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Cryptosporidium is one of the commonest opportunistic parasites. But, its chemotherapeuticoptions are limited, with controversy about the role of apoptosis in cryptosporidiosis. Caspasesare key molecules of apoptosis. The study assessed the role of apoptosis in cryptosporidiosisby studying the relationship between the effects of phenyl vinyl sulfone (PVS), nitazoxanide(NTZ) and combined therapy on Cryptosporidium parvum infection and caspase 3immunostaining. Ninety female laboratory bred Swiss Albino mice were divided into twomajor groups; immunocompetent and immunosuppressed. Both groups were divided into thefollowing subgroups, for each one respectively: negative control (1 & 6), infected control (2& 7), infected treated with PVS (3 & 8), infected treated with NTZ (4 & 9) and infected treatedcombined (5 & 10). Sacrification were done on 18th day post infection.Histopathological study of ileum was done and endogenous developmental stages werecounted. Also, caspase 3 immunohistochemical staining was carried out on ileal sections.Combined therapy in groups 5 &10 showed the highest reduction in mean number of endogenousdevelopmental stages as in G10 (P

Background: The discoidin domain receptor-1 (DDR1) is a non-integrin collagen receptor recently implicated in the collective cell migration of other cancer types. Objective: To review the immunohistochemical expression of discoidin domain receptor1 (DDR1) in non-neoplastic skin disease. Data Sources: A systematic search of MEDLINE (PubMed, Medscape, Science Direct. EMF-Portal) and internet was conducted on all articles published from 2002 to 2021. Study Selection: English-language reports of immunohistochemical expression of DDR1 on non-neoplastic skin disease. The initial search presented 90 articles where 30 studies had the inclusion criteria. Then, they were divided into 12 studies about immunopathogenesis of non-neoplastic skin disease, 9 studies about expression of discoidin domain receptor1 and 9 studies emphasized DDR1 expression in non-neoplastic skin disease. Data Extraction: Articles not reporting on immunohistochemical expression of DDR1 in non-neoplastic skin disease in the title or abstract were not included. 9 independent investigators extracted data on methods. Findings: Interaction of DDR1 with various receptors is important for the regulation of cell survival, migration, and differentiation in development and pathological conditions. The discovery of inhibitors of DDR1 kinase activity might be beneficial in several pathological conditions where DDR1 has been identified as a potential therapeutic target. Conclusion: Our review reported that the knowledge of the main cells and cytokines involved in the immunopathogenesis of non-neoplastic skin disease is essential for dermatologists to understand better the disease as well as the mechanism of action of the biologics, drugs that revolutionized the treatment of non-neoplastic skin disease in the last two decades.

Background: Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune blistering disease. PV autoantibodies disrupt desmosomal adhesion and cause acantholysis. Previous researches have shown that stem cells are indirectly involved as a result of desmoglein deficiency. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) as a follicular stem cell marker was evaluated in aim to correlate its intensity of expression with disease severity. Objective: To correlate LGR5 intensity of expression with disease severity. Patient and methods: This prospective cross sectional study was carried out on 20 PV patients. Patients were subjected to complete history taking, general, dermatological examination and assessment of disease severity by the Pemphigus Vulgaris Activity Score (PVAS), histopathological and immunohistochemical expression of LGR5 were done. Results: All studied cases showed positive cytoplasmic basal LGR5 expression in patchy manner. 75% of cases had mild intensity of expression, 15% had moderate intensity and their Histo (H) score ranged from 50-130 with Mean ±SD 110±18.92. There were no significant correlation between PVAS scores ''skin, mucosa and total involvement'' and H score of LGR5 expression. Conclusion: The current study could shed a new light on the disease and its correlation with stem cells, LGR5 as a stem cell marker could be related to the healing process in PV. However, it didn't correlate PVAS scores either in skin, mucosa or total involvement.

