Specific expression profile of follicular fluid-derived exosomal microRNAs in patients with diminished ovarian reserve.

BACKGROUND: Diminished ovarian reserve (DOR) is defined as a reduction in ovarian reserve and oocyte quality. The pathophysiology of DOR has not been completely explained as of yet. Scholars have uncovered a large number of exosomes that have been detected in follicular fluid, and exosomal miRNAs have been proven to play a critical role in controlling ovarian disorders and follicle formation. We focused on the expression profile of follicular fluid-derived exosomal microRNAs (miRNAs) and attempted to understand if their role is connected to the pathomechanism of DOR. METHODS: The follicular fluid-derived differentially expressed exosomal miRNAs (DEmiRs) between patients with DOR and those with normal ovarian function were investigated using the next-generation sequencing (NGS) method. The main metabolic and signaling pathways of DEmiRs were identified using the KEGG pathway database, disease ontology (DO) analysis, and gene ontology (GO) analysis. In the end, a Protein-Protein Interaction (PPI) network was built to search for exosomal miRNAs and their target genes that were potentially strongly connected with DOR. RESULTS: In comparison to normal controls, 52 DEmiRs were discovered in follicular fluid-derived exosomes of DOR patients, of which 19 were up-regulated and 33 were down-regulated (|log2(fold change) |>2, P < 0.05). GO, DO analysis, and the KEGG pathway database revealed that many of these DEmiRs have broad biological roles that are connected to ovarian function and disorders. The top ten DEmiRs in terms of expression were then chosen for miRNA-mRNA interaction analysis. Totally, 8 experimentally supported miRNAs (hsa-miR-1246, hsa-miR-483-3p, hsa-miR-122-5p, hsa-miR-130b-3p, hsa-miR-342-3p, hsa-miR-625-3p, hsa-miR-675-3p, and hsa-miR-134-5p) and 126 target genes were filtrated by utilizing Cytoscape software. The module analysis findings of the PPI network showed that the main module cluster with a score > 6.0 (MCODE score = 15) had six hub genes, including IGFR, VEGFA, KRAS, ERBB2, RHOA, and PTEN (MCODE score = 11.472). CONCLUSION: Our data suggested a special expression profile of follicular fluid-derived exosomal miRNAs in patients with DOR, which was probably correlated to ovarian dysfunction and follicle formation. These results may give a unique insight into a better understanding of the molecular process in the pathogenesis of DOR or other ovarian diseases.

Microbial remediation of oil-contaminated shorelines: a review.

Frequent marine oil spills have led to increasingly serious oil pollution along shorelines. Microbial remediation has become a research hotspot of intertidal oil pollution remediation because of its high efficiency, low cost, environmental friendliness, and simple operation. Many microorganisms are able to convert oil pollutants into non-toxic substances through their growth and metabolism. Microorganisms use enzymes' catalytic activities to degrade oil pollutants. However, microbial remediation efficiency is affected by the properties of the oil pollutants, microbial community, and environmental conditions. Feasible field microbial remediation technologies for oil spill pollution in the shorelines mainly include the addition of high-efficiency oil degrading bacteria (immobilized bacteria), nutrients, biosurfactants, and enzymes. Limitations to the field application of microbial remediation technology mainly include slow start-up, rapid failure, long remediation time, and uncontrolled environmental impact. Improving the environmental adaptability of microbial remediation technology and developing sustainable microbial remediation technology will be the focus of future research. The feasibility of microbial remediation techniques should also be evaluated comprehensively.

Systematic Review and Meta-Analysis of O-RADS Ultrasound and O-RADS MRI for Risk Assessment of Ovarian and Adnexal Lesions.

