Esther Njoki Mwangi Maina - Academia.edu (original) (raw)
Papers by Esther Njoki Mwangi Maina
Acta Paediatrica, Jul 14, 2017
The Helping Babies Breathe (HBB) programme is known to decrease neonatal mortality in low-resourc... more The Helping Babies Breathe (HBB) programme is known to decrease neonatal mortality in low-resource settings but gaps in care still exist. This study describes the use of quality improvement to sustain gains in birth asphyxia-related mortality after HBB. Methods: Tenwek Hospital, a rural referral hospital in Kenya, identified high rates of birth asphyxia (BA). They developed a goal to decrease the suspected hypoxic-ischaemic encephalopathy (SHIE) rate by 50% within six months after HBB. Rapid cycles of change were used to test interventions including training, retention and engagement for staff/ trainees and improved data collection. Run charts followed the rate over time, and chi-square analysis was used. Results: Ninety-six providers received HBB from September to November 2014. Over 4000 delivery records were reviewed. Ten months of baseline data showed a median SHIE rate of 14.7/1000 live births (LB) with wide variability. Ten months post-HBB, the SHIE rate decreased by 53% to 7.1/1000 LB (p = 0.01). SHIE rates increased after initial decline; investigation determined that half the trained midwives had been transferred. Presenting data to administration resulted in staff retention. Rates have after remained above goal with narrowing control limits. Conclusion: Focused quality improvement can sustain and advance gains in neonatal outcomes post-HBB training. Key notes Helping Babies Breathe (HBB) is a neonatal resuscitation programme shown to decrease mortality but challenged in sustaining gains. This study describes a rural Kenyan hospital health professional team's use of quality improvement techniques to decrease HIE rates after HBB. In combination with HBB training, improvement of staff communication, ongoing refresher training, retention of skilled staff, and other interventions, the HIE rate decreased by over 50% over 10 months.
doi:10.1182/blood-2008-03-142950Prepublished online October 21, 2008;2009 113: 117-126€€€€Pamela ... more doi:10.1182/blood-2008-03-142950Prepublished online October 21, 2008;2009 113: 117-126€€€€Pamela Kearns, Francesco Falciani, Malcolm Taylor and Tatjana StankovicAgathanggelou, Anna Skowronska, Katie Mapp, Katrin Sameith, Judith E. Powell, Sarah Lawson, Eliot Marston, Victoria Weston, Jennifer Jesson, Esther Maina, Carmel McConville, Angelo€
Acta Paediatrica, 2017
AimThe Helping Babies Breathe (HBB) programme is known to decrease neonatal mortality in low‐reso... more AimThe Helping Babies Breathe (HBB) programme is known to decrease neonatal mortality in low‐resource settings but gaps in care still exist. This study describes the use of quality improvement to sustain gains in birth asphyxia‐related mortality after HBB.MethodsTenwek Hospital, a rural referral hospital in Kenya, identified high rates of birth asphyxia (BA). They developed a goal to decrease the suspected hypoxic‐ischaemic encephalopathy (SHIE) rate by 50% within six months after HBB. Rapid cycles of change were used to test interventions including training, retention and engagement for staff/trainees and improved data collection. Run charts followed the rate over time, and chi‐square analysis was used.ResultsNinety‐six providers received HBB from September to November 2014. Over 4000 delivery records were reviewed. Ten months of baseline data showed a median SHIE rate of 14.7/1000 live births (LB) with wide variability. Ten months post‐HBB, the SHIE rate decreased by 53% to 7.1/10...
Data in Brief, Oct 1, 2019
HeLa PC3 PNT1A Cytotoxicity Resazurin long been known that metabolically active cells change the ... more HeLa PC3 PNT1A Cytotoxicity Resazurin long been known that metabolically active cells change the resazurin from blue (oxidized) to red (reduced) forms, corresponding to the absorbance signals at a wavelength of 570nm (A570) and 600nm (A600) respectively, from which therefore the effects of any treatments on percentage cell viability/death can be elucidated. The raw data values of the treatments against the HeLa, PC3 and PNT1A cells are shown in the different Tables. Examples of how the data can be analyzed have been illustrated using different growth inhibition curves. The data can be used by academics, students, and researchers working on development of anticancer drugs.
