Endoplasmic reticulum stress in pancreatic ß-cell dysfunction: The potential therapeutic role of dietary flavonoids.

Diabetes mellitus (DM) is a global health burden that is characterized by the loss or dysfunction of pancreatic ß-cells. In pancreatic ß-cells, endoplasmic reticulum (ER) stress is a fact of life that contributes to ß-cell loss or dysfunction. Despite recent advances in research, the existing treatment approaches such as lifestyle modification and use of conventional therapeutics could not prevent the loss or dysfunction of pancreatic ß-cells to abrogate the disease progression. Therefore, targeting ER stress and the consequent unfolded protein response (UPR) in pancreatic ß-cells may be a potential therapeutic strategy for diabetes treatment. Dietary phytochemicals have therapeutic applications in human health owing to their broad spectrum of biochemical and pharmacological activities. Flavonoids, which are commonly obtained from fruits and vegetables worldwide, have shown promising prospects in alleviating ER stress. Dietary flavonoids including quercetin, kaempferol, myricetin, isorhamnetin, fisetin, icariin, apigenin, apigetrin, vitexin, baicalein, baicalin, nobiletin hesperidin, naringenin, epigallocatechin 3-O-gallate hesperidin (EGCG), tectorigenin, liquiritigenin, and acacetin have shown inhibitory effects on ER stress in pancreatic ß-cells. Dietary flavonoids modulate ER stress signaling components, chaperone proteins, transcription factors, oxidative stress, autophagy, apoptosis, and inflammatory responses to exert their pharmacological effects on pancreatic ß-cells ER stress. This review focuses on the role of dietary flavonoids as potential therapeutic adjuvants in preserving pancreatic ß-cells from ER stress. Highlights of the underlying mechanisms of action are also presented as well as possible strategies for clinical translation in the management of DM.

Assessment of Treatment Outcomes in the Management of Club foot using the Ponseti Technique: A cross-sectional study.

BACKGROUND: The Ponseti technique remains the preferred method for club foot treatment. Although measures of treatment outcomes have been well documented, there is no consensus on the determinants of those outcomes. This study aims to assess treatment outcomes and the factors which can influence treatment outcomes. MATERIALS AND METHODS: This is a cross-sectional study. A total of 472 children representing 748 feet in total were recruited. Patient characteristics such as age at presentation, gender, tenotomy, walking with or without deformity, parental educational status and occupation were documented. Outcomes of care were assessed using indictors such as parents' satisfaction with the outcome of treatment and the patients' ambulation without deformity. The relationships between the determinant factors and these outcomes were explored using multivariable binary logistic regression. RESULTS: Most of the children (69.1%) were aged below 2 years. Brace compliance was very high (89.9%). The pre-treatment average Pirani scores were 3.9 ± 1.8 and 4.3 ± 1.8 for the right and left feet, respectively. Majority (88.3%) of the children achieved ambulation without deformity, whereas most (87%) of the parents were satisfied with the treatment outcomes. In total, parental satisfaction with child's treatment outcomes was lower in parents who were not formally educated odds ratio (OR) = 0.19 (95% confidence interval [CI] 0.08-0.43), but parental satisfaction was lower if the child had higher Pirani score OR = 0.77 (95% CI 0.62-0.96). Children who had more casts applied to the affected foot were more likely to walk without deformity OR = 1.24 (95% CI 1.01-1.52). CONCLUSIONS: This study revealed that treatment outcomes in children with club foot can be determined by some sociodemographic and treatment-related factors.

Nourishing the Mind: How Food Security Influences Mental Wellbeing.

Food insecurity is a significant public health problem worldwide and critical to mental health. There is a complex relationship between food security and mental health. We carried out a narrative review study aiming to address how food insecurity impacts mental wellbeing by focusing on the mental health repercussions of food insecurity, recognizing its pivotal role in attaining Sustainable Development Goals 2 (on hunger) and 3 (on enhancing global wellbeing). A comprehensive search was conducted on PubMed and Google Scholar, incorporating Google searches for pertinent reports and policy documents. To address these questions, we emphasized and elucidated the interconnectedness between food security and mental health. The review shows that food security and mental health share a profound relationship influenced by multifaceted factors like socioeconomic conditions, access to nutritious food, and societal inequalities. We then provide recommendations for integrating food security into mental health strategies based on the insights and conclusions drawn. Strategies ranging from sustainable farming practices to urban agriculture initiatives and digital mental health services demonstrate avenues for enhancing food safety and mental wellbeing. This highlights the need for collaborative interdisciplinary efforts and systemic reforms to address these interconnected challenges.

