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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.

Background: Current trends in medical curricula are shifting from teaching histology and pathology as stand-alone disciplines. Therefore, it would be useful to examine the potential value of integrating these into the anatomical dissection experience. Objectives: The aim of this study was to assess the histologic reliability of tissues taken from embalmed cadavers in an anatomy laboratory. Materials and Methods: A total of 112 tissue samples were obtained using standard autopsy techniques from various organs (heart, lung, thyroid, skeletal muscle, bone and skin) of 11 cadavers available at the anatomy laboratory of Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia, in 2019. Samples were prepared using the standard paraffin procedure followed by cutting sections at 4-μm thickness and staining with standard hematoxylin and eosin stain. Using predefined criteria, the quality of the samples was evaluated by two board-certified histopathologists and each slide was categorized as good, satisfactory or poor. Results: Overall, 34.2% and 60.3% of the slides were of good and satisfactory quality, respectively. A significant difference in tissue quality was found between various organs. Thick skin and bone tissues had the highest “good” rating (84.6% and 81.8%, respectively), while thyroid and lung tissues had the highest “poor” rating (20% and 13.6%, respectively). Conclusion: Most of the tissues acquired from the embalmed cadavers were of good or satisfactory quality, thereby indicating the beneficial use of histological tissue from cadavers for educational purposes. Future research into how these findings translate into meaningful medical education would be beneficial.

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. Saudi Med J 2020; Vol. 41 (9): 938-946 doi: 10.15537/smj.2020.9.25348 How to cite this article: Al-Khater KM, Hegazi TM, Al-Thani HF, Al-Muhanna HT, Al-Hamad BW, Alhuraysi SM, Alsfyani WA, Alessa FW, Al-Qwairi AO, Al-Qwairi AO, Bayer SB, Siddiqui FB. Time of appearance of ossification centers in carpal bones. A radiological retrospective study on Saudi children. Saudi Med J. 2020 Sep;41(9):938-946. doi: 10.15537/smj.2020.9.25348.

Aim: To synthesize and examine the impact of free Eudragit® RS 100 nanoparticles (LN01), Quantum dots curcumin-loaded Eudragit RS 100 nanoparticles (LN04), and un-encapsulated curcumin nanoparticles (LN06) on cancerous and bacterial cells. Materials & methods: The LN01, LN04, LN06 were synthesized and characterized by Fourier transform infrared, ζ potential, UV–Vis spectroscopy, transmission electron microscopy and scanning electron microscopy and their biological activities were evaluated. Results: LN04 profoundly inhibited the growth of colon (HCT-116) cancerous cells (10.64% cell viability) and breast cancer (MCF-7) cells (10.32% cell viability) with compared to LN01 and LN06. Normal cells (HEK-293) did not show any inhibition after treatments. In addition, LN04 show better inhibitory action on bacterial growth compared with LN01 and LN06. Conclusion: We suggest that LN04 selectively target cancerous and bacterial cells and therefore possess potential anticancer and antibacterial capabilities.

Autophagy is a key metabolic process where cells can recycle its proteins and organelles to regenerate its own cellular building blocks. Chemotherapy is indispensable for cancer treatment but associated with various side-effects, including organ damage. Stem cell-based therapy is a promising approach for reducing chemotherapeutic side effects, however, one of its main culprits is the poor survival of transplanted stem cells in damaged tissues. Here, we aimed to test the effects of activating autophagy in adipose-derived mesenchymal stem/stromal cells (ADSCs) on the survival of ADSCs, and their therapeutic value in cisplatin-induced liver injury model. Autophagy was activated in ADSCs by rapamycin (50 nM/L) for two hours before transplantation and were compared to non-preconditioned ADSCs. Rapamycin preconditioning resulted in activated autophagy and improved survival of ADSCs achieved by increased autophagosomes, upregulated autophagy-specific LC3-II gene, decreased protein degradation/ubiquitination by downregulated p62 gene, downregulated mTOR gene, and finally, upregulated antiapoptotic BCL-2 gene. In addition, autophagic ADSCs transplantation in the cisplatin liver injury model, liver biochemical parameters (AST, ALT and albumin), lipid peroxidation (MDA), antioxidant profile (SOD and GPX) and histopathological picture were improved, approaching near-normal conditions. These promising autophagic ADSCs effects were achieved by modulation of components in TGF-β1/Smad and PI3K-AKT signaling pathways, besides reducing NF-κB gene expression (marker for inflammation), reducing TGF-β1 levels (marker for fibrosis) and increasing SDF-1 levels (liver regeneration marker) in liver. Therefore, current results highlight the importance of autophagy in augmenting the therapeutic potential of stem cell therapy in alleviating cisplatin-associated liver damage and opens the path for improved cell-based therapies, in general, and with chemotherapeutics, in particular.

