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Gebremedhn, S., A. Gad, H. S. Aglan, J. Laurincik, R. Prochazka, D. Salilew-Wondim, M. Hoelker, K. Schellander, and D. Tesfaye, "Extracellular vesicles shuttle protective messages against heat stress in bovine granulosa cells", Scientific Reports, vol. 10, no. 1: Nature Publishing Group, pp. 1–19, sep, 2020. AbstractWebsite

Elevated summer temperature is reported to be the leading cause of stress in dairy and beef cows, which negatively affects various reproductive functions. Follicular cells respond to heat stress (HS) by activating the expression of heat shock family proteins (HSPs) and other antioxidants. HS is reported to negatively affect the bi-directional communication between the follicular cells and the oocyte, which is partly mediated by follicular fluid extracellular vesicles (EVs) released from surrounding cells. As carriers of bioactive molecules (DNA, RNA, protein, and lipids), the involvement of EVs in mediating the stress response in follicular cells is not fully understood. Here we used an in vitro model to decipher the cellular and EV-coupled miRNAs of bovine granulosa cells in response to HS. Moreover, the protective role of stress-related EVs against subsequent HS was assessed. For this, bovine granulosa cells from smaller follicles were cultured in vitro and after sub-confluency, cells were either kept at 37 °C or subjected to HS (42 °C). Results showed that granulosa cells exposed to HS increased the accumulation of ROS, total oxidized protein, apoptosis, and the expression of HSPs and antioxidants, while the viability of cells was reduced. Moreover, 14 and 6 miRNAs were differentially expressed in heat-stressed granulosa cells and the corresponding EVs, respectively. Supplementation of stress-related EVs in cultured granulosa cells has induced adaptive response to subsequent HS. However, this potential was not pronounced when the cells were kept under 37 °C. Taking together, EVs generated from granulosa cells exposed to HS has the potential to shuttle bioactive molecules to recipient cells and make them robust to subsequent HS.

Ibrahim, S., M. Hedia, M. Taqi, M. Derbala, K. Mahmoud, Y. Ahmed, A. Sosa, Y. Saber, M. Hasanain, M. Nawito, et al., "Extracellular vesicles in low volume uterine lavage and serum: novel and promising biomarker for endometritis in Arabian mares", BMC Veterinary Research, vol. 18, issue 1, pp. 1-12, 2022.
Faruk, E. M., W. A. Alasmari, H. Fouad, O. E. Nafea, and R. A. A. Hasan, "Extracellular vesicles derived from bone marrow mesenchymal stem cells repair functional and structural rat adrenal gland damage induced by fluoride", Life Sciences, vol. 270: Pergamon, pp. 119122, 2021. Abstract
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Gebremedhn, S., A. Ali, A. Gad, R. Prochazka, and D. Tesfaye, "Extracellular Vesicles as Mediators of Environmental and Metabolic Stress Coping Mechanisms During Mammalian Follicular Development", Frontiers in Veterinary Science, vol. 7, pp. 961, 2020. AbstractWebsite

Extracellular vesicles are evolutionarily conserved nano-sized phospholipid membraned structures and released from virtually all types of cells into the extracellular space. Their ability to carry various molecular cargos (mRNA, miRNA, proteins, and lipids) from one cell to the other to exert functional impact on the target cells enables them to play a significant role in cell to cell communication during follicular development. As the molecular signals carried by extracellular vesicles reflect the physiological status of the cells of origin, they are expected to mediate any effect of environmental or metabolic stress on the follicualr cells and the growing oocyte. Recent studies have evidenced that reproductive cells exposed to various environmental stressors (heat and oxidative stress) released extracellular vesicles enriched with mRNA and miRNA associated with stress response mechanisms. Moreover, the metabolic status of post-calving cows could be well-reflected in the follicular extracellular vesicle's miRNA profile, which signified the potential role of extracellular cellular vesicle molecular signals in mediating the effect of metabolic stress on follicular and oocyte development. In the present review, the potential role of extracellular vesicles in mediating the effect of environmental and metabolic stress in various reproductive cells and oocytes are thoroughly discussed Moreover, considering the importance of extracellular vesicles in shuttling protective or rescuing molecular signals during stress, their potential usage as means of targeted delivery of molecules to mitigate the effect of stress on oocytes are addressed as the focus of future research.

