Biology subjects

Ahmad, M. H.

Publications and source records attributed to Ahmad, M. H..

3 recordsLinked to original sources

bioRxiv2023

RUNX1 is required in granulocyte-monocyte progenitors to attenuate inflammatory cytokine production by neutrophils

The transcription factor RUNX1 is mutated in familial platelet disorder with associated myeloid malignancies (FPDMM) and in sporadic myelodysplastic syndrome and leukemia. RUNX1 regulates inflammation in multiple cell types. Here we show that RUNX1 is required in granulocyte-monocyte progenitors (GMPs) to restrict the inflammatory response of neutrophils to toll-like receptor 4 (TLR4) signaling. Loss of RUNX1 in GMPs increased the TLR4 coreceptor CD14 on neutrophils, which contributed to neutrophils increased inflammatory cytokine production in response to the TLR4 ligand lipopolysaccharide. RUNX1 loss increased the chromatin accessibility of retrotransposons in GMPs and neutrophils and induced a type I interferon signature characterized by enriched footprints for signal transducer and activator of transcription (STAT1::STAT2) and interferon regulatory factors (IRF) in opened chromatin, and increased expression of interferon-stimulated genes. The overproduction of inflammatory cytokines by neutrophils was reversed by inhibitors of type I IFN signaling. We conclude that RUNX1 restrains the chromatin accessibility of retrotransposons in GMPs and neutrophils, and that loss of RUNX1 increases proinflammatory cytokine production by elevating tonic type I interferon signaling.

developmental biology↗

bioRxiv2022

Toxicological study on methanol root bark extract of Acacia sieberiana (Fabaceae) in Wistar rats

BackgroundThe plant Acacia sieberiana belongs to the family Fabaceae. It has been used in ethnomedical practice to manage bleeding, rheumatism, pain, pyrexia, kidney diseases, gastrointestinal problems, parasitic and infectious diseases, hepatitis, cough, epilepsy, mouth ulcer and many more. Phytochemical compounds such as ellagic acid, quercetin, isoferulic acid, gallic acid, kaempferol, luteolin, apigenin, glucoside dihydroacacipetalin, acacipetalin and many others were isolated from Acacia sieberiana. Previous pharmacological investigations have reported that the plant has anticancer, antimicrobial, antidiarrhoeal and antitrypanosomal effects. Despite the therapeutic properties of this plant, no safety information is available in the literature. Hence, this work intends to investigate the sub-acute toxicity effects of Acacia sieberiana root bark extract (ASE). The phytochemical and oral median lethal dose (LD50) evaluations on the ASE were done in line with the standard protocols. The sub-acute toxic effects of the ASE (250, 750, and 1,500 mg/kg) were investigated following administration of the ASE daily for 28-consecutive days based on the Organization of Economic Cooperation and Development (OECD) 407 protocols in rats. The weekly body weights were monitored and the rats were euthanized on the 29th day. The blood samples from the animals were obtained for biochemical and haematological determinations. The liver, kidney, lung and heart were removed for histological investigations. ResultsThe ASE revealed triterpenes, tannins, saponins, cardiac glycosides, flavonoids, and alkaloids. The oral LD50 values was >5,000 mg/kg. The ASE remarkably (p<0.05) declined the body weight of the rats in consideration to the control categories. There was also a remarkable (p<0.05) elevation in ALP, urea and lymphocytes. The cardiac histology revealed no abnormalities. However, the liver produced dose-dependent hepatocellular necrosis and vacuolations. Besides, lymphocyte hyperplasia and glomerular necrosis were observed in the kidneys and alveolar congestion in the lungs. ConclusionsThe ASE is relatively non-toxic on acute administration. In contrast, it could pose slight hepatic and renal toxicity on sub-acute administration.

pharmacology and toxicology↗

bioRxiv2022

Acacia sieberiana (Fabaceae) Attenuates Paracetamol and Bile Duct Ligation-Induced Hepatotoxicity via Modulation of Biochemical and Oxidative Stress Biomarkers

BackgroundThe plant Acacia sieberiana (Fabaceae) is traditionally used to manage hepatitis. This research work aims to investigate the hepatoprotective effectiveness of root bark extract of Acacia sieberiana (ASE) against paracetamol (PCM) and bile duct ligation (BDL)-induced hepatotoxicity. The phytochemical and median lethal dose (LD50) investigations were conducted. The rats were pre-treated with the ASE (250, 750, 1,500 mg/kg) once daily via oral route for 7 consecutive days. On the 8th day, liver injury was initiated by PCM administration (2g/kg). Similarly, in the BDL-induced liver injury, the animals were administered ASE (125, 250 and 380 mg/kg) intraperitoneally for 7 consecutive days. After 24 hours, blood samples and hepatic tissues were obtained for biochemical and histopathological investigations. ResultsPhytocomponents determination revealed glycosides, triterpenes, glycosides, saponins, tannins, flavonoids and alkaloids. The oral and intraperitoneal LD50 values of the ASE were >5,000 and 1,300 mg/kg, respectively. The ASE efficiently (p<0.05) decreased the alanine transaminase (ALT) and aspartate transaminase (AST) levels and elevated the albumin and total protein (TP) levels. The direct bilirubin effectively (p<0.05) decreased at 750 mg/kg. Besides, the extract efficiently elevated the glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in relation to the PCM hepatotoxic group. Also, the malondialdehyde (MDA) concentration was reduced by the ASE. Meanwhile, in the BDL- induced liver injury, the ASE remarkably (p<0.05) declined the AST, ALP, bilirubin and MDA. Besides, there was effective (p<0.05) elevation in SOD, GPx and CAT in the ASE-treated groups. The morphology of liver tissue was preserved at 125 and 250 mg/kg ASE groups from BDL-induced necrosis and vascular congestion. ConclusionThe study shows that the ASE has hepatoprotective actions against liver damage by possible modulation of biochemical and oxidative stress biomarkers

pharmacology and toxicology↗