Effect of intravenous anesthetic drugs on fertilization rate in oocyte retrieval.

BACKGROUND: The purpose of this study was to investigate the effects of intravenous anesthetic drugs on fertilization rate in subjects receiving oocyte retrieval by assisted reproduction technology (ART). METHODS: A retrospective cohort study was designed. The clinical information of subjects who received oocyte retrieval procedure was collected. The subjects were divided into two groups based on the type of anesthesia used: the no-anesthesia group and the intravenous anesthesia group. Propensity score matching (PSM) was performed and multiple linear regression analyses were conducted. Fertilization rate was compared between the two groups before and after PSM. RESULTS: A total of 765 subjects were divided into two groups: the no-anesthesia group (n = 482) and the intravenous anesthesia group (n = 283). According to propensity scores, 258 pairs of subjects were well matched, and the baseline data between the two groups were not significantly different (P > 0.05). Fertilization rate was 77% in the intravenous anesthesia group, and 76% in the no-anesthesia group, without significant between-group difference (P = 0.685). Before matching, Poisson regression analysis showed no effect of intravenous anesthetic drugs on fertilization rate (RR = 0.859, 95%CI: 0.59 to 1.25, P = 0.422). After matching, no difference was found either (RR = 0.935, 95%CI: 0.67 to 1.29, P = 0.618). CONCLUSION: Intravenous anesthetic drugs may exert no effects on fertilization rate in subjects receiving ART.

Exploring the Dual Functions of Distal Acyl Group Direction in Various Nucleophilic Environments.

A universal glycosylation strategy could significantly simplify glycoside synthesis. One approach to achieving this goal is through acyl group direction for the corresponding 1,2-, 1,3-, 1,4-, or 1,6-trans glycosylation; however, this approach has been challenging for glycosidic bonds that require distal equatorial-acyl group direction. We developed an approach in weakly nucleophilic environments for selective 1,4-trans glycosylation directed by the equatorial-4-O-acyl group. Here, we explored this condition in other distal acyl groups and found that, besides 1,n-trans direction, acyl groups also mediated hydrogen bonding between acyl groups and alcohols. The latter showed a diverse effect and classified the acyl group direction into axial and equatorial categories. Corresponding glycosylation conditions were distinguished as guidance for acyl group direction from either category. Hence, acyl group direction may serve as a general glycosylation strategy.

ß-l-Rhamnosylation and ß-d-Mannosylation Mediated by 4-O-Ester Groups in a Weakly Nucleophilic Environment.

eq-4-O-Acyl group directed ß-rhamnosylation and ß-mannosylation are achieved in a carborane or BARF anion formed weakly nucleophilic environment with the assistance of a 2,3-orthocarbonate group. The 4-O-acyl group plays a critical role in directing the ß-selectivity, and the weakly coordinating anion is essential to amplify this direction. The orthocarbonate group could be readily removed with 1,3-propanediol in the presence of BF3·Et2O.

Effect of topical antibiotics on the prevention and management of wound infections: A meta-analysis.

A meta-analysis research was implemented to appraise the effect of topical antibiotics (TAs) on the prevention and management of wound infections (WIs). Inclusive literature research was performed until April 2023, and 765 interconnected researches were reviewed. The 11 selected researches included 6500 persons with uncomplicated wounds at the starting point of the research: 2724 of them were utilising TAs, 3318 were utilising placebo and 458 were utilising antiseptics. Odds ratio (OR) and 95% confidence intervals (CIs) were utilised to appraise the consequence of TAs on the prevention and management of WIs by the dichotomous approach and a fixed or random model. TAs had significantly lower WI compared with placebo (OR, 0.59; 95% CI, 0.38-0.92, p = 0.02) and compared with antiseptics (OR, 0.52; 95% CI, 0.31-0.88, p = 0.01) in persons with uncomplicated wounds (UWs). TAs had significantly lower WIs compared with placebo and antiseptics in persons with UWs. However, caution needs to be taken when interacting with their values because of the low sample size of some of the chosen researches and low number of researches found for the comparisons in the meta-analysis.

Effects of lung-protective ventilation strategy on lung aeration loss and postoperative pulmonary complications in moderate-risk patients undergoing abdominal surgery.

