Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

The first Chinese National Union of Real-world Gynaecological Oncology Research and Patient Management Platform: A retrospective study.

OBJECTIVE: To produce high-quality, real-world evidence for oncologists by collating scattered gynaecologic oncology (GO) medical records in China. DESIGN: Retrospective study. SETTING: The National Union of Real-world Gynaecological Oncology Research and Patient Management Platform (NUWA platform). SAMPLE: Patient-centred data pool. METHODS: The NUWA platform integrated inpatient/outpatient clinical, gene and follow-up data. Data of 11 456 patients with ovarian cancer (OC) were collected and processed using 91 345 electronic medical records. Structured and unstructured data were de-identified and re-collated into a patient-centred data pool using a predefined GO data model by technology-aided abstraction. MAIN OUTCOME MEASURES: Recent treatment pattern shifts towards precision medicine for OC in China. RESULTS: Thirteen first-tier hospitals across China participated in the NUWA platform up to 7 December 2021. In total, 3504 (30.59%) patients were followed up by a stand-alone patient management centre. The percentage of patients undergoing breast cancer gene (BRCA) mutation tests increased by approximately six-fold between 2017 and 2018. A similar trend was observed in the administration rate of poly(ADP-ribose) polymerase inhibitors as first-line treatment and second-line treatment after September 2018, when olaparib was approved for clinical use in China. CONCLUSION: The NUWA platform has great potential to facilitate clinical studies and support drug development, regulatory reviews and healthcare decision-making.

Increased high-mobility group box 1 levels are associated with depression after acute ischemic stroke.

BACKGROUND AND PURPOSE: Increased high-mobility group box 1 (HMGB1) levels were found in patients after acute ischemic stroke. The aim of this study was to examine whether the circulating HMGB1 levels could predict the 3-month post-stroke depression (PSD). METHODS: The subjects were first-ever ischemic stroke patients who were hospitalized during the period from July 2020 to December 2020. HMGB1 concentrations were measured by enzyme-linked immunosorbent assay after admission. A 24-item Hamilton Depression Rating Scale was performed to evaluate PSD at 3 months after stroke. RESULTS: The analyses included 324 participants (mean age, 63.7 years; 171 male). Ninety-four patients (29.0%) were diagnosed as having PSD at 3 months. The median serum HMGB1 levels at admission was 7.5 ng/mL (IQR, 4.4-11.3 ng/mL). The PSD distribution across the HMGB1 quartiles ranged between 17.5% (first quartile) and 57.5% (fourth quartile). After covariate adjustments, the fourth quartile of HMGB1 was found to be associated with a higher risk of PSD (as compared with first HMGB1 quartile, odd ratio, 1.26; 95% confidence interval [CI], 1.17-1.35; P < 0.001). The area under the receiver operating characteristic curve of HMGB1 was 0.726 (95% CI 0.660-0.792) for PSD. Similar results were found when HMGB1 was analyzed as continuous variable. Furthermore, the optimal cutoff point of circulating HMGB1 levels was 8.6 ng/mL, with a sensitivity of 69.2% and a specificity of 73.9%. CONCLUSIONS: This study demonstrated that higher HMGB1 levels in the acute phase of ischemic stroke were associated with increased risk of PSD.

Melatonin provides protection against cisplatin-induced ovarian damage and loss of fertility in mice.

RESEARCH QUESTION: Can melatonin provide non-invasive ovarian protection against damage caused by cis-diamminedichloroplatinum (cisplatin) and preserve fertility in female cancer patients? And if so, what is the possible mechanism? DESIGN: Athymic BALB/c nude tumour-bearing female mice were used to demonstrate whether melatonin affects the antineoplastic effect when co-administrated with cisplatin. Sexually mature and newborn C57BL/6 female mice were used to evaluate the potential effects of melatonin on the ovarian follicle pool, pregnancy rate and litter number in cisplatin-treated mice. The ovaries underwent immunohistochemical, TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick-end labelling (TUNEL) and gene array analysis to explore the underlying mechanism. In addition, granulosa cells were isolated to investigate the potential protective mechanism of melatonin. RESULTS: Melatonin not only enhanced the anti-cancer effect of cisplatin in tumour-bearing nude mice, but also reduced ovarian toxicity and preserved long-term fertility in cisplatin-treated C57BL/6 female mice. When co-administrated, melatonin was able to reduce the DNA damage and toxic effects on lipid peroxidation in the ovaries caused by cisplatin. Specifically, melatonin was able to largely restore lipid peroxidation in granulosa cells and thus prevent ovarian follicles from being depleted. CONCLUSIONS: Melatonin has the potential to be used as a chemotherapeutic adjuvant to simultaneously improve the outcome of anti-cancer treatment and preserve ovarian function during cisplatin chemotherapy. Notably, its properties of DNA protection and antioxidant effects on follicles may benefit female cancer survivors and prevent premature ovarian failure as well as fertility loss caused by chemotherapy.

