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result(s) for
"Sayed, Shaheen"
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DEVELOPMENT OF THE LONGITUDINAL STUDY OF HEALTH AND AGEING IN KENYA (LOSHAK)
2023
Abstract
In Kenya, the number of adults aged ≥60 is expected to nearly quadruple by 2050, making it one of the most rapidly aging countries in Sub-Saharan Africa (SSA). Accordingly, we designed the Longitudinal Study of Health and Ageing in Kenya (LOSHAK) to generate novel data to address the health and economic consequences of this demographic transition. Modeled on the U.S. Health and Retirement Study (HRS), LOSHAK joins a network of harmonized studies on aging in >45 countries worldwide; however, LOSHAK will be only the second such study in SSA. LOSHAK will advance population aging research in low- and middle-income countries through the study of: (1) biomarkers and physiological measures; (2) the impacts of air pollution and climate vulnerability; (3) Alzheimer’s disease and related dementias, mental health, disability, caregiving, and psychosocial wellbeing; and (4) economic security, including the impact of social welfare. The current feasibility and initial pilot testing phase of LOSHAK is nested within the Kaloleni/Rabai Community Health and Demographic Surveillance System on the coast of Kenya and aims to validate measures and data collection procedures in a purposive sample of Kenyan adults aged ≥ 45 years. Among 205 participants surveyed, the mean age was 64 years, 58% were female, and 37% were currently employed. In the future, a full-scale Wave 1 LOSHAK will collect data from a nationally representative panel of Kenyans aged ≥45 years and will inform future public health and economic policy to address challenges related to rapid aging in Kenya and throughout SSA.
Journal Article
Alteration of MicroRNAs Regulated by c-Myc in Burkitt Lymphoma
2010
Burkitt lymphoma (BL) is an aggressive B-cell lymphoma, with a characteristic clinical presentation, morphology and immunophenotype. Over the past years, the typical translocation t(8;14) and its variants have been considered the molecular hallmark of this tumor. However, BL cases with no detectable MYC rearrangement have been identified. Intriguingly, these cases express MYC at levels comparable with cases carrying the translocation. In normal cells c-Myc expression is tightly regulated through a complex feedback loop mechanism. In cancer, MYC is often dysregulated, commonly due to genomic abnormalities. It has recently emerged that this phenomenon may rely on an alteration of post-transcriptional regulation mediated by microRNAs (miRNAs), whose functional alterations are associated with neoplastic transformation. It is also emerging that c-Myc modulates miRNA expression, revealing an intriguing crosstalk between c-Myc and miRNAs.
Here, we investigated the expression of miRNAs possibly regulated by c-Myc in BL cases positive or negative for the translocation. A common trend of miRNA expression, with the exception of hsa-miR-9*, was observed in all of the cases. Intriguingly, down-regulation of this miRNA seems to specifically identify a particular subset of BL cases, lacking MYC translocation. Here, we provided evidence that hsa-miR-9-1 gene is heavily methylated in those cases. Finally, we showed that hsa-miR-9* is able to modulate E2F1 and c-Myc expression.
Particularly, this study identifies hsa-miR-9* as potentially relevant for malignant transformation in BL cases with no detectable MYC translocation. Deregulation of hsa-miR-9* may therefore be useful as a diagnostic tool, suggesting it as a promising novel candidate for tumor cell marker.
Journal Article
Zingerone Attenuates Carfilzomib-Induced Cardiotoxicity in Rats through Oxidative Stress and Inflammatory Cytokine Network
by
Alshahrani, Saeed
,
Algassmi, Sameeh M.
,
Shaheen, Emad Sayed
in
Animals
,
Antioxidants
,
Antioxidants - metabolism
2022
Carfilzomib (CFZ) is an anticancer medication acting as a selective proteasome inhibitor. However, it can cause cardiovascular problems, increasing mortality and morbidity. This study aimed to investigate whether zingerone (ZRN) could help reduce carfilzomib-induced cardiotoxicity in Wistar albino rats. Rats were divided into five groups of six animals each. The first group received normal saline as a control (NC); the second group received multiple doses (six) of CFZ (4 mg/kg) intraperitoneally (IP); the third and fourth groups received zingerone (50 mg/kg and 100 mg/kg oral) along with six doses of CFZ for 16 days; and the fifth group received only 100 mg/kg zingerone orally. Hematological, biochemical, oxidative stress, and histopathological studies confirmed the findings of CFZ-induced cardiotoxicity. We found that ZRN significantly attenuated the effects of CFZ on oxidative stress by enhancing the antioxidant properties of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Additionally, ZRN reduces inflammatory cytokines and apoptotic markers, such as IL-1β, IL-6, TNFα, and caspase-3. Overall, zingerone prevents carfilzomib-induced cardiotoxicity in rats, as evidenced by histopathological studies.