BACKGROUND Abnormal autophagy is known to be associated with the pathogenesis of some skin disorders. The protein Beclin1 plays a central role in the machinery of autophagy. AIM To assess the expression of Beclin1 in psoriasis, using immunohistochemical study in lesional and perilesional skin in patients with psoriasis, and to compare the results with those of an apparently healthy control (HC) group. METHODS This case-control study enrolled a total of 40 participants: 20 patients with chronic plaque psoriasis and 20 age- and sex-matched, apparently HCs. Skin biopsies were taken from (i) lesional and (ii) perilesional skin of patients with psoriasis and from (iii) normal skin of HCs for immunohistochemical evaluation of Beclin1 expression. RESULTS Epidermal Beclin1 expression was positive in all three studied groups. There was a significant difference between the three studied groups regarding Beclin1 epidermal topographic distribution, epidermal staining intensity, H score and H-score category (P

Background: Myxovirus-resistance protein 1 (MXA) is a key mediator of the interferon-induced antiviral response and is tightly regulated by type I IFNs. The expression of type I IFN signaling components is markedly increased in psoriasis skin lesions. The role of MXA in psoriasis pathogenesis is still poorly understood. Objective: The aim was to investigate the role of MXA in psoriatic skin. Material and Methods: Medline databases (PubMed, and Medscape) and all materials available in the internet were searched. The search was performed in December 2020. Study selection: The initial search presented 120 articles. The number of studies that met the inclusion criteria was 17. The articles included diagnosed patients with chronic plaque psoriasis of both genders. Data synthesis: Significant data were collected. Then a structured review was performed. Data extraction: If the studies did not fulfill the inclusion criteria, they were excluded. Data from each eligible study were independently abstracted in duplicate using a data collection form to capture information on study characteristics, interventions, and quantitative results reported for each outcome of interest. Finding: In total 9 potentially relevant publications were included; it was found that cytoplasmic localization of MXA in the keratinocytes of the psoriatic skin might play a private role in psoriasis pathogenesis. Conclusion: Cytoplasmic localization of MXA in the keratinocytes of the psoriatic skin might play a private role in psoriasis pathogenesis. This can open a new gate for a target therapy in psoriasis.

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers in Egypt with fatal outcome. The molecular pathogenesis of this type of cancer is so complex involving interaction of several signaling pathways. Among those is Wingless (WNT)/β-catenin signaling pathway, which is frequently activated in HCC. Objectives: To investigate the relationship of different localization patterns of β-catenin in relation to different histopathologic parameters in Egyptian HCC cases. Patients and methods: One hundred and twenty-one (121) HCC specimens were subjected for β-catenin evaluation by immunohistochemistry. Results: The studied HCC cases showed β-catenin membranous expression in 47/121 (38.8%) of cases, while nucleocytoplasmic localization was observed in 31/121 (25.6%). Most of HCC cases that showed single tumor mass presentation exhibited negative nucleocytoplasmic expression pattern (79.2%, P=0.02). Membranous pool of β-catenin was associated with adverse prognostic factors like increased positivity among high-grade cases (P=0.04), higher H score value in cases having lymphovascular invasion, positive lymph node and higher (advanced) TMN stages (P = 0.01, 0.00, 0.00 &0.03 respectively). Conclusion: HCC cases showed heterogeneous β-catenin expression pattern. Membranous β-catenin localization was associated with aggressive prognostic parameters of HCC.

Background: Previous researches declared that scars are the end outcome of the natural healing and reparative process as a result of dermal fibrotic scar formation post inflammation. Few studies were conducted to explain the role of perilesional area in abnormal scar pathogenesis. Objective: To study the histopathological changes in different types of scars and adjacent apparently non-involved skin. Hopefully, this insight can set the route for newer therapeutic approaches. Patients and Methods: This prospective case control study was carried out on 30 participants divided into three groups. Group1 included ten keloid biopsies, Group2 included ten hypertrophic scar biopsies and Group3 included ten atrophic scar biopsies. Clinical assessment of scars was done. Skin biopsy specimens were taken from lesional and perilesional skin and sent to histopathology laboratory. Results: Increased epidermal thickening was significantly noted in 80% of perilesional specimens of keloid scar and that was significantly higher than lesional skin, while dermal fibroblasts/myofibroblasts were mildly increased in 80% of specimens and were associated with severe perivascular inflammatory infiltrates in 70% of perilesional specimens. Myofibroblasts/ fibroblasts and perivascular infiltrate were significantly higher in perilesional than lesional keloid skin. Epidermal thickening was significantly increased in all perilesional specimens of hypertrophic scar and was significantly higher than lesional skin. In dermis, hair follicles and sebaceous glands were identified in 100% of perilesional skin. Dermal cellularity was significantly mildly increased in 100% of perilesional specimens of atrophic and hypertrophic scars and both were significantly higher than normal skin. Conclusion: Perilesional area is a shadow area and may be a main player in abnormal scar pathogenesis and could be responsible for progression or regression of scar.