Novel loss-of-function variants expand ABCC9-related intellectual disability and myopathy syndrome.

Loss-of-function mutation of ABCC9, the gene encoding the SUR2 subunit of ATP sensitive-potassium (KATP) channels, was recently associated with autosomal recessive ABCC9-related intellectual disability and myopathy syndrome (AIMS). Here we identify nine additional subjects, from seven unrelated families, harbouring different homozygous loss-of-function variants in ABCC9 and presenting with a conserved range of clinical features. All variants are predicted to result in severe truncations or in-frame deletions within SUR2, leading to the generation of non-functional SUR2-dependent KATP channels. Affected individuals show psychomotor delay and intellectual disability of variable severity, microcephaly, corpus callosum and white matter abnormalities, seizures, spasticity, short stature, muscle fatigability and weakness. Heterozygous parents do not show any conserved clinical pathology but report multiple incidences of intra-uterine fetal death, which were also observed in an eighth family included in this study. In vivo studies of abcc9 loss-of-function in zebrafish revealed an exacerbated motor response to pentylenetetrazole, a pro-convulsive drug, consistent with impaired neurodevelopment associated with an increased seizure susceptibility. Our findings define an ABCC9 loss-of-function-related phenotype, expanding the genotypic and phenotypic spectrum of AIMS and reveal novel human pathologies arising from KATP channel dysfunction.

KNOWLEDGE OF ANTIMICROBIAL DRUG RESISTANCE (AMR) AMONG PATIENTS IN A GENERAL OUTPATIENT CLINIC IN ABUJA MUNICIPAL AREA COUNCIL (AMAC), FEDERAL CAPITAL TERRITORY, NIGERIA.

Introduction: Antimicrobial resistance (AMR) is currently prevalent and has the potential to affect everyone, of any age, in any country. In humans, animals, and the environment, antimicrobial-resistant microbes are quickly emerging and spreading. This study aims to assess the knowledge of Antimicrobial Drug Resistance (AMR) among patients in a General Outpatient Clinic in Abuja Municipal Area Council (AMAC), Federal Capital Territory, Nigeria. Methodology: This was a descriptive cross-sectional study among 400 clients in a district hospital done in 2022 using a multistage sampling technique. Data was collected using a self-administered structured questionnaire and analyzed and presented as tables, proportions, and percentages using the IBM SPSS 28 Statistical Package for the Social Sciences. Ethical approval was granted by Bingham University Teaching Hospital Ethical Research Committee, Jos, and Plateau State. Results: The study revealed that 8.5% of female respondents had good knowledge, 20.75% had fair knowledge while 27.75% had poor knowledge. Of all the male respondents, 8.5% had good knowledge, 13% had fair knowledge and 21.5% had poor knowledge. Summarily, only 68 (17.0%) of participants had good knowledge of antimicrobial resistance, 135 (33.75%) had fair knowledge of antimicrobial resistance, and 197 (49.25%) had poor knowledge of antimicrobial resistance. Test of association between knowledge of antimicrobial resistance and socio-demographics showed that marital status (χ² = 44.28, p < 0.045), Education (χ²= 123.80, p < 0.001), and Age (χ² = 112.95, p < 0.001) were statistically significant. Conclusion: The Federal, State, and Local governments, health care providers, and community health workers should focus on increasing awareness of AMR risk factors through health campaigns and programs that will aid behavioral change.

Pharmacological Potential of Betulin as a Multitarget Compound.

Betulin is a natural triterpene, usually from birch bark, known for its potential wound-healing properties. Despite having a wide range of pharmacological targets, no studies have proposed betulin as a multitarget compound. Betulin has protective effects against cardiovascular and liver diseases, cancer, diabetes, oxidative stress, and inflammation. It reduces postprandial hyperglycemia by inhibiting α-amylase and α-glucosidase activity, combats tumor cells by inducing apoptosis and inhibiting metastatic proteins, and modulates chronic inflammation by blocking the expression of proinflammatory cytokines via modulation of the NFκB and MAPKs pathways. Given its potential to influence diverse biological networks with high target specificity, it can be hypothesized that betulin may eventually become a new lead for drug development because it can modify a variety of pharmacological targets. The summarized research revealed that the diverse beneficial effects of betulin in various diseases can be attributed, at least in part, to its multitarget anti-inflammatory activity. This review focuses on the natural sources, pharmacokinetics, pharmacological activity of betulin, and the multi-target effects of betulin on signaling pathways such as MAPK, NF-κB, and Nrf2, which are important regulators of the response to oxidative stress and inflammation in the body.

