Isolation and Biological Evaluation of Alfa-Mangostin as Potential Therapeutic Agents against Liver Fibrosis.

The increased proliferation and activation of hepatic stellate cells (HSCs) are associated with liver fibrosis development. To date, there are no FDA-approved drugs for the treatment of liver cirrhosis. Augmentation of HSCs apoptosis is one of the resolutions for liver fibrosis. In this study, we extracted α-mangostin (1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9H-xanthen-9-one) from the fruit waste components of mangosteen pericarp. The isolated α-mangostin structure was determined and characterized with nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) and compared with those known compounds. The intracellular signaling pathway activities of α-mangostin on Transforming growth factors-beta 1 (TGF-ß1) or Platelet-derived growth factor subunit B (PDGF-BB) induced HSCs activation and were analyzed via Western blot and Real-time Quantitative Polymerase Chain Reaction (Q-PCR). α-Mangostin-induced mitochondrial dysfunction and apoptosis in HSCs were measured by seahorse assay and caspase-dependent cleavage. The in vivo anti-fibrotic effect of α-mangostin was assessed by carbon tetrachloride (CCl4) treatment mouse model. The data showed that α-mangostin treatment inhibited TGF-ß1-induced Smad2/3 phosphorylation and alpha-smooth muscle actin (α-SMA) expression in HSCs in a dose-dependent manner. Regarding the PDGF-BB-induced HSCs proliferation signaling pathways, α-mangostin pretreatment suppressed the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38. The activation of caspase-dependent apoptosis and dysfunction of mitochondrial respiration (such as oxygen consumption rate, ATP production, and maximal respiratory capacity) were observed in α-mangostin-treated HSCs. The CCl4-induced liver fibrosis mouse model showed that the administration of α-mangostin significantly decreased the expression of the fibrosis markers (α-SMA, collagen-a2 (col1a2), desmin and matrix metalloproteinase-2 (MMP-2)) as well as attenuated hepatic collagen deposition and liver damage. In conclusion, this study demonstrates that α-mangostin attenuates the progression of liver fibrosis through inhibiting the proliferation of HSCs and triggering apoptosis signals. Thus, α-mangostin may be used as a potential novel therapeutic agent against liver fibrosis.

Impact of interleukin-10 gene polymorphisms on survival in patients with colorectal cancer.

Chronic inflammation is thought to be the leading cause of colorectal cancer, and interleukin-10 (IL10) has been identified as a potent immunomodulatory cytokine that regulates inflammatory responses in the gastrointestinal tract. Although several single nucleotide polymorphisms (SNPs) in IL10 have been associated with the risk of colorectal cancer, their prognostic significance has not been determined. Two hundred and eighty-two colorectal cancer patients were genotyped for two candidate cancer-associated SNPs in IL10. The associations of these SNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis and Cox regression model. The minor homozygote GG genotype of IL10 rs3021094 was significantly associated with a 3.30-fold higher risk of death compared with the TT+TG genotypes (P=0.011). The patients with IL10 rs3021094 GG genotype also had a poorer overall survival in Kaplan-Meier analysis (log-rank P=0.007) and in multivariate Cox regression model (P=0.044) adjusting for age, gender, carcinoembryonic antigen levels, tumor differentiation, stage, lymphovascular invasion, and perineural invasion. In conclusion, our results suggest that IL10 rs3021094 might be a valuable prognostic biomarker for colorectal cancer patients.

Prenatal diagnosis of fetal hepatoblastoma with a good neonatal outcome: case report and narrative literature review.

The authors report a case of congenital hepatoblastoma that was diagnosed in the antenatal period at 39 weeks' gestation. The infant was delivered vaginally without rupture of the tumor. The neonate then received chemotherapy and underwent surgical excision of the tumor. After 1 year, no tumor recurrence has been noted.

Clinical significance of runt-related transcription factor 1 polymorphism in prostate cancer.