Oncogene, Apr 11, 2005
Upregulation of hypoxia-inducible factors HIF-1 and HIF-2 is frequent in human cancers and may re... more Upregulation of hypoxia-inducible factors HIF-1 and HIF-2 is frequent in human cancers and may result from tissue hypoxia or genetic mechanisms, in particular the inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene (TSG). Tumours with VHL inactivation are highly vascular, but it is unclear to what extent HIFdependent and HIF-independent mechanisms account for pVHL tumour suppressor activity. As the identification of novel pVHL targets might provide insights into pVHL tumour suppressor activity, we performed gene expression microarray analysis in VHL-wild-type and VHL-null renal cell carcinoma (RCC) cell lines. We identified 30 differentially regulated pVHL targets (26 of which were 'novel') and the results of microarray analysis were confirmed in all 11 novel targets further analysed by real-time RT-PCR or Western blotting. Furthermore, nine of 11 targets were dysregulated in the majority of a series of primary clear cell RCC with VHL inactivation. Three of the nine targets had been identified previously as candidate TSGs (DOC-2/DAB2, CDKN1C and SPARC) and all were upregulated by wild-type pVHL. The significance for pVHL function of two further genes upregulated by wild-type pVHL was initially unclear, but re-expression of GNG4 (G protein gamma-4 subunit/ guanine nucleotide-binding protein-4) and MLC2 (myosin light chain) in a RCC cell line suppressed tumour cell growth. pVHL regulation of CDKN1C, SPARC and GNG4 was not mimicked by hypoxia, whereas for six of 11 novel targets analysed (including DOC-2/DAB2 and MLC2) the effects of pVHL inactivation and hypoxia were similar. For GPR56 there was evidence of a tissuespecific hypoxia response. Such a phenomenon might, in part, explain organ-specific tumorigenesis in VHL disease. These provide insights into mechanisms of pVHL tumour suppressor function and identify novel hypoxiaresponsive targets that might be implicated in tumorigen-esis in both VHL disease and in other cancers with HIF upregulation.
Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines sho... more Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines showed increased expression of hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2/Bikunin), a Kunitz-type protease inhibitor that regulates HGF activity. As activating mutations in the MET proto-oncogene (the HGF receptor) cause familial RCC, we investigated whether HAI-2/SPINT2 might act as a RCC tumor suppressor gene. We found that transcriptional silencing of HAI-2 in RCC cell lines was associated with promoter region methylation and HAI-2/SPINT2 protein expression was down-regulated in 30% of sporadic RCC. Furthermore, methylation-specific PCR analysis revealed promoter region methylation in 30% (19 of 64) of clear cell RCC and 40% (15 of 38) of papillary RCC, whereas mutation analysis (in 39 RCC cell lines and primary tumors) revealed a missense substitution (P111S) in one RCC cell line. Restoration of HAI-2/SPINT2 expression in a RCC cell line reduced in vitro colony formation, but the P111S mutant had no significant effect. Increased cell motility associated with HAI-2/SPINT2 inactivation was abrogated by treatment with extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phospholipase C-γ inhibitors, but not by an inhibitor of atypical protein kinase C. These findings are consistent with frequent epigenetic inactivation of HAI-2/SPINT2, causing loss of RCC tumor suppressor activity and implicate abnormalities of the MET pathway in clear cell and papillary sporadic RCC. This information provides opportunities to develop novel targeted approaches to the treatment of RCC.
Pharmacognosy Journal, Jul 15, 2019
Annona muricata L. 6 The Annona muricata tree is about 5-10 m tall and 15-83 cm in diameter with ... more Annona muricata L. 6 The Annona muricata tree is about 5-10 m tall and 15-83 cm in diameter with low branches. 7-9 It is widely distributed in the tropical regions of Central and South America, Western Africa, Central and Eastern Africa and Southeast Asia 3,6 at altitudes below 1200 m above sea level, with temperatures between 25 and 28°C, relative humidity between 60 and 80% and annual rainfall above 1500 mm. The fruit is an edible collective ovoid berry, dark green in color. Various medicinal uses have been reported across the globe ranging from the use of leaves, bark, roots, fruits and seeds of Annona muricata. 10 The most widely used preparation in traditional medicine is the decoction of bark, root, seed or leaf but applications are varied. Ethnobotanical studies have indicated that Annona muricata has been used as insecticide 11 and parasiticide. 12 Fruit juice and infusions of leaves ABSTRACT Background: Annona muricata, a tropical plant species belonging to family Annonaceae is one of the most used plants in folk medicine because of its many medicinal uses. Despite its wide usage, there is still need to continue scientifically evaluating its medicinal properties in order to avoid any adverse effects. Elucidating the detailed chemical composition of this plant is a significant step towards this evaluation. Objective: The aim of this study was to conduct LC MS analysis on the ethanolic extracts of fruits and leaves of Annona muricata for detection of novel metabolites. Materials and Methods: Leaves and fruits of Annona muricata were collected from Eastern Uganda during the month January 2018. Extraction was conducted using the tissue homogenization method and the extracts were analyzed on an LC/SQ MS detection system. The results were obtained by analyzing the MS spectra using the retentions time and fragmentation patterns on the NIST Library. Results: The study revealed that the fruits extracts contain 1,3-Dimethylthiourea and (4-chlorophenyl)-[4-(3-chlorophenyl)-2-[(Z)-3-(dimethylamino) prop-1-enyl]quinolin-6-yl]-(3-methylimidazol-4-yl)methanol, which are reported antioxidant and antineoplastic agents. The leaves contained 2,4,6-Tribromoaniline another antioxidant and antineoplastic agent, while compound (dichlorozirconium(2+);dimethyl-bis(2-methyl-4phenylinden-1-id-1-yl)silane was found in both extracts of fruits and leaves. Conclusion: The current study suggests that ethanolic extracts of fruits and leaves of Annona muricata contain compounds which are potent antioxidant, antineoplastic and therapeutic agents for various conditions and paves the way for the development of several treatment regimens from these plant parts. Finally, the compounds reported in this study have been identified for the first time as being found in Annona muricata.