Phytochemicals and bioactive compounds effective against acute myeloid leukemia: A systematic review.

This systematic review identified various bioactive compounds which have the potential to serve as novel drugs or leads against acute myeloid leukemia. Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy that arises from the dysregulation of cell differentiation, proliferation, and cell death. The risk factors associated with the onset of AML include long-term exposure to radiation and chemicals such as benzene, smoking, genetic disorders, blood disorders, advancement in age, and others. Although novel strategies to manage AML, including a refinement of the conventional chemotherapy regimens, hypomethylating agents, and molecular targeted drugs, have been developed in recent years, resistance and relapse remain the main clinical problems. In this study, three databases, PubMed/MEDLINE, ScienceDirect, and Google Scholar, were systematically searched to identify various bioactive compounds with antileukemic properties. A total of 518 articles were identified, out of which 59 were viewed as eligible for the current report. From the data extracted, over 60 bioactive compounds were identified and divided into five major groups: flavonoids, alkaloids, organosulfur compounds, terpenes, and terpenoids, and other known and emerging bioactive compounds. The mechanism of actions of the analyzed individual bioactive molecules differs remarkably and includes disrupting chromatin structure, upregulating the synthesis of certain DNA repair proteins, inducing cell cycle arrest and apoptosis, and inhibiting/regulating Hsp90 activities, DNA methyltransferase 1, and histone deacetylase 1.

Wnt/ß-catenin signaling pathway inhibitors, glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside-1, diosmin, and rutin in medicinal plants have better binding affinities and anticancer properties: Molecular docking and ADMET study.

Wnt/ß-catenin signaling pathway plays a role in cancer development, organogenesis, and embryogenesis. The abnormal activation promotes cancer stem cell renewal, proliferation, and differentiation. In the present study, molecular docking simulation and ADMET studies were carried out on selected bioactive compounds in search of ß-catenin protein inhibitors for drug discovery against cancer. Blind docking simulation was performed using PyRx software on Autodock Vina. ß-catenin protein (PDB ID: 1jdh) and 313 bioactive compounds (from PubChem database) with selected standard anticancer drugs were used for molecular docking. The ADMET properties of the best-performing compounds were calculated using SwissADME and pkCMS web servers. The results obtained from the molecular docking study showed that glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside-1, diosmin, and rutin had the best binding interactions with ß-catenin protein based on their binding affinities. Glycyrrhizic acid and solanine had the same and lowest binding energy of -8.5 kcal/mol. This was followed by polyphyllin I with -8.4 kcal/mol, and crocin, hypericin, and tubeimoside-1 which all had a binding energy of 8.1 kcal/mol. Other top-performing compounds include diosmin and rutin with binding energy of -8.0 kcal/mol. The ADMET study revealed that the following compounds glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside-1, diosmin, rutin, and baicalin all violated Lipinski's rule of 5 which implies poor oral bioavailability. However, based on the binding energy score, it was suggested that these pharmacologically active compounds are potential molecules to be tested against cancer.

Thrombotic Risk Assessment in Patients with Lymphoid Neoplasm seen at the Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State.

