Anticancer activity of aqueous myrrh extract alone and in combination with cisplatin in HeLa cells

Purpose: To study the impact of an aqueous myrrh extract on the proliferation of cervical cancer cells in vitro.Methods: First, 100 g of ground myrrh resin was boiled in 1000 mL of distilled water for 30 min. Different components of the decoction were identified using gas chromatography–mass spectrometry and high-performance liquid chromatography. The effects of high (20 μg/mL) and low (10 μg/mL) concentrations of cisplatin, serial concentrations of myrrh (20, 40, 60, and 80 μg/mL), and a combination of both were evaluated using cell proliferation assay, DNA fragmentation, and electron microscopy.Results: All four myrrh concentrations decreased the viability of HeLa cells (16.25 % p < 0.01). A significant further decrease occurred when myrrh was combined with 10 μg/mL cisplatin (11.42 % p < 0.01). This was confirmed by quantifying DNA fragmentation. Ultrastructurally, HeLa cells showed typical apoptosis after treatment with 10 μg/mL cisplatin or a high dose of myrrh. The use of 20 μg/mL cisplatin or the combined therapy resulted in cell necrosis with ruptured cell membranes and autophagosomes. The effect of combined therapy was more lethal than the effect of either of them alone.Conclusion: Myrrh induces apoptosis and autophagy and enhances the activity of cisplatin in vitro. It is potentially a basis for further studies of other types of cancer cell. The clinical use of myrrh in the palliative therapy of human cervical carcinoma might be justified.Keywords: Cervical cancer, Cell viability, Chemotherapy, DNA fragmentation, Myrrh, Cisplatin, Cell ultrastructure, HeLa cell

Biochemical and mineral compositions of six brown seaweeds collected from Red Sea at Hurghada Coast

484-491The biochemical and mineral compositions of six brown seaweeds collected during spring season from Red Sea at Hurghada coast were determined to evaluate their significance in animal nutrition. The results suggested that the highest ash and protein contents were recorded in Padina gymnospora (45.48%) and Sargassum muticum (5.31%), respectively. The carbohydrates content was > 24.0% in the studied seaweeds, while the fat content ranged from 0.11 to 0.27%, and the essential amino acids formed 38.13-42.34% of the total amino acids. Both Padina gymnospora and Turbinaria sp. had the majority of measured phenolic compounds. Also, the studied seaweed species were rich in vitamin B2 (> 105.0 ppm), except Sargassum aspirofolium. The highest/lowest vitamin C content existed in Sargassum muticum (11.76 ppm) and Sargassum aspirofolium (3.96 ppm), respectively. Moreover, the tested seaweeds exhibited high amounts of essential minerals. Therefore, Red Sea brown seaweeds are good food sources for animal nutrition

Neuroprotective effects of thymoquinone against cerebellar histopathological changes in propylthiouracilinduced hypothyroidism in adult rats

Purpose: To evaluate the effects of thymoquinone (TQ) on histological and immunohistochemical changes in the cerebellar cortex induced by propylthiouracil (PTU) treatment in rats.Methods: Thirty-two adult male albino rats were randomly divided into four groups: C, control; PTU, treatment with oral PTU to induce hypothyroidism; TQ, treatment with TQ; and PTU + TQ, concomitant treatment with oral PTU and TQ for 6 weeks. Cavalieri’s principle and physical dissector methods were employed for unbiased deduction of cerebellar granular layer volume, numerical density, and number of granular cells.Results: In the PTU group, hematoxylin and eosin (H&E)-stained sections revealed degeneration of Purkinje cells, neuronal loss, and spongiosis in the white matter. A decrease in the number of astrocytes-expressing glial fibrillary acidic protein (GFAP) and a significant decrease in granular layer cell density were also seen. Concomitant administration of TQ ameliorated histopathological changes, increased the proportion of GFAP-positive astrocytes, increased granular cell density, and significantly (p < 0.05) increased the levels of thyroid-stimulating hormones, T3 and T4.Conclusion: TQ treatment significantly decreases cerebellar changes resulting from PTU-induced hypothyroidism, and results in the retention of neuronal structural integrity in the cerebellar cortex.Keywords: Hypothyroidism, Cerebellum, Thymoquinone, Stereology, Glial fibrillary acidic protein, Neuronal structural integrit