Biotechnology journal international, Oct 18, 2019
Introduction: The biological green synthesis of nanoparticles via nanobiotechnology processes hav... more Introduction: The biological green synthesis of nanoparticles via nanobiotechnology processes have a significant potential to boost nanoparticles production without the use of harsh, toxic, and expensive chemicals commonly used in conventional physical and chemical processes. Annona muricata, a tropical plant belonging to family Annonaceae is one of the most used plants in folk medicine because of its many medicinal uses and therefore presents a strong candidate for use in green synthesis. Aims: The aim of this study was to optimize a method for the synthesis of Silver Nanoparticles (AgNPs) from ethanolic extracts of leaves of Annona muricata as well as to characterize the green synthesized AgNPs. Methodology: AgNPs were synthesized from Annona muricata leaves using AgNO 3 solution. The AgNPs were characterized using spectroscopy and microscopy techniques. Results: The formed AgNPs had an absorption maximum at 429 nm using UV-Visible spectroscopy and were stable under different pH, temperature, and storage conditions. Fourier transform infrared analysis revealed the different functional groups responsible for the synthesis and stabilization of the AgNPs. Scanning electron microscopy analysis revealed a spherical nature of the synthesized AgNPs. Energy dispersive x-ray spectroscopy analysis showed presence of Ag, O, and Cl with Ag having the highest composition at 60%. X-Ray Diffraction and Dynamic Light Scattering revealed a crystalline nature of AgNPs with an average size of 87.36 nm and a polydispersity index of 0.16 respectively. Transmission Electron Microscopy analysis further confirmed the crystalline and spherical nature of the AgNPs. Conclusion: In this article, an efficient, eco-friendly and low-cost method for the synthesis and recovery of stable AgNPs using Annona muricata leaves ethanolic extracts as both a reducing and capping agent has been reported for the first time. The synthesized AgNPs could be promising candidates for many biomedical, clinical, engineering, and polymer applications.
World Academy of Science, Engineering and Technology, International Journal of Medical and Health Sciences, Sep 25, 2015
Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines sho... more Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines showed increased expression of hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2/Bikunin), a Kunitz-type protease inhibitor that regulates HGF activity. As activating mutations in the MET proto-oncogene (the HGF receptor) cause familial RCC, we investigated whether HAI-2/SPINT2 might act as a RCC tumor suppressor gene. We found that transcriptional silencing of HAI-2 in RCC cell lines was associated with promoter region methylation and HAI-2/SPINT2 protein expression was down-regulated in 30% of sporadic RCC. Furthermore, methylation-specific PCR analysis revealed promoter region methylation in 30% (19 of 64) of clear cell RCC and 40% (15 of 38) of papillary RCC, whereas mutation analysis (in 39 RCC cell lines and primary tumors) revealed a missense substitution (P111S) in one RCC cell line. Restoration of HAI-2/SPINT2 expression in a RCC cell line reduced in vitro col...
Supplementary Table 1 from Tumor Suppressor Activity and Epigenetic Inactivation of Hepatocyte Gr... more Supplementary Table 1 from Tumor Suppressor Activity and Epigenetic Inactivation of Hepatocyte Growth Factor Activator Inhibitor Type 2/SPINT2 in Papillary and Clear Cell Renal Cell Carcinoma
Journal of Complementary and Alternative Medical Research
Introduction: Rhabdomyosarcoma is an aggressive solid tumour of skeletal muscles origin whose cur... more Introduction: Rhabdomyosarcoma is an aggressive solid tumour of skeletal muscles origin whose current treatment is associated with high expenses, severe side effects, drug resistance and tumour regrowth. There is a need to develop safer and more effective chemotherapeutic agents. Annona muricata is one of the widely used plants in treating various diseases due to its reported effectiveness. However, there is a dearth of scientific information regarding the efficacy of Annona muricata on rhabdomyosarcoma and its safety. This study aimed to evaluate the effects of Annona muricata ethanolic fruit extract on the antiproliferative activity and gene expression in RD cell line, including its biosafety in BALB/c mice. Materials and Methods: The resazurin metabolic assay was used to assess the antiproliferative and cytotoxic activities of Annona muricata ethanolic fruit extract on RD and Vero cells. Quantitative real-time polymerase chain reaction was used to assess the gene expression profi...
