LncRNA UNC5B-AS1 promotes malignant progression of prostate cancer by competitive binding to caspase-9.

OBJECTIVE: This study aims to investigate the expression of LncRNA UNC5B-AS1 in prostate cancer (PCa) and to further investigate whether it can prompt malignant progression of PCa via regulating caspase-9. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to examine UNC5B-AS1 expression in 50 pairs of tumor tissue specimens and paracancerous ones collected from PCa patients, and the interplay between UNC5B-AS1 expression and clinical indicators of PCa was also analyzed. Meanwhile, UNC5B-AS1 levels in PCa cell lines were also further verified by qRT-PCR. In addition, UNC5B-AS1 knockdown model was constructed using lentivirus in PCa cell lines, and cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), transwell and flow cytometry assays were performed to figure out the impact of UNC5B-AS1 on the biological function of PCa cells. Finally, cell recovery experiment was conducted to explore the underlying mechanism and the association between UNC5B-AS1 and caspase-9. RESULTS: QRT-PCR results suggested that UNC5B-AS1 expression in PCa tissue samples was remarkably higher than in adjacent ones, with a statistically significant difference. Compared with patients with low expression of UNC5B-AS1, patients with highly-expressed UNC5B-AS1 had a higher incidence of distant metastasis and more advanced pathological stage. At the same time, proliferation and invasion, as well as migration ability of cells in sh-UNC5B-AS1 group, was conspicuously attenuated while cell apoptosis ability was conversely enhanced. Furthermore, qRT-PCR results revealed that caspase-9 and UNC5B-AS1 showed a negative correlation in gene expression level in PCa tissues. The results of the luciferase reporter gene experiment demonstrated that UNC5B-AS1 can be targeted by caspase-9 through their binding site. Additionally, cell recovery experiment indicated that UNC5B-AS1 and caspase-9 can be mutually regulated, which then together affect the malignant progression of PCa. CONCLUSIONS: UNC5B-AS1 expression was found remarkably increased in both PCa tissues and cell lines, which was remarkably associated with pathological stage and incidence of distant metastasis of PCa patients. In addition, UNC5B-AS1 was able to accelerate the malignant progression of PCa by modulating caspase-9 expression.

Gestational diabetes mellitus: The prevalence, associated factors and foeto-maternal outcome of women attending antenatal care.

OBJECTIVE: The aim of the study is to determine the prevalence of gestational diabetes mellitus (GDM), its associated risk factors, foeto-maternal outcomes and prevalence of postnatal diabetes mellitus (DM). METHODS: This is a cross-sectional study using retrospective data from existing antenatal records of new antenatal women who registered at 72 public health clinics in Selangor in January 2014. RESULTS: A total of 745 antenatal records were reviewed. The prevalence of GDM women was 27.9% (n = 184). GDM risks were higher in women aged 35 years old and above and in those with maternal obesity. GDM women had a higher risk of having a non-spontaneous vaginal delivery compared to non-GDM women. The prevalence of postnatal DM among GDM mother was 12.1%. Working GDM mothers were at higher risk of developing postnatal DM. CONCLUSION: The prevalence of GDM among newly registered women attending antenatal public health care in Selangor was higher than previous studies. Health care personnel need to be vigilant in screening women with risk factors.

The cariogenicity of commercial infant formulas: a systematic review.

AIM: To systematically evaluate the cariogenic potential of various commercially available infant formulas. MATERIALS AND METHODS: A literature search was conducted using Pubmed and Scopus databases for articles published between 1966 and November 2014. Reference lists of all eligible studies were searched. Only human studies were included. Data extraction and risk of bias assessments were performed. RESULTS: Seven of the 83 articles identified were included in this review, of which six studies employed plaque harvesting methods, while one study utilised an intra-oral cariogenicity/in situ model. Three studies compared milk-based formulas (MBFs) and soy-based formulas (SBFs), two compared protein hydrolysate formulas (PHFs) with MBFs and SBFs, four compared formulas with various types of sugar, and two studies compared formulas with varying casein content. Based on a single study, SBFs were significantly more cariogenic than MBFs. Formulas containing only non-milk extrinsic sugars (NMES) and those containing lactose + NMES were found to be significantly more cariogenic than formulas containing only lactose. No significant correlation was found between cariogenicity and casein content in infant formula. The results of studies comparing PHFs with MBFs and SBFs were contradictory. Risk of bias assessment revealed that five studies were at moderate risk of bias, and two were assessed to be at high risk of bias. CONCLUSION: The result for cariogenicity of various types of infant formulas remains inconclusive, thus no concrete recommendations can be made. Further well-designed studies are needed to clarify the effect of casein content on cariogenicity.