BACKGROUND: Venous thromboembolism (VTE) is a cause of increased morbidity and mortality in cancer patients. VTE is the second leading cause of death in cancer patients. Risk assessment models have been developed to identify patients at risk of VTE for thromboprophylaxis. Risk scores of patients in our environment have not been adequately investigated. OBJECTIVE: The study evaluates the association of thrombotic risk assessment scores (using the modified Khorana risk assessment tool) and soluble P-selectin levels with thrombotic events in patients with lymphoid cancer. METHODS: This is a comparative cross-sectional study conducted at Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, Anambra State). Forty-five patients with lymphoid malignancy and 45 apparently healthy subjects participated in the study. The modified Khorana risk assessment score was used to assess cancer-associated thrombotic risk. Blood sample was collected for soluble P-selectin estimation. Data were analyzed with SPSS version 23. RESULTS: The age of subjects with lymphoid neoplasm and controls were 49.1±15.8 years, and 49.6±11.1 years respectively (p = 0.548). Subjects with lymphoid neoplasm consist of 26 (57.8%) males and 19 (42.2%) females while the controls consist of 25 (55.6%) males and 20 (44.4%) females. Non-Hodgkin's lymphoma was the most frequent of lymphoid neoplasm (18, 40.0%), followed by multiple myeloma (10, 22%), CLL (9, 20%), ALL (6, 13.0%) and Hodgkin's lymphoma (2, 4.0%). Thirty-five (77.8%) subjects with lymphoid neoplasm had intermediate risk scores and 10 (22.2%) had high-risk scores. Nineteen (42.2%) of the controls had intermediate risk and 26 (57.8%) low risk. The differences in proportion were statistically significant (p < 0.001). The median (IQR) levels of soluble P-selectin were significantly higher in patients with lymphoid neoplasm (12.2 vs. 7.0ng/mL, p <0.001). Three (6.6%) patients with lymphoid malignancies had deep vein thrombosis confirmed by a Doppler ultrasound scan. CONCLUSION: Lymphoid malignancy is associated with relatively higher thrombotic risk scores, sP-selectin levels, and venous thromboembolic events. CONTEXTE: La thromboembolie veineuse (TEV) est une cause de morbidité et de mortalité accrues chez les patients atteints de cancer. La TEV est la deuxième cause de décès chez les patients atteints de cancer. Des modèles d'évaluation des risques ont été mis au point pour identifier les patients présentant un risque de TEV en vue d'une thromboprophylaxie. Les scores de risque des patients dans notre environnement n'ont pas été étudiés de manière adéquate. OBJECTIF: L'étude évalue l'association des scores d'évaluation du risque thrombotique (en utilisant l'outil modifié d'évaluation du risque de Khorana) et des niveaux de P-sélectine soluble avec les événements thrombotiques chez les patients atteints d'un cancer lymphoïde. MÉTHODES: Il s'agit d'une étude transversale comparative menée au Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, État d'Anambra). Quarante-cinq patients atteints d'un cancer lymphoïde et 45 sujets apparemment sains ont participé à l'étude. Le score modifié d'évaluation du risque de Khorana a été utilisé pour évaluer le risque thrombotique associé au cancer. Un échantillon de sang a été prélevé pour l'estimation de la P-sélectine soluble. Les données ont été analysées avec SPSS version 23. RÉSULTATS: L'âge des sujets atteints de néoplasme lymphoïde et des témoins était respectivement de 49,1±15,8 ans et 49,6±11,1 ans (p = 0,548). Les sujets atteints de néoplasme lymphoïde sont 26 (57,8 %) hommes et 19 (42,2 %) femmes, tandis que les témoins sont 25 (55,6 %) hommes et 20 (44,4 %) femmes. Le lymphome non hodgkinien était le néoplasme lymphoïde le plus fréquent (18, 40 %), suivi du myélome multiple (10, 22 %), de la LLC (9, 20 %), de la LAL (6, 13 %) et du lymphome hodgkinien (2, 4 %). Trente-cinq (77,8 %) sujets atteints de néoplasmes lymphoïdes présentaient un score de risque intermédiaire et 10 (22,2 %) un score de risque élevé. Dix-neuf (42,2 %) des témoins présentaient un risque intermédiaire et 26 (57,8 %) un risque faible. Les différences de proportion étaient statistiquement significatives (p < 0,001). Les niveaux médians (IQR) de P-sélectine soluble étaient significativement plus élevés chez les patients atteints de néoplasme lymphoïde (12,2 vs. 7,0 ng/mL, p <0,001). Trois (6,6 %) patients atteints de tumeurs lymphoïdes ont présenté une thrombose veineuse profonde confirmée par une échographie Doppler. CONCLUSION: Les tumeurs malignes lymphoïdes sont associées à des scores de risque thrombotique, des taux de sP-sélectine et des événements thromboemboliques veineux relativement plus élevés. Mots-clés: Malignité lymphoïde, Thrombose, P-sélectine soluble, Scores d'évaluation du risqué.

Haematological and biochemical toxicity in freshwater fish Clarias gariepinus and Oreochromis niloticus following pulse exposure to atrazine, mancozeb, chlorpyrifos, lambda-cyhalothrin, and their combination.