BACKGROUND: There is a controversy about whether the use of a lung-protective ventilation strategy(LPVS) can reduce the incidence of postoperative pulmonary complications (PPCs) and improve the clinical outcomes in moderate-risk patients were assessed by the Assess Respiratory Risk in Surgical Patients in Catalonia(ARISCAT). METHODS: One hundred moderate-risk patients predicted by the ARISCAT, scheduled to undergo abdominal surgery were randomized into two groups: conventional ventilation strategy group (G0) and lung-protective ventilation strategy group (G1). Lung ultrasonography (LUS) and the LUS score were performed before induction of anesthesia (T0), 30min after extubation (T1), and 24h (T2), 72h (T3) after surgery. The incidence and severity of PPCs within the postoperative 7 days, the duration of postoperative oxygen supplementation, and postoperative hospital stay (PHS) were recorded. RESULTS: The LUS score of both groups at T1-3 was higher than those at T0 (P<0.05), moreover, the LUS score of G1 was lower than that of G0 at T1-3. The incidence of PPCs of G1 (10.9%) was lower than that of G0 (29.8%) (relative risk, 0.37; 95% confidence interval [CI], 0.14 to 0.93; P=0.02) and the severity of PPCs of G1 were lower than those of G0 (P<0.05). The PHS of G1 was less than that of G0 (8[7-10] vs. 9[8-11], P<0.05). CONCLUSIONS: The LPVS can decrease lung aeration loss assessed by LUS and reduce the incidence of PPCs in moderate-risk patients.

Lidocaine inhibits the proliferation and metastasis of epithelial ovarian cancer through the Wnt/ß-catenin pathway.

BACKGROUND: Lidocaine, an amide local anesthetic, has recently been found to have anticancer action in various cancer cells. However, the role of lidocaine in epithelial ovarian cancer (EOC) remains largely unknown. In the present study, we investigated how lidocaine regulates the progression of EOC. METHODS: Real-time polymerase chain reaction was used to examine the expression of Snail, Wnt, ß-catenin, E-cadherin, vimentin, matrix metalloproteinase (MMP)-7, MMP-9, and vascular endothelial growth factor in lidocaine-treated cells. Cell proliferation assays, cell apoptosis assays, and cell migration assays were employed to verify the function of lidocaine in EOC cells. Cell proliferation and cell migration assays were employed to verify the function of Wnt/ß-catenin signaling in lidocaine-treated EOC cells together with Wnt-overexpressing plasmids or inhibitor NVP-XAV939. RESULTS: Lidocaine could inhibit proliferation, migration, and invasion, and induce apoptosis in ovarian cancer cells lines in a dose-dependent manner. Wnt/ß-catenin signaling was involved in the suppression of epithelial-mesenchymal transition progression of ovarian cancer cells, which resulted in the downregulation of Snail and vimentin, as well as the upregulation of E-cadherin. Furthermore, overexpressed Wnt could reverse the carcinostatic effect of lidocaine, while Wnt inhibitor XAV-939 synergistically enhanced the antitumor effect of lidocaine. CONCLUSIONS: Mechanistically, lidocaine could inhibit the proliferation and metastasis of EOC by the Wnt/ß-catenin pathway to regulate the progression of EOC.

Ultrasound-Guided Rectus Sheath Block Combined with Butorphanol for Single-Incision Laparoscopic Cholecystectomy: What is the Optimal Dose of Ropivacaine?

PURPOSE: In recent years, ultrasound-guided rectus sheath block (RSB) has been widely used in postoperative analgesia of abdominal operation. However, there is no uniform standard for the optimal dose of local anesthetics (LA) under ultrasound-guided rectus sheath block. This study aimed to determine the dose of ropivacaine combined with butorphanol that is effective in 50% (ED50) and 95% (ED95) of subjects for successful pain-free ultrasound-guided RSB in single-incision laparoscopic cholecystectomy (SILC). PATIENTS AND METHODS: Twenty-four patients scheduled to undergo single-incision laparoscopic cholecystectomy received an ultrasound-guided RSB. The initial dose of ropivacaine injected was 1.7 mg/kg, which was subsequently increased or decreased by 0.2 mg/kg, depending on whether the previous patient was free from pain (numeric rating scale (NRS) score of incisional pain at rest within 12 h after operation ≤ 3). All patients were treated with butorphanol 0.02 mg/kg as preemptive analgesia. The ED50 and ED95 were calculated using a probit regression model. RESULTS: The ED50 and ED95 of ropivacaine combined with butorphanol in ultrasound-guided rectus sheath block for analgesia in SILC, which were calculated by the probit regression model, were 0.719 mg/kg (95% confidence interval (CI), 0.553 mg/kg-0.873 mg/kg) and 0.967 mg/kg (95% CI, 0.835 mg/kg-1.91 mg/kg), respectively. CONCLUSION: As part of a multimodal analgesia strategy, a dose of 0.719 mg/kg ropivacaine provided successful RSB under ultrasound guidance in 50% of the patients who underwent SILC. A dose of 0.967 mg/kg would be successful in 95% of patients.