Correction to: A reactive oxygen species scoring system predicts cisplatin sensitivity and prognosis in ovarian cancer patients.

Following publication of the original article [1], the authors reported an error in Fig. 1f.

A reactive oxygen species scoring system predicts cisplatin sensitivity and prognosis in ovarian cancer patients.

BACKGROUND: To reveal roles of reactive oxygen species (ROS) status in chemotherapy resistance and to develop a ROS scoring system for prognosis prediction in ovarian cancer. METHODS: We tested the sensitizing effects of ROS elevating drugs to cisplatin (cDDP) in ovarian cancer both in vitro and in vivo. A ROS scoring system was developed using The Cancer Genome Atlas (TCGA) database of ovarian cancer. The associations between ROS scores and overall survival (OS) were analyzed in TCGA, Tothill dataset, and our in-house dataset (TJ dataset). RESULTS: ROS-inducing drugs increased cisplatin-induced ovarian cancer cell injury in vitro and in vivo. ROS scoring system was established using 25 ROS-related genes. Patients were divided into low (scores 0-12) and high (scores 13-25) score groups. Improved patient survival was associated with higher scores (TCGA dataset hazard ratio (HR) = 0.43, P < 0.001; Tothill dataset HR = 0.65, P = 0.022; TJ dataset HR = 0.40, P = 0.003). The score was also significantly associated with OS in multiple datasets (TCGA dataset r2 = 0.574, P = 0.032; Thothill dataset r2 = 0.266, P = 0.049; TJ dataset r2 = 0.632, P = 0.001) and with cisplatin sensitivity in ovarian cancer cell lines (r2 = 0.799, P = 0.016) when used as a continuous variable. The scoring system showed better prognostic performance than other clinical factors by receiver operating characteristic (ROC) curves (TCGA dataset area under the curve (AUC) = 0.71 v.s. 0.65, Tothill dataset AUC = 0.73 v.s. 0.67, TJ dataset AUC = 0.74 v.s. 0.66). CONCLUSIONS: ROS status is associated with chemotherapy resistance. ROS score system might be a prognostic biomarker in predicting the survival benefit from ovarian cancer patients.

General Anesthesia may have Similar Outcomes with Conscious Sedation in Thrombectomy Patients with Acute Ischemic Stroke: A Real-World Registry in China.

BACKGROUND AND PURPOSE: Clinical trials showed that anesthesia may not influence the functional outcome in stroke patients with endovascular therapy; however, data are lacking in China. Using real-world registry data, our study aims to compare the effects of general anesthesia or conscious sedation on functional outcomes in stroke patients treated with thrombectomy in China. METHODS: Consecutive patients with acute anterior circulation stroke receiving thrombectomy in 21 stroke centers between January 2014 and June 2016 were included in this study. The propensity score analysis with 1: 1 ratio was used to match the baseline variables between patients with general anesthesia and the conscious sedation. The 90-day modified Rankin Scale (mRS), symptomatic intracranial hemorrhage (sICH), and death were compared between groups. RESULTS: Of the 698 patients undergoing endovascular treatment, 138 were treated with general anesthesia and 560 with conscious sedation. After propensity score matching, 114 general anesthesia and 114 conscious sedation patients were matched. The proportions of patients with 90-day mRS 0-2 were not significantly different between general anesthesia and conscious sedation groups (41.2% [47/114] vs. 46.5% [53/114], p = 0.470), nor were the rates of sICH (21.9% [25/114] vs. 12.3% [14/114], p = 0.072) and 90-day mortality (31.6% [36/114] vs. 21.9% [25/114], p = 0.145). CONCLUSION: Anesthesia patterns may have no significant impacts on clinical outcomes in patients with acute anterior circulation occlusion stroke undergoing endovascular treatment in the real-world practice in China.