Multidrug resistance gene (MDR1) polymorphisms may not be directly associated with response to imatinib in chronic myeloid leukemia.

Our study aimed to investigate the association between multidrug resistance (MDR1) gene polymorphisms and the response to imatinib (IM) in chronic myeloid leukemia (CML). An electronic databases in PubMed, Cochrane Library, Wanfang, China National Knowledge Infrastructure, and VIP were searched using combinations of keywords relating to MDR1 polymorphisms and the response to IM in CML. Studies retrieved from database searches were screened using stringent inclusion and exclusion criteria. The Comprehensive Meta-analysis 2.0 software was utilized for all statistical analyses. In total, 186 studies were initially retrieved, and 10 studies, involving 987 CML patients, were eventually included in this meta-analysis. Results of our study revealed no significant associations between MDR1 rs1045642, rs1128503, and rs2032582 polymorphisms and major molecular response and complete molecular response in CML patients. Significant differences were observed in the genotype frequencies of MDR1 rs1128503 under homozygous, heterozygous, and recessive models, between CML patients sensitive and resistant to IM. A significant difference in genotype frequencies of MDR1 rs2032582 was also observed under allele, homozygous, heterozygous, and recessive models between CML patients sensitive and resistant to IM. In conclusion, based on our meta-analysis, the MDR1 polymorphisms, rs1045642, rs1128503, and rs2032582, are not directly correlated with the curative effect of IM treatment of CML patients.

Headache in hemifacial spasm patients.

OBJECTIVES: To assess prevalence of headaches in patients with hemifacial spasm. To determine whether hemifacial spasm provokes headaches and identifies predictive factors. To evaluate whether botulinum toxin given for hemifacial spasm improves headaches. METHODS: Seventy patients with hemifacial spasm were evaluated for headaches. The relationship of headaches with hemifacial spasm, impact on quality of life (HIT-6), and improvement in headaches from botulinum toxin was recorded. Data on duration, severity, and impact on quality of life (HFS-7) of hemifacial spasm were collected. RESULTS: Hemifacial spasm-related headache was significantly associated with increased hemifacial spasm severity (P < 0.001) and HIT-6 (P = 0.024). Greater hemifacial spasm severity was predictive of hemifacial spasm-related headache (P = 0.006, OR 19.1, 95% CI 2.35-155.64). Botulinum toxin (BTX) for hemifacial spasm improved hemifacial spasm-related headaches (P < 0.001). CONCLUSIONS: Hemifacial spasm can complicate headaches, particularly in patients with greater hemifacial spasm severity. Individually tailored regimens of botulinum toxin may be indicated in these patients.

Clinical analysis of living related renal transplantation with donors older than 50 years in China.

OBJECTIVE: The objective of this study was to investigate whether kidney grafts from living related donors older than 50 years were safe for the donors and recipients in the long term. METHODS: One hundred seven living related donor kidney transplantations were performed in our center from April 1994 to December 2007. No prisoners or organs from prisoners were used in the collection of these data. Donors were divided into 2 groups: >50 years of age (range, 51-78 years), designated as the study group, and ≤50 years of age (range, 21-50 years), designated as the control groups. The mean time of follow-up was 49 months (range, 12-180 months). Clinical data were compared, including donor serum creatinine (Scr) levels, glomerular filtration rates (GFR) before and after the procedures operative complications, and postoperative short-term and long-term recovery of renal function in recipients as well as their complications and recipient and kidney survivals. RESULTS: All operations were successfully performed. Before the operation, the mean Scr and GFR were 82.16 ± 10.86 umol/L and 85.82 ± 6.26 mL/min, respectively, in the study group versus 78.66 ± 10.41 umol/L and 88.74 ± 9.44 mL/min, respectively, in the control group. There were no significant differences in mean Scr or GFR values between the groups at various preoperative or postoperative times (P > .05). No severe perioperative complications occurred, and no subsequent renal function failure was observed upon long-term follow-up of donors in the 2 groups. Comparisons of recipient age, gender ratio, duration on dialysis, HLA matches, cold/warm ischemia times, and immunosuppression therapy showed a correlations between the 2 groups. Mean Scr levels of recipients, which were compared from 1 week to 3 years following surgery, were slightly higher among the control than the study group, but the difference was not significant (P > .05). There were no significant differences between the study and control groups in 1-,3-,5-, and 8-year recipient/graft survival rates (P > .05). CONCLUSIONS: Long-term follow-up showed that transplantations using grafts from donors older than 50 years of age yielded similar results to those with younger donors.

Aerobic granules: a novel zinc biosorbent.