Perioperative Analgesic Effects of Preemptive Ultrasound-Guided Rectus Sheath Block Combined with Butorphanol or Sufentanil for Single-Incision Laparoscopic Cholecystectomy: A Prospective, Randomized, Clinical Trial.

PURPOSE: Pain after single-incision laparoscopic cholecystectomy (SILC), especially visceral pain, often troubles patients and doctors. Whether preemptive butorphanol can relieve visceral pain in patients undergoing SILC remains unknown. The goal of this study was to assess the efficacy of ultrasound-guided bilateral rectus sheath block (RSB) and butorphanol for perioperative analgesia in patients undergoing SILC. PATIENTS AND METHODS: Fifty-eight patients who met the criteria were randomly divided into two groups, both of which were given preemptive RSB. Patients were given either butorphanol 0.02mg/kg (group B, n=29) or sufentanil 0.1 µg/kg (group S, n=29) as preemptive analgesia. The primary outcome was the cumulative frequency of rescue analgesic request within 24 hours after operation. Secondary outcomes were numeric rating scale (NRS) scores (from 0 to 10) of incisional pain and visceral pain, the length of hospital stay and the incidence of postoperative adverse events. RESULTS: The frequency of postoperative rescue analgesic request of group S was significantly higher than that of group B (P=0.021). The NRS scores for visceral pain were lower in group B at 2, 6 and 12 hours after surgery than in group S (both P<0.001). The occurrence of postoperative nausea and vomiting (PONV) was significantly higher in group S. There were no significant differences between two groups for other outcomes. CONCLUSION: Butorphanol can provide sufficient visceral pain treatment after SILC than the dose of sufentanil in equal analgesic effect.

Superparamagnetic iron oxide nanoparticle-mediated expression of miR-326 inhibits human endometrial carcinoma stem cell growth.

Background: Previously, our group confirmed the presence of a subset of cancer stem cells in the tissues of endometrial carcinoma (ie, human endometrial carcinoma stem cells [HuECSCs]). However, the mechanisms by which microRNAs regulate the growth of HuECSCs remain elusive. Methods: We loaded miR-326 onto superparamagnetic iron oxide nanoparticles (miR-326@SPION) and transfected them into HuECSCs. Results: In the present study, we found that the expression levels of members of the G-protein coupled receptor 91 (GPR91)/signal transducer and activator of transcription 3 (STAT3)/vascular endothelial growth factor (VEGF) pathway were significantly elevated in CD44+/CD133+ HuECSCs. Luciferase reporter assays indicated that the succinate receptor 1 (SUCNR1) gene, also known as the G-protein coupled receptor 91 (GPR91) gene, was one of the potential targets of miR-326. Transmission electron microscopy revealed that the SPIONs could cross the cell membrane and accumulate in the cytoplasm. The overexpression of miR-326 significantly inhibited the proliferation and cell cycle progression of HuECSCs in vitro. MiR-326 overexpression also effectively inhibited the invasion and angiogenic capacities of HuECSCs in the extracellular matrix. Meanwhile, miR-326 overexpression significantly inhibited the tumorigenicity and tumour neovascularization capacity of HuECSCs in nude mice. Both quantitative real-time PCR and Western blotting confirmed that overexpression of miR-326 significantly reduced the expression of members of the GPR91/STAT3/VEGF pathway in HuECSCs, and the activity (level of phosphorylation) of key molecules in this pathway was also reduced. Conclusion: Collectively, we confirmed that SPIONs are highly efficient nanocarriers for nucleic acids, on which the loading of miR-326 inhibited the activation of the GPR91/STAT3/VEGF signaling pathway and significantly attenuated the activity of stem cells in endometrial carcinoma, both in vitro and in vivo.

Can apneic oxygen insufflation become a novel lung protective ventilation strategy? A randomized, controlled, blinded, single center clinical trial.