Association between procalcitonin levels and carotid atherosclerosis in acute ischemic stroke patients.

BACKGROUND AND PURPOSES: Procalcitonin has been suggested as a new risk factor in atherosclerotic disease. However, whether procalcitonin levels are associated with the risk of carotid atherosclerosis remains unclear. This study aimed to investigate the relationship between procalcitonin levels and carotid atherosclerosis among patients with first-ever acute ischemic stroke. METHODS: Two hundred and thirty consecutive patients were prospectively enrolled in this study. Serum procalcitonin concentrations were measured at admission for all patients. We also performed ultrasound examination to detect the mean carotid intima-media thickness, presence of carotid-wall thickening, plaque and significant stenosis. Multiple regression analysis was used to estimate the association between procalcitonin levels and carotid atherosclerosis. RESULTS: The median procalcitonin concentration was 0.051 µg/L (interquartile range, 0.036-0.080 µg/L). Of the 230 patients, 102 (44.3%) had carotid-wall thickening, 113 (49.1%) had plaque and 77 (33.5%) had significant stenosis. After adjusting for all potential confounders by multiple logistic regression analysis, patients with procalcitonin levels in the fourth quartile, compared with the first quartile, were more likely to have carotid-wall thickening [odds ratio 2.288, 95% confidence intervals 1.042-5.021, P = 0.039] and significant stenosis [odds ratio 3.871, 95% confidence intervals 1.690-8.867, P = 0.003]. Furthermore, the linear regression analysis revealed a significant positive correlation between procalcitonin levels and the mean carotid intima-media thickness (ß = 0.162, P = 0.012). CONCLUSIONS: Higher procalcitonin concentrations at admission might be associated with carotid-wall thickening and significant stenosis in ischemic stroke patients.

The Impacts of Peptic Ulcer on Stroke Recurrence.

BACKGROUND: Peptic ulcer has been associated with an increased risk of stroke. This study aimed to evaluate the impacts of peptic ulcer on stroke recurrence and mortality. SUBJECTS AND METHODS: Patients with first-ever ischemic stroke were retrospectively confirmed with or without a history of peptic ulcer. The primary end point was defined as fatal and nonfatal stroke recurrence. Risks of 1-year fatal and nonfatal stroke recurrence were analyzed with the Kaplan-Meier method. Predictors of fatal and nonfatal stroke recurrence were evaluated with the Cox proportional hazards model. RESULTS: Among the 2577 enrolled patients with ischemic stroke, 129 (5.0%) had a history of peptic ulcer. The fatal and nonfatal stroke recurrence within 1 year of the index stroke was higher in patients with peptic ulcer than in patients without peptic ulcer (12.4% versus 7.2%, P = .030). Cox proportional hazards model detected that age (hazard ratio [HR] = 1.018, 95% confidence interval [CI] 1.005-1.031, P = .008), hypertension (HR = 1.397, 95% CI 1.017-1.918, P = .039), and history of peptic ulcer (HR = 1.853, 95% CI 1.111-3.091, P = .018) were associated with stroke recurrence. CONCLUSIONS: Ischemic stroke patients with peptic ulcer may have an increased risk of stroke recurrence. The results emphasize the importance of appropriate prevention and management of peptic ulcer for secondary stroke prevention.

Blockage of glutaminolysis enhances the sensitivity of ovarian cancer cells to PI3K/mTOR inhibition involvement of STAT3 signaling.

The PI3K/Akt/mTOR axis in ovarian cancer is frequently activated and implicated in tumorigenesis. Specific targeting of this pathway is therefore an attractive therapeutic approach for ovarian cancer. However, ovarian cancer cells are resistant to PP242, a dual inhibitor of mTORC1 and mTORC2. Interestingly, blockage of GLS1 with a selective inhibitor, CB839, or siRNA dramatically sensitized the PP242-induced cell death, as evident from increased PARP cleavage. The anti-cancer activity of CB-839 and PP242 was abrogated by the addition of the TCA cycle product α-ketoglutarate, indicating the critical function of GLS1 in ovarian cancer cell survival. Finally, glutaminolysis inhibition activated apoptosis and synergistically sensitized ovarian cancer cells to priming with the mTOR inhibitor PP242. GLS1 inhibition significantly reduced phosphorylated STAT3 expression in ovarian cancer cells. These findings show that targeting glutamine addiction via GLS1 inhibition offers a potential novel therapeutic strategy to overcome resistance to PI3K/Akt/mTOR inhibition.

