Gastroprotective mechanism of Talinum triangulare on ethanol-induced gastric ulcer in Wistar rats via inflammatory, antioxidant, and H+/K+-ATPase inhibition-mediated pathways.

The increase in the incidence of gastric ulcer (GU) has posed major threat on public health. This research aimed to evaluate gastroprotective properties of the aqueous leaf extract of Talium triangulare (AETT) in ethanol-induced gastric ulceration. GU was induced via oral administration of single dose of 5 mLkg-1 of 90% ethanol in rats and protection of 200 mgkg-1 bw of AETT and 20 mgkg-1 bw of omeprazole was investigated for 14 d via oral treatment. Influence of AETT on anti-inflammatory, redox assays, ulcer index (UI), and gastric mucosa histological alterations were evaluated. Significant increase in myeloperoxidase (MPO) and tumor necrosis factor-alpha levels compared to untreated group established gastric inflammation in rats induced by ethanol. Gastric ulcerated group exhibited heightened oxidative stress with concurrent decline in activities of antioxidant enzymes. Ethanol exposure to rats resulted in induction of lipid peroxidation, prominently elevating gastric malondialdehyde (MDA) concentration. Nevertheless, treatment with AETT or omeprazole exhibited substantial anti-inflammatory effects within gastric mucosa by attenuating expression of markers associated with inflammation. AETT demonstrated reduction in concentrations of MDA and H2O2, thereby alleviating progression of lipid peroxidation cascades. Also, AETT exhibited mitigating effect on ethanol-induced oxidative harm by enhancing the functionality of protective enzymes and elevating glutathione (GSH) concentration. Overall, AETT exhibited enhancements in activities of cytoprotective antioxidant enzymes, mitigated impact of oxidative stress and inflammation, inhibited lipid peroxidation, and decreased UI score. These beneficial effects could be attributed to phytochemicals present in AETT including 6,10,14-trimethyl-2-pentadecanone and Phytol. Outcome of this study established the traditional herbal claims of AETT.

Prevalence of Cytopenia and its Correlation with Immunosuppression in Naïve HIV-1 Infected Patients Initiating First-Line Antiretroviral Therapy: A Pilot Study.

BACKGROUND: Cytopenias serve as common indicators and crucial predictive tools for evaluating disease progression and therapeutic outcomes in individuals with human immunodeficiency virus (HIV) infection. This study aimed to assess the prevalence of cytopenias and their correlation with the level of immunosuppression in treatment-naive HIV-infected participants after initiating highly active combined antiretroviral drug therapy (cART24). MATERIALS AND METHODS: This prospective study focused on evaluating cytopenia in 44 treatment-naive HIV-infected patients who consented to initiate cART and were consecutively enrolled. The research was conducted at the Nasara HIV Treatment & Care Centre of Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria, spanning from December 2016 to January 2018. Cytopenias, including anemia, leucopenia, lymphocytopenia, and thrombocytopenia, were defined and assessed according to World Health Organization guidelines. A combination of cross-sectional and longitudinal mixed-design two-step analysis was employed to validate our findings. RESULTS: The median time from enrollment to cART initiation was 7 days, following the universal test and treat protocol. The prevalence of cytopenia was 75% at the baseline before treatment and increased to 84% after cART24 administration. There were no statistically significant differences in the median values of immuno-hematological parameters between baseline and after cART24 initiation (P >0.05). In terms of longitudinal assessment, the prevalence of anemia, leucopenia, lymphopenia, and thrombocytopenia at baseline were 66%, 23%, 0%, and 11%, respectively, and after cART24, the rates were 66%, 29%, 5%, and 20%. Notably, the prevalence of cytopenia correlated with declining CD4+ T cell counts. Among instances of unicytopenia, 58% exhibited isolated anemia, 6% had lone leucopenia, and 6% had solitary thrombocytopenia. Additionally, 27% demonstrated bi-cytopenia, and 3% exhibited pancytopenia. Interestingly, none of the study participants presented with lymphopenia. The most common combination was anemia and thrombocytopenia. Both longitudinal and cross-sectional analytical findings were consistent. CONCLUSION: In treatment-naive HIV-infected individuals, the prevalence of cytopenias, particularly anemia and thrombocytopenia, was substantial and correlated with the degree of immunosuppression as indicated by CD4+ T cell counts. These cytopenias persisted despite initiation of cART24, highlighting the complexity of hematological manifestations in HIV infection. Our study underscores the significant hematopathological impact of HIV and antiretroviral therapy, highlighting the necessity for preventive strategies to mitigate these adverse effects.

