MicroRNA-155 and Disease-Related Immunohistochemical Parameters in Cutaneous Melanoma.

Cutaneous melanoma is a severe and life-threatening form of skin cancer with growing incidences. While novel interventions have improved prognoses for these patients, early diagnosis of targeted treatment remains the most effective approach. MicroRNAs have grown to good use as potential biomarkers for early detection and as targets for treatment. miR-155 is well-studied for its role in tumor cell survival and proliferation in various tissues, although its role in melanoma remains controversial. In silico data analysis was performed in the dbDEMC v.3 to identify differentially expressed miRNA. We validated gene targets in melanoma using TarBase v8.0 and miRPath v3.0 and determined protein-protein interactions of the target genes. One hundred forty patients (age range 21-90 years) with cutaneous melanoma who underwent resection were included. Molecular assessment using Real-Time RT-qPCR, clinicopathological associations, and a literature review for the different roles of miR-155 in melanoma were performed. Analysis of the dbDEMC reveals controversial findings. While there is evidence of upregulation of miR-155 in primary and metastatic melanoma samples, others suggest decreased expression in later-stage melanoma and cases with brain metastasis. miR-155 has been overexpressed in prior cases of melanoma and precancerous lesions, and it was found to be dysregulated when compared to benign nevi. While miR-155 expression was associated with favorable outcomes in some studies, others showed an association with metastasis. Patients with high levels of miR-155 also noted reduction after receiving anti-PD-1 treatment, correlated with more prolonged overall survival. In our patient's cohort, 22.9% relapsed during treatment, and 45% developed recurrence, associated with factors such as lymph node infiltration, high mitotic index, and positive staining for CD117. Although overall analysis revealed miR-155 downregulation in melanoma specimens compared to non-cancer tissues, increased expression of miR-155 was associated with cases of superficial spreading melanoma subtype (p = 0.005) and any melanoma with a high mitotic rate (p = 0.010). The analysis did not identify optimum cutoff values to predict relapse, recurrence, or mortality. In conclusion, miR-155 could have, in part, a potential prognostic utility in cutaneous melanoma. Further mechanistic studies are required to unravel the multifunctional role of miR-155 in melanoma.

Effect of Topical Application of Black Seed Oil on Imiquimod-Induced Psoriasis-like Lesions in the Thin Skin of Adult Male Albino Rats.

Psoriasis is a chronic inflammatory skin disease that affects about 1%-3% of the world's population. Black seed oil, i.e., the oil extracted from black seeds (Nigella sativa seeds), possesses a broad spectrum of pharmacological actions including anti-inflammatory, immunostimulatory, and antioxidant properties. This study aimed to investigate the effect of black seed oil on imiquimod (IMQ) induced psoriasis-like skin lesions. To this end, 30 male albino rats were divided into three groups: group I, control group; group II, psoriasis-induced group receiving daily topical applications of IMQ cream (5%) on the shaved back skin for 10 consecutive days; and group III, black seed oil group receiving a daily topical dose of black seed oil 5 mg/kg body weight for 10 days after induction of psoriasis. Animals of all groups were sacrificed and specimens obtained from the skin of the central part of the back were processed for histological and immunohistochemical staining with proliferating cell nuclear antigen (PCNA). IMQ application led to epidermal inflammation, hyperplasia and alterations in the normal appearance of keratinocytes with degenerative changes observed at both light and electron microscopic levels. Collagenous fibers were abundant in the dermis and PCNA-positive cells were detected in all layers of the epidermis. However, topical use of black seed oil strongly inhibited IMQ-induced psoriasis-like inflammation and alleviated all epidermal and dermal changes observed after IMQ application, allowing us to conclude that black seed oil can be used as an adjuvant topical therapy for treating psoriasis. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:166-174, 2018. © 2017 Wiley Periodicals, Inc.

Effect of Lycopene and Rosmarinic Acid on Gentamicin Induced Renal Cortical Oxidative Stress, Apoptosis, and Autophagy in Adult Male Albino Rat.

