Cytidine to uridine (C-to-U) editing is one type of substitutional RNA editing. It occurs in both mammals and plants. The molecular mechanism of C-to-U editing involves the hydrolytic deamination of a cytosine to a uracil base. C-to-U editing is mediated by RNA-specific cytidine deaminases and several complementation factors, which have not been completely identified. Here, we review recent findings related to the regulation and enzymatic basis of C-to-U RNA editing. More importantly, when C-to-U editing occurs in coding regions, it has the power to reprogram genetic information on the RNA level, therefore it has great potential for applications in transcript repair (diseases related to thymidine to cytidine (T>C) or adenosine to guanosine (A>G) point mutations). If it is possible to manipulate or mimic C-to-U editing, T>C or A>G genetic mutation-related diseases could be treated. Enzymatic and non-enzymatic site-directed RNA editing are two different approaches for mimicking C-to-U editing. For enzymatic site-directed RNA editing, C-to-U editing has not yet been successfully performed, and in theory, adenosine to inosine (A-to-I) editing involves the same strategy as C-to-U editing. Therefore, in this review, for applications in transcript repair, we will provide a detailed overview of enzymatic site-directed RNA editing, with a focus on A-to-I editing and non-enzymatic site-directed C-to-U editing.
T-box factors comprise an archaic family of evolutionary conserved transcription factors that regulate patterns of gene expression essential for embryonic development. The T-box transcription factor 3 (TBX3), a member of this family, is expressed in several tissues and plays critical roles in, among other structures, the heart, mammary gland and limbs and haploinsufficiency of the human TBX3 gene is the genetic basis for the autosomal dominant disorder, ulnar-mammary syndrome. Overexpression of TBX3 on the other hand has been linked to several cancers including melanoma, breast, pancreatic, liver, lung, head and neck, ovarian, bladder carcinomas and a number of sarcoma subtypes. Furthermore, there is strong evidence that TBX3 promotes oncogenesis by impacting proliferation, tumour formation, metastasis as well as cell survival and drug resistance. More recently, TBX3 was however shown to also have tumour suppressor activity in fibrosarcomas and thus its functions in oncogenesis appear to be context dependent. Identification of the upstream regulators of TBX3 and the molecular mechanism(s) underpinning its oncogenic roles will make valuable contributions to cancer biology.
Human papillomavirus (HPV) infections are common and generally harmless, but persistent infections can bring health problems like cancer and genital warts. For the uninfected group, HPV vaccines provide safe and effective protection, but they're type-restricted and expensive. For those infected, so far there have been a handful of treatments for HPV-associated benign or malignant diseases, traditional Chinese medicine being one of them. This systematic review focuses on the application of traditional Chinese medicine in HPV infection and related diseases on the basis of clinical findings. Moreover it covers compositions and mechanisms based on in vitro laboratory methods and animal models. Traditional Chinese medicine improves clinical index in the treatment of cervical cancer and genital warts; the mechanisms behind the effectiveness might be the regulation of cell apoptosis, viral gene transcription and translation, cell signal transduction pathways, and immune function.
We assessed the factors that influenced improvement or progression in human immunodeficiency virus (HIV)-infected patients who were receiving combination antiretroviral therapy (cART). This was a retrospective cohort study of HIV-infected patients receiving cART in Taizhou, Zhejiang, China, 2009-2015. Liver fibrosis was assessed by Fibrosis-4 (FIB-4) score. Improvement of liver fibrosis was defined as having > 30% decrease in FIB-4 from baseline, whereas progression of liver fibrosis was defined as having > 30% increase in FIB-4 score from baseline. A total of 955 HIV-infected patients were included. Of these, 808 (84.6%) were HIV-monoinfection, 125 (13.1%) were HIV/hepatitis B virus (HBV) coinfection and 29 (3.0%) were HIV/hepatitis C virus (HCV) coinfection. The median duration of treatment was 15 months. After treatment, 37.1% participants had > 30% decreases in FIB-4 index, 14.8% had > 30% increases in FIB-4 index, while the remaining 48.2% had stabilized FIB-4 index. In multivariate analysis, improvement of liver fibrosis was negatively associated with an older age, but was positively associated with baseline FIB-4 index and > 30% increases in CD4 cell count after ART. Progression of liver fibrosis was positively associated with an older age, but was negatively associated with gender and HIV transmission mode (male homosexual vs. male heterosexual, female heterosexual vs. male heterosexual), and baseline FIB-4 index. Our findings indicate that improvement of liver fibrosis could be achieved by early initiation of ART through better CD4 cell recovery. Liver fibrosis and hepatotoxicity associated with ART should be monitored as early as possible and throughout till the end of treatment, with special attention to the elderly and heterosexual men.