BACKGROUND. O-RADS ultrasound (US) and O-RADS MRI have been developed to standardize risk stratification of ovarian and adnexal lesions. OBJECTIVE. The purpose of this study was to perform a meta-analysis evaluating the diagnostic performance of O-RADS US and O-RADS MRI for risk stratification of ovarian and adnexal lesions. EVIDENCE ACQUISITION. We searched the Web of Science, PubMed, Cochrane Library, Embase, and Google Scholar databases from January 1, 2020, until October 31, 2022, for studies reporting on the performance of O-RADS US or O-RADS MRI in the diagnosis of malignancy of ovarian or adnexal lesions. Study quality was assessed with QUADAS-2. A hierarchic summary ROC model was used to estimate pooled sensitivity and specificity. Heterogeneity was assessed with the Q statistic. Metaregression analysis was performed to explore potential sources of heterogeneity. O-RADS US was compared with the International Ovarian Tumor Analysis (IOTA) simple rules and Assessment of Different Neoplasias in the Adnexa (ADNEX) model in studies providing head-to-head comparisons. EVIDENCE SYNTHESIS. Twenty-six studies comprising 9520 patients were included. O-RADS US was evaluated in 15 and O-RADS MRI in 12 studies; both systems were evaluated in one of the studies. Quality assessment revealed that risk of bias or concern about applicability most commonly related to patient selection. Pooled sensitivity and specificity of O-RADS US were 95% (95% CI, 91-97%) and 82% (95% CI, 76-87%) and of O-RADS MRI were 95% (95% CI, 92-97%) and 90% (95% CI, 84-94%). Analysis with the Q statistic revealed significant heterogeneity among studies of O-RADS US in both sensitivity and specificity (both p < .001) and among studies of O-RADS MRI in specificity (p < .001) but not sensitivity (p = .07). In metaregression, no factor was significantly associated with sensitivity or specificity of either system (all p > .05). O-RADS US showed no significant difference in sensitivity or specificity versus IOTA simple rules in four studies (sensitivity, 96% vs 93%; specificity, 76% vs 82%) or versus the ADNEX model in three studies (sensitivity, 96% vs 96%; specificity, 79% vs 78%). CONCLUSION. O-RADS US and O-RADS MRI both have high sensitivity for ovarian or adnexal malignancy. O-RADS MRI, but not O-RADS US, also has high specificity. CLINICAL IMPACT. Awareness of the diagnostic performance results regarding O-RADS US and O-RADS MRI will be helpful as these systems are increasingly implemented into clinical practice.

Diagnostic performance of the Bosniak classification, version 2019 for cystic renal masses: A systematic review and meta-analysis.

Purpose: To systematically assess the diagnostic performance of the Bosniak classification, version 2019 for risk stratification of cystic renal masses. Methods: We conducted an electronic literature search on Web of Science, MEDLINE (Ovid and PubMed), Cochrane Library, EMBASE, and Google Scholar to identify relevant articles between June 1, 2019 and March 31, 2022 that used the Bosniak classification, version 2019 for risk stratification of cystic renal masses. Summary estimates of sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) were pooled with the bivariate model and hierarchical summary receiver operating characteristic (HSROC) model. The quality of the included studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results: A total of eight studies comprising 720 patients were included. The pooled sensitivity and specificity were 0.85 (95% CI 0.79-0.90) and 0.68 (95% CI 0.58-0.76), respectively, for the class III/IV threshold, with a calculated area under the HSROC curve of 0.84 (95% CI 0.81-0.87). The pooled LR+, LR-, and DOR were 2.62 (95% CI 2.0-3.44), 0.22 (95% CI 0.16-0.32), and 11.7 (95% CI 6.8-20.0), respectively. The Higgins I 2 statistics demonstrated substantial heterogeneity across studies, with an I 2 of 57.8% for sensitivity and an I 2 of 74.6% for specificity. In subgroup analyses, the pooled sensitivity and specificity for CT were 0.86 and 0.71, respectively, and those for MRI were 0.87 and 0.67, respectively. In five studies providing a head-to-head comparison between the two versions of the Bosniak classification, the 2019 version demonstrated significantly higher specificity (0.62 vs. 0.41, p < 0.001); however, it came at the cost of a significant decrease in sensitivity (0.88 vs. 0.94, p = 0.001). Conclusions: The Bosniak classification, version 2019 demonstrated moderate sensitivity and specificity, and there was no difference in diagnostic accuracy between CT and MRI. Compared to version 2005, the Bosniak classification, version 2019 has the potential to significantly reduce overtreatment, but at the cost of a substantial decline in sensitivity.