OBJECTIVE: To investigate the association of RUNX1 rs2253319 with clinicopathological characteristics of prostate cancer (PCa) and disease recurrence after radical prostatectomy (RP). PATIENTS AND METHODS: Taking advantage of the systematic stage and grade for each tumor in a cohort of 314 patients with localized PCa receiving RP, we evaluated the associations of RUNX1 rs2253319 with age at diagnosis, preoperative prostate-specific antigen (PSA) level, Gleason score, surgical margin, pathologic stage, status of lymph node metastasis, and PSA recurrence after RP. RESULTS: The minor allele, T, and the minor homozygote TT genotype of RUNX1 rs2253319 were significantly associated with a 1.49- to 2.76-fold higher risk for advanced pathologic stage and a 3.35- to 9.52-fold higher risk for lymph node metastasis. RUNX1 rs2253319 TT genotype was also associated with poorer PSA-free survival compared with the major homozygote CC genotype in Kaplan-Meier analysis (log-rank test, P= 0.038) and multivariate Cox proportional hazards model adjusting for age and PSA concentration (P= 0.045). CONCLUSION: RUNX1 rs2253319 is associated with adverse clinicopathological features and might be a prognostic factor for the recurrence of PSA in patients with PCa receiving RP.

Association analysis of Wnt pathway genes on prostate-specific antigen recurrence after radical prostatectomy.

BACKGROUND: Approximately one-third of prostate cancer (PCa) patients show biochemical failure after radical prostatectomy (RP) and are prone to develop metastasis with significant mortality. Although aberrant Wnt/beta-catenin (CTNNB1) signaling has been observed in numerous types of human cancers, including PCa, to our knowledge there is currently no information on the role of Wnt signaling gene polymorphisms in PCa. METHODS: We comprehensively studied the contribution of genetic variations in CTNNB1 and adenomatous polyposis coli (APC), one of the key genes encoding the CTNNB1 destruction complex, to PCa risk and prognosis after RP using a hospital-based case-control study. We selected and genotyped 13 tagged single-nucleotide polymorphisms (tSNP) to predict common variants across entire APC and CTNNB1 genes in 307 patients with clinically localized PCa who received RP and 371 unaffected controls. RESULTS: Four tSNPs (rs3846716, rs2431238, rs41115, and rs565453) and a specific haplotype (GTAAGA) in the APC tumor suppressor gene were associated with a 0.57- to 0.71-fold lower risk of localized PCa. The association of tSNPs with prostate-specific antigen (PSA) recurrence in PCa patients was then analyzed by Kaplan-Meier analysis and Cox regression model. Interestingly, we found that the APC rs3846716 GA/AA genotypes were also significantly associated with poorer PSA-free survival (log-rank test, P = 0.037) compared with the GG genotype. CONCLUSIONS: This is the first report documenting the potential prognostic role of the APC rs3846716 GA/AA genotype on PSA recurrence after RP.

Prognostic significance of prostate cancer susceptibility variants on prostate-specific antigen recurrence after radical prostatectomy.

Recent genomewide association studies have identified several prostate cancer susceptibility variants. However, the association between these variants and biochemical failure in prostate cancer patients receiving radical prostatectomy has not been determined. We systematically evaluated 20 prostate cancer-associated single-nucleotide polymorphisms in a cohort of 320 localized prostate cancer patients receiving radical prostatectomy. Each single-nucleotide polymorphism found to be associated with the recurrence of prostate-specific antigen was further analyzed by Kaplan-Meier analysis and Cox regression model. Three prostate cancer susceptibility single-nucleotide polymorphisms (rs1447295 at 8q24, rs7920517 and rs10993994 at 10q11) were associated with prostate-specific antigen recurrence (P < 0.02). Of these, rs7920517 and rs10993994, which were in strong linkage disequilibrium (r(2) = 0.91), also showed significant associations with poor prostate-specific antigen-free survival following radical prostatectomy (log-rank test; P < 0.01). The associations remained significant in our multivariate Cox proportional hazards analysis after adjusting for other clinicopathologic risk covariates (P < 0.01). In conclusion, loci associated with risk for prostate cancer, such as rs7920517 and rs10993994, might also be used to predict the recurrence of prostate-specific antigen in prostate cancer patients receiving radical prostatectomy.