This study examined the re-entry characteristics and related predictors among HIV-infected methadone maintenance treatment (MMT) clients in Guangdong, China. Data on HIV-infected MMT clients was obtained from the clinic MMT registration system in Guangdong. Of the 653 participants, only 9.0% remained in the MMT program until the end of the study. For the drop-outs, 70.0% returned to MMT at least once by the end of the study. Re-entry was independently associated with marital status (ORnever married = 2.24, 95% CI: 1.02-4.93; ORmarried currently = 2.34, 95% CI: 1.05-5.22), being unemployed (OR = 1.92, 95% CI: 1.12-3.27), lower positive percentages of urine tests (OR<40% = 4.08, 95% CI: 2.21-7.54; OR40%-80% = 2.52, 95% CI: 1.39-4.56), higher maintenance doses (OR = 3.78, 95% CI: 2.21-7.54)and poorer MMT attendance percentages (OR<20% = 282.02, 95% CI: 62.75-1268.11; OR20-49% = 20.75, 95% CI: 10.52-40.93; OR50-79% = 6.07, 95% CI: 3.44-10.73). A higher re-entry frequency was independently associated with lower education level (ORjunior high school = 0.49, 95% CI: 0.26-0.93), average drug use times less than twice (OR = 0.64, 95% CI: 0.41-1.00), lower positive percentages of urine tests (OR = 0.39, 95% CI: 0.22-0.70) and poorer percentages of MMT attendance (OR<20% = 7.24, 95% CI: 2.99-17.55; OR20-49% = 14.30, 95% CI: 5.94-34.42; OR50-79% = 6.15, 95% CI: 2.55-14.85). Re-entry and repeated re-entry were prevalent among HIV-infected MMT clients in Guangdong, underscoring the urgent needs of tailored interventions and health education programs for this population.
Influenza, a disease caused by a respiratory virus, sickened over 5,043,127 citizens in Shenzhen, China, from January 2014 to April 2016. An accurate forecasting of outbreaks of influenza-like illness (ILI, here we refer to ILI as the upper respiratory infection) could facilitate public health officials to suggest public health actions earlier. In this study, a random forest regression constructed with a one-year period of factors was adopted to forecast the weekly ILI rate using the clinical data from Shenzhen Health Information Center. The following conclusions were drawn based on this method: i) Compared to the predication with 52 (one-year) history observations, the accuracy of the predication was improved by adding another 52 first-order difference variables: mean absolute percentage error (MAPE) decreased from 5.04% to 4.35% and mean squared error (MSE) decreased from 2.85E-04 to 1.97E-04. ii) The variables with the first-order difference seemed more significant than the original history observations during the predication. In addition, both the recent observations and the later observations seemed important in the predicating procedure. iii) Analysis using the Pearson correlation concluded that weather conditions, the influence of which could have been implied by history observations and seemed insignificant for the predication, showed correlation to the weekly average temperature and maximum temperature. The correlation coefficients were -0.3656 and -0.3583, respectively.
Tropomyosin-related kinase receptor B (TrkB) has been observed to be a common player in posttraumatic stress disorder (PTSD) and the regulation of serum lipids levels. However, interplays of PTSD with TrkB on serum lipids levels have not been explored yet. This study was to investigate the interplays of PTSD and TrkB rs1187327 on serum lipid profiles. Variants of TrkB rs1187327 of 709 high school students were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses and verified by DNA sequencing. The PTSD Checklist Civilian Version (PCL-C) was used to assess PTSD. Colorimetric methods were used to determine the serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and glucose. The results show that the GG homozygotes had a significantly higher level of HDL-C than the A allele carriers of TrkB rs1187327 after the adjustment for gender, age and body mass index (BMI) (1.44 ± 0.299 mmol/L vs. 1.39 ± 0.266 mmol/L, p = 0.036). When PTSD was taken into account, the higher than the A allele carriers level of HDL-C of the GG homozygotes was observed significant after the adjustment for gender, age and BMI only in the subjects without PTSD (1.44 ± 0.293 mmol/ L vs. 1.39 ± 0.267 mmol/L, p = 0.030), but not in the subjects with PTSD. These results suggest that the A allele of TrkB rs1187327 may be associated with decreased levels of serum HDL-C in general healthy adolescents, but not in adolescents with PTSD.