Nitric oxide-inhibited chloride transport in cortical thick ascending limbs is reversed by 8-iso-prostaglandin-F2α.

BACKGROUND: Sodium chloride (NaCl) reabsorption in the cortical thick ascending limb (cTAL) is regulated by opposing effects. Nitric oxide (NO) inhibits NaCl reabsorption while 8-iso-prostaglandin-F2α (8-iso-PGF2α) stimulates it. Their interaction has not been evaluated in the cTAL. Because 8-iso-PGF2α has considerable stability while NO is a free radical with a short half-life, we hypothesized that, in the cTAL, the inhibition of NaCl absorption will be reversed by 8-iso-PGF2α. METHODS: Chloride absorption (JCl) was measured in isolated perfused cTALs and whether the activation of protein kinase A (PKA) is required for this interaction. Since cyclic adenosine monophosphate (cAMP) is a major messenger for the 8-iso-PGF2α signaling cascade, and NO inhibits JCl by decreasing cAMP bioavailability, we measured 8-iso-PGF2α-stimulated cAMP in the presence of sodium nitroprusside (SNP). RESULTS: The NO donor, SNP (10-6 M), decreased JCl by 41%, while luminal 8-iso-PGF2α (100 µM) increased JCl to 315 ± 46 pmol/ min/mm (p < 0.003), reversing the effects of the NO donor. SNP inhibited JCl, 8-iso-PGF2α failed to increase JCl in the presence of H89. Basal cAMP was 56 ± 13 fmol/min/mm, in the presence of SNP 57 ± 6 fmol/min/mm, and 8-iso-PGF2α increased it to 92 ± 2 fmol/min/mm (p < 0.04). CONCLUSION: We concluded that 1) NO-induced inhibition of JCl in the cTAL can be reversed by 8-iso-PGF2α, 2) 8-iso-PGF2α and NO interaction requires PKA to control JCl, and 3) in the presence of NO, 8-iso-PGF2α continues to stimulate JCl because NO cannot reverse 8-iso-PGF2α-stimulated cAMP level.

Postmortem mitochondrial membrane permeability transition assessment of apoptotic cell death in brain and liver of insulin resistant, ovariectomised rats.

The adverse alterations in mitochondrial functions can affect neuronal function negatively, as they play a crucial role in neuronal plasticity and death. Direct measurements of mitochondrial activity, including membrane potential and ATP production, are not easily achieved in post-mortem brain and liver samples because most organ functions cease to work after death; in fact, with increasing post-mortem intervals (PMI), the brain and liver tissues deteriorate rapidly. Standard procedures of mitochondria isolation, protein determination expressed as BSA equivalent, and spectrophotometric assessment of pore opening at 540 nm were employed. Our results showed that (a) intact mitochondria may be isolated from rat brain and liver of these rats after storage in animal body (in situ) at -20 °C for 7 days (168 h, post-mortem), (b) some population of these mitochondria can still take up exogenous Ca2+ and (c) they can still resist osmotically induced large amplitude swelling in a suitable buffer. The need for mitochondrial purity, structural integrity and abundance for functional studies are common hindrances that can encumber mitochondrial research. Therefore, this study is significant to have shown that PMI up to 7 days did not extensively, diminish MMPT pore status in normal and diabetic, ovariectomised rats. This can be relevant for forensic data mining.

A systematic review on COVID-19 pandemic with special emphasis on curative potentials of Nigeria based medicinal plants.

Despite the frightening mortality rate associated with COVID-19, there is no known approved drug to effectively combat the pandemic. COVID-19 clinical manifestations include fever, fatigue, cough, shortness of breath, and other complications. At present, there is no known effective treatment or vaccine that can mitigate/inhibit SARS-CoV-2. Available clinical intervention for COVID-19 is only palliative and limited to support. Thus, there is an exigent need for effective and non-invasive treatment. This article evaluates the possible mechanism of actions of SARS-CoV-2 and present Nigeria based medicinal plants which have pharmacological and biological activities that can mitigate the hallmarks of the pathogenesis of COVID-19. SARS-CoV-2 mode of actions includes hyper-inflammation characterized by a severe and fatal hyper-cytokinaemia with multi-organ failure; immunosuppression; reduction of angiotensin-converting enzyme 2 (ACE2) to enhance pulmonary vascular permeability causing damage to the alveoli; and further activated by open reading frame (ORF)3a, ORF3b, and ORF7a via c-Jun N- terminal kinase (JNK) pathway which induces lung damage. These mechanisms of action of SARS-CoV-2 can be mitigated by a combination therapy of medicinal herbs based on their pharmacological activities. Since the clinical manifestations of COVID-19 are multifactorial with co-morbidities, we strongly recommend the use of combined therapy such that two or more herbs with specific therapeutic actions are administered to combat the mediators of the disease.

