Michael Ntim - Academia.edu (original) (raw)

Papers by Michael Ntim

The Journal of Neuroscience, Sep 12, 2022

Frontiers in Pediatrics

BackgroundNeonatal sepsis is still a major cause of death and morbidity in newborns all over the ... more BackgroundNeonatal sepsis is still a major cause of death and morbidity in newborns all over the world. Despite substantial developments in diagnosis, treatments, and prevention strategies, sepsis remains a common problem in clinical practice, particularly in low-resource countries.MethodsA retrospective cohort study of 238 neonates with positive blood culture-proven sepsis (in Muhimbili National Hospital) was conducted from January 2019 to December 2020. The outcomes of hospitalization were survival and death.ResultsIn total, 45.4% mortality resulted from 238 neonates who had sepsis exclusively based on blood culture positivity. A significant association was found between very low birth weight (VLBW), hyperglycemia, mechanical ventilation, and high neonatal mortality. Among the different clinical presentations of neonatal sepsis, lethargy, vomiting, and respiratory distress were found to be frequently associated with neonatal mortality. Furthermore, sepsis with Gram-negative bacter...

Neurochemical Research

Steroid receptor coactivator 1 (SRC-1) is one of the coactivators recruited by the nuclear recept... more Steroid receptor coactivator 1 (SRC-1) is one of the coactivators recruited by the nuclear receptors (NRs) when NRs are activated by steroid hormones, such as glucocorticoid. SRC-1 is abundant in hippocampus and hypothalamus and is also related to some major risk factors for depression, implicated by its reduced expression after stress and its effect on hypothalamus-pituitary-adrenal gland axis function. However, whether SRC-1 is involved in the formation of depression remains unclear. In this study, we firstly established chronic unpredictable stress (CUS) to induce depressive-like behaviors in mice and found that SRC-1 expression was reduced by CUS. A large number of studies have shown that neuroinflammation is associated with stress-induced depression and lipopolysaccharide (LPS) injection can lead to neuroinflammation and depressive-like behaviors in mice. Our result indicated that LPS treatment also decreased SRC-1 expression in mouse brain, implying the involvement of SRC-1 in the process of inflammation and depression. Next, we showed that the chronic unpredictable mild stress (CUMS) failed to elicit the depressive-like behaviors and dramatically promoted the expression of SRC-1 in brain of wild type mice. What's more, the SRC-1 knockout mice were more susceptible to CUMS to develop depressive-like behaviors and presented the changed expression of glucocorticoid receptor. However, SRC-1 deficiency did not affect the microglia activation induced by CUMS. Altogether, these results indicate a correlation between SRC-1 level and depressive-like behaviors, suggesting that SRC-1 might be involved in the development of depression induced by stress.

BioMed Research International, 2022

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related ... more Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths. Immune cells in the tumor microenvironment play an important role in the development of tumors. In this study, CIBERSORT was used to estimate the subset of the immune cells using bulk gene expression data (i.e., TCGA, GEO, and cBioPortal databases). 1,087 samples were included in the analysis. The results revealed that among the 22 immune cell subsets that were evaluated, resting and activated NK cells, macrophage M1 and M2, and resting mast cells are associated with significant improvements in patient survival of colorectal cancer. The 15-year survival rates for the training cohort showed 49.1% and 32.5%, respectively, for the low- and high-risk groups. Likewise, the validation and entire cohorts showed 77.3% versus 47.2% and 65.3% versus 46.5%, respectively, for the low- and high-risk groups. Also, the prognostic immune score in predicting the chemotherapy effects showed that t...