Journal Article
Design and characterization of Lactotransferrin peptide-loaded dextran-docosahexaenoic acid nanoparticles: an immune modulator for hepatic damage
by
Shaheen, Emad Sayed
,
Madkhali, Osama A.
,
Alshammari, Abdulrahman
in
631/154
,
631/250
,
639/925
2023
The primary objective of this research was to create injectable delivery formulations using Lactotransferrin (LTF) peptide-loaded dextran nanoparticles coated with docosahexaenoic acid. These nanoparticles, designated as LLDDNP, underwent a lyophilization process. The study encompassed a comprehensive investigation, including physicochemical characterization, in vivo assessment of biomarkers, and an examination of immune response through cytokine modulation. The zeta potential of LLDDNP was − 24.5 ± 12 mV, while their average particle size was 334.9 z.d.nm. The particles exhibited a conductivity of 2.10 mS/cm, while their mobility in the injectable dosage form was measured at − 3.65 µm cm/Vs. The scanning electron microscopy investigation, the lyophilization processes resulted in discrete particles forming particle aggregations. However, transmission electron microscopy analysis revealed that LLDDNP is spherical and smooth. The thermogram showed that about 95% of LLDDNP's weight was lost at 270 °C, indicating that the particles are extremely thermal stable. The XRD analysis of LLDDNP exhibited clear and distinctive peaks at
2θ
angles, specifically at 9.6°, 20.3°, 21.1°, 22°, 24.6°, 25.2°, 36°, and 44.08°, providing compelling evidence of the crystalline nature of the particles. According to proton NMR studies, the proton dimension fingerprint region of LLDDNP ranges from 1.00 to 1.03 ppm. The in vitro release of LTF from LLDDNP was found to follow zero-order kinetics, with a commendable R
2
value of 0.942, indicating a consistent and predictable release pattern over time. The in vivo investigation revealed a significant impact of hepatotoxicity on the elevation of various cytokines, including IL-1β, IL-6, IL-8R, TNF-α, IL-2, IL-4, IL-10, and IFN-γ. Additionally, the presence of hepatotoxicity led to an increase in apoptosis markers, namely caspase 3 and caspase 9, as well as elevated levels of liver biomarkers such as CRP, ALP, ALT, and AST. In contrast, the treatment with LLDDNP modulated the levels of all biomarkers, including cytokines level in the treatment group extremely high significant at
p
< 0.001.
Journal Article
Cathine and cathinone disposition kinetics and neurotransmitter profile in several organs of rats exposed to a single dose of Catha edulis (Vahl) Forssk. ex Endl. extract
2023
Catha edulis (Vahl) Forssk. ex Endl. (Khat) is a stimulant plant that contains cathine and cathinone, which its abuses induce euphoria, alertness, and motor activity. Since the toxicokinetics of these substances remain unclear, this study was carried out to investigate the disposition kinetics of cathine and cathinone, the neurotransmitter profile, following a single dose of C. edulis extract in rats.Twenty-four adult male Wistar albino rats (250–300 g) were randomly selected and divided into six groups of four rats each. All groups received a single oral dose of 2,000 mg/kg body weight, and blood and tissue samples from the brain, lung, heart, liver, and kidney were obtained at intervals of 0.5, 1, 2.5, 5, 12, and 24 h. The cathine and cathinone concentrations were identified and quantified using ion trap ultra-high performance liquid chromatography (HPLC-IT/MS). The neurotransmitter profile was detected using the quadrupole time of flight UPLC-QTOF/MS method.The lung, liver, and heart tissues attained the highest levels of cathine, while the highest level of cathinone was determined in the heart. Cathine and cathinone concentrations in the blood and heart peaked at 0.5 h. The concentrations peaked in the brain 2.5 h later, indicating that the heart had an immediate effect, whereas the brain had a longer-lasting one. They have longer half-lives (2.68 and 5.07 h, respectively) and may remain in the brain for longer durations (3.31 and 2.31 h, respectively). The neurotransmitters epinephrine, dopamine, norepinephrine, and serotonin were detected in a delayed, prolonged and organ-specific manner.Cathine and cathinone were deposited in considerable concentrations in all tissues analyzed, with the highest Cmax in the lung and Tmax in the heart tissues but not in the brain. In addition, neurotransmitters such as adrenaline, dopamine, norepinephrine, and serotonin were differentially detected in all tested samples in a organ-specific fashion. More study is needed to identify cathine and cathinone’s effects on neurotransmitter profiles. Nevertheless, these findings provided a further basis for experimental, clinical, and forensic investigations.