Gad, A., K. Joyce, N. G. Menjivar, D. Heredia, C. S. Rojas, D. Tesfaye, and A. Gonella-Diaza, "Extracellular vesicle-microRNAs mediated response of bovine ovaries to seasonal environmental changes", Journal of Ovarian Research, vol. 16, issue 1, pp. 101, 2023. AbstractWebsite

Among the various seasonal environmental changes, elevated ambient temperature during the summer season is a main cause of stress in dairy and beef cows, leading to impaired reproductive function and fertility. Follicular fluid extracellular vesicles (FF-EVs) play an important role in intrafollicular cellular communication by, in part, mediating the deleterious effects of heat stress (HS). Here we aimed to investigate the changes in FF-EV miRNA cargoes in beef cows in response to seasonal changes: summer (SUM) compared to the winter (WIN) season using high throughput sequencing of FF-EV-coupled miRNAs. In addition to their biological relevance, the potential mechanisms involved in the packaging and release of those miRNAs as a response to environmental HS were elucidated.

Heidy Abo El-Yazeed, M. Effat, M. El-Hariri, A. Prince, R. M. Alarousy, M. M. Eraqi, M. H. Hanafy, and E. Elsady, "Extracellular Protein Profile of Microsporum canis Secreted Proteolytic Enzymes (Exoantigens)", World Applied Sciences Journal, vol. 32, issue 12, pp. 2453-2458, 2014. 1543150818.6751extracellular_protein_profile_of_microsporum_canis.pdf
Heidy Abo El-Yazeed, M. Effat, M. El-Hariri, A. Prince, R. M. Alarousy, M. M. Eraqi, and M. H. H, "Extracellular Protein Profile of Microsporum canis Secreted Proteolytic Enzymes (Exoantigens)", World Applied Sciences Journal, vol. 32, issue 12, pp. 2453-2458, 2014. extracellular_protein_profile_of_microsporum_canis_secreted_proteolytic_enzymes_exoantigens.pdf
Moustafa, P. E., N. F. Abdelkader, S. A. El Awdan, O. A. El-Shabrawy, and H. F. Zaki, "Extracellular Matrix Remodeling and Modulation of Inflammation and Oxidative Stress by Sulforaphane in Experimental Diabetic Peripheral Neuropathy.", Inflammation, vol. 41, issue 4, pp. 1460-1476, 2018 Aug. Abstract

The peripheral nervous system is one of many organ systems that can be profoundly impacted in diabetes mellitus. Diabetic peripheral neuropathy has a significant negative effect on patients' quality of life as it begins with loss of limbs' sensation and may result in lower limb amputation. This investigation aimed at exploring the effect of sulforaphane on peripheral neuropathy in diabetic rats. Experimental diabetes was induced through single intraperitoneal injections of nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Rats were divided into five groups. Two groups were treated with saline or sulforaphane (1 mg/kg, p.o.). Three diabetic groups were either untreated or given sulforaphane (1 mg/kg, p.o.) or pregabalin (10 mg/kg, i.p.). Two weeks after drugs' administration, biochemical, behavioral, histopathological, and immunohistochemical investigations were carried out. Treatment with sulforaphane restored animals' body weight, reduced blood glucose, glycated hemoglobin, and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test, and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, and matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents. These results reveal the neuroprotective effect of sulforaphane against peripheral neuropathy in diabetic rats possibly through modulating oxidative stress, inflammation, and extracellular matrix remodeling. Graphical Abstract Diagram that illustrates the effects of sulforaphane in treating experimental diabetic peripheral neuropathy. In NA-STZ model of diabetes mellitus, sulforaphane, restored animals' body weight, reduced blood glucose, glycated hemoglobin and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents.

