Hypoxia inducible factor (HIF) is the master oxygen sensor within cells and is central to the regulation of cell responses to varying oxygen levels. HIF activation during hypoxia ensures optimum ATP production and cell integrity, and is associated both directly and indirectly with reactive oxygen species (ROS) formation. HIF activation can either reduce ROS formation by suppressing the function of mitochondrial tricarboxylic acid cycle (TCA cycle), or increase ROS formation via NADPH oxidase (NOX), a target gene of HIF pathway. ROS is an unavoidable consequence of aerobic metabolism. In normal conditions (i.e., physioxia), ROS is produced at minimal levels and acts as a signaling molecule subject to the dedicated balance between ROS production and scavenging. Changes in oxygen concentrations affect ROS formation. When ROS levels exceed defense mechanisms, ROS causes oxidative stress. Increased ROS levels can also be a contributing factor to HIF stabilization during hypoxia and reoxygenation. In this review, we systemically review HIF activation and ROS formation in the brain during hypoxia and hypoxia/reoxygenation. We will then explore the literature describing how changes in HIF levels might provide pharmacological targets for effective ischaemic stroke treatment. HIF accumulation in the brain via HIF prolyl hydroxylase (PHD) inhibition is proposed as an effective therapy for ischaemia stroke due to its antioxidation and anti-inflammatory properties in addition to HIF pro-survival signaling. PHD is a key regulator of HIF levels in cells. Pharmacological inhibition of PHD increases HIF levels in normoxia (i.e., at 20.9% O₂ level). Preconditioning with HIF PHD inhibitors show a neuroprotective effect in both in vitro and in vivo ischaemia stroke models, but post-stroke treatment with PHD inhibitors remains debatable. HIF PHD inhibition during reperfusion can reduce ROS formation and activate a number of cellular survival pathways. Given agents targeting individual molecules in the ischaemic cascade (e.g., antioxidants) fail to be translated in the clinic setting, thus far, HIF pathway targeting and thereby impacting entire physiological networks is a promising drug target for reducing the adverse effects of ischaemic stroke.

Cells respond to reduced oxygen availability predominately by activation of the hypoxia-inducible factor (HIF) pathway. HIF activation upregulates hundreds of genes that help cells survive in the reduced oxygen environment. The aim of this study is to determine whether chemical-induced HIF accumulation mimics all aspects of the hypoxic response of cells. We compared the effects of dimethyloxalylglycine (DMOG) (a HIF stabiliser) on PC12 cells cultured in air oxygen (20.9% O_2, AO) with those cultured in either intermittent 20.9% O₂ to 2% O₂ (IH) or constant 2% O₂ (CN). Cell viability, cell cycle, HIF accumulation, reactive oxygen species (ROS) formation, mitochondrial function and differentiation were used to characterise the PC12 cells and evaluate the impact of DMOG. IH and CN culture reduced the increase in cell numbers after 72 and 96 h and MTT activity after 48 h compared to AO culture. Further, DMOG supplementation in AO induced a dose-dependent reduction in the increase in PC12 cell numbers and MTT activity. IH-cultured PC12 cells displayed increased and sustained HIF-1 expression over 96 h. This was accompanied by increased ROS and mitochondrial burden. PC12 cells in CN displayed little changes in HIF-1 expression or ROS levels. DMOG (0.1 mM) supplementation resulted in an IH-like HIF-1 profile. The mitochondrial burden and action potential of DMOG-supplemented PC12 cells did not mirror those seen in other conditions. DMOG significantly increased S phase cell populations after 72 and 96 h. No significant effect on PC12 cell differentiation was noted with IH and CN culture without induction by nerve growth factor (NGF), while DMOG significantly increased PC12 cell differentiation with and without NGF. In conclusion, DMOG and reduced oxygen levels stabilise HIF and affect mitochondrial activity and cell behaviour. However, DMOG does not provide an accurate replication of the reduced oxygen environments.