Trichomonas vaginalis (T. vaginalis) is a flagellated protozoan parasite that infects humans worldwide. This study determined the sequence of the 18S ribosomal RNA gene of T. vaginalis infecting both females and males in Xinjiang, China. Samples from 73 females and 28 males were collected and confirmed for infection with T. vaginalis, a total of 110 sequences were identified when the T. vaginalis 18S ribosomal RNA gene was sequenced. These sequences were used to prepare a phylogenetic network. The rooted network comprised three large clades and several independent branches. Most of the Xinjiang sequences were in one group. Preliminary results suggest that Xinjiang T. vaginalis isolates might be genetically unique, as indicated by the sequence of their 18S ribosomal RNA gene. Low migration rate of local people in this province may contribute to a genetic conservativeness of T. vaginalis. The unique genetic feature of our isolates may suggest a different clinical presentation of trichomoniasis, including metronidazole susceptibility, T. vaginalis virus or Mycoplasma co-infection characteristics. The transmission and evolution of Xinjiang T. vaginalis is of interest and should be studied further. More attention should be given to T. vaginalis infection in both females and males in Xinjiang.
Paeoniflorin is an effective Chinese traditional medicine with anti-inflammatory and immune-regulatory effects. The aim of this study was to investigate the underlying renoprotective mechanism of Paeoniflorin. In vivo, db/db mice were intraperitoneally injected with Paeoniflorin at a dose of 15, 30, or 60 mg/kg respectively. The immunostaining of TLR2, TLR4, CD68, NF-kB p65 and the mRNA level of inflammatory factors, together with the protein expression of TLR2/4 signaling were evaluated. Our data demonstrated that Paeoniflorin could decrease the urinary albumin excretion rate and inhibit macrophage infiltration and activation through blockage of the TLR2/4 signaling pathway compared with the db/db group in vivo. In vitro, RAW264.7 cells were categorized into control, bovin serum albumin (BSA)-stimulated, advanced glycation end products (AGEs)-stimulated, Paeoniflorin intervention and oxidized phospholipid (OxPAPC)-inhibited groups. The cell viability, the optimal stimulated time and concentration were measured as well as the TLR2/4 signaling activation determined by RT-PCR, Western blot and ELISA. Our data demonstrated that Paeoniflorin reduced the AGEs-induced TLR2/4 activation and inflammatory responses, which was consistent with the TLR2/4 inhibitor group. These findings indicate that Paeoniflorin prevents macrophage activation via inhibition of TLR2/4 signaling expression in type 2 diabetic nephropathy.
Perihilar cholangiocarcinoma (pCC, also known as a Klatskin tumor) is the most common type of cholangiocarcinoma (CC). Preoperative biliary drainage (PBD) is indicated for pCC patients with acute cholangitis or patients who need portal vein embolization (PVE). However, the routine performance of PBD in other patients with pCC is still controversial. The current study retrospectively examined patients with pCC who did not undergo PVE and who did not have cholangitis who were seen at this Hospital to assess the advantages and disadvantages of PBD. This study also sought to find an optimal value of total bilirubin (TB) to indicate performing PBD. Between 2009 and 2014, after excluding patients with acute cholangitis and PVE, patients who had undergone hepatectomy for pCC were enrolled in this study. First, the surgical outcomes and postoperative outcomes were compared between PBD group and direct surgery group. Second, ROC curve analysis of a subgroup of patients was performed to find the best cut off value of TB for indicating the PBD. Third, the costs for patients, including the total charges and the charges per day were compared between the two groups. Subjects were 218 patients in total. Fifty-five patients underwent PBD. This group had a longer operative time [390 (210-700) vs. 360 (105-730) min, p = 0.013], and a longer hospital stay [20 (9-48) vs. 17 (6-93) days, p = 0.007], but underwent vascular resection and reconstruction less often [8 (14.5%) vs. 50 (30.7%), p = 0.019]. Mortality and morbidity were comparable between the two groups. ROC curve analysis of a subgroup of patients indicated that the cut-off value for total bilirubin was 218.75 μmol/L (12.4 mg/dL). The total hospital charges and the charges per day did not differ significantly for the two groups. Disadvantages of PBD were a longer operating time and a longer duration of hospitalization, but the short-term surgical outcomes and hospital charges of PBD group were comparable to the direct surgery group. PBD should be considered for patients when the diagnosis is still suspicious of pCC. Based on the current data, the optimal cut-off value for preoperative TB was 218.75 μmol/L (12.4 mg/dL) to indicate PBD for patients with pCC.