The endocrine system is very essential to maintain body homeostasis. Disturbance of endocrine function leads to well-established diseases; such as diabetes mellitus, thyroid and parathyroid disorders, infertility, and obesity. There is no absolute cure for these diseases; however, current treatment aims to monitor them and prevent their further progression. Scientists are working hardly to find better treatment strategies for endocrine disorders. Nanotechnology holds a great promise in finding solutions to these diseases, and this field is advancing very rapidly because of the targeted type of drug delivery, and hence, it reduced the side effects of the current medications. This chapter highlights the current state of researches concerning the use of nanotechnology in managing three examples of endocrine diseases: thyroid dysfunction, diabetes mellitus, and obesity. For example, nanotechnology has been implemented in finding non-invasive routes of insulin delivery such as oral, nasal, or transdermal routes. Glucose nanosensors have been invented in order to improve the accuracy of detection of serum glucose. It is important to emphasize that this field of research is still in the preclinical stage and more work is needed to provide evidence of its safety. Immune response and toxicity are the main issues that concern researchers when using nanotechnology.

Vitamin D is a fat-soluble vitamin that is obtained mainly from dietary products, supplements fatty fish, and sunlight-mediated conversion of the inactive form of vitamin D (7-dehydrocholesterol) to 1,25 dihydroxyvitamin D3. Vitamin D (calciferol), a prohormone, is vital for absorption of calcium and phosphorus minerals in the intestine. Vitamin D is beneficial for bone health, reducing diabetic risk, cardiovascular, hormone-related diseases, and cancer. Nowadays, a huge research is directed to the newly discovered functions of vitamin D, including cell differentiation and proliferation, and its role in the pathogenesis of inflammatory, autoimmune, and metabolic diseases. Several studies have shown influence of vitamin D in apoptosis and cell cycle regulation using proteolytic activity. Vitamin D has been found to be useful in the treatment of various diseases. Vitamin D downregulates serine proteases and matrix metalloproteinases and upregulates the angiogenesis inhibitor in tumors. Understanding its roles in various biological processes, vitamin D has been found to be a promising solution for various types of cancer and beneficial in the management of other types of diseases. This chapter presents comprehensive, up-to-date descriptive roles of vitamin D in the regulation of cell functions through modulation of proteases and protease inhibitors. Conclusively, vitamin D supplement alone or in combination with cancer therapy may help to prevent or reduce cancer incidence and mortality.

Thyroid gland has been implicated in the regulation of many functions using endocrine, paracrine and autocrine signals. Functional thyroid follicular cells derived from stem cells attracted a great interest from researchers as a strategy for thyroid's regenerative therapy. Thyroid has a very low rate of turnover; however, studies showed that the regenerative ability is enhanced following diseases or thyroidectomy, which promotes the role of stem cell. The objective of this review is to summarize the morphological characterization and the expression of stem cell genes/markers in the thyroid. Also, to highlight the mechanisms of tumor formation in thyroid via its stem cells. The most important thyroid stem cell's markers are: stem cell antigen 1 (SCA-1), octamer-binding transcription 4 (OCT-4), p63, CD34+ CD45-, paired box gene 8 (PAX-8), thyroid transcription factor 1 (TTF-1), thyroid transcription factor 2 (TTF-2), hematopoietically expressed homeobox protein HHEX, the transcription factor GATA-4, hepatocyte nuclear factor 4-α (HNF-4-α) and homeobox transcription factor Nanog (hNanog). This review highlights the functional characterization describing the mechanisms of stem cell's differentiation into functional thyroid follicle and proposing mechanisms involving in cancer formation through one of these cell types: fetal cell, thyroblasts, prothyrocytes, certain genetic mutation in the mature thyroid cells or presence of a special type of cells (cancer stem cell) which are responsible for different types of cancer formation. Understanding the mechanisms of thyroid's stem cell in cancer formation and the expression of the biomarkers in normal and abnormal thyroid status are promising physiological tools in promoting thyroid regeneration and in provision management for thyroid cancer.

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. Saudi Med J 2016; Vol. 37 (5): 521-526 doi:10.15537/smj.2016.5.13904 How to cite this article: Alrumaih RA, Ashoor MM, Obidan AA, Al-Khater KM, Al-Jubran SA. Radiological sinonasal anatomy. Exploring the Saudi population. Saudi Med J 2016; Vol. 37 (5): 521-526.

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.

The dorsal horn of the rat spinal cord contains a population of large neurons with cell bodies in laminae III or IV, that express the neurokinin 1 receptor (NK1r) and have long dorsal dendrites that branch extensively within the superficial laminae. In this study, we have identified a separate population of neurons that have similar dendritic morphology, but lack the NK1r. These cells also differ from the NK1r-expressing neurons in that they have significantly fewer contacts from substance P-containing axons and are not retrogradely labelled following injection of tracer into the caudal ventrolateral medulla. We also provide evidence that these cells do not belong to the postsynaptic dorsal column pathway or the spinothalamic tract. It is therefore likely that these cells do not have supraspinal projections. They may provide a route through which information transmitted by C fibres that lack neuropeptides is conveyed to deeper laminae. The present findings demonstrate the need for caution when attempting to classify neurons solely on the basis of somatodendritic morphology.

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. J. Comp. Neurol. 515:629–646, 2009. © 2009 Wiley-Liss, Inc.

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.