Frontiers in Aging Neuroscience, Mar 24, 2022

Aging is associated with physiological and pathological changes and presents health complications... more Aging is associated with physiological and pathological changes and presents health complications, such as dementia. Isolation has also been associated with the experience of growing old. Both have been linked individually to the incidence of cognitive decline. In this present study, the effects of these two phenomena have been looked at in animal models where aging was induced with D(+)Galactose in mice who underwent longterm post-weaned social isolation (L-PWSI). Assessing cognitive function using Y-maze, Morris water maze (MWM), and passive avoidance tests (PATs) confirmed that cognition is impaired in either of the treatments but worsened when the D(+)Galactose mice were subjected to L-PWSI. Moreover, a synaptic protein, PSD95, and dendritic spines density were significantly reduced in the L-PWSI and D(+)Galactose-treated mice. Our previous study revealed that autophagy deficit is involved in cognitive impairment in the L-PWSI model. Here, we first report the inhibited cell cycle in L-PWSI, combined with the decreased autophagy, aggravates cognitive impairment in D(+)Galactose-treated mice. Beyond these, the autophagy and cell cycle mechanisms that link isolation and aging have been explored. The close association between isolation and aging in humans is very real and needs much research attention going forward for possible therapeutic interventions.

Aging Cell, 2022

Aberrant increases in neuronal network excitability may contribute to cognitive deficits in Alzhe... more Aberrant increases in neuronal network excitability may contribute to cognitive deficits in Alzheimer's disease (AD). However, the mechanisms underlying hyperexcitability of neurons are not fully understood. Voltage-gated sodium channels (VGSC or Nav), which are involved in the formation of excitable cell's action potential and can directly influence the excitability of neural networks, have been implicated in AD-related abnormal neuronal hyperactivity and higher incidence of spontaneous non-convulsive seizures. Here, we have shown that the reduction of VGSC α-subunit Nav1.6 (by injecting adeno-associated virus (AAV) with short hairpin RNA (shRNA) into the hippocampus) rescues cognitive impairments and attenuates synaptic deficits in APP/PS1 transgenic mice. Concurrently, amyloid plaques in the hippocampus and levels of soluble Aβ are significantly reduced. Interfering with Nav1.6 reduces the transcription level of β-site APP-cleaving enzyme 1 (BACE1), which is Aβ-dependent. In the presence of Aβ oligomers, knockdown of Nav1.6 reduces intracellular calcium overload by suppressing reverse sodium-calcium exchange channel, consequently increasing inactive NFAT1 (the nuclear factor of activated T cells) levels and thus reducing BACE1 transcription. This mechanism leads to a reduction in the levels of Aβ in APP/PS1 transgenic mice, alleviates synaptic loss, improves learning and memory disorders in APP/PS1 mice after downregulating Nav1.6 in the hippocampus. Our study offers a new potential therapeutic strategy to counteract hippocampal hyperexcitability and subsequently rescue cognitive deficits in AD by selective blockade of Nav1.6 overexpression and/or hyperactivity.

Experimental Neurology, 2022

Acute stress exerts pleiotropic actions on learning behaviors. The induced negative effects are s... more Acute stress exerts pleiotropic actions on learning behaviors. The induced negative effects are sometimes adopted to measure the efficacy of particular drugs. Until now, there are no detailed experimental data on the time-gradient effects of acute stress. Here, we developed the time gradient acute restraint stress (ARS) model to precisely assess the roles of different restrain times on inducing acute stress. Time gradient ARS facilitates escape behaviors and learning outcomes, peaking at 2 h-ARS and then declining to baseline at 3.5 h-ARS as confirmed by time gradient post-stress data. Furthermore, time gradient ARS activates glucocorticoid receptor (GR) phosphorylation site at Serine211 (P S221) as an inverted V-shaped pattern peaking at 2 h-ARS, whereas that of the GR phosphorylation site at Serine226 (P S226) from 2 h-ARS to 3.5 h-ARS. The 2 h-ARS but not 3.5 h-ARS enhances synaptic plasticity and genes transcription associated with learning and memory in the hippocampus of male mice. The Cdk5 inhibitor, roscovitine, blocks this facilitation effect by intervening in GR phosphorylation at Serine211 in the 2 h-ARS mice. Altogether, these findings show that the time gradient ARS selectively activates GR phospho-isoforms and differentially influences the behaviors along with maintaining a relationship between 2 h-ARS and Cdk5/GR P S211-mediated transcriptional activity.