Journal Article
Design, Characterization, and Immune Augmentation of Docosahexaenoic Acid Nanovesicles as a Potential Delivery System for Recombinant HBsAg Protein
by
Shaheen, Emad Sayed
,
Elmobark, Mohamed Eltaib
,
Salawi, Ahmad
in
Aluminum
,
Antibodies
,
Antigens
2022
Recombinant HBsAg-loaded docosahexaenoic acid nanovesicles were successfully developed, lyophilized (LRPDNV) and characterized for their physico-chemical properties. The zetapotential (ZP) of LRPDNV was −60.4 ± 10.4 mV, and its polydispersity (PDI) was 0.201, with a % PDI of 74.8. The particle sizes of LRPDNV were 361.4 ± 48.24 z. d.nm and 298.8 ± 13.4 r.nm. The % mass (r.nm) of LRPDNV in a colloidal injectable system was 50, its mobility value was −3.417 µm cm/Vs, while the conductivity of the particles was 0.728 (mS/cm). Transmission electron microscopic (TEM) analysis showed smooth morphological characteristics of discrete spherical LRPDNV. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of LRPDNV revealed that LRPDNV is thermostable. The X-ray diffraction (XRD) studies showed a discrete crystalline structure of LRPDNV at 2θ. Nuclear magnet resonance (NMR) studies (1H-NMR and 13C-NMR spectrum showed the discrete structure of LRPDNV. The immunogenicity study was performed by antibody induction technique. The anti-HBs IgG levels were elevated in Wistar rats; the antibody induction was observed more in the product (LRPDNV) treatment group when compared to the standard vaccine group. The level of antibodies on the 14th and 30th day was 6.3 ± 0.78 U/mL and 9.24 ± 1.76 U/mL in the treatment and standard vaccine groups, respectively. Furthermore, the antibody level on the 30th day in the treatment group was 26.66 ± 0.77 U/mL, and in the standard vaccine group, the antibody level was 23.94 ± 1.62 U/mL. The LRPDNV vaccine delivery method released HBsAg sustainably from the 14th to the 30th day. The results of this study indicate the successful formulation of DHA nanovesicles which have great potential as an adjuvant system for the delivery of recombinant HBsAg protein.
Journal Article
Adenomatoid Tumor of the Testis: A Report of Two Cases and Literature Review
2025
Testicular adenomatoid tumor is a rare benign condition that can resemble testicular malignancies in its clinical presentation, potentially leading to overtreatment, such as radical orchidectomy. In our two case reports, we aim to better understand the behavior of this disease by examining its clinical presentation, as well as radiological, intraoperative, and pathological findings.
Journal Article
Dementia risk reduction in the African context: Multi‐national implementation of multimodal strategies to promote healthy brain aging in Africa (the Africa‐FINGERS project)
by
Merali, Zul
,
Ogunyemi, Adedoyin
,
Bosire, Edna
in
Africa - epidemiology
,
Alzheimer's disease
,
Brain
2024
Dementia prevention in Africa is critically underexplored, despite the continent's high prevalence of modifiable risk factors. With a predominantly young and middle‐aged population, Africa presents a prime opportunity to implement evidence‐based strategies that could significantly reduce future dementia cases and mitigate its economic impact. The multinational Africa‐FINGERS program offers an innovative solution, pioneering culturally sensitive, multidomain interventions tailored to the unique challenges of the region. Leveraging insights from landmark global studies such as Worldwide‐FINGERS and Alzheimer's Disease Neuroimaging Initiative, the program employs a multideterminant precision prevention framework, grounded in community based systems dynamics. Africa‐FINGERS further integrates cutting‐edge state‐of‐the‐art multimodal biomarker evaluations tailored to regional contexts, with the goal of advancing brain health and establishing a global standard for dementia prevention. This groundbreaking initiative highlights the potential for scalableand sustainable interventions, thus is poised to transform dementia risk reduction efforts across the continent.
Highlights
Dementia rates are escalating in Africa, largely due to longer life spans and increased prevalence of modifiable risk factors. Yet, few regional interventions have directly targeted lifestyle factors to reduce dementia risk.
The multinational Africa‐FINGERS study will address this gap by adapting the successful FINGERS lifestyle intervention to African populations.