Prenatal diagnosis of mos45,X/46,X,+mar in a fetus with normal male external genitalia and a literature review.

OBJECTIVE: Prenatal diagnosis of mos45,X/46,X,+mar is difficult in genetic counseling. Patients with the presence of a Y-derived marker may manifest male or female external genitalia. Here, we report a fetus with phenotypically male external genitalia of mos45,X/46,X,+mar. In addition, the cases with prenatally detected mos45,X/ 46,X,del(Y)(q11.2) and normal male external genitalia are reviewed. CASE REPORT: A 30-year-old, primigravid woman was referred for amniocentesis because of an abnormal Down syndrome screening result at 20 weeks' gestation. Cytogenetic analysis showed mos45,X/46,X,+mar without a normal Y chromosome. Prenatal ultrasound detected symmetric intrauterine growth restriction and normal male external genitalia. After termination of the pregnancy, a phenotypically normal male fetus was delivered smoothly without apparent structural defects. Based on conventional G-banded analysis, the marker chromosome appeared as a Y chromosome that originated with a deleted Yq, designated as del(Y)(q11.2). CONCLUSION: Based on a literature review, the addition of fluorescence in situ hybridization and molecular analysis to the conventional cytogenetic techniques can provide more accurate identification of a Y chromosome aberration in the prenatal detection of mos45,X/46,X,+mar, thus allowing more appropriate genetic counseling for the family.

Electroacupuncture reduces uterine artery blood flow impedance in infertile women.

OBJECTIVE: To evaluate the effects of electroacupuncture (EA) on pregnancy rate and uterine artery blood flow impedance in patients undergoing in vitro fertilization (IVF). MATERIALS AND METHODS: This prospective, randomized trial was carried out in the IVF center of China Medical University Hospital in Taiwan, from February 1, 2004 to January 30, 2005. A total of 44 patients were enrolled in the study. Of these, 30 were allocated to acupuncture, and 14 were allocated to no acupuncture. EA was performed four times, twice a week for 2 weeks, from day 2 of the study to the day before oocyte retrieval. After patients felt the needle reaction, the needles were attached to an electrical stimulator for 30 minutes. Clinical pregnancy and pulsatility index (PI) of right and left uterine arteries before and after EA were measured. RESULTS: There was no significant difference in pregnancy rate between the two groups (acupuncture group, 30%; non-acupuncture group, 28.6%). The mean PI of both uterine arteries was significantly reduced after EA (left uterine artery, 2.3 to 2.0; right uterine artery, 2.4 to 2.2). There was no significant change in PI in the group with no acupuncture (left uterine artery, 2.5 to 2.3; right uterine artery, 2.4 to 2.3). CONCLUSION: EA could be useful for reducing uterine artery blood flow impedance, but did not increase the pregnancy rate in patients undergoing IVF.

Surgical blood loss and laparoscopic-assisted vaginal hysterectomy.

OBJECTIVE: This study aimed to elucidate the possible relationship between surgical blood loss (SBL) and medical outcomes of laparoscopic-assisted vaginal hysterectomy (LAVH). MATERIALS AND METHODS: Patients who underwent LAVH performed by the same surgeon for benign gynecologic diseases from 2004 to 2006 were analyzed retrospectively. Patients were divided into two groups according to the amount of SBL (< 150 mL or > or = 150 mL, 75th percentile of mean SBL). Clinical medical outcomes of all women were analyzed to identify the effects of SBL during LAVH. RESULTS: A total of 133 women with benign gynecologic disease were included. Group 1 (SBL < 150 mL) consisted of 108 patients and Group 2 (SBL > or = 150 mL) consisted of 25 patients. The mean operative time for patients with SBL > or = 150 mL was 36.1 minutes longer than that for patients with SBL < 150 mL (p < 0.001). Mean hospital stay, mean shift in serum hemoglobin, mean shift in serum hematocrit and mean flatulence relief time were not significantly different between the two groups. CONCLUSION: Greater SBL (> or = 150 mL) during LAVH was significantly associated with longer operating time, but had no detrimental effect on short-term surgical outcomes. Thus, efforts to minimize intraoperative bleeding and so reduce operative time will be beneficial for women undergoing LAVH.

