Cisatracurium Retards Cell Migration and Invasion Upon Upregulation of p53 and Inhibits the Aggressiveness of Colorectal Cancer

Colorectal cancer (CRC) is reported to be the third and fourth, most diagnosed and cause of cancer associated deaths respectively. In 2012 for instance, about 1.4 million new cases were reported, and approximately 700,000 deaths recorded. Survival from CRC is dependent on the stage at which it is diagnosed coupled with appropriate surgical and medical intervention. Cisatracurium is widely used for skeletal muscle relaxation during abdominal surgeries, including bowel and colon surgeries. Recent studies reported that cisatracurium inhibits progression of human cancer cells, however, the mechanisms leading to the inhibition are yet to be completely understood. To elucidate mechanisms resulting particularly in tumor cell growth and metastasis, we developed ex vivo and in in vivo xenograft models of CRC. Cisatracurium caused upregulation of p53 and its down-stream genes and proteins known to regulate proliferation and metastasis in vitro and in vivo. Genomic analyses of CRC following cisatracurium treatment revealed moderate to high DNA damage, while functional analyses demonstrated significant tumor cells growth regression, as well as repression of migration and invasion. Importantly, cisatracurium increased E-Cadherin and CALD-1 but decreased SNAI-1 and SLUG levels in vitro and in vivo. Together, the findings demonstrate that elevation of p53 upon cisatracurium-induced genomic injury, represent a potential mechanism by which cisatracurium result in the suppression of CRC progression and metastasis

Antimicrobial resistance of clinical bacterial isolates according to the WHO’s AWaRe and the ECDC-MDR classifications: the pattern in Ghana’s Bono East Region

IntroductionAntimicrobial resistance (AMR) remains a significant health challenge globally and nations have the responsibility to maintain a constant surveillance of AMR, particularly for the emergence of multidrug-resistant (MDR) isolates to existing antibiotics. Against this backdrop, we applied the WHO’s AWaRe (ACCESS, WATCH, and RESERVE) antibiotics classification and the European Centre for Disease Prevention and Control (ECDC)’s multidrug resistance definition for AMR isolates from clinical specimens.MethodThis study reviewed bacterial culture and antibiotic sensitivity test outcomes. These results were then grouped according to the AWaRe and ECDC-MDR classifications.ResultsIn all, the culture and sensitivity results of the 3,178 clinical specimens were investigated, of which 59.5% were from female patients. The pathogens were isolated from 1,187 specimens (37.4%). The WHO’s ACCESS antibiotics, tetracycline, showed a relatively high level of insusceptibility, particularly among Gram-positive (GP) isolates (ranging from 66.7% to 76.7%), along with augmentin (ranging from 44.7% to 81.3%) and cloxacillin (ranging from 50.0% to 78.1%). However, the Gram-negative (GN) isolates showed a relatively high level of susceptibility to amikacin, augmentin, and nitrofurantoin. The WHO’s WATCH antibiotics, cefuroxime, ceftriaxone, cefotaxime, and ciprofloxacin showed a relatively high level of non-responsiveness among the GN isolates, particularly Proteus (ranging from 31.4% to 78.4%), Pseudomonas (ranging from 21.4% to 96.4%), and Enterobacter (ranging from 62.5% to 100%) spp. Among the WHO’s RESERVE antibiotics, resistance to ceftazidime was commonly associated with the GN coliform isolates: Eschericha coli, Klebsiella, and Citrobacter spp. Insusceptibility to meropenem was frequently observed in Staphylococcus spp., E. coli, coliforms, and Proteus spp. Out of the 1,187 isolates, 15.5% (184) were GAT (gentamycin, ampicillin, and tetracycline) MDR, of which 61% (112/184) were from specimens of female patients. The most predominant GAT-MDR isolates were Staphylococcus spp., E. coli, coliforms, and Klebsiella spp.ConclusionIn conclusion, the study revealed a relatively high level and diverse range of AMR. However, MDR in accordance with the ECDC definition was relatively low. There is, therefore, a need to have further research on AMR to inform national criteria for MDR in Ghana

Cytotoxic effect of interleukin-8 in retinal ganglion cells and its possible mechanisms

AIM: To investigate the effect of interleukin-8 (IL-8) on neural retinal ganglion cells (RGCs) and whether it can be alleviated by G31P. METHODS: RGC-5 cells were exposed to IL-8 with or without its specific receptor antagonist G31P for 24h, and the cell viability was assessed by Cell Counting Kit 8 (CCK-8). Apoptosis was measured by examining nuclear morphology and quantifying with flow cytometry. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot were used to investigate the expression of apoptosis-related genes. RESULTS: CCK-8 assay showed that IL-8 significantly inhibits the viability of RGC-5 cells in a dose-dependent manner. Cell apoptosis assays exhibited higher apoptotic rate in IL-8 treatment group compared to control group. We further found that IL-8 could promote Bax and caspase-3 expressions, but decrease the level of Bcl-2 in the aspect of mRNA and protein. However, pre-treatment with G31P partly attenuated these effects in RGC-5 cells (P<0.05). CONCLUSION: These results indicate that anti-proliferation effects of IL-8 through induction of cell apoptosis regulated by Bcl-2, Bax and caspase-3 expressions, can be ameliorated by G31P