The potency of common proinflammatory cytokines measurement for revealing the risk and severity of anxiety and depression in psoriasis patients.

OBJECTIVE: Proinflammatory cytokines mediate anxiety and depression in various ways, such as immunity, inflammation, and the hypothalamic-pituitary-adrenal axis. This study intended to further explore the linkage of common proinflammatory cytokine levels with anxiety and depression in psoriasis patients. METHODS: Totally, 150 psoriasis patients and 50 healthy controls (HCs) were included; the serum samples were collected, then common proinflammatory cytokines were measured by ELISA. Hospital Anxiety and Depression Scale (HADS) was assessed. RESULTS: HADS-anxiety (HADS-A) score, HADS-depression (HADS-D) score, TNF-α, IL-1ß, IL-6, IL-12, IL-17A, and IL-23 were all increased in psoriasis patients compared to HCs (all p < 0.05). In psoriasis patients, TNF-α (p = 0.001), IL-12 (p = 0.035), and IL-17A (p < 0.001), but not IL-1ß (p = 0.255), IL-6 (p = 0.248), and IL-23 (p = 0.216), were positively linked to HADS-A score. Meanwhile, TNF-α (p = 0.007) and IL-17A (p = 0.007) were enhanced in psoriasis patients with anxiety in contrast to those without anxiety; whereas IL-1ß (p = 0.178), IL-6 (p = 0.360), IL-12 (p = 0.239), and IL-23 (p = 0.450) were not different. TNF-α (p < 0.001), IL-1ß (p = 0.013), Il-17A (p < 0.001), and IL-23 (p = 0.023), but not IL-6 (p = 0.143) and IL-12 (p = 0.158), were positively linked to HADS-D score. Concurrently, TNF-α (p = 0.015), IL-17A (p < 0.001), and IL-23 (p = 0.017) were climbed in psoriasis patients with depression by comparison to those without depression; whereas IL-1ß (p = 0.113), IL-6 (p = 0.237), IL-12 (p = 0.660) did not differ. CONCLUSION: TNF-α, IL-17A, and IL-23 increments reflect anabatic anxiety and depression in psoriasis patients, uncovering the potency of proinflammatory cytokines measurement for monitoring or even preventing psoriasis patients' anxiety and depression.

Circulating microRNAs: Biomarkers of disease.

MicroRNAs are a class of endogenous noncoding single-stranded RNA molecules with approximately 20-24 nucleotides and are associated with a broad range of biological processes. Researchers found that microRNAs are abundant in tissues, and more importantly, there are also trace circulating microRNAs that exist in biological fluids. In recent years, circulating microRNAs had emerged as promising diagnostic and prognostic biomarkers for the noninvasive detection of diseases with high specificity and sensitivity. More importantly, specific microRNA expression signatures reflect not only the existence of early-stage diseases but also the dynamic development of advanced-stage diseases, disease prognosis prediction, and drug resistance. To date, an increasing number of potential miRNA biomarkers have been reported, but their practical application prospects are still unclear. Therefore, microRNAs, as potential diagnostic and prognostic biomarkers in a variety of diseases, need to be updated, as they are of great importance in the diagnosis, prognosis and prediction of therapeutic responses. In this review, we summary our current understanding of microRNAs as potential biomarkers in the major diseases (e.g., cancers and cardio-cerebrovascular diseases), which provide the basis for the design of diagnosis and treatment plan and the improvement of the cure rate.