World Academy of Science, Engineering and Technology, International Journal of Medical and Health Sciences, 2015
Advances in Bioscience and Biotechnology, 2021
Background: Rhabdomyosarcoma (RMS) is the most prevalent soft tissue sarcoma in children, represe... more Background: Rhabdomyosarcoma (RMS) is the most prevalent soft tissue sarcoma in children, representing approximately 50% of pediatric sarcomas and can develop in any part of the body though more frequently at the extremities. Aim: Evaluating the in vitro anti-proliferative activity of Dermaseptin B2 on Rhabdomyosarcoma RD (CCL-136TM) cells and its effect on the expression of MYC, FGFR1, NOTCH1, and CXCR7 genes involve in processes including proliferation, angiogenesis and metastasis. Methods: RD cells were grown in Dulbecco's Modified Eagle's Medium supplemented with 10% Fetal Bovine Serum. Exponentially growing cells were treated with Dermaseptin B2 and Antiproliferative activity was assayed using the resazurin and migration assays at three time-points. In order to determine the gene expression profiles of MYC, NOTCH1, FGFR1 and CXCR7, total RNA was extracted from the cells and q-RT-PCR was performed with β-Actin as reference gene. Results: Dermaseptin B2 inhibited the proliferation of RD cells in a time and concentration dependent manner as with IC 50 values of 7.679 µM, 7.235 µM, 5.993 µM. The 2-dimentional wound healing assay showed inhibition of migration and motility of the RD cells at time-points of 6, 24, 48 and 72-hours with the greatest inhibition observed at 72-hours. Dermaseptin B2 downregulated the
Journal of Advances in Medicine and Medical Research, 2021
Introduction: Breast cancer is major burden worldwide and the majority of breast cancers express ... more Introduction: Breast cancer is major burden worldwide and the majority of breast cancers express estrogen receptors (ER) suggesting a high dependence on estrogen hormone. Age is among the major determinants of breast cancer development, however, although Western Kenya is one of the areas with high breast cancer cases, age distribution of ER-positive breast cancer in the sub-region remains largely undocumented. Differentiation-related gene-1 (DRG1) is a metastasis suppressor and thus a potential biomarker for predicting level of metastasis but its potential application in assessing extent of metastasis of ER positive breast cancer has not been fully explored. This study therefore investigated the age distribution and the potential of expression of DRG1 in assessing metastasis of ER positive breast cancer. Materials and Methods: Breast cancer tumour blocks archived in safe cabins in the histology laboratory section, Moi Teaching and Referral hospital, Eldoret, Kenya were used. Clinico...
Medicine, 2021
Abstract An estimated 1.5 million Kenyans are HIV-seropositive, with 1.1 million on antiretrovira... more Abstract An estimated 1.5 million Kenyans are HIV-seropositive, with 1.1 million on antiretroviral therapy (ART), with the majority of them unaware of their drug resistance status. In this study, we assessed the prevalence of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors, and the variables associated with drug resistance in patients failing treatment in Nairobi, Kenya. This cross-sectional study utilized 128 HIV-positive plasma samples obtained from patients enrolled for routine viral monitoring in Nairobi clinics between 2015 and 2017. The primary outcome was human immunodeficiency virus type 1 (HIV-1) drug resistance mutation counts determined by Sanger sequencing of the polymerase (pol) gene followed by interpretation using Stanford's HIV Drug Resistance Database. Poisson regression was used to determine the effects of sex, viral load, age, HIV-subtype, treatment duration, and ART-regimen on the primary outcome. HIV-1 drug resistance mutations were found in 82.3% of the subjects, with 15.3% of subjects having triple-class ART resistance and 45.2% having dual-class resistance. NRTI primary mutations M184 V/I and K65R/E/N were found in 28.8% and 8.9% of subjects respectively, while NNRTI primary mutations K103N/S, G190A, and Y181C were found in 21.0%, 14.6%, and 10.9% of subjects. We found statistically significant evidence (P = .013) that the association between treatment duration and drug resistance mutations differed by sex. An increase of one natural-log transformed viral load unit was associated with 11% increase in drug resistance mutation counts (incidence rate ratio [IRR] 1.11; 95% CI 1.06–1.16; P < .001) after adjusting for age, HIV-1 subtype, and the sex-treatment duration interaction. Subjects who had been on treatment for 31 to 60 months had 63% higher resistance mutation counts (IRR 1.63; 95% CI 1.12–2.43; P = .013) compared to the reference group (<30 months). Similarly, patients on ART for 61 to 90 months were associated with 133% higher mutation counts than the reference group (IRR 2.33; 95% CI 1.59–3.49; P < .001). HIV-1 subtype, age, or ART-regimen were not associated with resistance mutation counts. Drug resistance mutations were found in alarmingly high numbers, and they were associated with viral load and treatment time. This finding emphasizes the importance of targeted resistance monitoring as a tool for addressing the problem.
