Cross-Sectional Study for Investigation of the Association Between Modifiable Risk Factors and Gastrointestinal Cancers at a Tertiary Hospital in Ghana.

BACKGROUND: Malignancies affecting the gastrointestinal tract are among the principal threats to global public health. In Ghana, these cancers are responsible for a significant number of hospitalizations and mortalities at major health facilities across the country. The increasing incidence of these malignancies necessitates an investigation of the association between lifestyle (modifiable risk factors) and these disorders. MAIN OBJECTIVE: To determine the association between lifestyle and gastrointestinal cancers of patients attending the Korle Bu Teaching Hospital (KBTH). STUDY DESIGN: This was a cross-sectional prospective study where demographic data were obtained from consenting patients diagnosed with gastrointestinal cancer at the oncology and surgical clinics of the KBTH. Diagnostic investigations, gastrointestinal cancer phenotype, year of diagnosis and treatment(s) received were also obtained from the participants. Information on smoking status, alcohol consumption, sources of dietary proteins, daily intake of water, and frequency of fruit intake were also obtained from the participants. Odds ratio and P-values were determined to ascertain whether there might be a significant association between gastrointestinal cancers and specified lifestyle. RESULTS: Colorectal cancers were the most prevalent form of gastrointestinal cancers among the participants. Alcohol consumption or smoking habits were not significantly associated with onset of gastrointestinal cancers among the study participants. There was a significant association but weak correlation between red meat consumption and the colorectal cancer. CONCLUSION: This study shows consumption of red meat to be a modifiable risk factor that is associated with lower gastrointestinal cancers in the study participants. Further longitudinal studies using large number of participants is needed for confirming the observations from this current study.

Transcriptomic analysis of marine endophytic fungi extract identifies highly enriched anti-fungal fractions targeting cancer pathways in HepG2 cell lines.

BACKGROUND: Marine endophytic fungi (MEF) are good sources of structurally unique and biologically active secondary metabolites. Due to the increase in antimicrobial resistance, the secondary metabolites from MEF ought to be fully explored to identify candidates which could serve as lead compounds for novel drug development. These secondary metabolites might also be useful for development of new cancer drugs. In this study, ethyl acetate extracts from marine endophytic fungal cultures were tested for their antifungal activity and anticancer properties against C. albicans and the human liver cancer cell line HepG2, respectively. The highly enriched fractions were also analyzed by high performance liquid chromatography coupled with high resolution mass spectrometry (HPLC-HRMS) and their effect on the HepG2 cells was assessed via transcriptomics and with a proliferation assay. RESULTS: We demonstrated that the fractions could reduce proliferation in HepG2 cells. The detailed transcriptome analysis revealed regulation of several cancer- and metabolism-related pathways and gene ontologies. The down-regulated pathways included, cell cycle, p53 signaling, DNA replication, sphingolipid metabolism and drug metabolism by cytochrome P450. The upregulated pathways included HIF-1 signaling, focal adhesion, necroptosis and transcriptional mis-regulation of cancer. Furthermore, a protein interaction network was constructed based on the 26 proteins distinguishing the three treatment conditions from the untreated cells. This network was composed of central functional components associated with metabolism and cancer such as TNF, MAPK, TRIM21 and one component contained APP. CONCLUSIONS: The purified fractions from MEF investigated in this study showed antifungal activity against C. albicans and S. cerevisiae alone or both and reduced proliferation of the human liver cancer cell line HepG2 implicating regulation of several cancer- and metabolism-related pathways. The data from this study could be instrumental in identifying new pathways associated with liver cancer anti-proliferative processes which can be used for the development of novel antifungal and anti-cancer drugs.

Overt and occult hepatitis B virus infection detected among chronic kidney disease patients on haemodialysis at a Tertiary Hospital in Ghana.