Africa‐FINGERS will pioneer a culturally informed, multidomain dementia risk reduction intervention in the African region through feasibility dementia prevention trials in rural and urban sites across Kenya and Nigeria in the first instance, enrolling 600 at‐risk adults (≥ 50 years). The program adopts participatory research methods to develop culturally appropriate interventions and build infrastructure to evaluate dementia biomarkers from ante and post mortem samples. A cost‐effectiveness analysis will be conducted to guide the strategic implementation of Africa‐FINGERS into regional health systems.
The Africa‐FINGERS strategy aligns with the Worldwide‐FINGERS framework and integrates the global Alzheimer's Disease Neuroimaging Initiative approach, emphasizing multimodal analysis.
Journal Article
Development of the Longitudinal Study of Health and Ageing in Kenya (LOSHAK)
2024
In Kenya, the number of adults aged ≥60 is expected to nearly quadruple by 2050, making it one of the most rapidly aging countries in Sub-Saharan Africa (SSA). Accordingly, we designed the Longitudinal Study of Health and Ageing in Kenya (LOSHAK) to generate novel data to address the health and economic consequences of this demographic transition. Specifically, LOSHAK will investigate the social, economic, environmental, biological, and policy processes that shape late-life health and economic well-being in Kenya. Modeled on the U.S. Health and Retirement Study (HRS), LOSHAK joins a network of harmonized studies on aging in >45 countries worldwide; however, LOSHAK will be only the 2nd such study in SSA. The current feasibility and pilot phase of LOSHAK will validate measures and data collection procedures in a purposive sample of Kenyan adults aged ≥45 years. We have linguistically and culturally translated instruments while aiming to maintain harmonization with both existing HRS network studies and the ongoing Kenya Life Panel Survey. The current phase of LOSHAK is nested within the Kaloleni/Rabai Community Health and Demographic Surveillance System on the coast of Kenya. LOSHAK will advance population aging research in low- and middle-income countries through the study of (a) biomarkers and physiological measures; (b) the impacts of air pollution and climate vulnerability; (c) Alzheimer’s disease and related dementias, mental health, disability, caregiving, and psychosocial wellbeing; and (d) economic security, including the impact of social welfare. LOSHAK will inform future public health and economic policy to address challenges related to rapid aging in Kenya and throughout SSA. Accordingly, this paper aims to introduce and provide a description of LOSHAK and its aims and objectives, as well as to inform the scientific community of current study activities being used to build toward the full population-representative study.
Journal Article
Hyphaene thebaica mart. extract attenuates oxidative stress and Bax- and Bcl-2-mediated apoptosis in ethanol-induced gastric ulcers in rats
by
Elhassan Taha, Manal
,
Shaheen, Emad
,
Madkhali, Ayman
in
Acetaldehyde
,
Alcohol
,
Alcohol, Denatured
2022
Objectives: Hyphaene thebaica Mart. (locally known as Doum) is a well-known tropical plant and is traditionally used for the treatment of gastrointestinal tract (GIT) ulcers. The current study aimed to investigate the antioxidative and gastroprotective properties of H. thebaica fruit rind extract against experimentally ethanol-induced gastric ulceration in Sprague-Dawley rats. Materials and Methods: Two experiments were carried out: first, with 20 animals for dose selection and safety of the extract; then, a second with 30 animals for the gastric ulcer model. The two selected doses of H. thebaica extract (250 and 500 mg/kg) and antiulcer drug (omeprazole: 20 mg/kg) were administered through oral gavage for 2 weeks prior to ulcer induction. Acidity, mucus weight, ulcer area, and histopathology were used to assess the gastroprotective effects of H. thebaica extract. The antioxidative properties were assessed using the lipid peroxidation assay, non-protein thiol levels, superoxide dismutase activity, nitric oxide assay, and immunohistochemical staining of mitochondria-regulated apoptosis proteins such as Bax and Bcl-2. Results: In the current study, no in vivo toxicity of H. thebaica extract was observed. In the gastric model, preadministration of H. thebaica resulted in a significant reduction in ulcer area and mucus weight in a dose-dependent manner. Moreover, gross and histological findings confirmed the gastroprotective properties of H. thebaica extract. Quantitative assessment of microscopic lesions revealed a significant difference between the groups. These properties were observed to be mediated through the modulation of oxidative stress. H. thebaica modulated the Bcl-2 and Bax proteins and inhibited apoptosis. Conclusion: The gastroprotective properties of H. thebaica nominate it as a potential nutraceutical candidate.
Journal Article