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1.
Virchows Arch ; 484(5): 827-836, 2024 May.
Article in English | MEDLINE | ID: mdl-38561462

ABSTRACT

Urothelial carcinoma (UC) of the bladder is a common cause of cancer-related death worldwide. Vasculogenic mimicry (VM) is a process by which the malignant cells can generate vascular-like structures formed of periodic acid-Schiff (PAS) positive/CD31 negative extracellular matrix independent of angiogenesis and thus promotes tumor progression. N-myc downstream-regulated gene 1 (NDRG1) is a protein that can modulate tumor angiogenesis; however, its role in regulating tumor angiogenesis and VM formation has not been previously investigated in UC. This study aims to evaluate the role of intra-tumor microvessel density (MVD) (as a surrogate measure of angiogenesis), VM, and NDRG1 in UC and their correlation with different clinicopathologic features, then assess the correlation between them in UC. Sixty specimens of UC of the bladder were included. PAS-CD31 immunohistochemical double staining method was used to evaluate the intra-tumor MVD and VM. Immunohistochemical expression of NDRG1 was also examined. VM and NDRG1 expression were detected in 41.7% and 83.3% of UC specimens respectively. The mean of intra-tumor MVD, VM area, and NDRG1 was significantly higher in tumors with higher grade, lymphovascular invasion, and higher T stage. NDRG1 expression was positively correlated with MVD and VM. We can suggest that MVD, VM, and NDRG1 may serve as poor prognostic markers for UC. The positive correlation between NDRG1 and both MVD and VM may provide the first evidence that NDRG1 can induce tumor angiogenesis and VM in UC which may offer a novel pathway for further therapeutic strategies.


Subject(s)
Cell Cycle Proteins , Intracellular Signaling Peptides and Proteins , Microvascular Density , Neovascularization, Pathologic , Urinary Bladder Neoplasms , Humans , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/metabolism , Male , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/blood supply , Urinary Bladder Neoplasms/metabolism , Middle Aged , Female , Aged , Cell Cycle Proteins/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/analysis , Adult , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/metabolism , Carcinoma, Transitional Cell/blood supply , Aged, 80 and over , Immunohistochemistry , Urothelium/pathology , Angiogenesis
2.
Med Mol Morphol ; 2024 Mar 24.
Article in English | MEDLINE | ID: mdl-38522060

ABSTRACT

This study aimed to examine the immunohistochemical expression of epithelial-mesenchymal transition biomarkers: P4HA2 and SLUG in colorectal carcinoma (CRC) specimens, then to assess their relation to clinicopathological features including KRAS mutations and patients' survival, and finally to study the correlation between them in CRC. The result of this study showed that SLUG and P4HA2 were significantly higher in association with adverse prognostic factors: presence of lympho-vascular invasion, perineural invasion, higher tumor budding, tumor stage, presence of lymph node metastasis, and presence of distant metastasis. CRC specimens with KRAS mutation were associated with significant higher SLUG and P4HA2 expression. High expression of both SLUG and P4HA2 was significantly unfavorable prognostic indicator as regards overall survival (OS) and disease-free survival (DFS). In KRAS mutated cases, high P4HA2 expression was the only significant poor prognostic indicator as regarding DFS. In conclusions, our data highlight that both SLUG and P4HA2 expression may serve as potentially important poor prognostic biomarkers in CRC and targeting these molecules may be providing a novel therapeutic strategy. In KRAS mutation group, high P4HA2 expression is the only independent prognostic factor for tumor recurrence, so it can be suggested to be a novel target for therapy.

