HPV18 L1 and long control region sequences variation and E6/E7 differential expression in nasopharyngeal and cervical cancers: a comparative study.

BACKGROUND: The role of high-risk human papillomaviruses (hr-HPVs) in cervical cancer (CC) pathogenesis has long been established. Knowledge about the involvement of hr-HPVs in the etiology of nasopharyngeal cancers (NPC) was not well appreciated until the early 2000s when a clear link began to emerge. However, it is not clear whether HPV oncogenesis in the different epithelial cancers is associated with L1 gene and long-control region (LCR) sequences variation. This study aimed to investigate the HPV18 L1 gene and LCR sequences variation in cervical and nasopharyngeal biopsies, and assessed E6 and E7 genes expression level in both cancers. METHOD: Four-hundred and three (403) formalin-fixed paraffin-embedded tissues originating from nasopharyngeal (NPC) (279) and cervical (CC) (124) sites were collected from a pathology laboratory, Pathologist Without Borders, Accra, Ghana. Haematoxylin and eosin staining was carried out to confirm the presence of cancer on prepared biopsy sections. DNA was extracted from the confirmed cancer biopsies, followed by PCR using MY09/GP5+ /6+ primers to detect the presence of HPV and specific primers for the amplification of L1 gene and LCR. Sanger sequencing was carried out to determine HPV genotypes, and L1 and LCR sequences variant of HPV18s in CC and NPC biopsies. The HPV18 E6/E7 mRNA expression pattern in both cancers was determined using RT-qPCR. RESULTS: Most of the NPC (45%) and CC (55%) biopsies were HPV18 positive. Comparison of HPV18 L1 sequences obtained from cervical and nasopharyngeal cancer tissues, the L1 sequences from the NPC were highly dissimilar with a 59-100% variation among themselves, and in relation to the reference strains. However, the L1 sequences from the CC were more similar with a 91.0-100% variation among the amplified sequences. Also, the LCR sequences from CC were quite different relative to that of NPC. Results for the differential expression of E6/E7 in the two cancers showed a higher fold change in E6 expression in the CC tissues than the NPC tissues while a reverse expression pattern was found for E7 gene. CONCLUSION: The current study reports for the first-time variations in HPV18 L1 and LCR sequences, and differential expression of E6/E7 genes in NPC compared to CC, suggesting a possible adaptation mechanism of the virus at different cancer sites.

Extracellular matrix metalloproteinases inducer gene polymorphism and reduced serum matrix metalloprotease-2 activity in preeclampsia patients.

Preeclampsia increases the risk of pregnancy-related complications, nevertheless a successful spiral vessel remodeling, and trophoblast invasion reduces disorders of pregnancy. Matrix metalloproteinase-2 (MMP-2) clears the path for trophoblast invasion, and activation of MMP-2 largely depends on extracellular matrix metalloproteinases inducer (EMMPRIN) protein. This study aimed to investigate EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia patients. Archival whole blood and serum samples of 74 preeclampsia and 66 normotensive pregnant women age-matched were used in this case-control study. Genomic DNA was extracted from the whole blood samples and EMMPRIN gene amplified with specific primers following fragments sequence mutation analysis. Serum MMP-2 activity was determined using enzyme-linked immunosorbent assay (ELISA) and socio-demographic data of participants retrieved from the database. Age of preeclampsia patients (32.78 ± 6.39) years and body mass index (BMI) (33.09 ± 7.27) kg/m2 compared with the normotensive counterparts (32.33 ± 5.56) years and (32.33 ± 5.56) kg/m2,respectively, were not statistically significant (P > 0.05). Serum matrix metalloprotease-2 (MMP-2) activity was significantly reduced in preeclampsia group (16.34 ± 7.07) compared with the normotensives (25.63 ± 4.56) (P < 0.001), and rs424243T/G variant (55.6%) was overrepresented among the cases compared with the normotensives (16.7%). The single-nucleotide polymorphism T/G was found to be associated with preeclampsia (odds ratio [OR] = 7.63; 95% confidence interval [CI] = 3.95-14.75; P < 0.0001). Decreased activity of MMP-2 and rs424243T/G SNP of EMMPRIN gene was reported in preeclampsia. These preliminary data warrant a further investigation into the relationship between EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia.

Paradox of COVID-19 in pregnancy: are pregnant women more protected against or at elevated risk of severe COVID-19?

Many underlying medical conditions have been linked to worse COVID-19 prognosis. Based on reports on SARS-CoV-1 and Middle East respiratory syndrome infections, pregnancy has been considered a predisposing factor to severe COVID-19, with pregnant women being a high-risk group for several physiological reasons. Specifically, pregnant women undergo physiological adaptations that predispose them to severe respiratory viral diseases, including SARS-CoV-2. However, a significant amount of evidence suggests that the clinical outcome of COVID-19 among pregnant women is not different from the general population. In view of this, this report discusses the physiological conditions in pregnant women that adversely affect their immunity, cardiovascular homeostasis, and their endothelial and coagulopathic functions, thereby making them more prone to severe viral infections. We also discuss how these physiological adaptations appear to paradoxically offer protection against severe COVID-19 among pregnant women.