Hepatitis B virus (HBV) infection is endemic in Ghana and chronic kidney disease patients on haemodialysis are a high-risk group for HBV infection. We determined the prevalence of overt and occult HBV infection among haemodialysis patients at the Korle Bu Teaching Hospital in Ghana. 104 consenting End Stage Renal Disease patients on long-term haemodialysis were recruited for the study and their socio-demographic, clinical and laboratory information were obtained using structured questionnaire. All the participants were tested for the hepatitis B surface antigen (HBsAg). The HBsAg-negative participants were re-tested for hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb) and HBV DNA using chemiluminescence and Roche COBAS Ampli-Prep/TaqMan analyser and real-time polymerase chain reaction. Eight (7.7%) of the total participants were positive for HBsAg. Among the 96 HBsAg-negative participants, 12.5% (12) were HBcAb-positive, 7.3% (7) had detectable HBV DNA (mean = 98.7±53.5 IU/mL) and 40.6% (39) were positive for HBsAb. Five out of the 7 HBV DNA-positive participants were males and only one participant was negative for HBcAb. Seventy-three out of the 96 HBsAg-negative participants were vaccinated and 37 of these vaccinated individuals had significant HBsAb titres (mean = 423.21± 380.72 IU/mL). Our data demonstrated that the prevalence of overt and occult HBV infection among the haemodialysis (HD) patients was 7.7% and 7.3%, respectively, and only 50.7% of those who showed proof of vaccination were protected from HBV infection.

Codeine dysregulates ribosome biogenesis in Escherichia coli with DNA double-strand breaks to chart path to new classes of antibiotics.

Aim: A bacterial genetics-guided approach was utilized for the discovery of new compounds affecting bacterial genome stability. Materials & methods: Fungal extracts and fractions were tested for genome instability-mediated antibacterial activity. Interaction assays and RT-qPCR were used to identify compounds that boost the activity of sub-minimum inhibitory concentration streptomycin and obtain insights on the molecular mechanisms of the primary hit compound, respectively. Results: Several extracts and fractions caused bacterial genome instability. Codeine, in synergy with streptomycin, regulates double-strand break (DSB) repair and causes bacterial ribosome dysfunction in the absence of DSBs, and dysregulation of ribosome biogenesis in a DSB-dependent manner. Conclusion: This study demonstrates a potential viable strategy that we are exploring for the discovery of new chemical entities with activities against Escherichia coli and other bacterial pathogens.

Sperm parameters and mitochondrial DNA sequence variants among patients at a fertility clinic in Ghana.

PURPOSE: The present study sought to investigate the common abnormalities and mtDNA mutations in the sperm of Ghanaian men attending the fertility Clinic at the Korle-Bu Teaching Hospital (KBTH). The study therefore provides a baseline data mtDNA mutations in a cross-section of Ghanaian men on referral to the fertility clinic at the KBTH. MATERIALS AND METHODS: The semen of 55 men attending the fertility clinic were collected from the Urology and the Obstetrics and Gynaecology Departments of the KBTH. Demographic and clinical data were also collected using questionnaires. Semen analyses were performed and were followed by amplification and purification of mtDNA from total DNA extracted from the semen. Sequencing of the mtDNA amplicons was performed using the next generation sequencer (Illumina-MiSeq). RESULTS: Asthenozoospermia, oligospermia and oligoasthenoteratozoospermia were observed in 1.79%, 5.36% and 28.57%, respectively, of the study participants. There was no association between drinking and/or smoking and history of gonorrhea infection on sperm status/morphology. A total of 785 point mutations were detected in the non-coding control regions, rRNA genes, tRNA genes and the coding regions of the mtDNA samples from the participants. Amongst these mutations, 16 transition mutations were predominantly detected in the mtDNA samples. Missense mutations that were present in only specific sperm abnormalities were identified and they may contribute to infertility in the study population. CONCLUSION: The present study has identified various abnormal sperm phenotypes that are prevalent in the study population and provided a baseline data on mtDNA mutations in the spermatozoa of the patients. A wide range of sperm abnormalities were detected in the study population with no association with life style or history of gonorrhea infection. The mtDNA point mutations detected in the selected genes that were analysed were mostly transition mutations. These transition mutations might be critical for the development of abnormal sperm phenotypes underlying male infertility in the Ghanaian population.

Correction: Sperm parameters and mitochondrial DNA sequence variants among patients at a fertility clinic in Ghana.

[This corrects the article DOI: 10.1371/journal.pone.0252923.].

Detection of Enterotoxigenic Escherichia coli in Rotavirus-Infected Ghanaian Children Diagnosed with Acute Gastroenteritis.

Diarrhea is a notable global health problem in several developing countries, especially in children. Prior to the introduction of the rotavirus vaccination program in Ghana, a surveillance study was conducted to investigate the prevalence of the disease caused by rotavirus in children. In this report, we re-used archival stool samples from the pre-vaccine surveillance study to provide information on prevalence of enterotoxigenic Escherichia coli in Ghanaian children. Re-analysis of the stool samples revealed co-infection of enterotoxigenic E. coli and rotavirus in 2% of the children whose samples were selected for this study. As Ghana is approaching 10 years post-implementation of the rotavirus vaccination program, the preliminary data presented in this report are a vital reference for subsequent studies aimed at ascertaining the effect of the vaccine on both rotavirus and enterotoxigenic E. coli.