Transient exposures to high or low concentrations of a single or mixture of pesticides are common in aquatic organisms. Routine toxicity tests disregard transient exposures and the influence of time when examining the toxicity of contaminants. This study investigated the haematological and biochemical responses of juvenile C. gariepinus and O. niloticus to pesticide pulse exposure using three exposure patterns. The patterns include 4-hour pulse exposure to a high pesticide concentration, then 28 days of depuration, continuous exposure to a low pesticide concentration for 28 days, and 4-hour pulse exposure to a high concentration followed by continuous exposure to a low pesticide concentration for 28 days. On days 1, 14, and 28, fish samples were collected for haematological and biochemical analysis. Results showed that red blood cell count, packed cell volume, haemoglobin, platelet count, total protein, and sodium ion decreased, while white blood cell count, total cholesterol, bilirubin, urea, and potassium ion increased in both fish species after pulse, continuous and pulse & continuous exposure to the pesticides (p < 0.05). However, pulse exposure to the pesticides did not significantly affect alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase activity, and creatinine levels. The changes in these biomarkers indicate that 4-hour pulse exposure to high concentration was as hazardous as 24-hour continuous exposure to low pesticide concentration (p > 0.05). The toxic effects of pulse exposure were largely reversible by day 14. Using C. gariepinus and O. niloticus, this study shows that brief exposure to high pesticide pesticides was as hazardous as continuous pesticide exposure.

Ameliorative Effect of Rice Husk Methanol Extract on Liver and Kidney Toxicities Induced by Subchronic Codeine Administration.

Background and Objective. Rice husk remains a key by-product of rice milling generated in significant amount. Accumulated evidence indicates that rice husk contains numerous bioactive compounds; however, its application is limited. This study was designed to introduce an in vivo application of rice husk extract, against opioid-induced liver and kidney injuries. Codeine was considered a psychotic inducer in this study due to its global alarming misuse recently. The hepatorenal ameliorative proclivity of rice husk extract against codeine-induced toxicity on the liver and kidney in male albino Wistar rats was examined. To this effect, thirty-six (36) albino Wistar rats of weight 100-110 g were utilized and weight-matched animals placed in 6 groups of 6 rats each. After 30 days of the combined administration of codeine and the rice husk extract, the experimental animals were assayed for basic liver and renal markers such as AST, ALP, ALT, total protein, albumin, conjugated and total bilirubin, urea, creatinine, and electrolytes (sodium, potassium, chloride, and bicarbonate). Rice husks were collected from a local rice mill, and the extraction was done with methanol. Findings. Rice husk extract (RHE) significantly ameliorated the recorded hepatic damage. More so, the extract showed a significant action on the renal markers as well. A histopathology examination of the liver and kidney tissues revealed that RHE showed a hepatorenal ameliorative potential in a dose-dependent manner. Conclusion. Phytonutrient from RH possesses a healing ability against opioid-induced hepatorenal toxicity. Thus, RH is safe for human and may be adopted to obviate and manage codeine-induced hepatorenal damage or injury. Significance and Novelty. Data on the application of RHE as a phytonutrient to combat liver and kidney injuries were demonstrated. Future studies should evaluate its potential on other organs.

Antimicrobial use among paediatric inpatients in a Nigerian tertiary hospital: A three-year point prevalence survey.

Aim: Antimicrobials are among the most widely prescribed therapeutic agents among paediatric population. Irrational use of these agents increases the risk of antimicrobial resistance. We described the prevalence and pattern of antimicrobial use among paediatric inpatients from 2017 to 2019. Subject and Method: The study was a repeated point prevalence survey over a 3-year period using the global point prevalence standardized tools among all paediatric inpatients. The prevalence of antimicrobial use, the prescription indicators and patterns of antimicrobial use were estimated. Result: Among 191 paediatric inpatients assessed, the 3-year period prevalence antimicrobial use was 85.9% (164/191) with prevalence of 80.6% in 2017, 94.6% in 2018, and 83.6% in 2019. Antimicrobial agents used ranged from one agent (20.1%) to five different agents (5.5%). Parenteral route (66.6%) was the preferred route of administration. The reason for the use of antimicrobial agents (92.6%) and the stop/review date (99.5%) were mostly well documented. Only 4.5% of the antimicrobial use were targeted. There were no antimicrobial guidelines or policy guiding the use of antimicrobial agents, except the national guideline on the treatment of malaria and tuberculosis. Ceftriaxone, a third generation cephalosporin was the most commonly used agent across the period under review. Community-acquired infection was the commonest indication for antimicrobial use. Conclusion: Our findings of high antimicrobial prevalence has raised the attention for the need to develop hospital-based antimicrobial guideline and antimicrobial stewardship program to protect the vulnerable children, their contacts and the environment from the impact of antimicrobial resistance.