Parasitic infections and maternal anaemia among expectant mothers in the Dangme East District of Ghana

Abstract Background Parasitic infections are of public health concern globally, particular among at risk groups such as pregnant women in developing countries. The presence of these parasites during pregnancy potentiate adverse effects to both the mother and the unborn baby. This study sought to establish the prevalence of some parasitic agents among antenatal attendees in the Dangme East District of Ghana. A cross-sectional prospective study was conduct between April and July, 2012. Venous blood specimens were collected from each participant for haemoglobin estimation and malaria microscopy. In addition participants\u2019 early morning mid-stream urine and stool specimens were analyzed microscopically for parasitic agents. Results A total of 375 pregnant women were involved in the study, of which anaemia was present in 66.4% (249/375). However, parasitic infections associated anaemia prevalence was 49.6% (186/375). In all, 186 cases of parasitic infections were observed; 171 (44.0%) were single isolated infections while 15 (4.0%) were co-infections. Plasmodium species were significantly associated with anaemia (13.3%, \u3c7 2 \ua0=\ua023.290, p \ua0<\ua00.001). Also, the presence of Schistosoma haematobium (3.7%, \u3c7 2 \ua0=\ua07.267, p \ua0=\ua00.008), Schistosoma mansoni (5.3%, \u3c7 2 \ua0=\ua05.414, p \ua0=\ua00.023) and hookworm (3.7%, \u3c7 2 \ua0=\ua011.267, p \ua0=\ua00.008) were significantly associated with anaemia in pregnancy. Except where co-infections exist (3.7%, \u3c7 2 \ua0=\ua011.267, p \ua0=\ua00.001), the rest of the single infections were insignificantly associated with anaemia. Collectively, intestinal helminthes were predominantly significant with anaemia in pregnancy ( p \ua0=\ua00.001, \u3c7 2 \ua0=\ua0107.800). Conclusion The study revealed relatively high prevalence of parasitic infections among the study population, suggesting that about three-quarters of the anaemic mothers are either single or co-infected with parasitic agents

EnDuo, a novel derivative of Endostar, inhibits the migration of colon cancer cells, suppresses matrix metalloproteinase-2/9 expression and impedes AKT/ERK activation

Background/aims: Colon cancer remains a life-threating disease with increasing morbidity and mortality worldwide despite the advancement in modern medical treatment. Therefore, novel and effective anti-colon cancers drugs are urgently needed. In this study, we investigated the anti-metastatic property EnDuo, a modified version of Endostar, and the underlying mechanisms. Methods: Colon cancer cells were treated with different concentrations of EnDuo (50 μg/mL, 100 μg/mL, 200 μg/mL), and Endostar (100 μg/mL) as positive control. Cell Counting Kit-8 assay was performed to test the effect of EnDuo on cell viability. A scratch wound assay and transwell assay were employed to evaluate the relocation and motility of malignant colon cells following treatment with EnDuo. Western blot analysis was used to determine inhibitory effects of EnDuo by detecting the phosphorylation level of AKT and ERK proteins, and the expression of MMP-2 and MMP-9 proteins. Results: Our results showed that EnDuo impedes the migration of colon cancer cells in a dose-dependent manner. At the molecular level, EnDuo induced a significant reduction in the phosphorylation of AKT and ERK proteins, and inhibited the expression of MMP-2 and MMP-9 proteins. Conclusions: Collectively, these results demonstrate that EnDuo exhibits a comparable anti-metastatic effect by suppressing the migration of colon cancer cells. Possibly, EnDuo interrupts the PI3K/AKT/ERK signaling pathway to arrest cell migration. Our study provides a novel insight to the potential clinical applications of EnDuo against colon cancers in the future

Prevalence of hookworm infection: a retrospective study in Kumasi

Objective: To establish the prevalence of hookworm infection among patients who reported at the parasitology laboratory of the Komfo Anokye Teaching Hospital for intestinal parasitic investigation. Method: This retrospective study covered available data from January 2001 to December 2011. Records of patients referred to the parasitology laboratory of the hospital were manually reviewed for hookworm infection. Data on age, sex and status of hookworm infection (either present or absent) were retrieved and analyzed by using Microsoft Excel 2007 statistical package. Results: A total of 47 147 patients was reported at the laboratory for intestinal parasitic investigation. Among these patients, 158 patient were positive, representing an overall prevalence of 0.3% (158/47 147). Among the positive cases, the study revealed that the proportion of individuals in age groups <1, 1 to 9, 10 to 19, 20 to 29 and 30 to 39 years were 1.3% (2), 10.8% (17), 16.5% (26), 27.2% (43) and 23.4% (37) respectively. Furthermore, people in age group 40 to 49, 50 to 59 and ≥60 years were infected in the proportion of 8.7% (14), 5.7% (9) and 7.0% (11) respectively. Among the infected patients, the number of females was 62.7% (99) while that of males was 37.3% (59). The yearly prevalence rate dropped consistently from 0.84% in 2001 to 0.11% in 2005. However it increased marginally in 2006 (0.27%) and dropped to 0.00% in 2011. Conclusion: Hookworm infestation was found to be generally high between April and August. However the overall prevalence was relatively low among the study population