3.
Int J Dermatol ; 63(5): 632-638, 2024 May.
Article in English | MEDLINE | ID: mdl-38159109

ABSTRACT

BACKGROUND: Microneedling is a technique of repeated puncturing or drilling of the skin to induce repair and collagen induction. There are many reported important factors determining the efficacy of microneedling treatment. The extent of injury needed to produce the desired effect in each condition is one of these important factors. OBJECTIVES: We designed the present split-face comparative study to evaluate the use and effectiveness of two different depths of penetration of Dermapen needles in the management of atrophic postacne scars. PATIENTS AND METHODS: The present study involved 14 subjects with atrophic postacne scars. In each patient, both sides of the face were treated with six sessions of microneedling, using Dermapen at 2-week intervals. A split-face study design was performed. The right (Rt) side of the face was treated with Dermapen using 2.5 mm needle length, while the left (Lt) side was treated using 1.5 mm needle length. RESULTS: There was a significantly better percentage of improvement of acne scars on the Rt side of the face compared to the Lt side (P = 0.02) after six sessions. Both sides of the face showed improvement of collagen bundles and elastic fibers characteristics after six sessions. CONCLUSIONS: The use of 2.5 mm depth proved to be more effective both clinically and histologically in the management of atrophic postacne scars.


Subject(s)
Acne Vulgaris , Atrophy , Cicatrix , Needles , Humans , Cicatrix/etiology , Cicatrix/therapy , Cicatrix/pathology , Cicatrix/diagnosis , Acne Vulgaris/complications , Acne Vulgaris/therapy , Adult , Female , Male , Atrophy/therapy , Young Adult , Collagen , Treatment Outcome , Cosmetic Techniques/instrumentation , Dry Needling/methods , Dry Needling/instrumentation , Elastic Tissue/pathology , Face , Percutaneous Collagen Induction
4.
Int J Exp Pathol ; 104(3): 128-139, 2023 06.
Article in English | MEDLINE | ID: mdl-36974470

ABSTRACT

This study highlights the prognostic impact of FOXP3 and CD68 expression in DLBCL, NOS and in its GCB and non-GCB subtypes. This may help the development of individualized therapy, prognostic prediction and therapy stratification.


Subject(s)
Germinal Center , Lymphoma, Large B-Cell, Diffuse , Humans , Germinal Center/metabolism , Germinal Center/pathology , Prognosis , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/pathology , Forkhead Transcription Factors/metabolism
5.
Int Immunopharmacol ; 117: 109927, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36848793

ABSTRACT

BACKGROUND: Apremilast (Apre), a novel phosphodiesterase-4 (PDE4) inhibitor, has been shown to have anti-inflammatory, immunomodulator, neuroprotective and senolytic properties, therefore, Apre like other PDE4 inhibitors may be a promising candidate for treatment of Alzheimer's disease (AD). OBJECTIVE: To evaluate the effectiveness of Apre on Alzheimer's like pathology and symptoms in an animal model. METHODS: The effects of Apre and cilostazol, a reference drug, on the behavioral, biochemical, and pathological features of Alzheimer's disease induced by a high-fat/high-fructose diet combined with low-dose streptozotocin (HF/HFr/l-STZ) were investigated. RESULT: Apre 5 mg/kg IP/day for 3 consecutive days per week for 8 weeks attenuated memory and learning deficits tested by novel object recognition, Morris water maze and passive avoidance tests. Apre treatment significantly decreased the number of degenerating cells, and abnormal suppression of gene expression of AMPA and NMDA receptor subunits in the cortex and hippocampus of the AD rat model compared to rats that received vehicle. A significant decrease in elevated levels of hippocampal amyloid beta, tau-positive cell count, cholinesterase activity, and hippocampal caspase-3, a biomarker of neurodegeneration, was also observed after treatment with Apre in AD rats compared to rats that received placebo. Furthermore, a significant decrease in pro-inflammatory cytokines, oxidative stress, insulin resistance and GSK-3 was demonstrated in AD aged rats treated by Apre. CONCLUSION: Our findings demonstrate that intermittent treatment with Apre can enhance cognitive function in HF/HFr/l-STZ rats which may be related to decreased pro-inflammatory cytokines, oxidative stress, insulin resistance and GSK-3ß.


