Self-assembly of CXCR4 antagonist peptide-docetaxel conjugates for breast tumor multi-organ metastasis inhibition

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

Letrozole versus gonadotropin-releasing hormone antagonist during luteal phase in the prevention of ovarian hyperstimulation syndrome: a randomized controlled trial / 中华妇产科杂志

Objective@#To explore and compare the preventive effect of using letrozole and gonadotropin-releasing hormone (GnRH) antagonist during luteal phase of patients at high risk for ovarian hyperstimulation syndrome (OHSS).@*Methods@#A total of 99 infertile women undergoing in vitro fertilization and embryo transfer or intracytoplasmic sperm injection with high risk for OHSS were enrolled in this randomized controlled trial.The letrozole group (n=51) received letrozole of 7.5 mg daily for 3 days;the GnRH antagonist group (n=48) were given cetrorelix of 0.25 mg subcutaneously daily for 3 days. Both groups received support therapy combined with embryo cryopreservation. The incidence of OHSS was surveyed. And the serum concentration of estradiol, LH and progesterone on days 3, 5 and 8 after oocytes retrieval were measured.@*Results@#There were no statistical differences in terms of baseline characteristics of patients and outcomes of controlled ovarian hyperstimulation between the two groups.The incidence of moderate and severe OHSS was found no significantly difference between letrozole group [11.8%(6/51)] and GnRH antagonist group [10.4%(5/48);P>0.05]. The estradiol concentration of the indicated days on days 3,5 and 8 after oocytes retrieval in letrozole group and GnRH antagonist group were (1 417±3 543) versus (15 210±9 921) pmol/L, (1 692±4 330) versus (18 680±11 567) pmol/L, (239±336) versus (3 582±5 427) pmol/L, respectively;compared with GnRH antagonist group, the estradiol level was significantly lower in the letrozole group (all P<0.01). The luteinizing hormone level in the letrozole group were (0.46±0.40), (0.56±0.55)and (0.67±0.58) U/L on days 3,5 and 8 after oocytes retrieval, which were significantly higher than those of GnRH antagonist group [(0.28±0.28), (0.30±0.19) and (0.45±0.37) U/L, respectively; all P<0.05]. There was no obvious differences on progesterone levels between letrozole group and GnRH antagonist group (all P>0.05),and on days 8 after oocytes retrieval,the level of progesterone in each group were significantly lower than those on day 3 and 5 after oocytes retrieval (P<0.05).@*Conclusion@#Letrozole has the same efficiency as GnRH antagonist for the prevention of OHSS, faster and cheaper to use, but its efficacy seems not to be related to the suppression of steroidogenic during the luteal phase.

Letrozole versus gonadotropin-releasing hormone antagonist during luteal phase in the prevention of ovarian hyperstimulation syndrome: a randomized controlled trial / 中华妇产科杂志

Objective:To explore and compare the preventive effect of using letrozole and gonadotropin-releasing hormone (GnRH) antagonist during luteal phase of patients at high risk for ovarian hyperstimulation syndrome (OHSS).Methods:A total of 99 infertile women undergoing in vitro fertilization and embryo transfer or intracytoplasmic sperm injection with high risk for OHSS were enrolled in this randomized controlled trial.The letrozole group ( n=51) received letrozole of 7.5 mg daily for 3 days;the GnRH antagonist group ( n=48) were given cetrorelix of 0.25 mg subcutaneously daily for 3 days. Both groups received support therapy combined with embryo cryopreservation. The incidence of OHSS was surveyed. And the serum concentration of estradiol, LH and progesterone on days 3, 5 and 8 after oocytes retrieval were measured. Results:There were no statistical differences in terms of baseline characteristics of patients and outcomes of controlled ovarian hyperstimulation between the two groups.The incidence of moderate and severe OHSS was found no significantly difference between letrozole group [11.8%(6/51)] and GnRH antagonist group [10.4%(5/48); P>0.05]. The estradiol concentration of the indicated days on days 3,5 and 8 after oocytes retrieval in letrozole group and GnRH antagonist group were (1 417±3 543) versus (15 210±9 921) pmol/L, (1 692±4 330) versus (18 680±11 567) pmol/L, (239±336) versus (3 582±5 427) pmol/L, respectively;compared with GnRH antagonist group, the estradiol level was significantly lower in the letrozole group (all P<0.01). The luteinizing hormone level in the letrozole group were (0.46±0.40), (0.56±0.55)and (0.67±0.58) U/L on days 3,5 and 8 after oocytes retrieval, which were significantly higher than those of GnRH antagonist group [(0.28±0.28), (0.30±0.19) and (0.45±0.37) U/L, respectively; all P<0.05]. There was no obvious differences on progesterone levels between letrozole group and GnRH antagonist group (all P>0.05),and on days 8 after oocytes retrieval,the level of progesterone in each group were significantly lower than those on day 3 and 5 after oocytes retrieval ( P<0.05). Conclusion:Letrozole has the same efficiency as GnRH antagonist for the prevention of OHSS, faster and cheaper to use, but its efficacy seems not to be related to the suppression of steroidogenic during the luteal phase.