Brain, Behavior, and Immunity, 2022

Tat-interacting protein 60 (TIP60) as nuclear receptors (NRs) coregulator, acts as a tumor suppre... more Tat-interacting protein 60 (TIP60) as nuclear receptors (NRs) coregulator, acts as a tumor suppressor and also has promising therapeutic potential to target Alzheimer's disease. Stress has been implicated in many psychiatric disorders, and these disorders are characterized by impairments in cognitive function. Until now, there are no experimental data available on the regulatory effect of TIP60 in acute stress and depression. There is also no definitive explanation on which specific modulation of target gene expression is achieved by TIP60. Here, we identify TIP60 as a novel positive regulator in response to acute restraint stress (ARS) and a potentially effective target of antidepressants. Firstly, we discovered increased hippocampal TIP60 expressions in the ARS model. Furthermore, using the TIP60 inhibitor, MG149, we proved that TIP60 function correlates with behavioral and synaptic activation in the two-hour ARS. Secondly, the lentivirus vector (LV)-TIP60overexpression (OE) was injected into the hippocampus prior to the chronic restraint stress (CRS) experiments and it was found that over-expressed TIP60 compensates for TIP60 decrease and improves depression index in CRS. Thirdly, through the intervention of TIP60 expression in vitro, we established the genetic regulation of TIP60 on synaptic proteins, confirmed the TIP60 function as a specific coactivator for PPARγ and found that the PPARγ-mediated TIP60 function modulates transcriptional activation of synaptic proteins. Finally, the LV-TIP60OE and PPARγ antagonist, GW9662, were both administered in the CRS model and the data indicated that blocking PPARγ significantly weakened the protective effect of TIP60 against the CRS-induced depression. Conclusively, these findings together support TIP60 as a novel positive factor in response to acute stress and interacts with PPARγ to modulate the pathological mechanism of CRS-induced depression.

Title: Sub-hypnotic dose of propofol as antiemetic prophylaxis attenuates intrathecal morphineind... more Title: Sub-hypnotic dose of propofol as antiemetic prophylaxis attenuates intrathecal morphineinduced postoperative nausea and vomiting, and pruritus in parturient undergoing cesarean section — a randomized control trial. Authors: Sylvanus Kampo (sylvanuskampo@yahoo.com) Alfred Afful (alfredo2k2@yahoo.com) Shiraj Mohammed (shirajm90@gmail.com) Michael Ntim (archangelmntim@yahoo.co.uk) Alexis Buunaaim (abuunaaim@yahoo.co.uk) Thomas Anabah (dranabah@gmail.com) Version: 3 Date: 26 Aug 2019 Author’s response to reviews: AUTHORS RESPONSE Dear Editor,

Science Journal of Clinical Medicine, 2018

Majority of noncommunicable diseases have strong association and are causally linked with four be... more Majority of noncommunicable diseases have strong association and are causally linked with four behavioral risk factors and these are the harmful use of alcohol, unhealthy diet, physical inactivity and tobacco use. The objective for this study was to determine the prevalence of alcohol consumption, smoking, physical activity, fruit and vegetable consumption among the participants and to determine the relationship between these risk factors and measures of obesity like body mass index, waist to hip ratio and waist circumference. This was a cross-sectional study undertaken in the outpatient clinics of Komfo Anokye Teaching Hospital (KATH) and a total of 424 patients were recruited. These were patients aged 20 years and over who were reporting for the first time to KATH. A questionnaire was administered (including the WHO STEPwise approach to Surveillance questionnaire) after obtaining informed consent, anthropometric measurements were then taken and blood investigations including fasti...