The role of sex steroid hormones in benign prostatic hyperplasia.

INTRODUCTION: The etiology of benign prostatic hyperplasia (BPH) remains a mystery to scientists; estrogen/androgen imbalance in aged men has been implicated. METHODS: Thirty (30) apparently healthy men and newly diagnosed BPH patients were recruited from the Ghana Police Hospital. Lower urinary tract syndrome (LUTS) and prostate volume were assessed via the prostate symptom score sheet (IPSS) and abdominopelvic scan, respectively. Laboratory assays for total prostate specific antigen (tPSA) and hormones [androstenedione (AED), testosterone (T), dihydrotestosterone (DHT), androstanedioladiol (3α-adiol), androstanediol (3ß-diol), estrone (E1) and estradiol (E2)] were performed via ELISA techniques. Non-parametric analyses were employed. p < 0.05 was considered significant. RESULTS: AED was significantly higher in controls compared to the BPH patients. AKRIC2 (3α-diol/DHT) was significantly higher in the BPH group (p < 0.001) whiles AKRIC1 (3ß-diol/DHT) was significantly lower. Estradiol was significantly higher in BPH (p= 0.029). Age correlated negatively with T, while a negative correlation was observed between TIPSS and 3ß-diol and AKRIC1. Also, prostate volume correlated negatively with fT.tPSA correlated positively with E2 and aromatase activity (E2/T) and negatively with fT. On multiple linear regression, DHT and 3ß-diol remained independent predictors for TIPSS and fT for tPSA. CONCLUSION: Estrogens and androstanediols seem to play a role in BPH development.

Dynamics of urinary oxidative stress biomarkers: 8-hydroxy-2'-deoxyguanosine and 8-isoprostane in uterine leiomyomas.

BACKGROUND: Perturbations of antioxidant levels and lipid peroxidation, but not oxidative DNA damage as a biomarker of oxidative stress have been reported in uterine myoma patients. AIMS: The study aimed at examining the patterns and influence of oxidative stress/damage biomarkers, 8-isoprostane (8-IP) and 8-hydroxy-2'-deoxyguanosine (8OHdG), on the ovulatory and luteal phases of normal and fibroid women. SETTINGS AND DESIGN: Twenty women diagnosed of fibroids (1-5 years) and 20 nonfibroid women were age-matched. Selection was randomly done at the National Obstetrics and Gynaecology Department. SUBJECTS AND METHODS: Three successive samples of urine were taken at 8:00 am on the 14(th), 18(th), and 21(st) days of the menstrual cycle. Mid-stream urine was collected from subjects, after they had cleaned genitals. The samples were kept in an ice chest, transported to the laboratory, and stored at - 70°C until the time of analysis. Samples were analyzed by ELISA technique using commercial kits for 8OHdG and 8-IP. Results were calculated using a computer program. STATISTICAL ANALYSIS USED: Statistical Package for Social Sciences, version 20.0, was used for data management and statistical analysis. The results were expressed as mean ± standard deviation. Differences in continuous data were compared using Student's t-test (two groups) and one-way ANOVA (three or more groups) followed by Bonferroni post hoc test. Relationship between variables was ascertained by Spearman's correlation coefficient. All results were considered significant at 5% level of probability. RESULTS: Significant differences were observed between day 14 and day 21 in control and test groups' estrogen levels (P = 0.0047 and P = 0.004, respectively). Significant progesterone differences were observed between control and test groups on the same days (P = 0.002 and P = 0.001, respectively). A positive correlation was observed between day 21 estrogen and progesterone levels (P = 0.0003) of the control group. Test group had higher levels of 8-IP and 8OHdG than control groups on day 21, with 8OHdG at maximum in the test group but minimum in the control group. The influence of 8OHdG was seen by a negative correlation with estrogen and progesterone on day 21 (P = 0.0002) and a positive correlation between 8OHdG and 8-IP on the same day in the test group. Finally, there was a positive correlation between 8-IP and 8OHdG on day 14, but a negative correlation on day 21 (P = 0.0016). CONCLUSIONS: Oxidative damage was absent in the control group but was very much present in the test group on day 14 and day 21 with progesterone and estrogen acting in concert with oxidative damage biomarkers. An inverse pattern of biomarkers was observed between control and fibroid groups. Oxidative stress biomarkers influenced hormonal levels and pattern of the fibroid group.

Croton membranaceus Improves Some Biomarkers of Cardiovascular Disease and Diabetes in Genetic Animal Models.