Background: Psoriasis is a chronic, inflammatory immune mediated skin disease characterized by dense infiltrates of immunocytes especially macrophages. Cross talk between immunocytes and keratinocytes is thought to mediate the disease. Hparanase 2 inhibits activity of Heparanase 1 which is involved in this cross talk by degradation of heparin sulphate chains in the basement membrane and extra cellular matrix (ECM). Objective: To assess the of Heparanase2 in psoriasis through its immunohistochemical expression in lesional and perilesional skin of psoriasis patients. Patients and Methods: This prospective case control study was carried out on a total number of 60 subjects, they included 30 patients with chronic plaque psoriasis and 30 age and gender matched apparently normal subjects as control group. Skin biopsies were taken for immunohistochemical evaluation of Heparanase 2 expression. Results: Our results showed significant difference between lesional, perilesional and control groups regarding the status of epidermal Heparanase 2 expression (P = 0.038). All lesional epidermal expression was negative while perilesional epidermal expression was negative in 24 (80%) cases and positive in 6 (20%) cases, control epidermal expression was negative in 27 (90%) cases and positive in 3 (10%) cases. There was no significant difference between the three studied groups regarding dermal Heparanase 2 expression (P = 0.318). Conclusion: Downregulation of Heparanase 2 could be incriminated in the pathogenesis of psoriasis. Heparanase 2 could have a protective role in skin.

Background: Despite the advance in treatment modalities of wide range inflammatory skin diseases, tripartite motif- containing (TRIM) proteins are expected to become a potential therapeutic target for prevention and treatment of dermatological disorders. Objective: Studying the role of TRIM proteins in inflammatory skin diseases. Material and Methods: We searched the PubMed and Google scholar databases for relevant studies that evaluated the expression of TRIM proteins in inflammatory skin diseases. Study Selection: All the studies were independently assessed for inclusion. They were included if they fulfilled the following criteria: published in English language, published in peer-reviewed journals, focused on the role of TRIM proteins in inflammatory skin diseases. The initial search presented 30 articles of which 8 met the inclusion criteria. The articles studied the effect of role of TRIM proteins in inflammatory skin diseases. Data Synthesis: Comparisons were made by structured review with the results tabulated. Conclusion: We concluded that TRIM proteins play an important role in inflammatory skin diseases development, prognosis and treatment.

Background: Light chain3 is a sensitive autophagy-related protein distributed within the mammalian tissues. The role of LC3 localization in psoriasis pathogenesis is still poorly understood. Objective: This study aimed to investigate, for the first time up to our knowledge, the localization of Light chain3 (LC3) in the keratinocytes of psoriatic skin by immunohistochemical study. Materials and methods: This prospective case case-control study was carried out on 30 patients presented with chronic plaque psoriasis versus 30 age and gender-matched apparently healthy volunteers. Clinical data were collected and Psoriasis Area and Severity Index (PASI) was assessed. From all controls and cases (lesional and perilesional), skin biopsies were taken and the epidermis was assessed for histopathological changes and LC3 immunoreaction. Results: There was a highly significant difference (P

Purpose To evaluate the role of autophagy related gene 7 (ATG7) in non-melanoma skin cancer. Subjects and Methods This retrospective and prospective case-control study was performed on 104 patients with non-melanoma skin cancer (NMSC) in addition to 20 apparently healthy subjects matched for age and sex as a control group. Multiple skin biopsies were taken for immunohistochemical evaluation of ATG7 expression. Results Both epithelial and stromal ATG7 were expressed in all participants while all patients showed nucleocytoplasmic localization and controls showed both cytoplasmic and nucleocytoplasmic expression. In addition, significantly higher H-scores of ATG7 in both epithelium and stroma were detected in patients compared to controls (P

