Phytic acid attenuates acetaminophen-induced hepatotoxicity via modulating iron-mediated oxidative stress and SIRT-1 expression in mice.

Introduction: Administration of high doses of acetaminophen (APAP) results in liver injury. Oxidative stress and iron overload play roles in the pathogenesis of APAP-induced hepatotoxicity. The present study assessed the potential hepatoprotective effects of phytic acid (PA), a natural antioxidant and iron chelator, on APAP-induced hepatotoxicity and the possible underlying mechanism through its effects on CYP2E1 gene expression, iron homeostasis, oxidative stress, and SIRT-1 expression levels. Methods: Twenty-four adult male albino mice were used in this study. Mice were divided into four groups (six mice in each group): control, APAP-treated, PA-treated and APAP + PA-treated groups. Liver function tests, serum and liver tissue iron load were evaluated in all the study groups. Hepatic tissue homogenates were used to detect oxidative stress markers, including malondialdehyde (MDA) and reduced glutathione (GSH). Histological hepatic evaluation and immunohistochemistry of SIRT-1 were performed. Quantitative real-time PCR was used for the assessment of CYP2E1 and SIRT-1 gene expressions. APAP-induced biochemical and structural hepatic changes were reported. Results: PA administration showed beneficial effects on APAP-induced hepatotoxicity through improvements in liver functions, decreased CYP2E1 gene expression, decreased serum and liver iron load, decreased MDA, increased GSH, increased SIRT-1 expression level and improvement in hepatic architecture. Conclusion: Conclusively, PA can be considered a potential compound that can attenuate acetaminophen-induced hepatotoxicity through its role as an iron chelator and antioxidant, as well as the up-regulation of SIRT-1 and down-regulation of CYP2E1.

Role of a metastatic suppressor gene KAI1/CD82 in the diagnosis and prognosis of breast cancer.

Globally, breast cancer is the most common type of cancer in females and is one of the leading causes of cancer death in women. The advancement in the targeted therapies and the slight understanding of the molecular cascades of the disease have led to small improvement in the rate of survival of breast cancer patients. However, metastasis and resistance to the current drugs still remain as challenges in the management of breast cancer patients. Metastasis, potentially, leads to failure of the available treatment, and thereby, makes the research on metastatic suppressors a high priority. Tumor metastasis suppressors are several genes and their protein products that have the capability of arresting the metastatic process without affecting the tumor formation. The metastasis suppressors KAI1 (also known as CD82) has been found to inhibit tumor metastasis in various types of solid cancers, including breast cancer. KAI1 was identified as a metastasis suppressor that inhibits the process of metastasis by regulating several mechanisms, including cell motility and invasion, induction of cell senescence, cell-cell adhesion and apoptosis. KAI1 is a member of tetraspanin membrane protein family. It interacts with other tetraspanins, chemokines and integrins to control diverse signaling pathways, which are crucial for protein trafficking and intracellular communication. It follows that better understanding of the molecular events of such genes is needed to develop prognostic biomarkers, and to identify specific therapies for breast cancer patients. This review aims to discuss the role of KAI1/CD82 as a prognosticator in breast cancer.

Time of appearance of ossification centers in carpal bones. A radiological retrospective study on Saudi children.

OBJECTIVES: To find reference data for the time of appearance of ossification centers in carpal bones and the lower ends of the radius and ulna in the Saudi population. In addition, to check the sequence of appearance of carpal bones and the relation of this sequence to the appearance of distal epiphyses of the radius and ulna. Methods: A retrospective radiological study was carried out between 2012 to 2020 at King Fahad Hospital of the University, Al-Khobar, Saudi Arabia. A sample of 279 hand/wrist plain radiographs of Saudi children was analyzed. RESULTS: The first bones at the wrist region to appear in Saudi children are the capitate, hamate, and distal epiphysis of the radius, and these appear during the first year of life. The other bones develop subsequently at yearly intervals, and the last one to appear is the pisiform, which arises at the end of the first decade of life. CONCLUSION: The sequence of appearance of carpal bones in the Saudi population is similar to what is described in the literature. However, the time of appearance of some of these bones is earlier than that in other populations.

Radiological sinonasal anatomy. Exploring the Saudi population.

OBJECTIVES: To assess the prevalence of common radiological variants of sinonasal anatomy among Saudi population and compare it with the reported prevalence of these variants in other ethnic and population groups.  METHODS: This is a retrospective cross-sectional study of 121 computerized tomography scans of the nose and paranasal sinuses of patients presented with sinonasal symptoms to the Department of Otorhinolarngology, King Fahad Hospital of the University, Khobar, Saudi Arabia, between January 2014 and May 2014.  RESULTS: Scans of 121 patients fulfilled inclusion criteria were reviewed. Concha bullosa was found in 55.4%, Haller cell in 39.7%, and Onodi cell  in 28.9%. Dehiscence of the internal carotid artery was found in 1.65%. Type-1 and type-2 optic nerve were the prevalent types. Type-II Keros classification of the depth of olfactory fossa was the most common among the sample (52.9%). Frontal cells were found in 79.3%; type I was the most common.   CONCLUSIONS: There is a difference in the prevalence of some radiological variants of the sinonasal anatomy between Saudi population and other study groups. Surgeon must pay special attention in the preoperative assessment of patients with sinonasal pathology to avoid undesirable complications.