MISA (Minimally Invasive Surfactant Administration) Versus Insure (Intubation, Surfactant, Extubation) In Preterms Less Than 34 Weeks With RDS

Background: Newborn Respiratory Distress Syndrome (RDS) or what is known as surfactant deficiency disorder is a syndrome that affects premature infants who are born prematurely and is caused by a developmental deficiency in the production of pulmonary surfactant or as it is called immature formation of the lungs, or as a result of a defect in the protein gene that forms pulmonary surfactant. Non-invasive positive pressure ventilation (NIPPV) is the first technique for respiratory therapy while MISA and InSurE are both the most commonly used in RDS. Objective: To compare the use of the MISA method and the InSurE method in the treatment of premature infants less than 34 weeks of gestational age with respiratory distress syndrome (RDS). Patients and methods: The sample size was 70 infants with gestational age less than 34 weeks with RDS. 35 newborn were enrolled in each group. First group received surfactant via MIST technique and the other 35 newborn received it via InSurE technique. Infants in the InSurE group required intubation, according to previous collected data from the neonatal intensive care unit (NICU) center. Results: After the injection of surfactant, the 13 (37%) infants needed another dose in the MIST group, while only 3 (8.57%) infants in the InSurE group needed a second dose of the same substance. Accordingly, the response of the MIST group was shown to be a less improvement than the InSurE group in the child's breathing methods. Conclusion: The MIST method was the most successful with a rate of 96.5% in terms of time and the child's response to treatment, and the researcher recommended that the reasons for the effectiveness of MISA in treating RDS should be studied. However duration of invasive mechanical ventilation were higher in MIST group than InSurE group

Histological, immunohistochemical and ultrastructural study of secondary compressed spinal cord injury in a rat model

Introduction. Spinal cord injury (SCI) is a life-disrupting condition in which the first few days are the most critical. Secondary conditions remain the main causes of death for people with SCI. The response of different cell types to SCI and their role at different times in the progression of secondary degeneration are not well understood. The aim of this study was to study the histopathological changes of compressed spinal cord injury (CSCI) in a rat model. Material and methods. Forty adult male Sprague-Dawley rats were divided into four groups. In group I, the rats were left without any surgical intervention (control). In group II, the rats were subjected to laminectomy without spinal cord compression (sham-operated). In group III, the rats were sacrificed one day after CSCI. In group IV, the rats were sacrificed seven days after CSCI. The light microscopy was employed to study the morphology using H&E, osmic acid staining and immunohistochemistry to detect glial fibrillary acidic protein (GFAP). The electron microscopy was applied for ultrastructure study. Results. Histopathological examination of the posterior funiculus of the white matter revealed minute hemorrhages and localized necrotic areas on day 1, which transformed to areas of cavitation and fibrinoid necrosis surrounded by a demarcating rim of numerous astrocytes by day 7. The mean percentage of area of GFAP expression increased significantly by day 7. Osmic acid staining revealed swollen nerve fibers after one day, while numerous fibers had been lost by day 7. An ultrastructure study revealed swollen redundant thinned myelin and myelin splitting, as well as degeneration of axoplasm on day 1. On day 7, layers of the myelin sheath were folded and wrinkled with partial or complete demyelination areas. The myelin lamellae were disorganized and loose. The G-ratio was significantly greater on day 1 than day 7 after CSCI. Conclusions. In the rat model of CSCI details of the progressive spinal cord injury can be analyzed by morphological methods and may be helpful in the identification of the onset and type of clinical intervention

Cellular Transplantation-Based Therapeutic Strategies for Spinal Cord Injuries: Preclinical and Clinical Updates