Slowing down age-related neurocognitive impairment has been a challenge. We evaluated the therapeutic effects of metformin in d-galactose-induced aging. Additionally, we studied the potential molecular mechanisms that could be responsible for metformin's anti-aging effects. Thirty male rats were equally divided into: 1—control group, which received saline solution, 2—d-galactose (D-gal) group, which received d-galactose (100 mg/kg/day) by gastric lavage for eight weeks, and 3—d-galactose + Metformin (D-gal + Met) treated group, which received d-galactose + metformin (200 mg/kg/day) by gastric lavage for eight weeks. Neurocognitive assessment was done. Measurement of inflammatory, oxidative stress, and BDNF biomarkers was performed. AMPK and PI3K genes expression were assessed. Hippocampal tissues were dissected for histopathological and immunohistochemical studies. D-gal resulted in neurocognitive impairments, elevation of inflammatory biomarkers, altered oxidative stress markers, decreased BDNF, decreased expression of synaptophysin and Bcl2 with increased expression of Caspase-3, and down-regulation of AMPK and PI3K genes. Neurodegenerative changes were present in the hippocampus. Metformin restored significantly D-gal induced neurodegenerative changes. We concluded that metformin could alleviate age-induced neurocognitive deficit via amelioration of neuroinflammation, attenuation of oxidative stress, reduction of apoptosis, as well as promotion of synaptic plasticity. These mechanisms could be mediated via the activation of the AMPK/BDNF/PI3K pathway.

Scars are the end outcome of healing. They are grouped into several types, the common of which are keloids, hypertrophic, and atrophic scars. The role of Krox20 in skin and hair physiology and pathology had emerged. Overexpression of Krox20 was sufficient to stimulate collagen gene expression and myofibroblast differentiation and is necessary for transforming growth factor-β (TGF-β) induced profibrotic responses.To investigate the role of Krox20 in abnormal scar pathogenesis. Hopefully, this insight can set the route for newer therapeutic approaches.This study was carried out on 30 cases (10 cases of keloids, 10 cases of atrophic scars, and 10 cases with hypertrophic scars [HTS]) and 10 age and gender-matched apparently healthy subjects as a control group. Thirty biopsies were taken from perilesional areas. Evaluation of Krox20 expression was done using standard immunohistochemical technique.Krox20 was downregulated in epidermis of scar biopsies compared with perilesional and normal skin (p = 0.02) while it was overexpressed in fibroblasts in lesional scar biopsies compared with perilesional and normal skin (p 0.001). Keloid cases have significantly higher Krox20 expression in fibroblasts compared with HTS cases (p 0.001). Krox20 had significantly nucleocytoplasmic pattern of staining in scar cases compared with normal skin (p 0.001).Krox20 overexpression may have a role in scar pathogenesis through upregulation of multiple genes associated with tissue remodeling and wound healing. This may open an avenue for research for new therapies based on Krox20 inhibition.

Autophagy dysregulation is involved in many diseases. The implication of autophagy in psoriasis pathogenesis is still uncertain. To investigate the role of Light Chain 3 (LC3), a good marker for autophagy, in psoriatic skin based on immunohistochemical study and correlate its expression - for the first time to the best of our knowledge - to clinicopathological data Prospective case-control study was conducted on 60 subjects (30 control, 30 psoriasis patients). Skin biopsies from control, lesional, and perilesional skin were processed for routine histopathological examination and LC3 immunoreaction assessment. There was a significant upregulation of the epidermal and dermal LC3 immunoreaction in the lesional skin compared with the control and perilesional skin specimens (

Background: Human JAKs are responsible for generating docking sites for human SSTAT phosphorylation. The role of JAKs in psoriasis pathogenesis has not been clearly explained. Aim: To investigate the role of JAK1 in psoriasis pathogenesis and to assess if this role is mediated through STAT3 or not, through evaluation of their immunohistochemical expression in the skin of psoriatic patients. Methods: This case-control study was carried out on 26 patients presenting with psoriasis vulgaris versus 26 age- and sex-matched apparently healthy volunteers. Psoriasis Area and Severity Index (PASI) scores were used to evaluate psoriasis severity. From all controls and cases (lesional and perilesional), skin biopsies were taken for histopathological and immunohistochemical JAK1 and STAT3 evaluation. Results: There was significant stepwise upregulation of JAK1 from controls to perilesional to lesional psoriatic skin of the patient group in both epidermis and dermis (P≤0.001 for both). Dermal JAK1 H-score was significantly associated with psoriasis severity (P=0.01). STAT3 was significantly overexpressed in lesional psoriatic skin over nonlesional skin (P