Reversal and Preventive Pleiotropic Mechanisms Involved in the Antipsychotic-Like Effect of Taurine, an Essential ß-Amino Acid in Ketamine-Induced Experimental Schizophrenia in Mice.

Schizophrenia is a life disabling, multisystem neuropsychiatric disease mostly derived from complex epigenetic-mediated neurobiological changes causing behavioural deficits. Neurochemical disorganizations, neurotrophic and neuroimmune alterations are some of the challenging neuropathologies proving unabated during psychopharmacology of schizophrenia, further bedeviled by drug-induced metabolic derangements including alteration of amino acids. In first-episode schizophrenia patients, taurine, an essential ß-amino acid represses psychotic-symptoms. However, its anti-psychotic-like mechanisms remain incomplete. This study evaluated the ability of taurine to prevent or reverse ketamine-induced experimental psychosis and the underlying neurochemical, neurotrophic and neuroinmune mechanisms involved in taurine's clinical action. The study consisted of three different experiments with Swiss mice (n = 7). In the drug alone, mice received saline (10 mL/kg/p.o./day), taurine (50 and 100 mg/kg/p.o./day) and risperidone (0.5 mg/kg/p.o./day) for 14 days. In the preventive study of separate cohort, mice were concomitantly given ketamine (20 mg/kg/i.p./day) from days 8 to 14. In the reversal study, mice received ketamine for 14 days before taurine or risperidone treatments from days 8 to 14 respectively. Afterwards, stereotypy behaviour, social, non-spatial memory deficits, and body weights were assessed. Neurochemical (dopamine, 5-hydroxytryptamine, glutamic acid decarboxylase, (GAD)), brain derived-neurotrophic factor (BDNF) and pro-inflammatory cytokines [tumor necrosis factor-alpha, (TNF-α), interleukin-6, (IL-6)] were assayed in the striatum, prefrontal-cortex and hippocampal area. Taurine attenuates ketamine-induced schizophrenia-like behaviour without changes in body weight. Taurine reduced ketamine-induced dopamine and 5-hydroxytryptamine changes, and increased GAD and BDNF levels in the striatum, prefrontal-cortex and hippocampus, suggesting increased GABAergic and neurotrophic transmissions. Taurine decreases ketamine-induced increased in TNF-α and IL-6 concentrations in the striatum, prefrontal-cortex and hippocampus. These findings also suggest that taurine protects against schizophrenia through neurochemical modulations, neurotrophic enhancement, and inhibition of neuropathologic cytokine activities.

Development and formulation of antidiabetic property of Anarcadium occidantale-based solid lipid microparticles.

Anacardium occidentale (AO) possesses potent anti-diabetic properties, owing to its high phytochemicals content. This study attempted to maximise the efficacy of AO by encapsulating it in a solid lipid microparticle (SLMs) formulation. Leaves of AO were extracted with water and formulated into SLMs using a lipid matrix composed of P90H and Dika fat. Characterisation of the SLMs include morphology, particle size, pH, encapsulation efficiency percentage, in vitro release and anti-diabetic properties. SLMs were spherical with sizes ranging from 16.7 ± 0.8 µm to 40.12 ± 2.34 µm and had a fairly stable pH over time. Highest drug entrapment was 87%. Batch A2 exhibited an even release of 89%, sustained over time, and a mean percentage reduction in glucose of 25.9% at 12 h after oral administration to study animals. Anacardium occidentale-loaded SLMs exhibited a good hypoglycaemic effect and can be used in the management of diabetes.

Potential Role of Polyphenolic Flavonoids as Senotherapeutic Agents in Degenerative Diseases and Geroprotection.