Acta Paediatrica, Jul 14, 2017
The Helping Babies Breathe (HBB) programme is known to decrease neonatal mortality in low-resourc... more The Helping Babies Breathe (HBB) programme is known to decrease neonatal mortality in low-resource settings but gaps in care still exist. This study describes the use of quality improvement to sustain gains in birth asphyxia-related mortality after HBB. Methods: Tenwek Hospital, a rural referral hospital in Kenya, identified high rates of birth asphyxia (BA). They developed a goal to decrease the suspected hypoxic-ischaemic encephalopathy (SHIE) rate by 50% within six months after HBB. Rapid cycles of change were used to test interventions including training, retention and engagement for staff/ trainees and improved data collection. Run charts followed the rate over time, and chi-square analysis was used. Results: Ninety-six providers received HBB from September to November 2014. Over 4000 delivery records were reviewed. Ten months of baseline data showed a median SHIE rate of 14.7/1000 live births (LB) with wide variability. Ten months post-HBB, the SHIE rate decreased by 53% to 7.1/1000 LB (p = 0.01). SHIE rates increased after initial decline; investigation determined that half the trained midwives had been transferred. Presenting data to administration resulted in staff retention. Rates have after remained above goal with narrowing control limits. Conclusion: Focused quality improvement can sustain and advance gains in neonatal outcomes post-HBB training. Key notes Helping Babies Breathe (HBB) is a neonatal resuscitation programme shown to decrease mortality but challenged in sustaining gains. This study describes a rural Kenyan hospital health professional team's use of quality improvement techniques to decrease HIE rates after HBB. In combination with HBB training, improvement of staff communication, ongoing refresher training, retention of skilled staff, and other interventions, the HIE rate decreased by over 50% over 10 months.
doi:10.1182/blood-2008-03-142950Prepublished online October 21, 2008;2009 113: 117-126€€€€Pamela ... more doi:10.1182/blood-2008-03-142950Prepublished online October 21, 2008;2009 113: 117-126€€€€Pamela Kearns, Francesco Falciani, Malcolm Taylor and Tatjana StankovicAgathanggelou, Anna Skowronska, Katie Mapp, Katrin Sameith, Judith E. Powell, Sarah Lawson, Eliot Marston, Victoria Weston, Jennifer Jesson, Esther Maina, Carmel McConville, Angelo€
Acta Paediatrica, 2017
AimThe Helping Babies Breathe (HBB) programme is known to decrease neonatal mortality in low‐reso... more AimThe Helping Babies Breathe (HBB) programme is known to decrease neonatal mortality in low‐resource settings but gaps in care still exist. This study describes the use of quality improvement to sustain gains in birth asphyxia‐related mortality after HBB.MethodsTenwek Hospital, a rural referral hospital in Kenya, identified high rates of birth asphyxia (BA). They developed a goal to decrease the suspected hypoxic‐ischaemic encephalopathy (SHIE) rate by 50% within six months after HBB. Rapid cycles of change were used to test interventions including training, retention and engagement for staff/trainees and improved data collection. Run charts followed the rate over time, and chi‐square analysis was used.ResultsNinety‐six providers received HBB from September to November 2014. Over 4000 delivery records were reviewed. Ten months of baseline data showed a median SHIE rate of 14.7/1000 live births (LB) with wide variability. Ten months post‐HBB, the SHIE rate decreased by 53% to 7.1/10...
Data in Brief, Oct 1, 2019
HeLa PC3 PNT1A Cytotoxicity Resazurin long been known that metabolically active cells change the ... more HeLa PC3 PNT1A Cytotoxicity Resazurin long been known that metabolically active cells change the resazurin from blue (oxidized) to red (reduced) forms, corresponding to the absorbance signals at a wavelength of 570nm (A570) and 600nm (A600) respectively, from which therefore the effects of any treatments on percentage cell viability/death can be elucidated. The raw data values of the treatments against the HeLa, PC3 and PNT1A cells are shown in the different Tables. Examples of how the data can be analyzed have been illustrated using different growth inhibition curves. The data can be used by academics, students, and researchers working on development of anticancer drugs.