OBJECTIVE: The aim of this study was to determine whether a AOI strategy on non-ventilated lung could reduce the regional and systemic proinflammatory cytokine and oxidative stress response associated with esophagectomy, and to evaluate whether AOI can be used as a novel lung protective ventilation strategy. Its impact on oxygenation after OLV, surfactant protein A, B, C (SP-A, B, C), postoperative hospital stay and postoperative pulmonary complications (PPCs) was also evaluated. METHODS: Fifty-four adults (ASA II-III) undergoing esophagectomy with OLV were enrolled in the study. Patients were randomly assigned into 2 groups: control group (group C) and treated group (group T). Group C was treated with traditional OLV mode,while group T was given AOI of 5 L/min oxygen on the non-ventilated lung immediately at the beginning of OLV. Arterial blood gas was analyzed before and after OLV. A bronchoalveolar lavage(BAL) was performed after OLV on the non-ventilated lung. Proinflammatory cytokine, oxidative stress markers(TNF-α, NF-κB,sICAM-1,IL-6,IL-10,SOD,MDA) and SP-A, B, C were analyzed in serum and BALF as the primary endpoint.The clinical outcome determined by PPCs was assessed as the secondary endpoint. RESULTS: Patients with AOI had better oxygenation in the recovery period, oxygenation index(OI) (394[367-426] and 478[440-497]mmHg, respectively) of group T at T2 and T3 were significantly higher than those (332[206-434] and 437[331-512]mmHg, respectively) of group C. OLV resulted in an increase in the measured inflammatory markers in both groups, however, the increase of inflammatory markers upon OLV in the group C was significantly higher than those of group T. OLV resulted in an increase in the measured SP-A, B, C in serum of both groups. However, the levels of SP-A, B, C of group T were lower than those of group C in serum after OLV, and the results in BALF were the opposite. The BALF levels of SOD(23.88[14.70-33.93]U/ml) of group T were higher than those(15.99[10.33-24.16] U/ml) of group C, while the levels of MDA in both serum and BALF of group T(8.60[4.14-9.85] and 1.88[1.33-3.08]nmol/ml, respectively) were all lower than those of group C (11.10[6.57-13.75] and 1.280[1.01-1.83]nmol/ml) after OLV. There was no statistical difference between the two groups in terms of postoperative hospital stay and the incidence of PPCs. CONCLUSION: AOI on non-ventilated lung during OLV can improve the oxygenation function after OLV, relieve the inflammatory and oxidative stress response in the systemic and non-ventilated lung after OLV associated with esophagectomy. TRIAL REGISTRATION: ChiCTR-IOR-17011037 . Registered on 31 March 2017.

A facile approach for synthesis of nano-CeO2 particles loaded co-polymer matrix and their colossal role for blood-brain barrier permeability in Cerebral Ischemia.

A prospective resource of pharmacological treatment of ischemic brains stroke is rapid interference using potential neuroprotective materials. Cerium oxide nanoparticles have been shown to defend against blood brain barrier damage in cerebral ischemic brain stroke. While cerium oxide nanoparticles is highly permeable across the blood-brain barrier and also these nanoparticles are effective antioxidants, due to its ability to either donate or obtain electrons with alternative +3 and +4 valence states. This oxidation state of cerium oxide has shown efficiency in neutralizing generated free radicals in biological systems has been explored action for cerebral ischemic brain stroke. The nanoparticles are encapsulated on the poly-(lactide-co-glycolide)-polyethyleneglycol copolymer matrixes as nanoparticulate delivery vehicles and it can be enhanced brain targeted drug delivery. Furthermore, the results of spectroscopic and microscopic analysis confirmed that peripheral PEG-PLGA co-polymer chains provide excellent reactivity with nanoparticles which might improve the interface bonds of the nanocomposite formation. Mainly, neuroprotective properties of prepared CeO2-PEG/PLGA matrixes with and without nanoparticles are comparatively studied by using transient middle cerebral artery occlusion (MCAO) model of brain stroke. The prepared CeO2 nanoparticles combined with effective PEG/PLGA matrixes exhibited greater efficacy resulted in a lessening of focal ischemia by 60% and 78% decrease in brain edema in comparable to the control animals. The results are demonstrated that the neuroprotective efficiency of CeO2 nanoparticles with PEG/PLGA has enhanced and primarily protected the brain cortex areas from ischemic damage.