AIMS: Aerobic granules are aggregates with a compact and porous microbial structure. In view of the potential use of aerobic granules as biosorbents for Zn(II) removal from industrial wastewater, this study investigated the effects of initial Zn(II) and aerobic granule concentrations on the kinetics of Zn(II) biosorption on the aerobic granule surface. METHODS AND RESULTS: Acetate-fed aerobic granules with a mean diameter of 1.0 mm were used as biosorbents. Results showed that the kinetics of Zn(II) biosorption on the aerobic granule surface were related to both initial Zn(II) and granule concentrations. It was found that the real driving force for Zn(II) biosorption on the aerobic granule surface could be described by the ratio of initial Zn(II) concentration (Co) to initial granule concentration (Xo), rather than individual Co or Xo. The Co/Xo ratio provides a unified basis for interpretation of the biosorption data obtained under different initial conditions. The maximum biosorption capacity of Zn(II) by aerobic granules was 270 mg g(-1). CONCLUSIONS: It appears that the aerobic granule can be used as an effective biosorbent for efficient removal of Zn(II) or other types of heavy metals from industrial wastewater. SIGNIFICANCE AND IMPACT OF THE STUDY: This study could lead to the development of a novel granular biosorbent for the removal of heavy metals from wastewater. A simple and compact aerobic granule-based biosorber could be expected.

Pharmacological profiles of 5-phenylmethylenehydantoin and its methoxy substituted derivatives.

5-Phenylmethylenehydantoin (5-PMH) and 5-(o-methoxyphenyl)methylenehydantoin (5-o-MPMH) were found to have anticonvulsant activities with ED50 values of 48 and 73 mg/kg as compared to 11 mg/kg for phenytoin. The log dose-logit plots yielded nearly parallel straight lines for all three compounds, indicating that they may have the same mechanism of action. The meta- and paramethoxy isomers of 5-o-MPMH, 5-m-MPMH and 5-p-MPMH, did not show any anticonvulsant activity up to 200 mg/kg. In addition, 5-o-MPMH induced neurological deficits as shown by marked effects on rota-rod performance in the dose range of 50-90 mg/kg. Above 100 mg/kg, 5-o-MPMH caused a loss of the righting reflex in mice for up to 2.3 hr at 200 mg/kg. In contrast, 5-PMH, 5-m-MPMH and 5-p-MPMH may have slight sedative effects, but only 5-m-MPMH decreased rota-rod performance significantly at 90 mg/kg. None of the three was hypnotic up to 200 mg/kg in dose. It is therefore inferred that 5-o-MPMH causes general CNS depression via a mechanism distinct from that of its anticonvulsant effects which is shared by phenytoin and 5-PMH. 5-o-MPMH increased jumping latency in the hot plate test in the same dose range as it causes neurological deficit. 5-o-MPMH also appeared to have a similar degree of toxicity in mice as diazepam judging from rough estimates of their LD50/HD85 ratios.

N-demethylation of methyl and dimethyl derivatives of phenytoin and their anticonvulsant activities in mice.

Anticonvulsant activities of 3-methylphenytoin (3-MP) and 1,3-dimethylphenytoin (1,3-DMP) were observed to peak 3 hr after i.p. administration of the drugs dissolved in dimethylsulphoxide (DMSO), while maximal activity was obtained within 15 min with phenytoin. HPLC was employed to monitor the plasma concentrations of all three compounds at various time intervals after injecting 3-MP or 1,3-DMP. In both cases, phenytoin appeared in the plasma, gradually reaching 14-15 micrograms/ml in 3 hr. The time course of increase in plasma phenytoin levels correlated with that of anticonvulsant activities. It was also found that 1,3-DMP gave rise to a major unidentified metabolite as well as 3-MP and phenytoin. This unidentified metabolite eluted only half a minute in front of 3-MP in the HPLC. Mice injected with high doses of 3-MP (100 mg/kg) in DMSO exhibited severe epileptiform activities. Phenobarbital, diazepam and clonazepam were found to protect against such seizures, but not phenytoin, carbamazepine and valproic acid. This shows that 3-MP is at least a pro-convulsant, taking into account that its effects might have been enhanced by DMSO. Unlike phenytoin, 3-MP lacked the ability to inhibit synaptosomal uptakes of both glutamate and GABA. This difference may be related to the fact that phenytoin, but not 3-MP, possesses potent anticonvulsant activity.

Adverse drug reaction reporting in the Singapore General Hospital.

Adverse Drug Reaction reporting was made mandatory in the Singapore General Hospital in January 1978. Reports on a total of 59 patients were received on 34 drugs ranging from antibiotics to Chinese medicine. Antimicrobial drugs topped the list of adverse reactions. The most frequently reported drugs in decreasing order of reports were ampicillin, allopurinol, aspirin compound preparations, cloxacillin, digoxin, streptomycin, penicillins and insulins. Allergies were the most common reactions seen.