Oncogene, Apr 11, 2005
Upregulation of hypoxia-inducible factors HIF-1 and HIF-2 is frequent in human cancers and may re... more Upregulation of hypoxia-inducible factors HIF-1 and HIF-2 is frequent in human cancers and may result from tissue hypoxia or genetic mechanisms, in particular the inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene (TSG). Tumours with VHL inactivation are highly vascular, but it is unclear to what extent HIFdependent and HIF-independent mechanisms account for pVHL tumour suppressor activity. As the identification of novel pVHL targets might provide insights into pVHL tumour suppressor activity, we performed gene expression microarray analysis in VHL-wild-type and VHL-null renal cell carcinoma (RCC) cell lines. We identified 30 differentially regulated pVHL targets (26 of which were 'novel') and the results of microarray analysis were confirmed in all 11 novel targets further analysed by real-time RT-PCR or Western blotting. Furthermore, nine of 11 targets were dysregulated in the majority of a series of primary clear cell RCC with VHL inactivation. Three of the nine targets had been identified previously as candidate TSGs (DOC-2/DAB2, CDKN1C and SPARC) and all were upregulated by wild-type pVHL. The significance for pVHL function of two further genes upregulated by wild-type pVHL was initially unclear, but re-expression of GNG4 (G protein gamma-4 subunit/ guanine nucleotide-binding protein-4) and MLC2 (myosin light chain) in a RCC cell line suppressed tumour cell growth. pVHL regulation of CDKN1C, SPARC and GNG4 was not mimicked by hypoxia, whereas for six of 11 novel targets analysed (including DOC-2/DAB2 and MLC2) the effects of pVHL inactivation and hypoxia were similar. For GPR56 there was evidence of a tissuespecific hypoxia response. Such a phenomenon might, in part, explain organ-specific tumorigenesis in VHL disease. These provide insights into mechanisms of pVHL tumour suppressor function and identify novel hypoxiaresponsive targets that might be implicated in tumorigen-esis in both VHL disease and in other cancers with HIF upregulation.
Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines sho... more Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines showed increased expression of hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2/Bikunin), a Kunitz-type protease inhibitor that regulates HGF activity. As activating mutations in the MET proto-oncogene (the HGF receptor) cause familial RCC, we investigated whether HAI-2/SPINT2 might act as a RCC tumor suppressor gene. We found that transcriptional silencing of HAI-2 in RCC cell lines was associated with promoter region methylation and HAI-2/SPINT2 protein expression was down-regulated in 30% of sporadic RCC. Furthermore, methylation-specific PCR analysis revealed promoter region methylation in 30% (19 of 64) of clear cell RCC and 40% (15 of 38) of papillary RCC, whereas mutation analysis (in 39 RCC cell lines and primary tumors) revealed a missense substitution (P111S) in one RCC cell line. Restoration of HAI-2/SPINT2 expression in a RCC cell line reduced in vitro colony formation, but the P111S mutant had no significant effect. Increased cell motility associated with HAI-2/SPINT2 inactivation was abrogated by treatment with extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phospholipase C-γ inhibitors, but not by an inhibitor of atypical protein kinase C. These findings are consistent with frequent epigenetic inactivation of HAI-2/SPINT2, causing loss of RCC tumor suppressor activity and implicate abnormalities of the MET pathway in clear cell and papillary sporadic RCC. This information provides opportunities to develop novel targeted approaches to the treatment of RCC.
Pharmacognosy Journal, Jul 15, 2019
Annona muricata L. 6 The Annona muricata tree is about 5-10 m tall and 15-83 cm in diameter with ... more Annona muricata L. 6 The Annona muricata tree is about 5-10 m tall and 15-83 cm in diameter with low branches. 7-9 It is widely distributed in the tropical regions of Central and South America, Western Africa, Central and Eastern Africa and Southeast Asia 3,6 at altitudes below 1200 m above sea level, with temperatures between 25 and 28°C, relative humidity between 60 and 80% and annual rainfall above 1500 mm. The fruit is an edible collective ovoid berry, dark green in color. Various medicinal uses have been reported across the globe ranging from the use of leaves, bark, roots, fruits and seeds of Annona muricata. 10 The most widely used preparation in traditional medicine is the decoction of bark, root, seed or leaf but applications are varied. Ethnobotanical studies have indicated that Annona muricata has been used as insecticide 11 and parasiticide. 12 Fruit juice and infusions of leaves ABSTRACT Background: Annona muricata, a tropical plant species belonging to family Annonaceae is one of the most used plants in folk medicine because of its many medicinal uses. Despite its wide usage, there is still need to continue scientifically evaluating its medicinal properties in order to avoid any adverse effects. Elucidating the detailed chemical composition of this plant is a significant step towards this evaluation. Objective: The aim of this study was to conduct LC MS analysis on the ethanolic extracts of fruits and leaves of Annona muricata for detection of novel metabolites. Materials and Methods: Leaves and fruits of Annona muricata were collected from Eastern Uganda during the month January 2018. Extraction was conducted using the tissue homogenization method and the extracts were analyzed on an LC/SQ MS detection system. The results were obtained by analyzing the MS spectra using the retentions time and fragmentation patterns on the NIST Library. Results: The study revealed that the fruits extracts contain 1,3-Dimethylthiourea and (4-chlorophenyl)-[4-(3-chlorophenyl)-2-[(Z)-3-(dimethylamino) prop-1-enyl]quinolin-6-yl]-(3-methylimidazol-4-yl)methanol, which are reported antioxidant and antineoplastic agents. The leaves contained 2,4,6-Tribromoaniline another antioxidant and antineoplastic agent, while compound (dichlorozirconium(2+);dimethyl-bis(2-methyl-4phenylinden-1-id-1-yl)silane was found in both extracts of fruits and leaves. Conclusion: The current study suggests that ethanolic extracts of fruits and leaves of Annona muricata contain compounds which are potent antioxidant, antineoplastic and therapeutic agents for various conditions and paves the way for the development of several treatment regimens from these plant parts. Finally, the compounds reported in this study have been identified for the first time as being found in Annona muricata.