One of the most common metabolic illnesses in the world is diabetes mellitus. This metabolic disease is responsible for a large percentage of the burden of kidney damage and dysfunction. The goal of this study was to look into the renal function of diabetic patients using metformin monotherapy who came to Mosul's Al-Wafaa diabetes care and research facility. During the period 1 January 2021 to 30 April 2021, 47 patients with T2DM (age 50.48 7.74 years) were enrolled in this case-control study. These patients' results were compared to a control group of 47 seemingly healthy people (age 45.89 9.06 years). All participants' demographic and medical histories were acquired through the delivery of a questionnaire. Blood samples were collected and tested for the mt-ND1 gene, HbA1c, uric acid, urea, and creatinine, among other things. In diabetics, there were extremely significant increases in HbA1c, Urea, and Creatinine (p < 0.001, 0.003, and 0.043, respectively) when compared to the control group. In diabetic patients, however, uric acid levels did not change significantly. HbA1c and uric acid had a strong negative connection (r = -0.045 and 0.05, respectively). In diabetic individuals, the number of mitochondrial copies was substantially lower than in the control group (p < 0.001). In comparison to non-diabetic controls, diabetic patients treated with mono-metformin treatment had a lower mitochondrial copy number and moderate renal impairment.

Otomycosis is a fungal infection that frequently involves the external auditory canal. In this study, we aimed to isolation and identification the fungal isolates as etiological agents of otomycosis from some hospitals and clinics in Mosul with determination of their virulence factors of fungal etiological agents. Positive fungal infection was found in (43) samples (71.6%). The most common fungal pathogens were Candida and Aspergillus species, with Candida parapsilosis being the predominant isolates in (11) samples (16.6%). Otomycosis was more common in Female in (26) samples (43.3%).Otomycosis was the highest prevalence aged group 15-40 years (19) samples (31.3%). The present study of virulence factors revealed that the highest biofilm formation isolates were C. parapsilosis is (10) isolates which were distributed between (2) strong and (8) weak biofilm formation.Where C.trpicales, was recorded as least isolates for biofilm production.

Background: Oxidative stress is defined as condition when reactive oxidative species generation exceed the physiological level, and overcome the antioxidant capacity which lead to biomolecules damage, excessive peroxidation of lipid, damage of DNA strands ,impairs gene expression, mitochondrial dysfunction and play a main role in the pathophysiology of many diseases. Aim of the study: This study was aimed to investigate protective role of N-acetyl cysteine (NAC) as antioxidant on mitochondrial gene expression and copy number against oxidative stress damage in salivary glands Material and Methods: Forty adult male albino rats were used in this study. Animals were divided into 4 groups: Group1 (Control negative, n=10): Normal diet and tap water for drinking intraperitoneally for 4weeks. Group2: (Control positive, H2O2) (n=10) normal diet and drinking water contain 0.5% H2O2 daily to induce oxidative stress for 4weeks. Group3: N-acetyl cysteine (NAC, n=10) normal diet and tap water for drinking injected daily with NAC 150 mg /kg (i.p.) For 4weeks. Group4: (Protected group) (NAC+H2O2) (n=10) normal diet and drinking water contain 0.5% H2O2 daily to induce oxidative stress, injected daily with NAC 150 mg. /kg ( i.p.) for 4weeks. Tissues were collected after 4 weeks of experiment, all animal groups were euthanized and salivary glands were removed for genomic and histopathologic study. Result: The results showed that oxidative stress induced by H2O2 cause significant reduction in the mitochondrial copy number in salivary gland tissue and induce severe necrosis and degeneration in control positive group while protected group with NAC showed no significant changes in mitochondrial copy number and no necrosis or degeneration in salivary gland tissue Conclusion: N-acetyl cysteine protects the mitochondrial copy number of salivary glands from reduction by oxidative stress and prevents histopathological changes.