Identification of a Novel Model for Predicting the Prognosis and Immune Response Based on Genes Related to Cuproptosis and Ferroptosis in Ovarian Cancer.

(1) Background: Ovarian cancer (OV) presents a high degree of malignancy and a poor prognosis. Cell death is necessary to maintain tissue function and morphology. Cuproptosis and ferroptosis are two novel forms of death, and we look forward to finding their relationship with OV and providing guidance for treatment. (2) Methods: We derived information about OV from public databases. Based on cuproptosis-related and ferroptosis-related genes, a risk model was successfully constructed, and exceptional subtypes were identified. Next, various methods are applied to assess prognostic value and treatment sensitivity. Besides, the comprehensive analysis of the tumor environment, together with immune cell infiltration, immune function status, immune checkpoint, and human HLA genes, is expected to grant assistance for the prognosis and treatment of OV. (3) Results: Specific molecular subtypes and models possessed excellent potential to predict prognosis. Immune infiltration abundance varied between groups. The susceptibility of individuals to different chemotherapy drugs and immunotherapies could be predicted based on specific groups. (4) Conclusions: Our molecular subtypes and risk model, with strong immune prediction and prognostic prediction capabilities, are committed to guiding ovarian cancer treatment.

Glial Fibrillary Acidic Protein Levels in Post-Stroke Depression: A Prospective Ischemic Stroke Cohort.

Background and Purpose: Increased glial fibrillary acidic protein (GFAP) levels were found in cerebrovascular disease patients. The pathogenesis of depression after ischemic stroke remains largely unknown. Here, we aim to determine whether GFAP concentrations were associated with post-stroke depression (PSD) at 3 months. Methods: From March 2022 to September 2022, patients with first-ever ischemic stroke were prospectively recruited. GFAP concentrations were detected within 24 h using an enzyme-linked immunosorbent assay. The PSD was defined as a Hamilton Depression Rating Scale 24-Item score ≥ 8. Results: A total of 206 subjects with ischemic stroke (mean age: 63.6 years; 49.0% female) were enrolled. During the 90-day follow-up, 57 participants (27.7%) were observed in PSD. The median serum GFAP concentrations were 0.67 ng/mL. After adjustment for the covariates, higher increased GFAP levels were associated with increased risk of PSD (odds ratio [OR], 7.12; 95% confidence interval [CI], 3.29-15.44; P < 0.001). Also, the multivariate-adjusted OR of PSD associated with the fourth quartile of GFAP was 10.89 (95% CI, 3.53-33.60; P < 0.001) compared with the first quartile. Furthermore, the restricted cubic spline confirmed a linear association between GFAP and the risk of PSD (P for linearity < 0.001). Conclusion: Our results indicated that increased circulating GFAP concentrations were significantly correlated with the risk of PSD at 3 months. Measuring the GFAP levels after ischemic stroke may add some values for the risk stratifying of PSD.

Leukoaraiosis Mediates the Association of Total White Blood Cell Count With Post-Stroke Cognitive Impairment.

BACKGROUND AND PURPOSE: The inflammatory response could play a key role in cognitive impairment. However, there has been limited research into the association between total white blood cell (WBC) count and post-stroke cognitive impairment (PSCI), and the significance of leukoaraiosis (LA) in this relationship is unknown. We aimed to examine the total WBC count in relation to PSCI and whether this association was mediated by LA. METHODS: Consecutive patients with first-ever ischemic stroke were prospectively enrolled from October 2020 to June 2021. The total WBC count was measured after admission. Cognitive function evaluations were performed at the 3-month follow-up using Mini-mental State Examination (MMSE). We defined the PSCI as an MMSE score <27. RESULTS: A total of 276 patients (mean age, 66.5 years; 54.7% male) were included in this analysis. Among them, 137 (49.6%) patients experienced PSCI. After adjustment for potential confounders, higher total WBC count was significantly correlated with an increased risk of LA [per 1-SD increase, odds ratio (OR), 1.39; 95% CI 1.06-1.82; p = 0.017] and PSCI (per 1-SD increase, OR, 1.51; 95% CI 1.12-2.04; p = 0.006). Furthermore, mediation analysis demonstrated that the association between total WBC count and PSCI was partly mediated by LA (the regression coefficient was changed by 9.7% for PSCI, and 12.4% for PSCI severity, respectively). CONCLUSION: Increased total WBC count is a risk factor for PSCI. The presence of LA was partially responsible for the PSCI in patients who had a higher total WBC count.