DNA double-strand break formation and repair as targets for novel antibiotic combination chemotherapy.

An unrepaired DNA double-strand break (DSB) is lethal to cells. In bacteria, DSBs are usually repaired either via an error-prone pathway, which ligates the ends of the break or an accurate recombination pathway. Due to this lethality, drugs that induce persistent DSBs have been successful in bacterial infection treatment. However, recurrent usage of these drugs has led to emergence of resistant strains. Several articles have thoroughly reviewed the causes, mechanisms and effects of bacterial drug resistance while others have also discussed approaches for facilitating drug discovery and development. Here, we focus on a hypothetical chemotherapeutic strategy that can be explored for minimizing development of resistance to novel DSB-inducing compounds. We also highlight the possibility of utilizing bacterial DSB repair pathways as targets for the discovery and development of novel antibiotics.

Wood-decaying fungi found in Southern Ghana: A potential source of new anti-infective compounds.

Background: Discovery of bioactive natural products are instrumental for development of novel antibiotics. The discovery and development of natural products such as penicillin represented a major milestone in the treatment of bacterial infections. Currently, many antibiotics have lost their relevance in clinics due to the emergence of drug-resistant microbial pathogens. Hence, there is the need for continuous search of new compounds endowed with potent antimicrobial activity. Methods: In this study, wood-decaying fungi (WDF) from Ghana were explored for their potential as sources of novel antimicrobial compounds with intent of expanding the effort into a drug discovery programme in the near future. Extracts from cultures of 54 morphologically distinct WDF isolates were analyzed for the presence of antimicrobial agents. Results: The extracts from 40 out of the 54 WDF isolates exhibited significant antimicrobial activity against either Staphylococcus aureus, Escherichia coli or Candida albicans. Fractionation of these bioactive extracts, followed by bioassay of the organic fractions obtained, indicate that extracts exhibiting antimicrobial activity against more than one of the three test organisms could be attributed to the presence of different bioactive compounds. Analysis of the composition of the extracts revealed that terpenes were predominant. Conclusions: This study suggests that a significant proportion of WDF in Ghana produce antimicrobial compounds which could be potential sources of novel anti-infective agents and support the plans of developing a drug discovery programme in Ghana based on the fermentation of WDF.

Characterization of Two New Multidrug-Resistant Strains of Mycobacterium smegmatis: Tools for Routine In Vitro Screening of Novel Anti-Mycobacterial Agents.

Mycobacterium tuberculosis is a pathogen of global public health concern. This threat is exacerbated by the emergence of multidrug-resistant and extremely-drug-resistant strains of the pathogen. We have obtained two distinct clones of multidrug-resistant Mycobacterium smegmatis after gradual exposure of Mycobacterium smegmatis mc² 155 to increasing concentrations of erythromycin. The resulting resistant strains of Mycobacterium smegmatis exhibited robust viability in the presence of high concentrations of erythromycin and were found to be resistant to a wide range of other antimicrobials. They also displayed a unique growth phenotype in comparison to the parental drug-susceptible Mycobacterium smegmatis mc² 155, and a distinct colony morphology in the presence of cholesterol. We propose that these two multidrug-resistant clones of Mycobacterium smegmatis could be used as model organisms at the inceptive phase of routine in vitro screening of novel antimicrobial agents targeted against multidrug-resistant Mycobacterial tuberculosis.

Dynamics of RecA-mediated repair of replication-dependent DNA breaks.

Chromosomal replication is the major source of spontaneous DNA double-strand breaks (DSBs) in living cells. Repair of these DSBs is essential for cell viability, and accuracy of repair is critical to avoid chromosomal rearrangements. Repair of replication-dependent DSBs occurs primarily by homologous recombination with a sister chromosome. However, this reaction has never been visualized at a defined chromosomal locus, so little is known about its spatial or temporal dynamics. Repair of a replication-independent DSB generated in Escherichia coli by a rare-cutting endonuclease leads to the formation of a bundle of RecA filaments. In this study, we show that in contrast, repair of a replication-dependent DSB involves a transient RecA focus localized in the central region of the cell in which the DNA is replicated. The recombining loci remain centrally located with restricted movement before segregating with little extension to the period of postreplicative sister-chromosome cohesion. The spatial and temporal efficiency of this reaction is remarkable.