Biotechnology journal international, Oct 18, 2019
Introduction: The biological green synthesis of nanoparticles via nanobiotechnology processes hav... more Introduction: The biological green synthesis of nanoparticles via nanobiotechnology processes have a significant potential to boost nanoparticles production without the use of harsh, toxic, and expensive chemicals commonly used in conventional physical and chemical processes. Annona muricata, a tropical plant belonging to family Annonaceae is one of the most used plants in folk medicine because of its many medicinal uses and therefore presents a strong candidate for use in green synthesis. Aims: The aim of this study was to optimize a method for the synthesis of Silver Nanoparticles (AgNPs) from ethanolic extracts of leaves of Annona muricata as well as to characterize the green synthesized AgNPs. Methodology: AgNPs were synthesized from Annona muricata leaves using AgNO 3 solution. The AgNPs were characterized using spectroscopy and microscopy techniques. Results: The formed AgNPs had an absorption maximum at 429 nm using UV-Visible spectroscopy and were stable under different pH, temperature, and storage conditions. Fourier transform infrared analysis revealed the different functional groups responsible for the synthesis and stabilization of the AgNPs. Scanning electron microscopy analysis revealed a spherical nature of the synthesized AgNPs. Energy dispersive x-ray spectroscopy analysis showed presence of Ag, O, and Cl with Ag having the highest composition at 60%. X-Ray Diffraction and Dynamic Light Scattering revealed a crystalline nature of AgNPs with an average size of 87.36 nm and a polydispersity index of 0.16 respectively. Transmission Electron Microscopy analysis further confirmed the crystalline and spherical nature of the AgNPs. Conclusion: In this article, an efficient, eco-friendly and low-cost method for the synthesis and recovery of stable AgNPs using Annona muricata leaves ethanolic extracts as both a reducing and capping agent has been reported for the first time. The synthesized AgNPs could be promising candidates for many biomedical, clinical, engineering, and polymer applications.
World Academy of Science, Engineering and Technology, International Journal of Medical and Health Sciences, Sep 25, 2015
Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines sho... more Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines showed increased expression of hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2/Bikunin), a Kunitz-type protease inhibitor that regulates HGF activity. As activating mutations in the MET proto-oncogene (the HGF receptor) cause familial RCC, we investigated whether HAI-2/SPINT2 might act as a RCC tumor suppressor gene. We found that transcriptional silencing of HAI-2 in RCC cell lines was associated with promoter region methylation and HAI-2/SPINT2 protein expression was down-regulated in 30% of sporadic RCC. Furthermore, methylation-specific PCR analysis revealed promoter region methylation in 30% (19 of 64) of clear cell RCC and 40% (15 of 38) of papillary RCC, whereas mutation analysis (in 39 RCC cell lines and primary tumors) revealed a missense substitution (P111S) in one RCC cell line. Restoration of HAI-2/SPINT2 expression in a RCC cell line reduced in vitro col...
Supplementary Table 1 from Tumor Suppressor Activity and Epigenetic Inactivation of Hepatocyte Gr... more Supplementary Table 1 from Tumor Suppressor Activity and Epigenetic Inactivation of Hepatocyte Growth Factor Activator Inhibitor Type 2/SPINT2 in Papillary and Clear Cell Renal Cell Carcinoma
Journal of Complementary and Alternative Medical Research
Introduction: Rhabdomyosarcoma is an aggressive solid tumour of skeletal muscles origin whose cur... more Introduction: Rhabdomyosarcoma is an aggressive solid tumour of skeletal muscles origin whose current treatment is associated with high expenses, severe side effects, drug resistance and tumour regrowth. There is a need to develop safer and more effective chemotherapeutic agents. Annona muricata is one of the widely used plants in treating various diseases due to its reported effectiveness. However, there is a dearth of scientific information regarding the efficacy of Annona muricata on rhabdomyosarcoma and its safety. This study aimed to evaluate the effects of Annona muricata ethanolic fruit extract on the antiproliferative activity and gene expression in RD cell line, including its biosafety in BALB/c mice. Materials and Methods: The resazurin metabolic assay was used to assess the antiproliferative and cytotoxic activities of Annona muricata ethanolic fruit extract on RD and Vero cells. Quantitative real-time polymerase chain reaction was used to assess the gene expression profi...