Background Vitiligo is an acquired autoimmune skin disorder. The often-visible lesions of vitiligo have a major impact on patients' quality of life and the results of the treatment regimens on offer are unsatisfactory, so there is a need for new therapeutic regimens. Recent advances in vitiligo pathogenesis have led to recognition of the importance of the JAK-STAT pathway as an attractive therapeutic option. Purpose To evaluate role of JAK1 and STAT3 in vitiligo. Methods This prospective case-control study was carried out on 35 patients presenting with vitiligo and 20 apparently healthy age- and sex-matched volunteers. Skin biopsies from controls and cases were taken for histopathological and immunohistochemical JAK1 and STAT3 evaluation. Results Epidermal and dermal overexpression of STAT3 was noted in lesional skin compared to the other groups (P=0.02 and P

Background and Aims: Despite the advance in treatment modalities, Hepatocellular Carcinoma (HCC) remains a com-mon cause of cancer morbidity and mortality worldwide. Lipogenic pathway is expected to become a potential thera-peutic target for prevention and treatment of HCC.Aim of Study: Studying the role of lipogenic pathway in hepatocellular carcinoma.Material and Methods: We searched the PubMed and Google scholar databases for relevant studies that evaluated the expression of lipogenic pathway markers; Sterol Regulatory Element-binding Protein1 (SREBP1), Fatty Acid Synthase (FASN) and Stearoyl-CoA Desaturase1 (SCD1) in human HCC tissues.Results: This review included 12 studies that enrolled 1031 patients with HCC or chronic hepatitis and normal subjects. SREBP1, FASN and SCD1 were overexpressed in HCC. SREBP1 expression was positively correlated with FASN and SCD expressions (r=0.74, pConclusion: We concluded that lipogenic pathway acti-vation plays an important role in HCC development and prognosis. This review was registered with PROSPERO (CRD 42018087933).

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes functional disability due to bone destruction and severe joint pain. Current anti-rheumatic treatments develop severe complications and do not provide complete remission. Gold nanoparticles (AuNPs) have garnered attention because of their unique physical and chemical properties. In this study, we have evaluated the therapeutic effects of gold nanospheres (AuNSs) with two different ligands (targeted-nanoparticles) against collagen-induced arthritis (CIA) and compared the outcomes with conventional methotrexate (MTX) and biological (infliximab) treatments. Clinical evaluation was performed by radiographic and histological examinations. The bioaccumulation of AuNSs in vital organs was assessed. The mechanistic studies targeting pro-inflammatory/anti-inflammatory and angiogenic mediators' expressions were performed. Radiographic examination showed that the targeted AuNSs reduced joint space narrowing and bone erosion. Moreover, histopathological examination of rat ankle joints demonstrated that targeted AuNSs reduce bone and cartilage degeneration/inflammation. Gold nanospheres-conjugated with nucleus localized peptide (nuclear membrane-targeted) (AuNSs@NLS) has resolved bone destruction and inflammation compared to gold nanospheres-conjugated at polyethylene glycol (AuNSs@PEG). Although the AuNSs accumulated in different organs in both cases, they did not induce any toxicity or tissue damage. The two different targeted AuNSs significantly suppress inflammatory and angiogenic mediators' expression and induced anti-inflammatory cytokine production, but the AuNSs@NLS had superior therapeutic efficacy. In conclusion, these results suggested that nuclear membrane-targeted AuNSs effectively attenuated arthritis progression without systemic side effects.