Moustafa, P. E., N. F. Abdelkader, S. E. A. Awdan, O. A. El-Shabrawy, and H. F. Zaki, "Extracellular Matrix Remodeling and Modulation of Inflammation and Oxidative Stress by Sulforaphane in Experimental Diabetic Peripheral Neuropathy", Inflammation, vol. 41, issue 4, pp. 1460-1476, 2018. sfn_neuropathy.pdf
Gramoun, A., D. P. Trebec, N. Azizi, and M. F. Manolson, "The extracellular matrix proteins, fibronectin and vitronectin, have a biphasic effect on osteoclastogenesis.", JOURNAL OF BONE AND MINERAL RESEARCH, vol. 21: AMER SOC BONE & MINERAL RES 2025 M ST, NW, STE 800, WASHINGTON, DC 20036-3309 USA, pp. S162–S162, 2006. Abstract
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Attallah, A. M., D. Omran, M. M. Omran, M. A. Abdelrazek, R. Zayed, R. E. Essawey, S. Saif, A. Farid, M. Hassany, A. Yosry, et al., "Extracellular Matrix Proteins Substantiate IL-28B T allele Effect on Histological Outcome of Chronic Hepatitis C.", Annals of hepatology, vol. 17, issue 4, pp. 569-576, 2018. Abstract

INTRODUCTION AND AIM: The correlation between interleukin-28B (IL-28B) polymorphisms and chronic hepatitis C (CHC) progression is debatable. Here, we aimed to evaluate the relation between IL-28B C/T genotypes and the development of cirrhotic liver. Extracellular matrix (ECM) proteins, FibroScan and model for end-stage liver disease (MELD) were used to substantiate the severity of liver disease.

MATERIAL AND METHODS: IL-28B rs12979860, liver stiffness and ECM proteins were assessed in 272 CHC patients.

RESULTS: Cirrhosis percentage increased to 10%, 52% and 96% with the increasing number of T alleles (CC, CT and TT, respectively). Also, elevated ECM proteins levels were correlated with the increasing number of T alleles. Interestingly, among cirrhotic patients, liver stiffness, MELD and ECM proteins were significantly (P < 0.0001) higher in patients with TT more than CT genotype. FibroScan, hyaluronic acid, Laminin, Collagen IV and the N-terminal pro-peptide of collagen type III have high accuracy to differentiate liver status in CC from TT genotype. Area under receiver-operating characteristic curve (95% CI) were 1.0 (1.0-1.0), 0.97 (0.96- 1.0), 0.93 (0.85-1.0), 0.98 (0.97-1.0) and 0.93 (0.91-0.97), respectively.

CONCLUSION: This study suggests that IL-28B T allele affects the natural course of CHC type 4 and also suggests that carriage of the IL-28B C allele protects from unfavorable clinical outcomes in CHC as coexistence of C allele with T allele reduced cirrhosis severity.