Disease-Specific Autoantibodies Induce Trained Immunity in RA Synovial Tissues and Its Gene Signature Correlates with the Response to Clinical Therapy.

Much evidence suggests that trained immunity is inappropriately activated in the synovial tissue in rheumatoid arthritis (RA), but the underlying mechanism remains unclear. Here, we describe how RA-specific autoantibody deposits can train human monocytes to exert the hyperactive inflammatory response, particularly via the exacerbated release of tumor necrosis factor α (TNFα). Comparative transcriptomic analysis by plate-bound human IgG (cIgG) or ß-glucan indicated that metabolic shift towards glycolysis is a crucial mechanism for trained immunity. Moreover, the cIgG-trained gene signatures were enriched in synovial tissues from patients with ACPA- (anticitrullinated protein antibody-) positive arthralgia and undifferentiated arthritis, and early RA and established RA bore a great resemblance to the myeloid pathotype, suggesting a historical priming event in vivo. Additionally, the expression of the cIgG-trained signatures is higher in the female, older, and ACPA-positive populations, with a predictive role in the clinical response to infliximab. We conclude that RA-specific autoantibodies can train monocytes in the inflamed lesion as early as the asymptomatic stage, which may not merely improve understanding of disease progression but may also suggest therapeutic and/or preventive strategies for autoimmune diseases.

Two ADP-glucose pyrophosphorylase subunits, OsAGPL1 and OsAGPS1, modulate phosphorus homeostasis in rice.

Plant acclimatory responses to phosphate (Pi) starvation stress include the accumulation of carbohydrates, namely sugar and starch. However, whether altered endogenous carbohydrate profile could in turn affect plant Pi starvation responses remains widely unexplored. Here, two genes encoding the large and small subunits of an ADP-glucose pyrophosphorylase (AGP) in rice (Oryza sativa), AGP Large Subunit 1 (AGPL1) and AGP Small Subunit 1 (AGPS1), were functionally characterized with regard to maintenance of phosphorus (P) homeostasis and regulation of Pi starvation signaling. AGPL1 and AGPS1 were both positively responsive to nitrogen (N) or Pi deprivation, and expressed in almost all the tissues except in the meristem and mature zones of root. AGPL1 and AGPS1 physically interacted in chloroplast, and catalyzed the rate-limiting step of starch biosynthesis. Low-N- (LN) and low-Pi (LP)-triggered starch accumulation in leaves was impaired in agpl1, agps1 and apgl1 agps1 mutants compared with the wild-type plants. By contrast, mutation of AGPL1 and/or AGPS1 led to an increase in the content of the major sugar, sucrose, in leaf sheath and root under control and LN conditions. Moreover, the Pi accumulation was enhanced in the mutants under control and LN conditions, but not LP conditions. Notably, the LN-induced suppression of Pi accumulation was compromised attributed to the mutation of AGPL1 and/or AGPS1. Furthermore, the increased Pi accumulation was accompanied by the specific suppression of OsSPX2 and activation of several Pi transporter genes. These results indicate that a balanced level of carbohydrates is vital for maintaining plant P homeostasis.

Bioremediation of intertidal zones polluted by heavy oil spilling using immobilized laccase-bacteria consortium.

Heavy oil pollution in the intertidal zones has become a worldwide environmental problem. In this study, bioremediation on heavy oil pollutants in the intertidal zones using an immobilized laccase-bacteria consortium system was evaluated with the aid of intertidal experimental pools built in the coastal area. It is found that degradation efficiency of the immobilized laccase-bacteria consortium for heavy oil was 66.5% after 100 days remediation, with the reaction rate constant of 0.018 d-1. Gas Chromatograph-Mass Spectrometer analysis shows that degradation efficiency of saturated hydrocarbons and aromatic hydrocarbons were 79.2% and 78.7%, which were 64.9% and 65.1% higher than control. It is further seen that degradation of long-chain n-alkanes of C26-C35 and polycyclic aromatic hydrocarbons with more than three rings were significant. Metagenomic analysis indicates that the immobilized laccase-bacterial consortium has not only increased the biodiversity of heavy oil degrading bacteria, but also accelerated the degradation of heavy oil.