Collateral projections of neurons in laminae I, III, and IV of rat spinal cord to thalamus, periaqueductal gray matter, and lateral parabrachial area.

Projection neurons in lamina I, together with those in laminae III-IV that express the neurokinin 1 receptor (NK1r), form a major route through which nociceptive information reaches the brain. Axons of these cells innervate various targets, including thalamus, periaqueductal gray matter (PAG), and lateral parabrachial area (LPb), and many cells project to more than one target. The aims of this study were to quantify projections from cervical enlargement to PAG and LPb, to determine the proportion of spinothalamic neurons at lumbar and cervical levels that were labelled from PAG and LPb, and to investigate morphological differences between projection populations. The C7 segment contained fewer lamina I spinoparabrachial cells than L4, but a similar number of spino-PAG cells. Virtually all spinothalamic lamina I neurons at both levels were labelled from LPb and between one-third and one-half from PAG. This suggests that significant numbers project to all three targets. Spinothalamic lamina I neurons differed from those labelled only from LPb in that they were generally larger, were more often multipolar, and (in cervical enlargement) had stronger NK1r immunoreactivity. Most lamina III/IV NK1r cells at both levels projected to LPb, but few were labelled from PAG. The great majority of these cells in C7 and over one-fourth of those in L4 were spinothalamic, and at each level some projected to both thalamus and LPb. These results confirm that neurons in these laminae have extensive collateral projections and suggest that different neuronal subpopulations in lamina I have characteristic patterns of supraspinal projection.

Large projection neurons in lamina I of the rat spinal cord that lack the neurokinin 1 receptor are densely innervated by VGLUT2-containing axons and possess GluR4-containing AMPA receptors.

Although most projection neurons in lamina I express the neurokinin 1 receptor (NK1r), we have identified a population of large multipolar projection cells that lack the NK1r, are characterized by the high density of gephyrin puncta that coat their cell bodies and dendrites, and express the transcription factor Fos in response to noxious chemical stimulation. Here we show that these cells have a very high density of glutamatergic input from axons with strong immunoreactivity for vesicular glutamate transporter 2 that are likely to originate from excitatory interneurons. However, they receive few contacts from peptidergic primary afferents or transganglionically labeled Adelta nociceptors. Unlike most glutamatergic synapses in superficial laminas, those on the gephyrin-coated cells contain the GluR4 subunit of the AMPA receptor. A noxious heat stimulus caused Fos expression in 38% of the gephyrin-coated cells but in 85% of multipolar NK1r-immunoreactive cells. These findings are consistent with the suggestion that there is a correlation between function and morphology for lamina I neurons but indicate that there are at least two populations of multipolar neurons that differ in receptor expression, excitatory inputs, and responses to noxious stimulation. Although there are only approximately 10 gephyrin-coated cells on each side per segment in the lumbar enlargement, they constitute approximately 18% of the lamina I component of the spinothalamic tract at this level, which suggests that they play an important role in transmission of nociceptive information to the cerebral cortex. Our results also provide the first evidence that postsynaptic GluR4-containing AMPA receptors are involved in spinal nociceptive transmission.

A quantitative study of spinothalamic neurons in laminae I, III, and IV in lumbar and cervical segments of the rat spinal cord.

The major ascending outputs from superficial spinal dorsal horn consist of projection neurons in lamina I, together with neurons in laminae III-IV that express the neurokinin 1 receptor (NK1r) and have dendrites that enter the superficial laminae. Some neurons in each of these populations belong to the spinothalamic tract, which conveys nociceptive information via the thalamus to cortical areas involved in pain. A projection from the cervical superficial dorsal horn to the posterior triangular nucleus (PoT) has recently been identified. PoT is at the caudal end of the thalamus and was not included in injection sites in many previous retrograde tracing studies. We have injected various tracers (cholera toxin B subunit, Fluoro-Gold, and fluorescent latex microspheres) into the thalamus to estimate the number of spinothalamic neurons in each of these two populations, and to investigate their projection targets. Most lamina I and lamina III/IV NK1r-immunoreactive spinothalamic neurons in cervical and lumbar segments could be labeled from injections centered on PoT. Our results suggest that there are 90 lamina I spinothalamic neurons per side in C7 and 15 in L4 and that some of those in C7 only project to PoT. We found that 85% of the lamina III/IV NK1r-immunoreactive neurons in C6 and 17% of those in L5 belong to the spinothalamic tract, and these apparently project exclusively to the caudal thalamus, including PoT. Because PoT projects to second somatosensory and insular cortices, our results suggest that these are major targets for information conveyed by both these populations of spinothalamic neurons.