Subject(s)
Alzheimer Disease , Diabetes Mellitus, Type 2 , Insulin Resistance , Phosphodiesterase 4 Inhibitors , Rats , Animals , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Rats, Wistar , Phosphodiesterase 4 Inhibitors/therapeutic use , Phosphodiesterase 4 Inhibitors/pharmacology , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Hippocampus , Streptozocin , Cytokines/metabolism , Diabetes Mellitus, Type 2/metabolism , Disease Models, Animal , Maze Learning
6.
Arch Dermatol Res ; 315(6): 1675-1688, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36809409

ABSTRACT

Alopecia areata (AA) is a common cause of hair loss with no available universally successful treatment. Thus, new innovative treatments are urgently needed. This research aimed to evaluate the effectiveness of fractional carbon dioxide laser (FCL) alone or combined with triamcinolone acetonide (TA) solution, platelet-rich plasma (PRP), or vitamin D3 solution in treating AA. Sixty-four AA patients with 185 lesions were recruited and divided into four treatment groups. All patients received FCL either alone (group A, n = 19) or followed by topical TA (group B, n = 16) or PRP (group C, n = 15), or vitamin D3 solution (group D, n = 14). The response was assessed using Alopecia Areata Severity Index (AASI), MacDonald Hull and Norris grading, and trichoscopy. Histopathological features and immunohistochemical decorin expression were studied. All groups showed significant improvement in AASI compared to the baseline, with insignificant differences between them. Post-treatment, trichoscopic features of disease activity significantly decreased in all groups. Compared to control biopsies, both anagen follicles and decorin expression were significantly decreased in all pretreatment specimens. After treatment, all groups showed significantly increased anagen follicles and decorin expression compared to the baseline. Accordingly, FCL is an effective treatment for AA alone or combined with TA, PRP, or vitamin D3 solution. In AA, Decorin expression was downregulated, while enhanced expression following successful treatment occurred. This suggests the role of decorin in AA pathogenesis. However, further research is still recommended to clarify the exact role of decorin in AA pathogenesis and to investigate the therapeutic benefits of decorin-based therapy.


Subject(s)
Alopecia Areata , Lasers, Gas , Humans , Alopecia Areata/drug therapy , Pharmaceutical Preparations , Lasers, Gas/therapeutic use , Decorin/therapeutic use , Treatment Outcome , Triamcinolone Acetonide/therapeutic use , Cholecalciferol/therapeutic use
7.
Arch Physiol Biochem ; 129(4): 854-869, 2023 Dec.
Article in English | MEDLINE | ID: mdl-33507837

ABSTRACT

In this study, we investigated the ability of N-acetyl cysteine (NAC) to alleviate the metabolic disorders in fructose-induced metabolic syndrome (MS) in male rats and to examine its protective effect on aortic and cardiac tissues via its influence on cardiotrophin-1 (CT-1) expression. NAC (20 mg/kg b.w./day) was administered to fructose induced MS animals for 12 weeks. Chronic fructose consumption (20% w/v) increased body weight gain, relative heart weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), insulin resistance (IR), and associated with metabolic alterations. Histological and immunohistochemical examination revealed aortic stiffness and myocardial degeneration and fibrosis together with increased CT-1 expression. Treatment with NAC improved IR, SBP, DBP, and mitigated dyslipidaemia and oxidative stress. Additionally, NAC down-regulated CT-1 expression in the heart and aorta. These findings demonstrated the protective effect of NAC against aortic and myocardial degeneration and fibrosis through down-regulation of CT-1 in fructose induced MS animal model.