Background The prevalence of hypertension and obesity has increased significantly in recent decades. Hypertension and obesity often coexist, and both are associated with increased cardiovascular mortality. Obese hypertensive patients usually require special anti-hypertensive treatment strategy due to the increased risk of treatment resistance. Molecules that can target both obesity and hypertension underlying pathologies should get more attention. Herein, we evaluated the therapeutic effects of telmisartan, with special interest in visceral adipose tissue dysfunction, in obesity-related hypertension rat model. Methods Thirty male Wistar rats weighing 150–200 g were equally divided into: 1—Control group (fed normal laboratory diet for 24 weeks), 2—Diet-induced obesity group (DIO, fed high fat diet for 24 weeks), and 3—Diet-induced obesity treated with telmisartan group (DIO + Tel, fed high fat diet and received telmisartan for 24 weeks). At the end of the study, anthropometrical parameters were evaluated. Systolic blood pressure and heart rate were measured. Blood samples were collected for the measurement of serum lipids, adipokines, cardiac, renal, inflammatory, and oxidative stress biomarkers. Kidneys were removed and used for histopathological studies, and visceral adipose tissue was utilized for histopathological, immunohistochemical and RT-PCR studies. Results High fat diet resulted in obesity-related changes in anthropometrical parameters, elevation of blood pressure, increase in heart rate, higher serum levels of cardiac, inflammatory and kidney function biomarkers, with altered serum lipids, adipokines and oxidative stress markers. Morphological changes (H&E and PAS-stained sections) were noticed in kidneys and visceral adipose tissue. Immunohistochemistry and RT-PCR studies confirmed adipose tissue dysfunction and over-expression of inflammatory and oxidative stress proteins. Telmisartan countered obesity-induced alterations in cardiovascular, renal, and adipose tissue functions. Conclusion Adipose tissue dysfunction could be the core pathophysiology of obesity-related hypertension. Besides its anti-hypertensive effect, telmisartan had profound actions on visceral adipose tissue structure and function. Attention should be given to polymodal molecules targeting adipose tissue-related disorders.

Neocryptolepine (5-methyl-5H-indolo[2,3-b] quinoline) analogs were synthesized and evaluated in vitro and in vivo for their effect versus Ehrlich ascites carcinoma (EAC). The analogs showed stronger cytotoxic activity against EAC cells than the reference drug. The in vivo evaluation of the target compounds against EAC-induced solid tumor in the female albino Swiss mice revealed a remarkable decrease in the tumor volume (TV) and hepatic lipid peroxidation. A noticeable increase of both superoxide dismutase (SOD) and catalase (CAT) levels was reported (p &lt, 0.001), which set-forth proof of their antioxidant effect. In addition, the in vitro antioxidant activity of the neocryptolepine analogs was screened out using the DPPH method and showed promising activities activity. The histopathological investigations affirmed that the tested analogs have a remarkable curative effect on solid tumors with minimal side-effect on the liver. The study also includes illustrated mechanism of the antitumor activity at the cell level by flow cytometry. The cell cycle analysis showed that the neocryptolepine analogs extensively increase the aggregation of tumor cells in three phases of the cell cycle (G0/G1, S and G2/M) with the emergence of a hypo-diploid DNA content peak (sub-G1) in the cell cycle experiments, which is a clear-cut for the apoptotic cell population. Furthermore, the immunological study manifested a significant elevation in splenic lymphocyte count (p &lt, 0.001) with the elevation of the responsiveness of lymphocytes to phytohemagglutinin (PHA). These results indicate that these naturally-based neocryptolepine alkaloids exhibit marked antitumor activity in vivo and represent an important lead in the development of natural-based anticancer drugs.

Background: Autophagy is an essential cellular mechanism that plays the "housekeeping" role in normal physiological processes, including the removal of long-lived, harvested, and misfolded proteins, damaged organs. On the other hand, under conditions causing cellular stress, such as malnutrition, hypoxia, oxidative stress, pathogen infections, radiation or cancer medication, there is an increase in the degree of autophagy, which leads to adaptation and cell survival. With the current interest in autophagy, this process appears to affect every organ and modify growing list of disease processes. The skin acts as the first line of defense against different environmental stresses; However, only a few studies have investigated the effect of autophagy on the pathogenesis of skin diseases. The level of autophagy may reflect the degree of some diseases; Therefore, detecting the level of autophagy may be an indirect means to assess some diseases. Objective: to provides an overview of recent findings relevant to the role of autophagy in non-neoplastic skin diseases. Conclusion: Autophagy plays an important role in mitigating or exacerbating various skin diseases. Understanding the mechanisms of autophagy and their regulation in different tissues and cells under healthy and stressful conditions will help better understand the etiology of skin diseases and develop more effective therapeutic approaches.