Cellular senescence, a hallmark of ageing, contributes to tissue or organ dysfunction and the pathophysiology of diverse age-related diseases (ARD) by various mechanisms. Targeting it by selective elimination of senescent cells (SCs) or blocking senescence-associated secretory phenotypes (SASP) with natural or synthetic compounds has been suggested to improve lifespan. Dietary phytochemicals possess a broad spectrum of biochemical and pharmacological effects that are beneficial to human health. Flavonoids, which are widely consumed in fruits and vegetables worldwide, are emerging as potential therapeutic agents to mitigate senescence. Naringenin, hesperetin, hesperidin, quercetin, fisetin, kaempferol, rutin, apigenin, luteolin, nobiletin, tangeretin, genistein, wogonin, epigallocatechin gallate (EGCG), theaflavin-3-gallate (TF2A), and procyanidin C1 possess potent antisenescence effects. A single biochemical process may not explain their pleiotropic pharmacological impact. Flavonoids directly modulate underlying cellular senescence processes or interact with molecular targets that regulate ageing-related pathways. This review discusses the potential use of flavonoids to mitigate senescence and consequently delay the onset of ageing-related diseases. We also highlight the underlying mechanisms of action of flavonoids as potential senotherapeutics and reflect on future perspectives and possible strategies to optimize and increase the translatability from bench to bedside in senotherapy.

Zoom-based GROW coaching intervention for improving subjective well-being in a sample of school administrators: A randomized control trial.

Background/objective: Poor subjective well-being is a risk factor for poor health; and threatens school administrators' leadership roles and overall occupational and personal outcomes. Online digital care and coaching such as Zoom-delivered GROW (Z-GROW) coaching may be an invaluable approach to building resilience and improving well-being. This study investigated the effectiveness of the Z-GROW coaching model in enhancing self-reported well-being in a sample of school administrators in South-East Nigeria. Method: A randomized control trial was conducted with a sample of 109 school administrators who met the inclusion criteria. Participants were allocated into Z-GROW (N = 55) and waitlist control (N = 54) groups. A 2-hour Z-GROW programme was delivered to the Z-GROW intervention group weekly for 9 weeks. Subjective well-being was measured using the Satisfaction with Life Scale (SWLS), the Scale of Positive and Negative Experience (SPANE), and the Flourishing Scale (FS). Data were collected on three occasions: pre-intervention, post-intervention, and follow-up using the same measures. All data were analyzed using descriptive and inferential statistics. The presentation of data was supported by figures and charts. Results: Results revealed that school administrators' three dimensions of subjective well-being significantly improved following the Z-GROW intervention. It was further shown that the improved state of participants was sustained through a 3-monthfollow-up assessment. Conclusion: Based on the findings, it can be concluded that intervention using GROW coaching in the zoom platform improves the self-reported well-being of school administrators. The outcomes of this study present the Z-GROW model as a viable intervention for subjective well-being and other mental health conditions among school administrators. Through the Z-GROW model, employees can access occupational health coaching from the comfort of their homes.

Antidiabetic effects of Psidium x durbanensis Baijnath & Ramcharun ined. (Myrtaceae) leaf extract on streptozotocin-induced diabetes in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psidium guajava L. leaves are used to treat diabetes in South African folkloric medicine and in other parts of the world. Psidium x durbanensis Baijnath & Ramcharun ined. (PD) is a natural sterile hybrid and congener of Psidium guajava that is expected to share the medicinal properties of the genus Psidium and is widely distributed in South Africa. AIM OF THE STUDY: This study investigates the antioxidant, antidiabetic effects, and mechanisms of action of hydro-methanolic leaf extracts of PD on streptozotocin-induced diabetes in rats. MATERIAL AND METHODS: Phytochemical constituents of hydro-methanolic extract of PD were analyzed by gas chromatography-mass spectrometry (GC-MS). Male Wistar rats 250-300 g body weight (BW) were rendered diabetic after a single intraperitoneal injection with streptozotocin, 45 mg/kg BW. The diabetic rats were treated with hydro-methanolic (20:80 v/v) leaf extracts of PD (400 mg/kg/BW) or subcutaneous injections of regular insulin (2.0U/kg/BW, bid) for 56 days. The body weights of the animals were recorded daily. Fasting blood glucose, glucose tolerance tests, and insulin resistance index were measured. The effects of the extracts on total superoxide dismutase, catalase, and reduced glutathione activities, histopathology, and gene expression of insulin receptor substrate 1 and glucose transporter 4 were determined in the liver, pancreas, and gastrocnemius muscles of the rats. RESULTS: In the acute toxicity studies, there were no signs of toxicity observed for PD up to 2000 mg/kg BW doses. Diabetic animals showed significant weight loss, elevated and reduced fasting blood glucose and insulin, respectively, impaired glucose tolerance and diminished antioxidant enzymes' activities compared to controls. Treatment with PD hydro-methanolic leaf extracts improved body weight, glucose tolerance, insulin resistance, and antioxidant enzymes but not plasma insulin in diabetic animals compared to controls, respectively. GC-MS analysis identified organic acids, alcohols, vitamins, terpenoids, and esters in the extracts. Treatment with PD improved glucose uptake by stimulating mRNA expression of GLUT 4 in gastrocnemius muscles of diabetic animals compared to the untreated control and also restored histological aberrations in the pancreas and liver of diabetic rats compared with the untreated control rats. CONCLUSION: Collectively, the present study suggests that treatment with PD leaf extracts significantly ameliorated diabetes symptoms and oxidative stress in rats, and these effects may be linked to the bioactive phytoconstituents present in the plant. This study further suggests that PD improves insulin resistance by increasing glucose uptake in gastrocnemius muscles in an insulin-independent manner.