Subject(s)
Insulin Resistance , Metabolic Syndrome , Animals , Male , Rats , Acetylcysteine/pharmacology , Aorta , Down-Regulation , Fibrosis , Fructose/adverse effects , Fructose/metabolism , Metabolic Syndrome/metabolism , Oxidative Stress , Rats, Wistar
8.
Gastroenterology Res ; 15(5): 268-277, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36407805

ABSTRACT

Solitary fibrous tumors (SFTs) are rare fibroblastic/myofibroblastic proliferations that occur in a wide range of anatomical sites. These tumors have nonspecific clinical presentations often with unpredictable biological behavior. SFTs can be slow growing low-risk tumors or rapidly growing high-risk tumors. They show a wide variety of histological features and typically are characterized by NAB2-STAT6 fusion. SFTs of the ischiorectal fossa are rare, with few studies reported in the literature to date. Here, we report a 90-year-old male who had a road traffic accident in October 2018. A pelvic computed tomography (CT) revealed a mass measuring 3.5 × 2.5 cm in the right ischiorectal fossa. Histopathology of the CT-guided biopsies confirmed the diagnosis of low-grade SFT. No surgical intervention was needed since the patient was asymptomatic. In January 2022, a follow-up CT showed a gradual increase in tumor size (5 × 3.5 × 3 cm), but not infiltrating the surrounding structures. However, the patient complained of constipation, which warranted a surgical excision of the mass. Subsequently, immunohistological examination reconfirmed the diagnosis of low-risk SFT. Here, we discussed the clinicopathological features of the case and the relevant literature about pelvic SFTs. In conclusion, SFTs should be considered in the differential diagnosis of any ischiorectal mass. It is recommended that tissue samples be obtained, and immunohistology should be performed.

9.
Biomacromolecules ; 23(4): 1803-1811, 2022 04 11.
Article in English | MEDLINE | ID: mdl-35319861

ABSTRACT

With the goal of achieving high barrier with bio-based materials, for example, for packaging applications, a series of novel furfural-based polyesters bearing sulfide-bridged difuran dicarboxylic acid units with high oxygen barrier properties were synthesized and characterized. For the novel poly(alkylene sulfanediyldifuranoate)s, a 11.2-1.9× higher barrier improvement factor compared to amorphous poly(ethylene terephthalate) was observed which places the novel polyesters in the top class among previously reported 2,5-furandicarboxylic acid (FDCA) and 2,2'-bifuran-based polyesters. Titanium-catalyzed polycondensation reactions between the novel synthesized monomer, dimethyl 5,5'-sulfanediyldi(furan-2-carboxylate), and four different diols, ethylene glycol, 1,3-propanediol, 1,4-butanediol, and 1,5-pentanediol, afforded difuran polyesters with high intrinsic viscosities (0.76-0.90 dL/g). These polyesters had good thermal stability, decomposing at 342-363 and 328-570 °C under nitrogen and air, respectively, which allowed processing them into free-standing films via melt-pressing. In tensile testing of the film specimens, tensile moduli in the range of 0.4-2.6 GPa were recorded, with higher values observed for the polyesters with shorter diol units. Interestingly, besides the low oxygen permeability, the renewable sulfide-bridged furan monomer also endowed the polyesters with slight UV shielding effect, with cutoff wavelengths of ca. 350 nm, in contrast to FDCA-based polyesters, which lack significant UV light absorption at over 300 nm.


Subject(s)
Furaldehyde , Polyesters , Oxygen , Sulfides , Sulfur
10.
Eur J Pharmacol ; 921: 174873, 2022 Apr 15.
Article in English | MEDLINE | ID: mdl-35283111