Desmoplastic fibromas are rare benign bone tumors occurring primarily in long bones and mandible. In this case report, we present a desmoplastic fibroma originating from the left frontal bone. This is an exceptionally rare presentation of this pathology and the associated imaging and pathologic slides are highly educational. We discuss the relevance to the literature and how to manage these patients clinically.

Introduction. Not only is diabetic nephropathy (DN) the most common cause of end-stage renal disease worldwide, but it also increases the risk of mortality up to fourteen times compared to normoalbuminuric diabetic patients. Aim. The aim of the current study was the evaluation of the renoprotective effects of vitamin D in DN and the possible interplay between autophagy and mTOR pathways. Materials and Methods. Fifty male Wistar albino rats were divided (10/group) into control, DN group, insulin-treated DN group, vitamin D-treated DN group, and combined insulin and vitamin D-treated DN group. Assessments of systolic blood pressure, albuminuria, creatinine clearance, serum glucose, insulin, urea, creatinine, inflammatory cytokines, oxidative stress markers, and rat kidney gene expression of mTOR were performed. Histopathological and immunohistochemical assessments of autophagy marker LC3 in rat kidneys were also performed. Results. DN was associated with significant increases in SBP, urinary albumin, serum glucose, urea, creatinine, inflammatory cytokines, MDA, and mTOR gene expression (P<0.05). However, there was significant decrease in creatinine clearance, serum insulin, GSH, and H score value of LC3 when compared with control group (P<0.05). The combination of insulin and vitamin D treatment significantly restored DN changes when compared with the other treated groups, except in oxidative stress markers where there was an insignificant difference between the combination-treated and insulin-treated groups (P>0.05). Conclusion. It has been concluded that vitamin D is a potent adjuvant therapy in treatment of DN via downregulation of mTOR gene expression, stimulation of autophagy, and antioxidant, anti-inflammatory, and hypotensive effects.

The role of gold nanoparticles (AuNPs) in the treatment of autoimmune diseases remains mysterious. Therefore, we investigated the effect of AuNPs on collagen-induced arthritis (CIA) and the impact of particle size on the tissue distribution of AuNPs. CIA model was set up in Wistar rats using bovine collagen type ІІ. CIA rats were then divided into five groups: CIA model (positive control), AuNPs treated- (sphere shape with size: 5, 25, and 75 nm), and methotrexate (MTX)-treated-rats. Untreated rats were run in parallel as normal control. At the end of the experiment, the radiographic assessment was done. Histopathological changes in the joints and vital organs were investigated. Liver- [aspartate transaminase (AST) and alanine transaminase (ALT)] and kidney- (creatinine) functions were measured. The gold bio-accumulation was measured quantitatively with inductively coupled plasma mass spectrometry (ICP-MS). Histopathological results revealed that AuNPs reduced the severity of arthritic symptoms in CIA rats. No histological changes were detected in vital organs. Importantly, AuNPs were deposited in all the examined organs, and the accumulation was size-dependent, with 75 nm demonstrated the least distributed one. Our results revealed that AuNPs decreased both liver and kidney functions as compared to normal controls. In conclusion, our data shed light on the therapeutic efficacy of AuNPs in experimental rheumatoid arthritis compared with a choice size (25 nm). Further investigations to investigate the immunological changes associated with AuNPs are in process.