Gentamicin nephrotoxicity accounts for 10%-15% of all cases of acute renal failure. Several natural antioxidants were found to be effective against drug-induced toxicity. The possible protective effects of lycopene (Lyc) and rosmarinic acid (RA) alone or combined on gentamicin (Gen) induced renal cortical oxidative stress, apoptosis, and autophagy were evaluated. Sixty-three rats were randomly divided into seven groups named: control, group II received RA 50 mg/kg/day, group III received Lyc 4 mg/kg/day, group IV received Gen 100 mg/kg/day, group V (RA + Gen), group VI (Lyc + Gen), and group VII (RA + Lyc + Gen). At the end of the experiment, kidney functions were estimated then the kidneys were sampled for histopathological, immunohistochemistry, and biochemical studies. Administration of rosmarinic acid and lycopene decreased elevated serum creatinine, blood urea nitrogen, renal malondialdehyde and immunoexpression of the proapoptotic protein (Bax), autophagic marker protein (LC3/B), and inducible nitric oxide synthase (iNOS) induced by gentamicin. They increased reduced glutathione, glutathione peroxidase, superoxide dismutase, and immunoexpression of the antiapoptotic protein (Bcl2). They also improved the histopathological changes induced by gentamicin. The combination therapy of rosmarinic acid and lycopene shows better protective effects than the corresponding monotherapy. Anat Rec, 300:1137-1149, 2017. © 2016 Wiley Periodicals, Inc.

Effect of Potassium Bromate on the Liver of Adult Male Albino Rat and A Possible Protective Role of Vitamin C: Histological, Immunohistochemical, and Biochemical Study.

Potassium bromate (KBrO3 ) is a food additive which is used primarily as a maturing agent for flour. It is proved as a toxic agent with significant reduction in the activities of antioxidant capacity. The therapeutic efficacy of vitamin C as antioxidant may provide a possible solution to KBrO3 mediated oxidative damage. Twenty four adult male albino rats were used to evaluate the protective role of vitamin C against KBrO3 induced hepatotoxicity and divided into four groups; Group 1 (control), Group 2: received 30 mg/Kg/day vitamin C orally for 4 weeks, Group 3: received 20 mg/Kg/dose KBrO3 orally twice weekly for 4 weeks and Group 4: received both KBrO3 and vitamin C. Liver specimens were processed for histological study by light and electron microscopes and stained immunohistochemically to detect glial fibriller acidic protein (GFAP). Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated as well as the levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities in all dissected tissues were determined. KBrO3 induced histological alterations in the form of degeneration, cellular infiltration and significant increase in collagen deposition in portal tracts with a significant increase in immunoexpression of GFAP. Significant rise in serum levels of AST, ALT, and MDA in liver tissues were recorded. However, levels of GSH and SOD were significantly decreased. Most of these changes were improved by vitamin C treatment. In conclusion, vitamin C ameliorates the histological and biochemical alterations of the liver induced by KBrO3 . Anat Rec, 299:1256-1269, 2016. © 2016 Wiley Periodicals, Inc.

Effect of pycnogenol and spirulina on vancomycin-induced renal cortical oxidative stress, apoptosis, and autophagy in adult male albino rat.