ABSTRACT

Several studies have suggested that phosphodiesterase (PDE) inhibitors may be a disease-modifying for Alzheimer's disease (AD). Cilostazol (CSZ) has been shown to be a new treatment for cognitive impairment with limited efficacy. Our aim was to investigate the effect of caffeine on the efficacy of CSZ against STZ-induced type 2 diabetes (T2D)-related cognitive impairment in high fat/high fructose fed rats. The efficacy of low doses of caffeine, CSZ, and CSZ plus caffeine against abnormal behavioral, biochemical, histological, or genetic changes of animal models of AD was examined. Eight weeks treatment with CSZ plus caffeine was more effective than CSZ or caffeine in improving impaired behavioral tests for cognition and memory. Histological examination exhibited a significant augmentation in the efficacy of CSZ by caffeine in protecting neurons from damage in T2D rats. Importantly, CSZ and caffeine normalized the accumulation of Amyloid beta (Aß-42) and phosphorylated tau protein (p-tau) positive cells in the brain of T2D rats. CSZ or CSZ plus caffeine reversed low glutamate gene expression, elevated cholinesterase level, and elevated caspase-3 activity in T2D rats. Furthermore, CSZ plus caffeine was significantly more effective than CSZ or caffeine in inhibiting the increase in malondialdehyde (MDA) level, total oxidative stress, pro-inflammatory cytokines and glucogen synthase kinase-3 beta (GSK-3ß) in the hippocampus of T2D rats. Also, CSZ plus caffeine was more effective than CSZ or caffeine in alleviating insulin resistance and hypercholesterolemia in T2D rats. Our findings suggest the possibility of effective treatment of AD by enhancing the therapeutic potential of CSZ through combined treatment with lower doses of caffeine. The enhancement of CSZ effect by caffeine is attributed to the increased inhibitory effect of CSZ on insulin resistance, GSK-3ß activity, hypercholesterolemia, oxidative stress and pro-inflammatory cytokines.


Subject(s)
Alzheimer Disease , Diabetes Mellitus, Type 2 , Alzheimer Disease/metabolism , Amnesia , Amyloid beta-Peptides/metabolism , Animals , Caffeine/pharmacology , Caffeine/therapeutic use , Cilostazol/pharmacology , Cilostazol/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Disease Models, Animal , Fructose/therapeutic use , Glycogen Synthase Kinase 3 beta , Rats
11.
Ann Diagn Pathol ; 55: 151831, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34634762

ABSTRACT

BACKGROUND: Breast cancer (BC) is a heterogeneous disease with different clinically heterogeneous phenotypes. Triple negative BC (TNBC) (ER-/PR-/HER2-) and triple positive BC (TPBC) (ER+/PR+/HER2+) are characterized by unique clinical behavior and therapeutic challenges. However, their exact molecular pathogenesis is not well studied. This study aims to evaluate the immunohistochemical expression of androgen receptor (AR) and c-Myc in TPBCs and TNBCs, correlate their expression with the clinicopathologic features, and assess the correlation between AR and c-Myc expression in TPBCs and TNBCs. MATERIAL AND METHODS: AR and c-Myc were immunohistochemically assessed in 45 TNBC and 15 TPBC specimens. RESULTS: AR expression was detected in 17.7% of TNBC and in all TPBC specimens. c-Myc was expressed in 46.7% of TNBC and in all TPBC specimens. AR and c-Myc expression in TNBC was not associated with any of the clinicopathological features. In TPBC, AR expression was higher in older age, larger size, higher stage, and lymph node metastasis while c-Myc expression was higher in tumors with perineural invasion. This is the first study that reported a significant positive correlation between AR and c-Myc expression in TNBC and TPBC. CONCLUSION: The current results suggested that AR and c-Myc proteins may contribute to the pathogenesis of TNBC and TPBC. The positive correlation between the two proteins in these subtypes sheds new light on a distinct pathway by which BC cells can modulate their proliferation. Targeting both molecules may provide new therapeutic approaches to improve therapeutic sensitivity and patients' outcomes of these subtypes.