Spinal cord injury (SCI) is a distressing neurological condition that causes loss of neural tissue, with subsequent damages to neural circuitry, and loss of sensorimotor function. The SCIs have an estimated incidence rate of ~80 cases per million populations. Till date, no ratified effective therapeutic strategy for SCIs exist; however, recent advancements in regenerative medicines to protect and regenerate damaged/lost neural tissues following SCIs have shown promising results in preclinical and clinical trials. Moreover, there is a greater need to fully understand underlying mechanisms following cellular transplantation that can be achieved through proper differentiation of desired cell type, and their in-vivo tracking of migration, proliferation and integration into the host system. Furthermore, techniques that can prevent teratomas formation following cellular transplantation have been reported. In addition to the ongoing comprehensive neuroregenerative and neuroprotective therapeutic strategies for SCIs, novel technologies are emerging including neuroscience-based computational and robotic rehabilitational therapies. These improved strategies in combination with cell-based therapeutic approaches are opening new avenues for future research to completely cure SCIs. Herein, we intended to review pathophysiological mechanisms following SCI, preclinical and clinical updates of cellular transplantation, the extent of success from these transplantations, associated controversies and other emerging technologies

Dermoscopy in the Diagnosis of Mycosis Fungoides: Can it Help?

Introduction: The diagnosis of mycosis fungoides (MF) is challenging since it can mimic a variety of benign skin conditions. Multiple biopsies for histopathologic and immunohistochemical examination are required to diagnose MF. Dermoscopy is an affordable, non-invasive device with expanding indi-cations in dermatology, Objectives: To investigate the dermoscopic morphology of MF variants and assess the correlation between dermoscopic criteria, histopathologic, and immunohistochemical findings, Methods: We included 88 patients with several MF variants (classic, hypopigmented, hyperpigment-ed, poikilodermatous, erythrodermic, and folliculotropic).The diagnosis was histopathologically and immunohistochemically confirmed. Dermoscopic findings were collected, statistically analyzed, and correlated with the results of histopathology and immunohistochemistry, Results: All patients had MF diagnosis in H&E-stained sections.The majority revealed positive stain-ing with CD3, 4, 8 and negative CD7. Orange-red areas of discoloration, short linear, and spermato-zoa like blood vessels are the most frequent dermoscopic findings, while an analysis per MF variant was also performed.The frequently observed dermoscopic structures in classic MF were patchy whit-ish scales, dotted, short linear vessels, and spermatozoa-like vessels, Conclusions: Dermoscopy reveals a repetitive dermoscopic pattern in MF (non-homogenous pink to erythematous background, patchy areas of orange discoloration, patchy whitish scales, dotted and short linear blood vessels with some variations according to the clinical variant