Patient-controlled Intravenous Analgesia With Combination of Dexmedetomidine and Sufentanil on Patients After Abdominal Operation: A Prospective, Randomized, Controlled, Blinded, Multicenter Clinical Study.

OBJECTIVE: To investigate the effect of combination of dexmedetomidine and sufentanil on patient-controlled intravenous analgesia (PCIA) in patients after abdominal operation and to assess the safety and validity of this treatment. METHODS: This is a prospective, randomized controlled, blinded, multicenter clinical study. A total of 210 patients from 9 clinical research centers underwent selective abdominal operation with general anesthesia were enrolled in the study, including laparoscopic-assisted abdominal operation on stomach, intestines or open surgery on stomach, intestines, kidneys and liver, the American Society of Anesthesiologists status I to II. Patients were randomly assigned into 2 groups: control group (group C) sufentanil 100 µg+normal saline 100 mL in total and test group (group D) sufentanil 100 µg+ dexmedetomidine 200 µg+normal saline 100 mL in total. PCIA was set as follow: background infusion of sufentanil 2 µg/h, bolus dose of sufentanil 2 µg, lockout interval 5 minutes. Main measure indices were analgesic consumption, pressing times and effective pressing times of analgesic pump, usage count, and consumption of remedy drug. Validity indices were visual analog scale (VAS) scores and patient satisfaction. Drug safety indices were hemodynamic parameters, drug side effects, and anal exhaust time. RESULTS: In total, 203 cases were analyzed. Seven cases were eliminated for incomplete data record. The total consumption of sufentanil (µg) in 24 hours after operation of group C and group D were 56.9±21.5 and 49.8±15.5, respectively, and the difference was statistically significant (P<0.05). Pressing times of analgesic pump in 24 hours after operation of group C and group D were 9.47±16.07 and 5.02±5.56 times, respectively, and the difference was statistically significant (P<0.05). Effective pressing times of analgesic pump in 24 hours after operation of group C and group D were 7.8±9.7 and 4.57±5.02 times, respectively, and the difference was statistically significant (P<0.05). Resting VAS scores and movement VAS scores at 2, 4, 8, and 24 hours postoperatively were statistically different (P<0.05). Usage times of rescue drug (pethidine) of group C and group D were 9 and 1, mean rank 118.13 and 85.71, respectively, and the difference was statistically significant (P<0.05). Mean rank of general satisfaction of group C and group D were 98.99 and 105.04, respectively, and the difference was statistically significant (P<0.05). Incidence rate of nausea in group C and group D within 24 hours after surgery was 25% and 12.5%, and of vomiting 18.2% and 6.25%, respectively and of vomiting and the difference was statistically significant. CONCLUSIONS: Compared with sufentanil PCIA alone, the combination of dexmedetomidine and sufentanil for PCIA after abdominal operation could reduce sufentanil consumption, decrease VAS scores, lower the rate of nausea and vomiting, and improve patient satisfaction.

Sedative effect of dexmedetomidine in spinal-epidural anesthesia on hysteromyomectomy.

To investigate the sedative effect of dexmedetomidine in spinal-epidural anesthesia on hysteromyomectomy a total of 100 hysteromyomectomy patients were randomly divided into the control group and the observation group with 50 in each group. Patients in the control group received the general anesthesia, while those in the observation group received spinal-epidural anesthesia, and intravenous injection of dexmedetomidine. For maintenance of anesthesia, ropivacaine was adopted for both groups. Before anesthesia, at 30 min and 60 min after anesthesia, we measured the heart rate (HR), bispectral index (BIS) and sedative effect. Before anesthesia, HR, BIS and Ramsay scores were compared between two groups, and the results showed that differences had no statistical significance (p>0.05); but at 30 min after anesthesia, HR and BIS of patients in the observation group were significantly lower than those in the control group (p<0.05), and Ramsay score was higher than the control group (p<0.05). No statistical significance was found in differences of the incidence rate of adverse reactions between two groups (p>0.05). Application of dexmedetomidine in spinal-epidural anesthesia gains promising sedative effect and safety in hysteromyomectomy, which is worthy of being promoted in clinical treatment.

Up-regulation of miR-370-3p restores glioblastoma multiforme sensitivity to temozolomide by influencing MGMT expression.