Subject(s)
Breast Neoplasms/metabolism , DNA-Binding Proteins/metabolism , Receptors, Androgen/metabolism , Transcription Factors/metabolism , Triple Negative Breast Neoplasms/metabolism , Adult , Female , Humans , Immunohistochemistry , Middle Aged , Prognosis , Signal Transduction , Treatment Outcome
12.
Life Sci ; 280: 119706, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34102190

ABSTRACT

AIMS: Cigarette smoking (CS) is the main cause of chronic obstructive pulmonary disease (COPD). Endothelial dysfunction is related to the severity of pulmonary disease in COPD. This study aimed to evaluate the effectiveness of single and combined administration of pioglitazone (Pio) and irbesartan (Irb) against COPD-induced endothelial dysfunction in mice and the involvement of NO and H2S in their effects. MATERIALS AND METHODS: Adult male Swiss mice (n = 40, weighing 25-30 g) were assigned into 5 groups. The normal control group received 1% carboxy methyl cellulose (CMC). The CS group was exposed to CS and administered 1% CMC for 3 months. The CS + Pio, CS + Irb, and CS + Pio/Irb groups were subjected to CS and received Pio (60 mg/kg), Irb (50 mg/kg), and their combination respectively, daily orally for 3 months. Body weight gain, mean blood pressure, urinary albumin, serum NO and ET-1 levels with TNF-α and IL-2 levels in lung tissue and bronchoalveolar lavage were measured. Lung H2S and ET-1 levels, protein expression of PPARγ in lung and VEGF in lung and aortic tissues with histological changes were assessed. KEY FINDINGS: Our results illustrated that CS induced a model of COPD with endothelial dysfunction in mice. Pio/Irb singly and in combination elicited protective effects against the pathophysiology of the disease with more improvement in the combined group. There is a strong correlation between NO and H2S as well as the other measured parameters. SIGNIFICANCE: Collectively, both drugs performed these effects via their anti-inflammatory potential and increasing H2S and NO levels.


Subject(s)
Antihypertensive Agents/therapeutic use , Cigarette Smoking/adverse effects , Hypoglycemic Agents/therapeutic use , Irbesartan/therapeutic use , Pioglitazone/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Animals , Disease Models, Animal , Endothelium/drug effects , Endothelium/pathology , Lung/drug effects , Lung/pathology , Male , Mice , Pulmonary Disease, Chronic Obstructive/etiology , Pulmonary Disease, Chronic Obstructive/pathology , Smoke/adverse effects
13.
Reprod Toxicol ; 96: 57-66, 2020 09.
Article in English | MEDLINE | ID: mdl-32512129

ABSTRACT

Ketamine, a dissociative anesthetic, recently has spread as a recreational drug. Its abuse lead to neurobehavioral disturbance in addition to toxic effects on other body organs. To evaluate the toxic effects of chronic administration of low ketamine doses on the memory, testicles, and erection, explore its pathophysiology through oxidative stress mechanism and examine the ameliorating effect of N-acetyl cysteine (NAC). A total of 40 male albino rats were assigned to control, vehicle, ketamine only I.P. (10 mg/kg), and ketamine (10 mg/kg) + NAC (150 mg/kg) groups. Assessment of memory affection and erectile function by Passive Avoidance, Novel Object Recognition, and copulatory tests were performed. Estimation of malondialdehyde (MDA), catalase (CAT), and total antioxidant capacity (TAC) in serum and prefrontal & hippocampal homogenate, and luteinizing hormone (LH), testosterone in serum were done. Prefrontal cortex, hippocampus, and testes were collected for histopathology. Chronic ketamine administration induced significant memory deficits (P < 0.05), reduced erectile function (P < 0.05), severe hypospermatogenesis, increased MDA, reduced CAT, TAC levels in serum, and tissue homogenate (P < 0.05) and reduction of LH, and testosterone (P < 0.05). Treatment with NAC resulted in significant improvement of memory function, improved erectile function, and decrease in oxidative injury in both serum and tissue homogenates. Testosterone and LH levels exhibited significant difference between treatment groups and controls (P < 0.05). NAC reduced the deleterious histopathological changes. These data suggest that long-term ketamine affects short and long memory, induces erectile and testicular dysfunction through oxidative stress. Co-administration with NAC ameliorates these toxic effects.