Vancomycin-induced nephrotoxicity has been reported to occur in 5%-25% of patients who were administered with it. Several natural antioxidants were found to be effective against drug-induced toxicity. We evaluated the possible protective effects of spirulina and pycnogenol alone or in combination on vancomycin-induced renal cortical oxidative stress. Forty-nine rats were randomly divided into 7 groups: group I, control; group II, received spirulina 1000 mg/kg per day; group III, received pycnogenol 200 mg/kg per day; group IV, received vancomycin 200 mg/kg per day every 12 h; group V, (spirulina + vancomycin); group VI, (pycnogenol + vancomycin); and group VII, (pycnogenol + spirulina + vancomycin). At the end of the experiment, kidney functions were estimated and then the kidneys were removed, weighed, and sampled for histopathological, immunohistochemistry, and biochemical studies. Administration of spirulina and pycnogenol alone or in combination decreased elevated serum creatinine, blood urea nitrogen, renal malondialdehyde, and immunoexpression of the proapoptotic protein (Bax), autophagic marker protein (LC3/B), and inducible nitric oxide synthase induced by vancomycin. They increased reduced glutathione, glutathione peroxidase, superoxide dismutase, and immunoexpression of the antiapoptotic protein (Bcl2). They also ameliorated the morphological changes induced by vancomycin. The combination therapy of spirulina and pycnogenol showed better protective effects than the corresponding monotherapy.

6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats.

Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degeneration that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin 'therapy' has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections.

Effect of bisphenol A on morphology, apoptosis and proliferation in the resting mammary gland of the adult albino rat.

Bisphenol A (BPA) is a synthetic oestrogen that is extensively used in a wide range of daily used plastic products. This makes it one of the environmental chemicals that may have impact on human health. Due to its oestrogenic effect, BPA might affect the mammary gland. This study aimed to investigate the influence of BPA on the histological structure of the mammary gland of the adult female albino rat and its effect on epithelial cell proliferation and apoptosis status, in addition to its possible modulating effect on estrogen receptor expression. Thirty female adult albino rats were divided into control and experimental groups. The rats in the experimental group were gavaged with 5 mg/kg BPA daily for 8 weeks. The mammary glands were dissected and processed for histological and immunohistochemical stains for Ki-67, activated caspase-3 and estrogen receptor alpha (ER-α). BPA induced an increase in the number and size of the acini and ducts in the mammary gland of treated rats with hyperplasia of their lining epithelial cells. The collagen fibre content was significantly increased in the connective tissue stroma separating the ducts. Immunohistochemical results showed a significant increase in Ki-67 and caspase-3, but a non-significant increase in ER-α expression. Bisphenol A induced structural changes and affected the proliferation rate of mammary glands, so it might be one of the predisposing factors for breast cancer.

Protective effect of hesperidin against lung injury induced by intestinal ischemia/reperfusion in adult albino rats: histological, immunohistochemical and biochemical study.

Hesperidin is a naturally common flavonoid. It is an abundant and cheap by-product of citrus cultivation. It is reported to have antioxidative, anti-inflammatory and anticarcinogenic effects. This work was performed to investigate the possible protective role of hesperidin in ameliorating the effect of experimentally induced intestinal ischemia/reperfusion injury (I/R) on lung tissue, histologically, immunohistochemically and biochemically. Thirty male Wistar adult albino rats were randomized into three groups named: group I (control group); group II (I/R); and group III (I/R with hesperidin). Intestinal I/R was induced by occluding the superior mesenteric artery for 60 min, followed by 120 min of reperfusion period. Animals were given hesperidin orally 1h before the onset of ischemia. At the end of the reperfusion period the lung tissues were extracted for histopathological examination and immunohistochemical detection of the distribution of inducible nitric oxide synthase (iNOS). Pulmonary edema was evaluated by lung tissue wet/dry weight ratios. The levels of malondialdehyde (MDA, a biomarker of oxidative damage), myeloperoxidase (MPO, an index of the degree of neutrophil accumulation) and glutathione (GSH, a biomarker of protective oxidative injury) were also determined in all dissected tissues. Pretreatment with hesperidin (in group III) alleviated lung morphological changes noticed in I/R group and the levels of MDA and MPO were significantly decreased whereas those of GSH were significantly increased. Immunohistochemical study revealed a significant decrease in the iNOS. Hesperidin also significantly alleviated the formation of pulmonary edema as evidenced by the decreased organ wet/dry weight ratios. Hesperidin exerts a protective effect against lung damage induced by intestinal I/R injury in rats by reducing oxidative stress.