MicroRNAs (miRNA) are believed to play an important role in glioblastoma multiforme (GBM)chemotherapy. Our study aims to investigate potential miRNA biomarkers in GBM. Sixty GBM patients, which were given temozolomide (TMZ) chemotherapy and recurrent radiotherapy, were recruited. miRNA array was performed in cancerous and in paired normal tissues. Microarray results were further validated by a quantitative real-time PCR in selected tissues and GBM cell lines. TMZ resistance cells were developed and cell proliferation along with colony formation assays was determined. Our study employed H2AX formation and flow cytometry to analyse the role of miRNA in DNA damage and apoptosis. Our study illustrated 16 miRNA in which 9 were up-regulated and 7 down-regulated. and their differential expression were demonstrated in a recurrent GBM tissue. Among them, miRNA-370-3p demonstrated the highest level of down- regulation in tissues and in TMZ resistance cells. miRNA-370-3p mimic increased its expression and sensitivity of GBM cells to TMZ by suppressing the self-reparative ability of tumour cell DNA. O(6)-methylguanine-DNA methyltransferase (MGMT) was identified as the direct target gene of miR-370-3p, and it was found to be inversely correlated with miR-370-3p expression in tissue samples obtained. Thus, our study demonstrated a critical clinical role of an up-regulated miR-370-3p expression in glioblastoma multiforme chemotherapy sensitivity.

The direct electrophilic cyanation of ß-keto esters and amides with cyano benziodoxole.

The direct electrophilic α-cyanation of ß-keto esters and amides has been developed using a hypervalent iodine benziodoxole-derived cyano reagent. The procedure is accomplished within 10 min and without the use of any catalyst in DMF, at room temperature. Thus, the highly functionalized quaternary carbon-centered nitriles were produced in high to excellent yields.

MicroRNA-134 suppresses endometrial cancer stem cells by targeting POGLUT1 and Notch pathway proteins.

We aimed to ascertain the role of microRNAs (miRNAs) in regulating human endometrial cancer stem cells (HuECSCs). The expression level of miRNA-134 (miR-134), a member of the DLK1-DIO3 genomic imprinted miRNA cluster, differed significantly between HuECSCs and human endometrial cancer cells (HuECCs). miR-134 inhibited HuECSCs proliferation and migration by targeting protein O-glucosyltransferase 1 (POGLUT1) expression. Exogenous miR-134 overexpression downregulated POGLUT1 and Notch pathway proteins in HuECSCs in vitro. miR-134 overexpression affected the G2/M phase of HuECSCs and suppressed the growth of xenograft tumours formed. Thus, endogenous miR-134 regulation in HuECSCs may suppress tumourigenesis in human endometrial carcinoma.

Cisplatin targets the stromal cell-derived factor-1-CXC chemokine receptor type 4 axis to suppress metastasis and invasion of ovarian cancer-initiating cells.

In ovarian cancer, CD44+/CD117+ stem cells, also known as cancer-initiating cells (CICs), are highly proliferative and invasive. Therefore, the CD44+/CD117+ subpopulation is thought to be an important target for novel therapeutic strategies. In this study, we investigated the effects of cisplatin (CDDP) on metastasis and invasion suppression of ovarian CICs by targeting the CXC chemokine receptor-4 (CXCR4) signaling pathway in vitro and in vivo. CD44+/CD117+ ovarian CICs were enriched from human primary ovarian tumor tissues and confirmed by flow cytometry sorting. A 3-(4,5-dimethylthiazol-2-yl)-2.5-dipheny-tetrazolium bromide (MTT) assay revealed significant inhibition of proliferation of ovarian CICs with increasing CDDP drug concentrations. Moreover, colony formation and transwell migration assays indicated that CDDP significantly suppressed the invasive capacity of ovarian CICs in vitro. The expression levels of stromal cell-derived factor (SDF)-1, CXCR4, matrix metalloproteinase (MMP) 2, and MMP9 mRNA and protein levels were significantly reduced in CDDP-treated cells compared to untreated ovarian CICs. Furthermore, xenograft experiments confirmed that CDDP suppressed the growth of xenograft tumors formed by ovarian CICs in vivo. In addition, CXCR4 agonist (diprotin A) treatment of ovarian CICs weakened the effects of CDDP and enhanced SDF-1-CXCR4 axis expression in ovarian CICs. Thus, the SDF-1-CXCR4 axis is an important mediator of proliferation and invasion in CXCR4-overexpressing ovarian cancer-initiating cells (OCICs). Furthermore, CDDP inhibits invasion and metastasis of OCICs by targeting SDF-1-CXCR4 axis expression.