Subject(s)
Acetylcysteine/therapeutic use , Analgesics/toxicity , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Erectile Dysfunction/chemically induced , Erectile Dysfunction/drug therapy , Ketamine/toxicity , Testis/drug effects , Acetylcysteine/pharmacology , Animals , Antioxidants/metabolism , Behavior, Animal/drug effects , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/pathology , Erectile Dysfunction/metabolism , Erectile Dysfunction/pathology , Female , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Luteinizing Hormone/blood , Male , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathology , Rats , Sperm Count , Sperm Motility/drug effects , Testis/pathology , Testosterone/blood
14.
J Cosmet Laser Ther ; 21(7-8): 382-389, 2019.
Article in English | MEDLINE | ID: mdl-31554441

ABSTRACT

Background: Melasma is a common acquired facial hyperpigmented skin disorder. Platelet-rich plasma (PRP) is autologous plasma containing higher than normal platelets concentrations. Recently, PRP has been used as a therapeutic modality in melasma with significant clinical improvement, possibly due to its abundant contents of growth factors such as TGF-ß. The latter represents a natural multifunctional polypeptide that negatively regulates melanocyte differentiation and therefore reduces skin hyperpigmentation. To date, the expression pattern of TGF-ß protein in skin of melasma patients following PRP injection is unknown. Here we hypothesize that "injection of PRP in the lesional skin of melasma patients is associated with alterations of TGF-ß protein expression".Patients and Methods: The study included 20 adult patients with melasma. Autologous PRP was delivered into the lesional skin either through microneedling or as intradermal microinjections. TGF-ß protein expression was immunohistochemically examined in the perilesional and lesional skins before and after PRP treatment and in the healthy skins of nine volunteers (control group).Results: TGF-ß protein was expressed within the epidermis, dermal adnexal structures, vascular endothelium, nerves and arrector pili muscle fibers of the healthy skins (control group), perilesional and lesional skins of melasma patients before and after treatment with PRP. Before treatment with PRP, the expression ofTGF-ß protein in the lesional (1.26 ± 0.41) and perilesional (1.68 ± 0.51) skins of melasma patients were significantly lower than that in the healthy skins (2.26 ± 0.37, p value<.05). After treatment with PRP, the expression of TGF-ß protein was significantly increased in the lesional (2.15 ± 0.44) skin of melasma patients.Conclusions: Our study provides the first indication about increased TGF-ß protein expression in skin of melasma patients after PRP treatment. The alterations of TGF-ß protein in skin of melasma patients not only support its roles in the development of this condition but also have some therapeutic ramifications.


Subject(s)
Melanosis/metabolism , Melanosis/therapy , Platelet-Rich Plasma , Skin/metabolism , Transforming Growth Factor beta/biosynthesis , Adult , Female , Humans , Male
15.
Ann Diagn Pathol ; 38: 138-144, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30597358

ABSTRACT

Nrf2 and Bach1 are important transcriptional factors that protect against reactive oxygen species (ROS). Although aberration of these molecules was associated with malignant transformation and progression, their aberration pattern in colorectal carcinoma (CRC) is not yet fully studied. In this study, Nrf2 and Bach1 were immunohistochemically examined in 93 formalin-fixed paraffin-embedded blocks of colonic tumors (65 carcinoma with their corresponding surgical margins and 28 adenomas). Nrf2 expression was gradually increased in the apparently normal mucosa (57 ±â€¯41)-adenoma (90 ±â€¯36)-carcinoma (198 ±â€¯78) direction and only showed significant higher mean of expression in CRC with brisk inflammatory peritumoral response. The mean of Bach1 expression was highest in apparently normal colonic mucosa (267 ±â€¯16), lowest in adenoma (53 ±â€¯31) and high in carcinoma tissues (194 ±â€¯93). Significant higher mean of expression was detected in carcinoma with: LN metastasis (p = 0.04), lymphovascular invasion (p = 0.024); perineural invasion (p = 0.03) and advanced pathological stage (p < 0.001). Significant higher mean of expression of Nrf2 and Bach1 was detected in adenoma specimens with high grade dysplasia (p = 0.016 and p = 0.024) respectively. In conclusion, Nfr2 and Bach1 expression are altered in CRC but in different way. Nrf2 is gradually increasing from normal mucosa to adenoma and was highest in carcinoma but was not associated with features of tumor invasiveness. Bach1 was highest in normal mucosa; less in adenoma then increased in carcinoma and was associated with features of tumor invasiveness and metastasis. This may indicate a possible role of Nrf2 in CRC carcinogenesis and a role of Bach1 in CRC progression.