High Specific Capacitance of the Electrodeposited MnO2 on Porous Foam Nickel Soaked in Alcohol and its Dependence on Precursor Concentration.

In this work, we used the mixed solution of manganese acetate and sodium sulfate to deposit manganese dioxide on the three-dimensional porous nickel foam that was previously soaked in alcohol, and then the effects of solution concentrations on their capacitance properties were investigated. The surface morphology, microstructure, elemental valence and other information of the material were observed by scanning electron microscope (SEM), Transmission Electron Microscope (TEM), X-ray photoelectron spectroscopy (XPS), etc. The electrochemical properties of the material were tested by Galvanostatic charge-discharge (GCD), Cyclic Voltammetry (CV), Chronoamperometry (CA), Electrochemical impedance spectroscopy (EIS), etc. The MnO2 electrode prepared at lower concentrations can respectively reach a specific capacitance of 529.5 F g-1 and 237.3 F g-1 at the current density of 1 A g-1 and 10 A g-1, and after 2000 cycles, the capacity retention rate was still 79.8% of the initial capacitance, and the energy density can even reach 59.4 Wh Kg-1, while at the same time, it also has a lower electrochemical impedance (Rs = 1.18 Ω, Rct = 0.84 Ω).

C8-Substituted Imidazotetrazine Analogs Overcome Temozolomide Resistance by Inducing DNA Adducts and DNA Damage.

Temozolomide (TMZ) is the standard of care chemotherapeutic agent used in the treatment of glioblastoma multiforme. Cytotoxic O6-methylguaine lesions formed by TMZ are repaired by O6-methyl-guanine DNA methyltransferase (MGMT), a DNA repair protein that removes alkyl groups located at the O6-position of guanine. Response to TMZ requires low MGMT expression and functional mismatch repair. Resistance to TMZ conferred by MGMT, and tolerance to O6-methylguanine lesions conferred by deficient MMR severely limit TMZ clinical applications. Therefore, development of new TMZ derivatives that can overcome TMZ-resistance is urgent. In this study, we investigated the anti-tumor mechanism of action of two novel TMZ analogs: C8-imidazolyl (377) and C8-methylimidazole (465) tetrazines. We found that analogs 377 and 465 display good anticancer activity against MGMT-overexpressing glioma T98G and MMR deficient colorectal carcinoma HCT116 cell lines with IC50 value of 62.50, 44.23, 33.09, and 25.37 µM, respectively. Analogs induce cell cycle arrest at G2/M, DNA double strand break damage and apoptosis irrespective of MGMT and MMR status. It was established that analog 377, similar to TMZ, is able to ring-open and hydrolyze under physiological conditions, and its intermediate product is more stable than MTIC. Moreover, DNA adducts of 377 with calf thymus DNA were identified: N7-methylguanine, O6-methylguanine, N3-methyladenine, N3-methylthymine, and N3-methylcytidine deoxynucleotides. We conclude that C8 analogs of TMZ share a mechanism of action similar to TMZ and are able to methylate DNA generating O6-methylguanine adducts, but unlike TMZ are able at least in part to thwart MGMT- and MMR-mediated resistance.

Anti-inflammatory effect of 4-methylcyclopentadecanone in rats submitted to ischemic stroke.

