A Review of the Relationship between the Immune Response, Inflammation, Oxidative Stress, and the Pathogenesis of Sickle Cell Anaemia.

Sickle cell anaemia (SCD) is a life-threatening haematological disorder which is predominant in sub-Saharan Africa and is triggered by a genetic mutation of the ß-chain haemoglobin gene resulting in the substitution of glutamic acid with valine. This mutation leads to the production of an abnormal haemoglobin molecule called haemoglobin S (HbS). When deoxygenated, haemoglobin S (HbS) polymerises and results in a sickle-shaped red blood cell which is rigid and has a significantly shortened life span. Various reports have shown a strong link between oxidative stress, inflammation, the immune response, and the pathogenesis of sickle cell disease. The consequence of these processes leads to the development of vasculopathy (disease of the blood vessels) and several other complications. The role of the immune system, particularly the innate immune system, in the pathogenesis of SCD has become increasingly clear in recent years of research; however, little is known about the roles of the adaptive immune system in this disease. This review examines the interaction between the immune system, inflammation, oxidative stress, blood transfusion, and their effects on the pathogenesis of sickle cell anaemia.

Understanding the Complex Milieu of Epithelial-Mesenchymal Transition in Cancer Metastasis: New Insight Into the Roles of Transcription Factors.

Epithelial-mesenchymal transition (EMT) is a physiological program during which polarised, immobile epithelial cells lose connection with their neighbours and are converted to migratory mesenchymal phenotype. Mechanistically, EMT occurs via a series of genetic and cellular events leading to the repression of epithelial-associated markers and upregulation of mesenchymal-associated markers. EMT is very crucial for many biological processes such as embryogenesis and ontogenesis during human development, and again it plays a significant role in wound healing during a programmed replacement of the damaged tissues. However, this process is often hijacked in pathological conditions such as tumour metastasis, which constitutes the most significant drawback in the fight against cancer, accounting for about 90% of cancer-associated mortality globally. Worse still, metastatic tumours are not only challenging to treat with the available conventional radiotherapy and surgical interventions but also resistant to several cytotoxic agents during treatment, owing to their anatomically diffuse localisation in the body system. As the quest to find an effective method of addressing metastasis in cancer intervention heightens, understanding the molecular interplay involving the signalling pathways, downstream effectors, and their interactions with the EMT would be an important requisite while the challenges of metastasis continue to punctuate. Unfortunately, the molecular underpinnings that govern this process remain to be completely illuminated. However, it is becoming increasingly clear that EMT, which initiates every episode of metastasis, significantly requires some master regulators called EMT transcription factors (EMT-TFs). Thus, this review critically examines the roles of TFs as drivers of molecular rewiring that lead to tumour initiation, progression, EMT, metastasis, and colonisation. In addition, it discusses the interaction of various signalling molecules and effector proteins with these factors. It also provides insight into promising therapeutic targets that may inhibit the metastatic process to overcome the limitation of "undruggable" cancer targets in therapeutic design and upturn the current spate of drug resistance. More so, it extends the discussion from the basic understanding of the EMT binary switch model, and ultimately unveiling the E/M cellular plasticity along a phenotypic spectrum via multiple trans-differentiations. It wraps up on how this knowledge update shapes the diagnostic and clinical approaches that may demand a potential shift in investigative paradigm using novel technologies such as single-cell analyses to improve overall patient survival.

Assessment of iron status and interplay between lipid peroxidation and antioxidant capacity in common hemoglobin variants in Osun State, southwestern Nigeria.

Hemoglobin (Hb) and iron are prooxidants in nature and sources of free radicals in the biological system of all Hb phenotypes. Recent evidence linked abnormal hemoglobin S and C (HbSC) in sickle cell disease (SCD) to various complications in multiple oxidative processes. However, similar studies in relation to abnormal Hb traits are sparse. Besides, reports on activities of antioxidant enzymes and iron status in SCDs are still contradictory. This study assessed the interplay between lipid peroxidation and antioxidant defense capacity in various Hb variants. We enrolled 193 participants with different Hb phenotypes. They were consecutive patients with sickle cell anemia (HbSS, n = 32) and hemoglobin SC (HbSC) disease (n = 28) regularly followed up in a steady state. Other participants were subjects with abnormal Hb traits (HbAS, n = 50; HbAC, n = 33) and normal controls (HbAA, n = 50). The hematocrit (Hct) level, hemoglobin (Hb) concentration, iron status, and biochemical parameters including malondialdehyde (MDA), total antioxidant status (TAS), superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzymes were investigated simultaneously. The MDA and SOD levels were significantly higher (P < 0.05) in Hb variants in order of HbSS>HbSC>HbAC>HbAS when compared with controls. Conversely, GPx and TAS levels showed significant reductions (P < 0.05). Similarly, Hct, Hb, and iron concentrations showed significant reductions (P < 0.05) sequentially following HbAC > HbAS > HbSC > HbSS compared with controls. The results suggest that both SCDs and the carriers were relatively more vulnerable to systemic oxidative stress against normal phenotype, and may be owing to ineffective antioxidant mechanisms needed for keeping spontaneous generations of free radicals in control without necessarily iron-mediated.

Hepatotoxicity and nephrotoxicity evaluation in Wistar albino rats exposed to Morinda lucida leaf extract.

BACKGROUND: Aqueous extract of Morinda lucida benth leaf is consumed in Southern Nigeria in the treatment of malaria without any regard for its safety. AIM: The aim of the study was to investigate the effects of ingestion of the ethanolic leaf extract of the plant on liver and kidney functions in Wistar albino rats. MATERIALS AND METHODS: Acute oral toxicity test was performed to determine the LD(50); sub-chronic toxicity study was then carried out by oral administration of different doses of the extract on daily basis to different groups of rats for 42 days. The animals were subsequently sacrificed, and liver and kidney functions assessed biochemically using standard techniques. RESULTS: The acute oral toxicity result, LD(50,) revealed Morinda lucida leaf extract to be non-lethal at 6400mg/kg body weight. The results obtained for liver and kidney function parameters indicated that ingestion of Morinda lucida leaf extract has no toxic effect on liver and kidney functions. CONCLUSION: The results can form the basis for clinical trials in humans.

Histopathological changes in Wistar albino rats exposed to aqueous extract of unripe Carica papaya.

BACKGROUND: Exposure of animals to xenobiotics may or may not trigger adverse response at cellular levels. Aqueous extract of unripe Carica papaya is consumed by sickle cell patients as antisickling agent in Western Nigeria. AIM: This study was undertaken to investigate the effects of Carica papaya on certain organs in Wister albino rats exposed to aqueous extract of unripe Carica papaya. MATERIALS AND METHODS: Different doses of aqueous extract of unripe Carica papaya were administered orally daily for 42 days to six groups of rats. At the end of exposure, the animals were sacrificed and tissue sections were prepared from livers, kidneys, hearts and small intestines using standard techniques. RESULTS: Histopathological results showed that no pathological changes were observed in tissue sections of experimental animals when compared with tissue sections of the same organs in control animals. CONCLUSION: No pathological changes were elicited in the organs of rats exposed to aqueous extract of unripe Carica papaya.