Plant Flavonoids on Oxidative Stress-Mediated Kidney Inflammation

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Simple Summary: Increased stress is often observed in patients with kidney diseases, contributing to renal injury progression. Flavonoids are naturally occurring plant compounds with known health benefits, including antiapoptotic, anti-inflammatory, and antioxidant properties. Flavonoids can protect the kidney by improving antioxidant status, ameliorating excess reactive oxygen species levels, and acting as Nrf2-mediators in generating antioxidant responses in the body. Flavonoids also modulate inflammatory markers, exert anti-inflammatory effects, and protect the cells from apoptotic cell death in the kidney. Interestingly, few clinical trials have reported a direct correlation between a flavonoid-rich diet and better kidney disease prognosis. However, flavonoids have a low bioavailability in the body, making it essential to understand better their molecular mechanism of action. We suggest that a flavonoid-rich diet could have promising nephroprotective effects and beneficial outcomes in treating patients with kidney diseases. Abstract: The kidney is susceptible to reactive oxygen species-mediated cellular injury resulting in glomerulosclerosis, tubulointerstitial fibrosis, tubular cell apoptosis, and senescence, leading to renal failure, and is a significant cause of death worldwide. Oxidative stress-mediated inflammation is a key player in the pathophysiology of various renal injuries and diseases. Recently, flavonoids’ role in alleviating kidney diseases has been reported with an inverse correlation between dietary flavonoids and kidney injuries. Flavonoids are plant polyphenols possessing several health benefits and are distributed in plants from roots to leaves, flowers, and fruits. Dietary flavonoids have potent antioxidant and free-radical scavenging properties and play essential roles in disease prevention. Flavonoids exert a nephroprotective effect by improving antioxidant status, ameliorating excessive reactive oxygen species (ROS) levels, and reducing oxidative stress, by acting as Nrf2 antioxidant response mediators. Moreover, flavonoids play essential roles in reducing chemical toxicity. Several studies have demonstrated the effects of flavonoids in reducing oxidative stress, preventing DNA damage, reducing inflammatory cytokines, and inhibiting apoptosis-mediated cell death, thereby preventing or improving kidney injuries/diseases. This review covers the recent nephroprotective effects of flavonoids against oxidative stress-mediated inflammation in the kidney and their clinical advancements in renal therapy.Peer reviewe

Chemosensetizing and cardioprotective effects of resveratrol in doxorubicin- treated animals

BACKGROUND: Doxorubicin (DOX), an anthracycline antibiotic is one of the most effective anticancer drug used in the treatment of variety of cancers .Its use is limited by its cardiotoxicity. The present study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of mammary carcinoma (Ehrlich ascites carcinoma) to the action of DOX and at the same time its protective effect against DOX-induced cardiotoxicity in rats. METHODS: Ehrlich ascites carcinoma bearing mice were used in this study. Percent survival of tumor bearing mice was used for determination of the Cytotoxic activity of DOX in presence and absence of RSVL. Uptake and cell cycle effect of DOX in tumor cells in the presence of RSVL was also determined. Histopatholgical examination of heart tissues after DOX and/or RSVL therapy was also investigated. RESULTS: DOX at a dose level of 15 mg/kg increased the mean survival time of tumor bearing mice to 21 days compared with 15 days for non tumor-bearing control mice. Administration of RSVL at a dose level of 10 mg/kg simultaneously with DOX increased the mean survival time to 30 days with 70% survival of the tumor-bearing animals. RSVL increased the intracellular level of DOX and there was a strong correlation between the high cellular level of DOX and its cytotoxic activity. Moreover, RSVL treatment showed 4.8 fold inhibition in proliferation index of cells treated with DOX. Histopathological analysis of rat heart tissue after a single dose of DOX (20 mg/kg) showed myocytolysis with congestion of blood vessels, cytoplasmic vacuolization and fragmentation. Concomitant treatment with RSVL, fragmentation of the muscle fiber revealed normal muscle fiber. CONCLUSION: This study suggests that RSVL could increase the cytotoxic activity of DOX and at the same time protect against its cardiotoxicity

DNA-dependent protein kinase: Epigenetic alterations and the role in genomic stability of cancer

DNA-dependent protein kinase (DNA-PK), a member of phosphatidylinositol-kinase family, is a key protein in mammalian DNA double-strand break (DSB) repair that helps to maintain genomic integrity. DNA-PK also plays a central role in immune cell development and protects telomerase during cellular aging. Epigenetic deregulation due to endogenous and exogenous factors may affect the normal function of DNA-PK, which in turn could impair DNA repair and contribute to genomic instability. Recent studies implicate a role for epigenetics in the regulation of DNA-PK expression in normal and cancer cells, which may impact cancer progression and metastasis as well as provide opportunities for treatment and use of DNA-PK as a novel cancer biomarker. In addition, several small molecules and biological agents have been recently identified that can inhibit DNA-PK function or expression, and thus hold promise for cancer treatments. This review discusses the impact of epigenetic alterations and the expression of DNA-PK in relation to the DNA repair mechanisms with a focus on its differential levels in normal and cancer cells