A thesis submitted to the Department of Materials Engineering of the Faculty of Materials and Che... more A thesis submitted to the Department of Materials Engineering of the Faculty of Materials and Chemical Engineering, in partial fulfillment of the requirement for the degree of MASTER OF SCIENCE, in Environmental Resources Management,2011

Journal of Advanced Research

Journal of Cellular and Molecular Medicine

PeerJ

Background Alzheimer’s disease (AD), being a complex disorder, is affected either by genetic or e... more Background Alzheimer’s disease (AD), being a complex disorder, is affected either by genetic or environmental factors or both. It is observed that there is an excessive accumulation of amyloid β (Aβ) in the extracellular space of the brain. AD is the first neurodegenerative disease in the elderly, and so far there is no effective treatment. In recent years, many studies have reported that Alzheimer’s disease has a relationship with gut microflora, indicating that regulating gut microbiota could offer therapeutic intervention for AD. This study explored the effect Bifidobacteria has in averting AD. Methods WT and APP/PS1 mice were used for the experiments. The mice were randomly assigned to four groups: WT group, WT + Bi group, AD group (APP/PS1 mouse) and AD + Bi group (Bifidobacteria-treated APP/PS1 mouse). Treatment with Bifidobacteria lasted for 6 months and mice were prepared for immunohistochemistry, immunofluorescence, Thioflavin S staining, Western blotting, PCR and Elisa qua...

Frontiers in Oncology

Background: The incidence of colorectal cancer (CRC) has been increasing worldwide in recent year... more Background: The incidence of colorectal cancer (CRC) has been increasing worldwide in recent years. Targeting cancer stem cells (CSCs) in CRC remains a difficult challenge. KDM2B and EZH2 play important role in the maintenance of CSCs' self-renewal capacity and tumorigenic ability; however, the biological functions of those genes in CRC remain unclear. In this study, we aimed to define the contribution of the expression of KDM2B in the features of CRC and establish the relationship between KDM2B and EZH2 in colorectal CSCs.Methods: The expression of KDM2B and EZH2 in the specimens of CRC and CRC cell lines were analyzed by immunohistochemistry, Western blot, and immunofluorescence. The underlying mechanisms of altered expressions of KDM2B and EZH2 and their impact on the biologic features of CRC and stemness in CRC were investigated.Results: The KDM2B gene was highly expressed in CRC tissues, and its overexpression positively correlated with tumor stages and tumor/node/metastasi...

Frontiers in Aging Neuroscience

BMC Health Services Research, Jan 29, 2020

BackgroundThe burden of hypertension in many low-and middle-income countries is alarming and requ... more BackgroundThe burden of hypertension in many low-and middle-income countries is alarming and requires effective evidence-based preventative strategies that is carefully appraised and accepted by key stakeholders to ensure successful implementation and sustainability. We assessed nurses’ perceptions of a recently completed Task Shifting Strategy for Hypertension control (TASSH) trial in Ghana, and facilitators and challenges to TASSH implementation.MethodsFocus group sessions and in-depth interviews were conducted with 27 community health nurses from participating health centers and district hospitals involved in the TASSH trial implemented in the Ashanti Region, Ghana, West Africa from 2012 to 2017. TASSH evaluated the comparative effectiveness of the WHO-PEN program versus provision of health insurance for blood pressure reduction in hypertensive adults. Qualitative data were analyzed using open and axial coding techniques with emerging themes mapped onto the Consolidated Framework for Implementation Research (CFIR).ResultsThree themes emerged following deductive analysis using CFIR, including: (1) Patient health goal setting- relative priority and positive feedback from nurses, which motivated patients to make healthy behavior changes as a result of their health being a priority; (2) Leadership engagement (i.e., medical directors) which influenced the extent to which nurses were able to successfully implement TASSH in their various facilities, with most directors being very supportive; and (3) Availability of resources making it possible to implement the TASSH protocol, with limited space and personnel time to carry out TASSH duties, limited blood pressure (BP) monitoring equipment, and transportation, listed as barriers to effective implementation.ConclusionAssessing stakeholders’ perception of the TASSH implementation process guided by CFIR is crucial as it provides a platform for the nurses to thoroughly evaluate the task shifting program, while considering the local context in which the program is implemented. The feedback from the nurses informed barriers and facilitators to implementation of TASSH within the current healthcare system, and suggested system level changes needed prior to scale-up of TASSH to other regions in Ghana with potential for long-term sustainment of the task shifting intervention.Trial registrationTrial registration for parent TASSH study: {"type":"clinical-trial","attrs":{"text":"NCT01802372","term_id":"NCT01802372"}}NCT01802372. Registered February 27, 2013.