The differences between the perfusion areas of portal vein and the drainage areas of hepatic vein result in the occurrence of either ischemic or congested areas after liver resection. To elucidate which factors are related to the differences between these areas of segment (S) 6 were therefore investigated. The portal-vein-based and hepatic-vein-based regional planes of S6 were defined using the region-growing and Voronoi tessellation methods in 103 consecutive patients who undergo liver resection. Finally, factors related to the difference between the perfusion and drainage areas of S6 were identified. The S6 regional plane based on the portal was coincident with that of hepatic veins (non-difference group) in 57 patients (55.3%), but was discordant on the ventral side (S6-dominant group) in 43 patients (41.7%) and the dorsal side (S5-dominant group) in 3 patients (3.0%). The presence of a proximal branch of the first portal 6 (S6-dominant group vs. non-difference group, 72.1% vs. 17.0%, p < 0.001) and the presence of an inferior right hepatic vein (S6-dominant group vs. non-difference group, 72.1% vs. 43.9%, p = 0.008) suggested large S6 ventrally. The median volume difference between the perfusion area of the portal vein and drainage area of the hepatic vein in S6 was 73 mL (range: 29-189 mL). In conclusion, preoperative 3D-simulation may enhance the preciseness of anatomic liver resection.
Preoperative evaluation of liver functional reserve is important in hepatobiliary surgery. Although the indocyanine green retention rate at 15 minutes (ICG-R15) is the gold standard for this purpose, a new method without technical complexity would be preferable. We assessed the usefulness of the previously established index of convexity (IOC). In total, 159 consecutive patients who underwent both technetium-99m-galactosyl human serum albumin (99mTc-GSA) scintigraphy and the ICG-R15 were included. Correlation coefficients between indices from 99mTc-GSA scintigraphy and blood examinations including ICG-R15 were evaluated, and a conversion formula from the IOC to the ICG-R15 was established. The IOC was calculated as [L(15) × 2 − L(3) − L(27)] / [L(27) − L(3)], where L(t) indicates the radiation counts within the whole liver at t minutes after 99mTc-GSA injection. The IOC showed a significantly stronger correlation with the ICG-R15 (r = −0.532, p < 0.001) than the index of blood clearance (HH15) and the receptor index (LHL15). A formula for estimating ICG-R15 from IOC was "ICG-R15 = −31.0 × IOC + 30.1". In conclusion, the IOC is a better index for evaluating preoperative liver functional reserve than the conventional indices. A formula for estimating ICG-R15 from the IOC will be useful.
In patients at risk of hepatocarcinogenesis, tumors are frequently detected with atypical radiological patterns related to hepatocellular carcinoma (HCC) on imaging studies. Despite their high potential for malignancy, whether to resect such lesions immediately is controversial. Based on histological findings, patients with non-enhanced tumors or enhanced tumors without washout were divided into two groups: those with tumors that should be treated containing well, moderately, and poorly differentiated HCC (Group 1), and those that can be observed containing early HCC, hepatocellular adenoma, focal nodular hyperplasia, dysplastic nodules, and regenerative nodules (Group 2), and we elucidated the clinical correspondence to these tumors. Seventy-two patients had a single tumor with atypical radiological pattern: 39 patients had HCC (Group 1), while 33 patients had benign tumors or early HCC (Group 2). Among nine baseline variables, serum α-fetoprotein (AFP) level in Group 1 (median, 13.2 ng/mL; range, 0.6-5881.6) was significantly higher than that in Group 2 (5.6 ng/mL; 0.8-86.3, P = 0.003). The cut-off value of AFP was 36.4 ng/mL for prediction of Group 1, and the median overall and recurrence-free survival periods of 23 patients in the high-AFP (≥ 36.4 ng/mL) group (5.3 years; 95%CI, 2.1 – N.A. and 1.6 years; 0.5-2.2) were significantly shorter than those of the 49 patients in the low-AFP (< 36.4) group (7.5 years; 7.5 – N.A., P = 0.047, and 2.8 years; 1.9-3.3, P = 0.001). Taken together, HCC-related tumors with an atypical radiological pattern could be observed unless serum AFP level is elevated.