Subject(s)
Basic-Leucine Zipper Transcription Factors/metabolism , Carcinogenesis/metabolism , Carcinoma/pathology , Colorectal Neoplasms/pathology , NF-E2-Related Factor 2/metabolism , Adenoma/pathology , Adult , Aged , Biomarkers, Tumor/metabolism , Disease Progression , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness/pathology , Signal Transduction/physiology
16.
Int J Clin Exp Pathol ; 11(6): 3176-3185, 2018.
Article in English | MEDLINE | ID: mdl-31938447

ABSTRACT

This study aims to (1) evaluate the immunohistochemical expression of ERα, ERα36 and ERß in combination in human renal cell carcinoma (RCC) and nearby non-tumorous tissue (2) correlate their expression pattern with the clinicopathological parameters and prognosis of the patients; this may provide a new insight into prediction of the disease outcome and understanding its progression. The three markers showed positive cytoplasmic (± membranous) staining pattern in tumor cells. The tubules in the nearby non-tumorous tissue showed either nuclear (± cytoplasmic) staining pattern (ERα and ERß) or only cytoplasmic staining pattern (ERα36). The mean of cytoplasmic expression of ERα, ERα36 and ERß was significantly higher in association with poor prognostic factors: larger tumor size (P<0.0001) for each, late clinical stage (P<0.0001) for each, higher nuclear grade (P = 0.003, P = 0.002 and P = 0.022) respectively, and presence of lymphovascular invasion (P<0.0001, P = 0.006 and P<0.0001) respectively. We have demonstrated for the first time that patients whose tumors express high cytoplasmic levels of ERα, ERα36 or ERß experience shorter overall survival and disease-free survival. The independent role of ER subunits as markers of poor prognosis is proven only for ERß and ERα36 but not ERα. In conclusion, our results indicate that the main staining pattern of ERα, ERα36 and ERß in RCC is cytoplasmic with relation of this pattern to bad prognosis. So we can suggest the assessment of these receptors as markers of poor prognosis in RCC patients.

17.
Pathophysiology ; 24(2): 81-89, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28285737

ABSTRACT

Bisphenol A (BPA), a widely used industrial chemical, is known to disrupt endocrine function. This study aimed to investigate the impact of chronic exposure to BPA on the lung tissue of adult male rats as well as any possible alleviating effects resulting from selenium (Se) treatment. Chronic exposure to BPA resulted in prominent inflammation and oxidative stress responses as evidenced by an increase in levels of malondialdehyde (MDA), reduced concentrations of superoxide dismutase (SOD), and upregulation of Interleukin-18 (IL-18) expression in lung tissue. In addition, chronic exposure led to modulation of the fibrosis-related gene expression, as we observed augmented follistatin-like1 (FSTL1) expression and diminished a disintegrin and metalloproteinase with thrombospondin motif 5 (ADAMTS5) expression. Se treatment remarkably mitigated changes in the expression of these dysregulated markers of lung injury. The biochemical changes were consistent with the histopathological findings, where cellular infiltration and inflammatory fibrotic changes were observed following BPA administration and a lessening of these effects with concomitant Se treatment. Taken together, the results from the study reveal that chronic exposure to BPA may promote the development of pulmonary inflammatory diseases with possible induction of lung fibrosis. Se treatment effectively suppressed oxidative stress, inflammation, and fibrosis, suggesting that Se has the potential to be used as a therapeutic agent in the treatment of pulmonary inflammatory diseases.

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