Fecal microbiota transplantation mitigates vaginal atrophy in ovariectomized mice.

Vulvovaginal atrophy (VVA) is a common menopause-related symptom affecting more than 50% of midlife and older women and cancer patients whose ovarian function are lost or damaged. Regardless of estrogen deficiency, whether other factors such as the gut microbiota play role in VVA have not been thoroughly investigated. To this end, we performed ovariectomy on 12-weeks' old mice and follow-up at 4 weeks after ovariectomy, and observed atrophied vagina and an altered gut microbiota in ovariectomized mice.. We further performed fecal microbiota transplantation with feces from another cohort of ovary-intact fecund female mice to the ovariectomized ones, and found that the vaginal epithelial atrophy was significantly alleviated as well as the gut microbiota was pointedly changed. All these results suggest that ovarian activity has some influence on the gut microbiota, and the latter from the ovary-intact female mice can somehow make the vagina of mice deficient in ovarian function healthier maybe by up-expressing ESR1 in vaginal cells and enhancing regeneration in vagina. This kind of association between gut microbiota and vaginal health need further exploration such that it may provide an alternative treatment by modulating gut microbiota in patients suffering from VVA but may be reluctant to hormone therapy.

Aberrant oligodendroglial LDL receptor orchestrates demyelination in chronic cerebral ischemia.

Oligodendrocytes express low-density lipoprotein receptor (LDLR) to endocytose cholesterol for the maintenance of adulthood myelination. However, the potential role of LDLR in chronic cerebral ischemia-related demyelination remains unclear. We used bilateral carotid artery stenosis (BCAS) to induce sustained cerebral ischemia in mice. This hypoxic-ischemic injury caused a remarkable decrease in oligodendroglial LDLR, with impaired oligodendroglial differentiation and survival. Oligodendroglial cholesterol levels, however, remained unchanged. Mouse miR-344e-3p and the human homolog miR-410-3p, 2 miRNAs directly targeting Ldlr, were identified in experimental and clinical leukoaraiosis and were thus implicated in the LDLR reduction. Lentiviral delivery of LDLR ameliorated demyelination following chronic cerebral ischemia. By contrast, Ldlr-/- mice displayed inadequate myelination in the corpus callosum. Ldlr-/- oligodendrocyte progenitor cells (OPCs) exhibited reduced ability to differentiate and myelinate axons in vitro. Transplantation with Ldlr-/- OPCs could not rescue the BCAS-induced demyelination. Such LDLR-dependent myelin restoration might involve a physical interaction of the Asn-Pro-Val-Tyr (NPVY) motif with the phosphotyrosine binding domain of Shc, which subsequently activated the MEK/ERK pathway. Together, our findings demonstrate that the aberrant oligodendroglial LDLR in chronic cerebral ischemia impairs myelination through intracellular signal transduction. Preservation of oligodendroglial LDLR may provide a promising approach to treat ischemic demyelination.

Association between glutathione peroxidase-3 activity and carotid atherosclerosis in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: Deficiency of glutathione peroxidase 3 (GPx3) has been recognized as an independent risk factor for cardiovascular events. However, little is known regarding the role of GPx3 in carotid atherosclerosis, which is ubiquitously observed in type 2 diabetes mellitus (T2DM). This study aimed to investigate the relationship between GPx3 activity and carotid atherosclerosis among patients with T2DM. METHODS: From January 2018 to December 2018, 245 consecutive patients with T2DM were enrolled in this observational study. Assessment of serum GPx3 activity was performed after admission. We also used carotid ultrasound to measure the mean carotid intima-media thickness (CIMT) and to assess the presence of carotid plaque. RESULTS: Of the 245 patients, the median serum GPx3 activity was 22.5 U/ml (interquartile range, 12.4-35.9 U/ml). Carotid plaque was observed in 113 (46.1%) patients, and mean CIMT was 0.8 ± 0.1 mm. Univariate analysis showed that age, smoking, previous coronary heart disease, carotid plaque, and level of mean CIMT and hypersensitive C-reactive protein were significantly associated with decreasing tertile of GPx3. Furthermore, after adjusting for all potential confounders by multivariable logistic regression analysis, PGx3 activity was significantly and independently associated with the mean CIMT (ß = -.406, p = .002) and carotid plaque (first tertile of GPx3, odds ratio, 1.870, 95% confidence intervals, 1.124-3.669, p = .024). CONCLUSIONS: This study demonstrated that serum GPx3 activity was inversely associated with mean CIMT and carotid plaque, suggesting that lower GPx3 activity may be an independent predictor for carotid atherosclerosis in T2DM.