Assessing the knowledge of expectant mothers on mother–to-child transmission of viral hepatitis B in Upper West region of Ghana

Abstract Background Viral Hepatitis B is of a major public health concern globally, especially in developing countries. Expectant mothers’ knowledge of Mother-To-Child Transmission (MTCT) of the disease is significant in preventing the spread from an infected mother to her child. This study sought to assess the expectant mothers’ knowledge of Mother-To-Child Transmission of viral hepatitis B in the Wa Municipality and Lawra District of Upper West Region, Ghana. Methods A descriptive cross-sectional study with a multi-stage sampling technique was employed to select a total of 450 study respondents (expectant mothers), and a semi-structured questionnaire was used for the data collection. Respondents were interviewed using face-to-face interview technique. Results Majority (54.0%) of the respondents were aged between 25 and 35 years and the results were similar in both districts. Overall, 62.4% (281/450) of the respondents had at least Junior High level education, and 76.2% (343/450) were multigravida. Educational levels among respondents in the two areas were above 50.0% and considered relatively high. Respondents’ general knowledge of hepatitis B infection and disease was 46.0% (208/450). However, there was a slight difference between the two districts (40.1% in Lawra District and 51.6% in Wa Municipality). The overall knowledge level on MTCT of viral hepatitis B among the respondents was 34.7% (156/450): the Wa Municipality recorded higher knowledge (43.3%) compared to 24.8% in Lawra District. Conclusion The knowledge level of the expectant mothers on MTCT of viral hepatitis B is relatively low in Upper West Region, Ghana. Majority of the respondents had some form of formal education. The age, marital status, education, occupation, gravity and family setup were found to be associated with knowledge of Hepatitis B infection and MTCT. Thus, there is urgent need to intensify efforts of health staff to educate expectant mothers. In addition, home education and outreach activities should be intensified on HBV infection as well as MTCT. Consequently, planning, implementation and execution of preventive activities, especially in the antenatal clinics should critically consider the social and demographic variations of mothers

<it>In vitro</it> antimicrobial activity of ethanolic fractions of <it>Cryptolepis sanguinolenta</it>

<p>Abstract</p> <p>Background</p> <p>Following claims that some plants have antimicrobial activities against infectious microbes, the <it>in vitro</it> antimicrobial activities of different solvent fractions of ethanolic extract of <it>Cryptolepis sanguinolenta</it> were evaluated against eight standard bacteria and clinical isolates.</p> <p>Methods</p> <p>The solvent partitioning protocol involving ethanol, petroleum ether, chloroform, ethyl acetate and water, was used to extract various fractions of dried pulverized <it>Cryptolepis sanguinolenta</it> roots. Qualitative phyto-constituents screening was performed on the ethanol extract, chloroform fraction and the water fraction. The Kirby Bauer disk diffusion method was employed to ascertain the antibiogram of the test organisms while the agar diffusion method was used to investigate the antimicrobial properties of the crude plant extracts. The microplate dilution method aided in finding the MICs while the MBCs were obtained by the method of Nester and friends. The SPSS 16.0 version was used to analyze the percentages of inhibitions and bactericidal activities.</p> <p>Results</p> <p>The phytochemical screening revealed the presence of alkaloids, reducing sugars, polyuronides, anthocyanosides and triterpenes. The ethanol extract inhibited 5 out of 8 (62.5%) of the standard organisms and 6 out of 8 (75%) clinical isolates. The petroleum ether fraction inhibited 4 out of 8 (50%) of the standard microbes and 1 out of 8 (12.5%) clinical isolates. It was also observed that the chloroform fraction inhibited the growth of all the organisms (100%). Average inhibition zones of 14.0 ± 1.0 mm to 24.67 ± 0.58 mm was seen in the ethyl acetate fraction which halted the growth of 3 (37.5%) of the standard organisms. Inhibition of 7 (87.5%) of standard strains and 6 (75%) of clinical isolates were observed in the water fraction. The chloroform fraction exhibited bactericidal activity against all the test organisms while the remaining fractions showed varying degrees of bacteriostatic activity.</p> <p>Conclusion</p> <p>The study confirmed that fractions of <it>Cryptolepis sanguinolenta</it> have antimicrobial activity. The chloroform fraction had the highest activity, followed by water, ethanol, petroleum ether and ethyl acetate respectively. Only the chloroform fraction exhibited bactericidal activity and further investigations are needed to ascertain its safety and prospects of drug development.</p