Analysis of risk factors associated with vaginal erosion after synthetic sling procedures for stress urinary incontinence.

The goal of this study was to analyze the risk factors associated with vaginal erosion after synthetic sling procedure for stress urinary incontinence. Follow-up evaluations were at 1 week, 1 to 3 months, 6 months, and annually after the operation. The evaluations included detailed history taking, vaginal examinations, and perineal ultrasonographic urethrocystography. The vaginal erosion rate (6/239) after the synthetic sling procedure was 2.5%. We assessed the relationship between clinical features and vaginal erosion. Of these, only diabetes mellitus (DM) was a significant risk factor for vaginal erosion. Women with DM were 8.3 times more at risk than women without DM for developing vaginal erosion after synthetic sling procedure (p < 0.05). The vaginal erosion-free rate during the 24-month follow-up decreased significantly in women with DM. The rate of vaginal erosion associated with type III multifilamentous polypropylene sling (intravaginal slingplasty) is 10.7% more than that with type I monofilament polypropylene sling (such as tension-free vaginal tape and inside out transobturator vaginal tape) (p = 0.054). Women with DM should be informed that vaginal erosion is a possible complication after synthetic sling procedure.

Successful treatment of uterine arteriovenous malformation with percutaneous embolization.

OBJECTIVE: Uterine arteriovenous malformation (AVM) is a rare condition and can be life-threatening if not managed properly. We report a case that was diagnosed by typical ultrasound imaging and treated successfully with uterine arterial embolization. CASE REPORT: A 28-year-old female, gravida 4, para 3, abortus 1, presented with massive vaginal bleeding 19 days after a termination of pregnancy due to fetal anomaly. After a dilatation and curettage 3 years previously, typical ultrasound image findings and a declining pattern of serum beta-hCG (human chorionic gonadotrophin), acquired AVM was highly suspected. The patient underwent bilateral uterine arterial embolization. Four weeks later, there was nearly complete resolution of the AVM and the patient's menstrual cycle was restored 6 weeks after embolization. CONCLUSION: AVM can be diagnosed at an early stage with the aid of history taking and ultrasound. Percutaneous embolotherapy is a safe and effective treatment for AVM, especially when fertility preservation is desired.

Fetal atrial flutter: a case report and experience of sotalol treatment.

OBJECTIVE: Fetal tachyarrhythmia may cause fetal hydrops and lead to fetal morbidity and mortality. Supraventricular tachycardia and atrial flutter have been the most diagnosed. We present a case of fetal atrial flutter diagnosed during the second trimester treated with digoxin and sotalol and delivered at term. CASE REPORT: A 30-year-old primigravid woman was diagnosed with fetal atrial flutter at the gestational age of 25 weeks with atrial rates of 480-520 bpm and ventricular rates of 200-250 bpm. Initially, she was treated with digoxin then with a combination of digoxin and sotalol. The fetal heart beat slowed after sotalol treatment but did not return to sinus rhythm. The fetus was delivered vaginally. Neonatal echocardiography showed a small apical ventricular septal defect and small patent ductus arteriosus. Electrocardiography also revealed atrial flutter with occasional atrial fibrillation. CONCLUSION: The efficacy of antiarrhythmic drug therapy for fetal atrial flutter has not been well established. In our case, we used sotalol combined with digoxin and the fetal heart beat slowed after therapy. Sotalol may be considered the drug of choice for fetal atrial flutter. If the fetal atrial flutter is resistant to these therapies, a combination of other congenital cardiac diseases or organic abnormalities should be considered.