World Academy of Science, Engineering and Technology, International Journal of Medical and Health Sciences, 2015
Advances in Bioscience and Biotechnology, 2021
Background: Rhabdomyosarcoma (RMS) is the most prevalent soft tissue sarcoma in children, represe... more Background: Rhabdomyosarcoma (RMS) is the most prevalent soft tissue sarcoma in children, representing approximately 50% of pediatric sarcomas and can develop in any part of the body though more frequently at the extremities. Aim: Evaluating the in vitro anti-proliferative activity of Dermaseptin B2 on Rhabdomyosarcoma RD (CCL-136TM) cells and its effect on the expression of MYC, FGFR1, NOTCH1, and CXCR7 genes involve in processes including proliferation, angiogenesis and metastasis. Methods: RD cells were grown in Dulbecco's Modified Eagle's Medium supplemented with 10% Fetal Bovine Serum. Exponentially growing cells were treated with Dermaseptin B2 and Antiproliferative activity was assayed using the resazurin and migration assays at three time-points. In order to determine the gene expression profiles of MYC, NOTCH1, FGFR1 and CXCR7, total RNA was extracted from the cells and q-RT-PCR was performed with β-Actin as reference gene. Results: Dermaseptin B2 inhibited the proliferation of RD cells in a time and concentration dependent manner as with IC 50 values of 7.679 µM, 7.235 µM, 5.993 µM. The 2-dimentional wound healing assay showed inhibition of migration and motility of the RD cells at time-points of 6, 24, 48 and 72-hours with the greatest inhibition observed at 72-hours. Dermaseptin B2 downregulated the
Journal of Advances in Medicine and Medical Research, 2021
Introduction: Breast cancer is major burden worldwide and the majority of breast cancers express ... more Introduction: Breast cancer is major burden worldwide and the majority of breast cancers express estrogen receptors (ER) suggesting a high dependence on estrogen hormone. Age is among the major determinants of breast cancer development, however, although Western Kenya is one of the areas with high breast cancer cases, age distribution of ER-positive breast cancer in the sub-region remains largely undocumented. Differentiation-related gene-1 (DRG1) is a metastasis suppressor and thus a potential biomarker for predicting level of metastasis but its potential application in assessing extent of metastasis of ER positive breast cancer has not been fully explored. This study therefore investigated the age distribution and the potential of expression of DRG1 in assessing metastasis of ER positive breast cancer. Materials and Methods: Breast cancer tumour blocks archived in safe cabins in the histology laboratory section, Moi Teaching and Referral hospital, Eldoret, Kenya were used. Clinico...
Medicine, 2021
Abstract An estimated 1.5 million Kenyans are HIV-seropositive, with 1.1 million on antiretrovira... more Abstract An estimated 1.5 million Kenyans are HIV-seropositive, with 1.1 million on antiretroviral therapy (ART), with the majority of them unaware of their drug resistance status. In this study, we assessed the prevalence of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors, and the variables associated with drug resistance in patients failing treatment in Nairobi, Kenya. This cross-sectional study utilized 128 HIV-positive plasma samples obtained from patients enrolled for routine viral monitoring in Nairobi clinics between 2015 and 2017. The primary outcome was human immunodeficiency virus type 1 (HIV-1) drug resistance mutation counts determined by Sanger sequencing of the polymerase (pol) gene followed by interpretation using Stanford's HIV Drug Resistance Database. Poisson regression was used to determine the effects of sex, viral load, age, HIV-subtype, treatment duration, and ART-regimen on the primary outcome. HIV-1 drug resistance mutations were found in 82.3% of the subjects, with 15.3% of subjects having triple-class ART resistance and 45.2% having dual-class resistance. NRTI primary mutations M184 V/I and K65R/E/N were found in 28.8% and 8.9% of subjects respectively, while NNRTI primary mutations K103N/S, G190A, and Y181C were found in 21.0%, 14.6%, and 10.9% of subjects. We found statistically significant evidence (P = .013) that the association between treatment duration and drug resistance mutations differed by sex. An increase of one natural-log transformed viral load unit was associated with 11% increase in drug resistance mutation counts (incidence rate ratio [IRR] 1.11; 95% CI 1.06–1.16; P < .001) after adjusting for age, HIV-1 subtype, and the sex-treatment duration interaction. Subjects who had been on treatment for 31 to 60 months had 63% higher resistance mutation counts (IRR 1.63; 95% CI 1.12–2.43; P = .013) compared to the reference group (<30 months). Similarly, patients on ART for 61 to 90 months were associated with 133% higher mutation counts than the reference group (IRR 2.33; 95% CI 1.59–3.49; P < .001). HIV-1 subtype, age, or ART-regimen were not associated with resistance mutation counts. Drug resistance mutations were found in alarmingly high numbers, and they were associated with viral load and treatment time. This finding emphasizes the importance of targeted resistance monitoring as a tool for addressing the problem.