Attallah, A. M., D. Omran, M. M. Omran, M. A. Abdelrazek, R. Zayed, R. E. Essawey, S. Saif, A. Farid, M. Hassany, A. Yosry, et al., "Extracellular Matrix Proteins Substantiate IL-28B T allele Effect on Histological Outcome of Chronic Hepatitis C", Ann Hepatol. , vol. 17, issue 4, pp. 569-576, 2018.
Gramoun, A., D. P. Trebec, N. Azizi, J. Sodek, and M. F. Manolson, "Extracellular matrix proteins affect both osteoclast formation and resorptive activity", JOURNAL OF BONE AND MINERAL RESEARCH, vol. 22: AMER SOC BONE & MINERAL RES 2025 M ST, NW, STE 800, WASHINGTON, DC 20036-3309 USA, pp. S151–S151, 2007. Abstract
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Gramoun, A., D. P. Trebec, N. Azizi, J. Sodek, and M. F. Manolson, "The Extracellular Matrix Protein Fibronectin Positively Regulates the Osteoclast Function", JOURNAL OF BONE AND MINERAL RESEARCH, vol. 23: AMER SOC BONE & MINERAL RES 2025 M ST, NW, STE 800, WASHINGTON, DC 20036-3309 USA, pp. S259–S259, 2008. Abstract
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Iftikhar, T., G. Bell, Y. Gao, J. R. Todd, P. Christen, N. Angeles, A. Farres, S. Revah, M. R. Egmond, and W. P. Antheunisse, "Extracellular lipase production by a sapwood-staining fungus Ophiostoma piceae.", Biotechnology, vol. 1, issue 1: orgz, pp. 1703-1719, 1981. Abstract
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Osman, M., and et al, "Extracapsular dissection versus superficial parotidectomy in treatment of benign parotid tumors.( Prof. Emad Daif was a peer reviewer for this article).", Egyptian Journal of Oral & Maxillofacial Surgery, vol. 7, issue 1, pp. 9-14, 2016.
Obeida, A., H. M. Taher, B. Magdy, M. Gad, A. Nayef, S. A. Tawfik, M. Ahmed, A. Amr, M. Elbarbary, M. A. Kotb, et al., Extra-testicular Intra-scrotal Median Raphe Epidermoid Cyst Mimicking Polyorchidism in a Child, , vol. 3, issue 2, pp. 119 - 125, 2023. AbstractWebsite

Epidermoid cysts are encapsulated sebaceous cysts that contain keratin. They present at any age, yet they are commoner in adults. They mainly affect face, neck, trunk and to a lesser extent groin, but can potentially arise as a subepidermal nodule anywhere on the body. They develop from the follicular infundibulum, and are different from dermoid cysts as epidermoid cysts do not contain other adnexal structures of embryonic origin. Epidermoid cysts are mostly silent but can rupture, get inflamed, become infected or develop daughter cysts. Very rarely epidermoid cysts develop in proximity to testicles. They can be mistaken for a testicular tumor. The pre- operative diagnosis is essential to avoid unindicated testicular surgery. Magnetic resonance imaging (MRI) is vital for diagnosis. We report a 6-year-old child with a long standing painless scrotal swelling thought by the parents to be polyorchidism. They were alarmed by its recent rapid growth. By examination it was a median raphe cyst. Pre-operative imaging and operative surgical removal proved it to be an inflamed epidermoid cyst. The surgery was uncomplicated and the child had an uneventful recovery. Testicular epidermoid cysts in children are exceptionally rare, yet they can present as median raphe cysts. Inflammation within the epidermoid cyst presents clinically as rapid painless growth. Clinical examination, high index of suspicion and pre-operative MRI avoid unnecessary testicular surgery.

A, O., N. A. Magdy B, Gad M, A. A. Tawfik S, Ahmed M, E. B. M, K. MA, and A. K. S. Ahmed S, "Extra-testicular Intra- scrotal Median Raphe Epidermoid Cyst Mimicking Polyorchidism in a Child.", Pediatric Sciences Journal, vol. 3, issue 2, pp. 119-125, 2023. cupsj_volume_3_issue_2_pages_119-125.pdf
A, O., N. A. Magdy B, Gad M, A. A. Tawfik S, Ahmed M, E. B. M, K. MA, and A. K. S. Ahmed S, "Extra-testicular Intra- scrotal Median Raphe Epidermoid Cyst Mimicking Polyorchidism in a Child.", Pediatric Sciences Journal, vol. 3, issue 2, pp. 119-125, 2023. cupsj_volume_3_issue_2_pages_119-125.pdf
Tawfik, A. R., and E. -elD. A. - H. Korshy, "Extra-anatomical trans-obturator bypass, modifications of the technique 10 cases report and review of literature", C3 conference, Orlando Florida USA, 2013. surgeon_a0.pdf
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