INTRODUCTION: Cardiovascular disease (CVD) accounts for 17.3 million deaths per year globally. In Ghana, CVD accounts for 22.2% of deaths. Croton membranaceus (CM) Mull. Arg. (Euphorbiaceae), a medicinal plant in Ghana is mainly used traditionally for the treatment of benign prostatic hyperplasia and measles. However, some hypoglycaemic and hypotensive effects have recently been reported but not scientifically examined. AIM: The study aimed at establishing whether Croton membranaceus (CM) used for prostatitis had any effect on CVD markers. MATERIALS AND METHODS: In experiment 1, lipid profile changes were determined. Twenty four male Spontaneously Hypertensive Rats (SHR) were divided into 4 groups. Low (LD), intermediate (ID) and high dose (HD) groups received 25, 50 and 100 mg/kg b.wt. CM aqueous root extracts (CMARE) for 60 days, respectively, the controls received distilled water. In experiment 2, blood glucose levels (BGL) were determined. 21 db/db mice were divided into 3 groups of 7 mice each alongside db/+ mice (7) (negative control). Groups 1 and 2 received 250 mg/kg b.wt CMARE and metformin, respectively. Group 3 (positive control) and db/+ mice (negative control) received distilled water. Mice were monitored for 15 hours. Data collected were analysed using SPSS version 20. RESULTS: Hypotriglyceridaemic effect was observed (p=0.005). High Density Lipoprotein cholesterol (HDL) and Low Density Lipoprotein cholesterol (LDL) showed significant increases (p=0.013) and decreases (p=0.003), respectively. A significant CRP reduction was observed for ID and HD groups (p = 0.010, p = 0.011, respectively). BGL was reduced in Metformin and Croton groups (p=0.000; p= 0.006, respectively) after 3 hours. CONCLUSION: In conclusion, CMARE has positive effects on some CVD biomarkers and a hypoglycaemic effect.

Effect of hormonal contraceptives on lipid profile and the risk indices for cardiovascular disease in a Ghanaian community.

BACKGROUND: Hormonal contraceptives (HCs) have been shown to alter lipid profile among various population groups with different patterns of dyslipidemia and cardiovascular (CV) risk. The study aimed at determining the lipid profile pattern and CV risk in a Ghanaian cohort. METHODS: Purposive random sampling was done. Forty-seven and 19 cases were on oral contraceptives (OCs) and injectable contraceptives (ICs), respectively; five were on subdermal implant. Twenty-four non-users served as controls. Biodemographic and lipid profiles were determined. Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), and very-low-density lipid lipoprotein cholesterol (VLDLC), were determined. Castelli index I and II were calculated. RESULTS: The mean age difference between the HC and control groups was insignificant. However, diastolic blood pressure (BP) differences were significant (P=0.006). The body mass index (BMI) of the OC and IC groups were significantly different from the control group (P=0.003 and P=0.008, respectively). TC levels for the control and case groups were 3.35±0.62 mmol/L and 4.07±0.91 mmol/L, respectively (P=0.002). LDLC levels for the control and case groups were 1.74±0.57 mmol/L and 2.38±0.84 mmol/L, respectively (P=0.003). Castelli index I (TC/HDLC) and II (LDLC/HDLC) were significantly different between the control and OC groups (P=0.026 and P=0.014, respectively). Spearman's rho correlation showed significant influence of HC use on TG (P=0.026), TC (P=0.000), LDLC (P=0.004), and VLDLC (P=0.026) over time. CONCLUSION: HC use is associated with significant increases in BMI, diastolic BP, TC, LDLC, and Castelli index I and II. These changes carry a potential risk in the development of CV disease.

Mutagenicity of edible palm oil on the Ghanaian market before and after repeated heating.

Red palm oil produced in Ghana largely by village folks has never been tested for its mutagenic potential. The study aimed at determining the mutagenicity of high-energy heated red palm oil (RRPO) and refined, bleached imported palm oil (PO) on the Ghanaian market. Samples of RRPO and PO were 1× and 5× heated for 10 min at 180 °C with a cooling period of 5 h in-between. Unheated, together with heated samples, were tested for mutagenicity using Salmonella typhimurium TA 98 and TA 100 tester stains. Unheated PO was negative for the Ames mutagenicity test with TA 98 strain. However, 1× and 5× heated PO were mutagenic (P = 0.05, each). Testing PO, using TA 100 strain was negative. RRPO was mutagenic with TA 98 strain for heated oils (P = 0.05, each). Assays with TA 100 strain showed highly significant mutations (P = 0.001, each) that increased with increasing heating frequency. PO 1× and 5× heated samples caused significant frameshift mutation in the S. typhimurium TA 98 strain. RRPO caused highly significant point and frameshift mutations in heated samples. Furthermore, unheated RRPO mutagenic potential has serious health implications.