Microarray analysis of microRNA expression patterns in the semen of infertile men with semen abnormalities.

MicroRNAs (miRNAs) play a crucial role in tissue development and the pathology of many diseases, however, the effects and roles of miRNAs in the development of semen abnormalities in infertile males have not yet been investigated. In this study, we analyzed and compared the miRNA expression profiles of abnormal semen from 86 infertile males with normal semen from 86 healthy males using an miRNA microarray. In total, 52 miRNAs were differentially expressed between the abnormal semen of infertile males and the normal semen of healthy males. The differential expression of selected miRNAs was validated by real time qRT-PCR and northern blotting: miR-574-5p, miR-297, miR-122, miR-1275, miR-373, miR-185 and miR-193b were upregulated (fold change>1.5, p<0.001) and miR-100, miR-512-3p, miR-16, miR-19b, miR-23b and miR-26a were downregulated (fold change<0.667, p<0.001) in the semen of infertile males with semen abnormalities. In conclusion, this study provides new insights into specific miRNAs that are associated with semen abnormalities in infertile males.

Isolation and characterization of proliferative, migratory and multidrug-resistant endometrial carcinoma-initiating cells from human type II endometrial carcinoma cell lines.

Although the highly proliferative, migratory and multidrug resistant phenotype of human type II endometrial carcinoma (EC) is well characterized, improved clinical treatments have not yet been developed. In this study, CD44 and CD133 were used as markers to screen, isolate and enrich carcinoma-initiating cells (CICs) from the human type II EC cell lines KLE and ANCA3. Using flow cytometry, we identified a subpopulation of KLE and ANCA3 cells which express high levels of both CD44 and CD133 on the cell membrane. CD44+/CD133+ EC-CICs exhibited high levels of stemness marker genes, and possessed a higher migratory and invasive ability than CD44-/CD133- endometrial carcinoma cells (EC-CCs). CD44+/CD133+ EC-CICs were also more resistant to growth inhibition induced by the chemotherapeutic drugs cisplatin and paclitaxel. Additionally, CD44+/CD133+ EC-CICs readily established tumors in vivo in a relatively short time. In conclusion, CD44+/CD133+ cells possessing the characteristics of CICs can be reliably sorted from KLE and ANCA3 human type II EC cell lines, and represent a valuable model for studying cancer cell physiology and multidrug resistance. Further characterization of CD44+/CD133+ KLE and ANCA3 cells may have a profound impact on the selection of individual treatment strategies, clinical outcomes and design of the next generation of chemotherapeutic agents for type II EC.

MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells.

In ovarian cancer, CD44(+) /CD117(+) stem cells, also known as cancer-initiating cells (CICs), are highly proliferative, have a low degree of differentiation, and are resistant to chemotherapeutics. Therefore, the CD44(+) /CD117(+) subpopulation is thought to be an important target for novel therapeutic strategies. In this study, we investigated the role of microRNA-199a (miR-199a) in ovarian cancer stem cells. Luciferase reporter gene assays confirmed that miR-199a targets CD44 via an miR-199a-binding site in the 3'-UTR. CD44(+) /CD117(+) ovarian CICs were enriched from human primary ovarian tumor tissues and confirmed by flow cytometric sorting. miR-199a was cloned and transfected into ovarian CICs. CD44 mRNA and protein expression was significantly decreased in miR-199a-transfected ovarian CICs as compared with miR-199a mutant-transfected and untransfected cells. Cell cycle analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide proliferation assays, the colony formation assay and the transwell migration assay indicated that miR-199a significantly affected cell cycle regulation and suppressed the proliferation and invasive capacity of ovarian CICs in vitro. miR-199a significantly increased the chemosensitivity of ovarian CICs to cisplatin, pacitaxel, and adriamycin, and reduced mRNA expression of the multidrug resistance gene ABCG2 as compared with miR-199a mutant-transfected and untransfected cells. The expression of stemness markers was also significantly reduced in miR-199a-transfected CICs as compared with miR-199a mutant-transfected and untransfected ovarian cells. Furthermore, xenograft experiments confirmed that miR-199a suppressed the growth of xenograft tumors formed by ovarian CICs in vivo. Thus, expression of endogenous mature miR-199a may prevent tumorigenesis in human ovarian cancer by regulating expression of its target gene CD44.