endocannabinoids in OVC remains unclear. In this study, we aimed to combine endocannabinoids, anandamide (AEA), and 2-arachidonoylglycerol (2-AG) with chemotherapeutic drugs as a combination approach to treat OVC. Our results showed that OVC cells expressed both cannabinoid receptors (CBR), CB1 and CB2, suggesting the possibility of endocannabinoid system (ECS) as a target. We found that the anti-chemoresistance effect mediated by endocannabinoids was caused by upregulation of ceramide levels, leading to severe endoplasmic reticulum (ER) stress and increased autophagy in chemoresistant cancer cells. Therefore, chemoresistant cancer cell growth was inhibited, and cell apoptosis was induced under combined treatments. Based on our results, endocannabinoids overcomed chemoresistance of OVC cells in vitro. Our findings suggest that drugs targeting ECS may have the potential to be adjuvants for chemotherapy by increasing the efficacy of chemotherapeutic drugs and decreasing their side effects.

CASZ1 promotes migration, invasion, and metastasis of lung cancer cells by controlling expression of ITGAV.

CASZ1, a zinc finger transcription factor with two isoforms, is known to play important roles in cardiac and neural development. The abnormal expression of CASZ1 is also frequently found in a variety of tumors but has different effects on different tumors; for example, it acts as a tumor suppressor in neuroblastoma but promotes cancer metastasis in ovarian cancer. However, the effect of CASZ1 in lung cancer, the most lethal cancer, remains unclear. Here, we found that the expression of CASZ1 in lung cancer is positively associated with cancer metastasis and poor prognosis. The overexpression of CASZ1b promotes lung cancer cell migration, invasion, and epithelial-mesenchymal transition and is associated with poor prognosis in lung cancer patients. The knockdown of CASZ1 resulted in the suppression of epithelial-mesenchymal transition, migration, and invasion of lung cancer cells and reduced metastasis in vivo. The results of an RNA-sequencing analysis of CASZ1-silenced cells showed that CASZ1 considerably affected the integrin-mediated pathways. CASZ1 bound to the ITGAV promoter and transcriptionally regulated ITGAV expression. Our findings demonstrate that CASZ1 plays an oncogenic role in lung cancer and that CASZ1 promotes lung cancer migration, invasion and metastasis is mediated by ITGAV.

Setting up a specialized maternity unit in a tertiary hospital: An oasis for pregnant women with COVID-19 during the pandemic.

OBJECTIVE: The COVID-19 pandemic has had an enormous impact on society and the medical environment in Taiwan in 2022. As pregnant women with COVID-19 are at higher risk for multiple complications, Taiwan needs a COVID-19 specialized maternity unit to improve the quality of maternal and neonatal care. MATERIALS AND METHODS: We share our experience with specialized maternity unit for pregnant women with COVID-19 at the National Cheng Kung University Hospital, where we can have careful evaluation, safe birth, and comprehensive postpartum care. RESULTS: Our COVID-19 specialized maternity unit enrolled 253 pregnant women with COVID-19, 90 (35.6%) pregnant women were admitted to the specialized maternity unit, and 71 (28.1%) pregnant women gave birth during hospitalization in two months. All pregnant women recovery well and real-time polymerase chain reaction tests on all infants were negative for COVID-19. CONCLUSION: A specialized maternity unit can provide pregnant women with a safe birth environment, immediate maternity care, and high medical quality. It can also help health workers in non-specialized maternity units deal with COVID-19-related psychological stress. Therefore, setting up one specialized maternity unit in the city during the pandemic should be guardedly considered.

Optimization of aptamer selection on an automated microfluidic system with cancer tissues.

Cancer is among the world's most deadly inflictions, and early diagnosis is critical. Aptamers have shown utility as cancer probes since they can be screened rapidly in vitro against cancer tissues using systematic evolution of ligands by exponential enrichment (SELEX) process. However, bench-top SELEX procedures are relatively labor-intensive and time-consuming; ideally, they could instead be carried out on microfluidic devices, yet this requires optimization of buffer and reaction conditions. Herein an integrated microfluidic system (IMS) was established to automatically carry out the optimization of aptamer selection. A "formulation chip" was developed that could mix salt solutions at differing final concentrations, and the resulting optimal binding buffer was transferred to another "optimization-SELEX chip" for the following tissue-SELEX. Two aptamers were successfully screened; one of which, H-45, exhibited high specificity and affinity towards ovarian cancer tissue samples, suggesting that this IMS might be a promising device for screening of cancer associated aptamers for cancer diagnosis.