This study aimed to investigate the anti-inflammatory effect of 4-methylcyclopentadecanone (4-MCPC) in rats suffering from a cerebral ischemia/reperfusion (I/R) injury. In this study, the focal cerebral ischemia in rats was induced by middle cerebral artery occlusion (MCAO) for 2 h, and the rats were treated with 4-MCPC (8 mg/kg) just 0.5 h before reperfusion. The ischemic infarct volume was recorded 24 h after the MCAO. In addition, myeloperoxidase (MPO) activity and TNF-α and IL-1ß levels in the ischemic cerebral cortex were determined by ELISA, while nuclear translocation of NF-κB p65 subunit and expression of p-IκBα were investigated by Western blotting. Our results showed that 4-MCPC treatment decreased infarct volume significantly, compared with I/R group (16.8%±7.5% vs. 39.7%±10.9%); it reduced MPO activity (0.43 ± 0.10 vs. 1.00 ± 0.51 U/g) and expression levels of TNF-α (18.90 ± 3.65 vs. 35.87 ± 4.87 ng/g) and IL-1ß (1.68 ± 0.23 vs. 2.67 ± 0.38 ng/g) in ischemic brain tissues of rats. Further study revealed that 4-MCPC treatment markedly reduced nuclear translocation of NF-κB p65 subunit and expression of p-IκBα in ischemic cerebral cortex. Taken together, our results suggest that 4-MCPC protects against cerebral I/R injury and displays anti-inflammatory actions through inhibition of the NF-κB signal pathway.

A novel cycloartane triterpenoid from Cimicifuga induces apoptotic and autophagic cell death in human colon cancer HT-29 cells.

The extract from Cimicifuga, a genus of flowering plants, has been demonstrated to have mainly therapeutic effects on menstrual and menopausal symptoms and also exhibits immunomodulatory, anti-inflammatory and antimicrobial activity. Moreover, the anticancer effects of Cimicifuga have been reported, but the underlying mechanism causing cancer cell death has been poorly described. The present study was designed to investigate the antitumor effects and underlying molecular mechanisms of cimigenol (KY17), a novel cycloartane triterpenoid from Cimicifuga. KY17-induced autophagy and apoptotic cell death in human colon cancer cells (HT-29) was investigated. KY17 treatment induced growth inhibition and apoptotic cell death in a concentration-dependent manner. The induction of apoptosis was confirmed by a change in cell morphology, and an increase in the G2/M phase, as well as increased protein levels of cleaved-caspase-8 and -3; cleavage of poly(ADP-ribose) polymerase (PARP) in the HT-29 cells following KY17 treatment. In addition, autophagy was evaluated by the accumulation of acridine orange, the appearance of green fluorescent protein-light-chain 3 (LC3) punctate structures and increased levels of LC3-II protein expression. Furthermore, combination treatment with the autophagy inhibitor bafilomycin A1 enhanced the induction of apoptosis by KY17. Taken together, the present study provides new insight into the role of KY17 as a potential antitumor compound. Combination of KY17 with an autophagy inhibitor may be a valuable strategy for the chemoprevention or treatment of colon cancer.

The prognostic value of regional lymph node metastases in patients of Guangdong Province, China with differentiated thyroid cancer: A multicenter retrospective clinical study.

Although the prognostic value of nodal metastases in differentiated thyroid cancer remains controversial, it is of interest to evaluate and understand the different characteristics of predictive outcomes.A multicenter retrospective study was conducted in 215 untreated patients with differentiated thyroid cancer from July 1997 to July 2015 in 4 medical centers of Guangdong Province. A total of 107 patients with nodal metastases (group A) were compared to 108 patients without metastases (group B). The 5-year disease-free survival (DFS), overall survival (OS), and postoperative complications in both groups were calculated. Variables predictive of DFS and OS were evaluated in group A.The group A had lower 5-year DFS (69.16%, 11 months) and shorter median time of recurrence than those in group B (87.96%, 8.5 months, respectively, P < 0.001). The incidence of temporary hypoparathyroidism in group A is lower; whereas higher incidence of temporary unilateral vocal cord palsy, permanent hypoparathyroidism, permanent unilateral vocal cord palsy, and bilateral vocal cord palsy in group A were observed. Both univariate and multivariate analyses in group A revealed that age, pathological tumor node metastasis (pTNM) stage, and histology were related to DFS (P < 0.05); while pTNM stage and histology were related to OS only in univariate analyses.Positive nodal metastases have significant prognostic value in patients with differentiated thyroid cancer in Guangdong, China and primarily reduce DFS. Moreover, patients with positive nodal metastases who are >45 years and have higher pTNM stage or follicular histology tend to have poor prognosis. Selective lymph node dissection with appropriate postoperative treatment and frequent follow-up should be accorded to these vulnerable groups of patients.