In order to tackle the implant-related infection, a novel way was developed in this study to coat vancomycin particles mixed with controlled release coating materials onto the surface of titanium alloy by using an electrostatic dry powder coating technique. To characterize this sustained release antibacterial coating, surface morphology, in vitro and in vivo drug release were sequentially evaluated. In vitro cytotoxicity was tested by Cell Counting Kit-8 (CCK-8) assay and cytological changes were observed by inverted microscope. The antibacterial properties against MRSA, including a bacterial growth inhibition assay and a colony-counting test by spread plate method were performed. Results indicated that the vancomycin-coated sample was biocompatible for Human osteoblast cell line MG-63 and displayed effective antibacterial ability against MRSA. The coating film was revealed uniform by scanning electron microscopy. Both the in vitro and in vivo drug release kinetics showed an initially high release rate, followed by an extended period of sustained drug release over 7 days. These results suggest that with good biocompatibility and antibacterial ability, the sustained release antibacterial coating of titanium alloy using our novel electrostatic dry powder coating process may provide a promising candidate for the treatment of orthopedic implant-related infection.
Embryonic stem cells (ESCs) technology has garnered worldwide attention for its therapeutic applications in vivo. Researchers have previously shown that non-viral induced pluripotent stem cells (iPSCs) can be generated from urine. As a potential alternative, Urinary iPSCs (UiPSCs) are highly similar to embryonic stem cells (ESCs) in many aspects such as morphology, expression of pluripotency markers and the capacity to develop into three germ layers in vitro and in vivo. However, the degree of gene expression similarity between iPSCs and ESCs has not been completely elucidated. In the present study, we performed a comparative study on the gene expression profile between UiPSCs and ESCs using microarray technology, and identified 19 differentially expressed genes. Furthermore, four genes associated with reprogramming and differentiation including neuronatin (NNAT), piwilike RNA-mediated gene silencing 2 (PIWIL2), early growth response 1 (EGR1) and TATA-box binding protein associated factor 9b (TAF9B) were validated by quantitative real-time PCR (qRT-PCR) assays. Our results indicate that compared with ESCs, UiPSCs demonstrated a different pathway in reprogramming and differentiation preference from ESCs, and can be used as a potential tool in disease modeling, drug discovery and regenerative medicine.
This study reviewed and analyzed data on malaria cases in Yiwu from 2012 to 2016 via a webbased system for managing and reporting information on infectious diseases. A total of 161 cases were diagnosed (77.02% due to Plasmodium falciparum, 18.01% due to P. vivax, 4.35% due to P. ovale, and 0.62% due to P. malariae). One case was imported from Yunnan Province in China and the others were imported from overseas. The ratio of male to female patients was 7.47:1. The average age was 36.34 years (SD: 9.63). Most cases (87.58%) were imported from 1 of 30 countries in Africa. As malaria is gradually being eliminated in China, the main task at this stage has transitioned to the prevention and control of cases of imported malaria. Particular attention should be paid to malaria cases from Africa.
MicroRNAs are a class of small, endogenous, non-coding RNAs mediating posttranscriptional gene silencing. The current authors hypothesized that let-7f-5p is likely involved in cell invasion and proliferation by regulating the expression of target genes. The current study combined let-7f-5p with iTRAQ to assess its effect on gene expression in HeLa cells. Results indicated that 164 proteins were expressed at different levels in HeLa cells overexpressing let-7f-5p and negative controls and that 172 proteins were expressed at different levels in let-7f-5p-silenced HeLa cells and negative controls. Results indicated that let-7f-5p may suppress insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in HeLa cells.