Decreased Serum Retinoic Acid May Predict Poor Outcome in Ischemic Stroke Patients.

BACKGROUND AND AIMS: Decreased serum retinoic acid (RA) levels have been shown to be linked with increased mortality in cardiovascular diseases. This study aimed to investigate the relationship between serum RA and 3-month functional outcome after ischemic stroke. METHODS: Between January 2019 and September 2019, we prospectively recruited ischemic stroke patients within 24 hrs of symptom onset. Serum RA levels were measured for all patients at admission. The primary outcome was defined as poor functional outcome (modified Rankin Scale 3-6) at 90 days. The secondary outcome was defined as early neurological deterioration (END), which is considered as an increase of ≥1 point in motor power or total National Institutes of Health Stroke Scale score of ≥2 points within 7 days. RESULTS: A total of 217 patients were included in the analysis. The median RA levels were 2.9 ng/mL. Ninety-four (43.3%) and 65 (30.0%) patients experienced 3-month poor outcome and END, respectively. After adjusted for potential confounders, decreased levels of serum RA were associated with a higher risk of poor outcome (P for trend = 0.001) and END (P for trend = 0.002). Adding RA quartile to the existing risk factors improved risk prediction for poor outcome [net reclassification improvement (NRI) = 42.6%, P = 0.001; integrated discrimination improvement (IDI) = 5.7%, P = 0.001] and END (NRI index = 45.4%, P = 0.001; IDI = 4.3%; P = 0.005). CONCLUSION: Low serum RA levels at baseline were associated with poor prognosis at 90 days after ischemic stroke, suggesting that RA may be a potential prognostic biomarker for ischemic stroke.

MCP-1/CCR-2 axis in adipocytes and cancer cell respectively facilitates ovarian cancer peritoneal metastasis.

Ovarian cancer selective metastasizes to the omentum contributing to the poor prognosis associated with ovarian cancer. However, the mechanism underlining this propensity and therapeutic approaches to counter this process has not been fully elucidated. Here, we show that MCP-1 produced by omental adipocytes binding to its cognate receptor CCR-2 on ovarian cancer cells facilitates migration and omental metastasis by activating the PI3K/AKT/mTOR pathway and its downstream effectors HIF-1α and VEGF-A in cell lines, xenografts, and transgenic murine models. MCP-1 antibody significantly decreased tumor burden and increased survival of mice in vivo. Interestingly, metformin decreased omental metastasis at least partially by inhibiting MCP-1 secretion from adipocytes independent of direct effects on cancer cells. Together this suggests a novel target of MCP-1/CCR-2 axis that could benefit ovarian cancer patients.

Association between serum retinoic acid levels and risk of post-stroke depression in patients with ischemic stroke.

Previous studies suggest that retinoic acid (RA) can exert neuroprotective function in ischemic stroke. However, its role in post-stroke depression (PSD) has still been unclear. We sought to investigate the relationship between circulating RA levels and PSD in patients with ischemic stroke. From September 2018 to March 2019, we prospectively screened patients with ischemic stroke who were hospitalized within 7 days of symptoms onset. RA levels were measured after admission. All patients were followed up at 3 months after stroke. Diagnosis of PSD was made in line with the Chinese version of Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. PSD risk was estimated using multivariable regression models. In total, 352 ischemic stroke patients were enrolled for the final analysis. Up to 3 months after symptoms onset, 102 subjects experienced PSD. PSD patients showed significantly lower RA levels at baseline as compared to non-PSD patients. In univariate logistic analysis, reduced levels of RA was a significant predictor of PSD. These results were further confirmed in multivariate regression additionally controlled for possible relevant confounders. Our study shows that decreased serum RA levels at admission might be associated with 3-month PSD in ischemic stroke patients.