Effects of adding bulking agent, inorganic nutrient and microbial inocula on biopile treatment for oil-field drilling waste.

Contamination from oil-field drilling waste is a worldwide environmental problem. This study investigated the performance of four bench-scale biopiles in treating drilling waste: 1) direct biopile (DW), 2) biopile plus oil-degrading microbial consortium (DW + M), 3) biopile plus microbial consortium and bulking agents (saw dust) (DW + M + BA), 4) biopile plus microbial consortium, bulking agents, and inorganic nutrients (Urea and K2HPO4) (DW + M + BA + N). Ninety days of biopiling removed 41.0%, 44.0%, 55.7% and 87.4% of total petroleum hydrocarbon (TPH) in the pile "DW", "DW + M", "DW + M + BA", and "DW + M + BA + N" respectively. Addition of inorganic nutrient and bulking agents resulted in a 56.9% and 26.6% increase in TPH removal efficiency respectively. In contrast, inoculation of hydrocarbon-degrading microorganisms only slightly enhanced the contaminant removal (increased 7.3%). The biopile with stronger contaminant removal also had higher pile temperature and lower pile pH (e.g., in "DW + M + BA + N"). GC-MS analysis shows that biopiling significantly reduced the total number of detected contaminants and changed the chemical composition. Overall, this study shows that biopiling is an effective remediation technology for drilling waste. Adding inorganic nutrients and bulking agents can significantly improve biopile performance while addition of microbial inocula had minimal positive impacts on contaminant removal.

Upregulation of H19 promotes invasion and induces epithelial-to-mesenchymal transition in esophageal cancer.

Long non-coding RNAs (lncRNAs) have previously been reported to be involved in cancer invasion, proliferation and apoptosis. However, the association between the lncRNA, H19, and esophageal cancer (EC) has remained elusive. In the present study, reverse transcription quantitative-polymerase chain reaction revealed that the expression of H19 was significantly increased and associated with tumor depth and metastasis in 133 EC samples. Furthermore, MTT and Transwell assays revealed that overexpression of H19 in vitro promoted the proliferation and invasion of EC cell lines, whereas knockdown of H19 inhibited the proliferation and invasion of EC cell lines. In addition, it was identified that an upregulation of H19 induced epithelial-to-mesenchymal transition, while the opposite effect was observed following the downregulation of H19. In conclusion, H19 has a significant role in the development of EC and may serve as a potential prognostic marker and therapeutic target for EC.

Efficacy and prognosis of neoadjuvant chemotherapy is correlated with breast cancer molecular classification.