Identification of cryptic structural chromosomal aberrations in parents through detection of copy number variations in miscarriage tissues / 中华医学遗传学杂志

Objective@#To explore the genetic cause for abnormal pregnancies through detecting chromosomal copy number variations (CNVs) in abortic tissues by next generation sequencing (NGS).@*Methods@#NGS technique was used to detect CNVs in abortion tissues. Parental chromosomal karyotypes were predicted based on the results. The aberrant chromosomal segments of the parents were accurately mapped by G-banding karyotyping analysis and fluorescence in situ hybridization (FISH).@*Results@#In addition to numerical chromosomal aberrations, 12 microdeletion/microduplications were detected by NGS. For 8 families where both parents accepted chromosomal karyotyping, 4 carriers of chromosomal abnormalities were identified. One marker chromosome was missed by karyotyping analysis, and a mother was confirmed to carry a cryptic balanced translocation by FISH.@*Conclusion@#NGS can facilitate detection of cryptic chromosomal translocations in couples with repeated pregnancy failure and is of great value for detecting abnormal CNVs for its high sensitivity.

Identification of cryptic structural chromosomal aberrations in parents through detection of copy number variations in miscarriage tissues / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic cause for abnormal pregnancies through detecting chromosomal copy number variations (CNVs) in abortic tissues by next generation sequencing (NGS).@*METHODS@#NGS technique was used to detect CNVs in abortion tissues. Parental chromosomal karyotypes were predicted based on the results. The aberrant chromosomal segments of the parents were accurately mapped by G-banding karyotyping analysis and fluorescence in situ hybridization (FISH).@*RESULTS@#In addition to numerical chromosomal aberrations, 12 microdeletion/microduplications were detected by NGS. For 8 families where both parents accepted chromosomal karyotyping, 4 carriers of chromosomal abnormalities were identified. One marker chromosome was missed by karyotyping analysis, and a mother was confirmed to carry a cryptic balanced translocation by FISH.@*CONCLUSION@#NGS can facilitate detection of cryptic chromosomal translocations in couples with repeated pregnancy failure and is of great value for detecting abnormal CNVs for its high sensitivity.

Effects of rosiglitazone on the expression of nuclear factor-κB P65 and metalloproteinase-9 mRNA in peripheral blood monocyte-derived macrophages in patients with coronary artery disease / 中华急诊医学杂志

Objective To investigate the effects and mechanisms of rosiglitazone on the expressions of nuclear factor-κB and matrix metalloprotease (MMP-9) in peripheral blood monocyte-derived macrophages (MDMs) in patients with coronary heart disease. Method This was a clinical case-control study. Forty-eight actue coronary symdrome (ACS) patients (ACS group), and 20 patients with stable angina (SA) (control group) were collected. They were performed coronary arteriography in the Department of Cardiology of the Second Xiangya Hospital from March to April in 2007. Exclusion criteria included acute infection, trauma or surgery patients within four weeks, cerebral vascular accident, liver and kidney dysfunction, cancer, and so on. The peripheral blood mononuclear cells were isolated and transformed into MDMs with macrophage colony-stimulating factor treatment. The transformed MDMs were randomly assigned into subgrougs and incubated with 0 /μmol/L, 1 μmol/L, 10 μmol/L, 20 μmol/L of rosiglitazone respectively. The expressions of PPAR-γ mRNA, MMP-9 mRNA were determined by RT-PCR and nuclear factor-κB P65 (NF-KB P65) expression by immunohistochemistry. Multiple comparisons were examined for significant differences using analysis of variance (ANOVA). Results The basal expression of PPAR-y mRNA was lower, in contrast, the levels of NF-KB P65 and MMP-9 mRNA were higher in ACS group than control group. PPAR-γ mRNA expression were significantly upregulated in both ACS and control groups with rosiglitazone treatment. PPAR-γ mRNA expression was positive correlation, while the expressions of MMP-9 mRNA were negative correlation with the rosiglitazone concentration in the ACS group. Rosiglitazone inhibited the expression of NF-KB in a concentration-independent manner in ACS and control groups. Conclusions The expression of PPAR-y mRNA is inhibited, while the activity of NF-KB and expression of MMP-9 mRNA are enhanced in MDMs of ACS cases. Rosiglitazone intervention may inhibit NF-KB activity and MMP-9 expression by upregulation of PPAR-y expression in MDMS of patiens with ACS.

Study on the level of placental urocortin and corticotropin-releasing hormone receptor 2? of preeclampsia / 中华妇产科杂志

Objective To determine the relation between the expression of urocortin and corticotropin-releasing hormone receptor 2? (CRH-R2?) in the placenta and pathogenesis of preeclampsia. Methods Placentas were collected from 20 pregnant women with preeclampsia as study group and 20 normal pregnant women as control group. Urocortin mRNA and CRH-R2? mRNA were measured by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Urocortin peptide was measured by immunohistochemistry. Results (1) The mRNA expression of urocortin was significantly higher (P

Level of urocortin mRNA during labor and eff ect of urocortin on myometrial contractility in vitro / 中华妇产科杂志

Objective To examine the expression of urocortin mRNA during labor and the effect of uroco rtin on myometrial contractility, and to investigate its role in the onset and p rogress of labor. Methods (1) Semi-quantitative reverse transcription-polymerase chain reaction (RT -PCR),using ?-actin as internal standard was applied to determine the levels of urocortin mRNA in human placenta and myometrium from the group of cesarean se ction before (10 cases) and during (10 cases in latent phase and 10 cases in act ive phase) labor.(2) The isolated myometrial strips of pregnant women (n=24 ) were prepared.The effects of urocortin with or without prostaglandin F 2? (PGF 2?) and oxytocin on myometrial contractility were evaluated by area s under the curve. Results (1) Semi-quantitative RT-PCR showed that the expression level of urocortin mRN A in placenta and myometrium after the onset of labor were higher than before la bor (1.23 ?0.52, 1.32?0.22; 0.83?0.38, 0.94?0.13, respectively, P0.05). Conclusion The study indicates urocortin may indirectly m odulate myometrial contractility during labor.