Eicosapentaenoic acid prevents salt sensitivity in diabetic rats and decreases oxidative stress.

OBJECTIVES: Salt sensitivity (SS) is associated with increased cardiovascular risk in patients with Type 2 diabetes mellitus (T2-DM) due to an increase in renal oxidation. ω-3 polyunsaturated fatty acids have shown antioxidant effects, but a typical Western diet contains limited content. In particular, ω-3 polyunsaturated fatty acids are able to activate nuclear factor erythroid 2-related factor 2 (Nrf-2) to prevent diabetes mellitus-related complications by mitigating oxidative stress. Therefore, we hypothesized that eicosapentaenoic acid (EPA; ω-3) modulates SS in rats with T2-DM by decreasing renal oxidative stress via Nrf-2 activation and enhancing the antiinflammatory response via interleukin (IL) 6 modulation. METHODS: Three-month-old male rats (n = 40) were fed with a Normal Na-diet (NNaD) and randomly selected into four groups: Healthy Wistar nondiabetic rats (Wi), diabetic controls (eSS), arachidonic acid-treated eSS (AA; ω-6), and EPA-treated eSS (ω-3). After 1 year, rats were placed in metabolic cages for 7 d and fed a NNaD, followed by a 7-d period with a High Na-diet (HNaD). Systolic blood pressure, body weight, serum IL-6 and reactive oxygen species (ROS) levels were determined at the end of each 7-d period. Glycated hemoglobin (HbA1c), triacylglycerol, creatinine, and cholesterol levels were determined. ROS levels and Nrf-2 expression in kidney lysates were also assayed. Histologic changes were evaluated. A t test or analysis of variance was used for the statistical analysis. RESULTS: After a HNaD, systolic blood pressure increased in both the control eSS and AA groups, but not in the EPA and Wi groups. However, HbA1c levels remained unchanged by the treatments, which suggests that the observed beneficial effect was independent of HbA1c levels. The IL-6 levels were higher in the eSS and AA groups, but remained unaltered in EPA and Wi rats after a HNaD diet. Interestingly, EPA protected against serum ROS in rats fed the HNaD, whereas AA did not. In kidney lysates, ROS decreased significantly in the EPA group compared with the eSS group, and Nrf-2 expression was consistently higher compared with the AA and eSS groups. Diabetic rats presented focal segmental sclerosis, adherence to Bowman capsule, and mild-to-moderate interstitial fibrosis. EPA and AA treatment prevented kidney damage. CONCLUSIONS: An adequate ω3-to-ω6 ratio prevents SS in diabetic rats by a mechanism that is independent of glucose metabolism but associated with the prevention of renal oxidative stress generation. These data suggest that EPA antioxidant properties may prevent the development of hypertension or kidney damage.

Phytomodulatory effects of silver nanoparticles on Corchorus olitorius: Its antiphytopathogenic and hepatoprotective potentials.

This study has reported the effects of biogenic silver nanoparticles (AgNPs) using cocoa pod extract on physiological tolerance indices, antioxidant activity and hepatoprotective potentials of Corchorus olitorius as well as its efficiency for controlling soil phytopathogens. C. olitorius seeds were grown in soil prepared with water (control), 0.05, 0.1, 0.15 and 0.2 mg AgNPs/g soil. C. olitorus grown with AgNPs had significantly (p < 0.05) higher free radical scavenging ability, ferric reducing ability, percentage germination, vigour indices, longer roots and shoots as well as lower moisture content over control. C. olitorius grown with AgNPs attenuated hydrogen peroxide (H2O2)-mediated reduction in catalase concentrations and H2O2-induced malondialdehyde elevations in liver. Efficiency of AgNPs to reduce soil phytopathogens (fungi and nematodes) revealed significant (p < 0.05) reduction in the incidences of soil and shoot Meloidogyne spp., Aspergillus terreus, A. niger, Fusarium spp. and Cladosporium spp. with increase in concentrations of AgNPs. More efficiently, there was complete extermination of A. niger and Fusarium spp. in the leaves of C. olitorius grown with AgNPs. Results in this study have shown the positive influence of AgNPs on C. olitorius by strengthening its resistance against fungi, and nematodes, improvement of its shelf-life, modulation of antioxidant activities and promotion of liver-detoxifying potentials.