Breast cancer is one of the most common cancers affecting women globally. Recent studies have begun to investigate the possibility of customized treatment options for individuals based on the specific cancer type. Here, we sought to analyze the relationship between the molecular classification of breast cancer and the efficacy and prognosis of neoadjuvant chemotherapy (NCT). The study included 100 breast cancer patients treated with an NCT regimen of epirubicin and docetaxel (ET) who were divided into groups based on cancer subtype (luminal, HER2 over-expression, and basal-like subtype). The nuclear classification, number of NCT cycles, pathological remission rate, and clinical curative effect, as well as the disease-free survival time (DFS) and the overall survival (OS), were compared across groups. The nuclear grade of participants in the basal-like group was significantly higher than those in the other groups but this group had fewer preoperative NCT cycles and lower pathological remission and clinical efficacy (Z=53.245, 50.077, 62.467, χ2=16.082, p<0.05). The OS and DFS of participants in the luminal subtype group were significantly higher than those in other groups while those in the basal-like subtype group were the lowest. The OS and DFS of participants who achieved pathological complete remission (pCR) through NCT treatment were significantly higher than those of the patients who had not achieved pCR through NCT treatment (χ2=9.558, 10.139, p<0.05). Therefore, we conclude that when NCT (ET regimen) is used in the treatment of breast cancer, the curative effects and prognosis appear to be correlated with the molecular classification of the tumor. Based on these results, clinicians should consider the molecular classification of the individual tumor to design the most effective treatment option.

Milk, yogurt, and lactose intake and ovarian cancer risk: a meta-analysis.

Inconclusive information for the role of dairy food intake in relation to ovarian cancer risk may associate with adverse effects of lactose, which has been hypothesized to increase gonadotropin levels in animal models and ecological studies. Up to now, several studies have indicated the association between dairy food intake and risk of ovarian cancer, but no identified founding was reported. We performed this meta-analysis to derive a more precise estimation of the association between dairy food intake and ovarian cancer risk. Using the data from 19 available publications, we examined dairy food including low-fat/skim milk, whole milk, yogurt and lactose in relation to risk of ovarian cancer by meta-analysis. Pooled odds ratio (OR) with 95% confidence interval (CI) were used to assess the association. We observed a slightly increased risk of ovarian cancer with high intake of whole milk, but has no statistical significance (OR = 1.228, 95% CI = 1.031-1.464, P = 0.022). The results of other milk models did not provide evidence of positive association with ovarian cancer risk. This meta-analysis suggests that low-fat/skim milk, whole milk, yogurt and lactose intake has no associated with increased risk of ovarian cancer. Further studies with larger participants worldwide are needed to validate the association between dairy food intake and ovarian cancer.

The alteration and clinical significance of Th1/Th2/Th17/Treg cells in patients with multiple myeloma.

Immunological T cells and associated cytokines have been shown to be involved in the pathogenesis of multiple myeloma (MM). However, the abnormal immune imbalance of T lymphocyte subsets on MM remains unknown. We investigate the proportions of T helper 1 (Th1)/Th2/Th17/T regulatory (Treg) cells in peripheral blood mononuclear cells (PBMCs) by flow cytometry (FCM), and serum levels of relevant cytokines in MM patients and controls were detected by enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expression of T-bet, STAT6, RORgammat, and Foxp3 was measured by real-time quantitative polymerase chain reaction (PCR). The CD4+ Th1 and CD4+ Th17 cells in patients with MM were significantly higher than those in health controls as well as the expression of T-bet and RORgammat mRNA. Furthermore, serum levels of interferon gamma (IFN-γ), IL-6, and IL-17A in MM group were greatly increased and significantly associated with each other. Significant differences on Th cells, cytokines, and transcription factors were observed on MM patients. The imbalance of T lymphocyte subsets was thought to contribute to the pathogenesis and underlying mechanisms of MM.

Synthesis and In-Vitro Cytotoxicity of (E)-N,2,3-Triarylacrylamide Derivatives as Analogs of Combretastatin A-4.

A new series of (E)-N,2,3-triarylacrylamide derivatives were designed and synthesized as potent anticancer agents. Cytotoxicity of the 26 target compounds was evaluated in vitro against six cancer cell lines (HCT116, A549, MDA-MB-468, HepG2, SKNMC and SK-OV-3) by Sulforhodamine B colorimetric assay. The most promising compound, 4h, was as potent as the reference drug cisplatin (DDP). Preliminary structure-activity relationship (SAR) data provided guidance for further design and discovery of (E)- N,2,3-triarylacrylamide scaffold anticancer agents.