Ficus exasperata Attenuates Acetaminophen-Induced Hepatic Damage via NF-κB Signaling Mechanism in Experimental Rat Model.

Ficus exasperata has been used to treat ulcer, diabetes, fever, and a variety of stress-related disorders. Acetaminophen (APAP) overdose is the most common cause of drug-induced acute liver injury. In this study, we evaluated the hepatoprotective effect and antioxidant capacity of ethanolic extract of F. exasperata (EFE) on acetaminophen-induced hepatotoxicity in albino rats. Rats were pretreated with EFE (150, 250, 500 mg/kg) and thereafter received 250 mg/kg APA intraperitoneally (i.p.). The normal control group received distilled water, while the negative control group received 250 mg/kg APAP, respectively. Hepatotoxicity and oxidative stress-antioxidant parameters were then assessed. Flavonoids, saponins, steroids, and glycosides, but not phenolics were detected by EFE phytochemical analysis. No mortality was recorded on acute exposure of rats to varying concentrations of APAP after 24 h; however, a dose-dependent increase in severity of convulsion, urination, and hyperactivity was observed. APAP overdose induced high AST, ALT, ALP, and total bilirubin levels in the serum, invoked lipid peroxidation, depleted GSH, decreased CAT, SOD, and GST levels, respectively. Nitric oxide (NO) level, myeloperoxidase activity, TNF-α, IL-1ß, NF-κB, COX-2, MCP-1, and IL-6 were also increased. Importantly, pretreatment of rats with EFE before acetaminophen ameliorated and restored cellular antioxidant status to levels comparable to the control group. Our results show and suggest the hepatoprotective effect of F. exasperata and its ability to modulate cellular antioxidant status supports its use in traditional medicine and renders it safe in treating an oxidative stress-induced hepatic injury.

Pharmaceutical and personal care products as emerging environmental contaminants in Nigeria: A systematic review.

The increasingly broad and massive use of pharmaceuticals (human, veterinary) and personal care products in industrially developing nations makes their uncontrolled environmental and ecological impact a true concern. Focusing on Nigeria, this systematic literature search (databases: PubMed, ScienceDirect, Google Scholar, EMBASE, Scopus, Cochrane library and African Journals Online) aims to increase visibility to the issue. Among 275 articles identified, 7 were included in this systematic review. Studies indicated the presence of 11 personal care products (15.94 %) and 58 pharmaceutical products (84.06 %) in surface and ground water, leachates, runoffs, sludge, and sediments. The 42.86% (3/7) of reviewed studies reported 17 analgesics; 71.42 % (5/7) reported 16 antibiotics; 28.57 % (2/7) reported 5 lipid lowering drugs; 28.57% reported anti-malaria and fungal drugs; 14.29 % (1/7) reported estrogen drugs. Different studies report on sunscreen products, hormone, phytosterol, insect repellent, and ß1 receptor. Gemfibrozil (<4-730 ng/L), Triclosan (55.1-297.7 ng/L), Triclocarban (35.6-232.4 ng/L), Trimethoprim (<1-388 ng/L) and Tramadol (<2-883 ng/L) had the highest range of concentrations. Findings confirm the need of i) legislation for environmental monitoring, including biota, ii) toxicological profiling of new market products, and iii) sensitization on appropriate use and disposal of pharmaceuticals and personal care products.