Endometrial carcinoma is the sixth most common cancer in women worldwide and the most common invasive cancer of the female genital tract in developed countries. It is hoped that through a better understanding of the alterations implicated in endometrial cancer pathogenesis and prognosis, a more complete profile of risk factors and targeted therapy can be developed. Hepsin is a member of the type II transmembrane serine protease family. The importance of hepsin in prostate cancer has been demonstrated by several studies. However, the role of hepsin in endometrial carcinoma is yet to be identified. This study aimed to evaluate the immunohistochemical expression of hepsin in endometrial carcinoma, trying to explore its diagnostic and prognostic value. This retrospective study was conducted on 27 endometrial carcinoma and 18 endometrial hyperplasia cases. Immunohistochemical expression of hepsin was evaluated in tissue specimens and results were correlated with the available clinicopathlogic parameters. Positive hepsin expression was seen in all (100%) carcinoma and 17/18 (94.44%) endometrial hyperplasia cases. The H-score of hepsin expression in endometrial carcinoma was significantly higher than that of hyperplasia cases (P=0.012). A significant negative association was found between hepsin expression in endometrial carcinoma cases regarding the grade and the size of tumors (P=0.018 and 0.008, respectively) as well as myometrial invasion (P=0.027). Hepsin could play an important role in the pathogenesis and the early carcinogenesis of endometrial carcinoma and could serve as a prognostic biomarker in this tumor.

Purpose To evaluate the role of autophagy related gene 7 (ATG7) in non-melanoma skin cancer. Subjects and Methods This retrospective and prospective case-control study was performed on 104 patients with non-melanoma skin cancer (NMSC) in addition to 20 apparently healthy subjects matched for age and sex as a control group. Multiple skin biopsies were taken for immunohistochemical evaluation of ATG7 expression. Results Both epithelial and stromal ATG7 were expressed in all participants while all patients showed nucleocytoplasmic localization and controls showed both cytoplasmic and nucleocytoplasmic expression. In addition, significantly higher H-scores of ATG7 in both epithelium and stroma were detected in patients compared to controls (P

Background Vitiligo is an acquired autoimmune skin disorder. The often-visible lesions of vitiligo have a major impact on patients’ quality of life and the results of the treatment regimens on offer are unsatisfactory, so there is a need for new therapeutic regimens. Recent advances in vitiligo pathogenesis have led to recognition of the importance of the JAK–STAT pathway as an attractive therapeutic option. Purpose To evaluate role of JAK1 and STAT3 in vitiligo. Methods This prospective case–control study was carried out on 35 patients presenting with vitiligo and 20 apparently healthy age- and sex-matched volunteers. Skin biopsies from controls and cases were taken for histopathological and immunohistochemical JAK1 and STAT3 evaluation. Results Epidermal and dermal overexpression of STAT3 was noted in lesional skin compared to the other groups (P=0.02 and P

Introduction: Tuberculosis (TB) of the upper genital tract is a rare disease worldwide. TB should be always considered in the differential diagnosis of a pelvic or adnexal mass as it may diagnosed as ovarian carcinoma but both have completely different treatment. Therefore, recognition of TB is important for surgeons and histopathologists, in order to set a proper plan for management and avoid unnecessary extensive therapy. Granulosa cell tumor of the ovary is a rare type of ovarian cancer that accounts for approximately 2% of all ovarian tumors. This type of tumor is known as a sex cord-stromal tumor and usually occurs in adults. Thorough search in English literature revealed only 2 case reports showed combination between genital TB and granulosa cell tumor. Case summary: A 68 years old female patient complained of vaginal bleeding for four months. She had no personal or family history of TB. An ultrasound study showed a 2x1.5 cm mixed echogenic mass in the right adnexa. Based on her clinical and imaging findings which suggestive of ovarian cancer, the patient underwent panhystrectomy and bilateral salpingoophrectomy. The gross examination of the specimen revealed distended and coiled tubes with right adnexal mass measured 2x1.5 cm and dissection of the uterus revealed erythematous endometrium with yellowish secretions. The histopathologic assessment of right adnexal mass revealed malignant neoplasm *Granulosa cell tumor* formed of short polygonal cells arranged in diffuse sheets with patternless pattern. The malignant cells showed nuclear grooving. There was no necrosis or other ovarian neoplastic element. The histopathologic assessment of both tubes and endometrium revealed infiltration by multiple nodular granulomas. Each granuloma was formed of multinucleated giant cells and epithelioid cells rimmed by lymphocytes with occasional central caseation *genital tuberculosis*. Conclusion: The conclusion of this case report is to stress upon keeping genital TB in mind as a potential differential diagnosis for ovarian carcinoma.

Background Psoriasis is a common chronic recurrent immune-mediated disease of the skin. Liver X receptor-alpha (LXR-α) is a member of the nuclear receptor family of transcription factors. LXR-α was found to be expressed in the skin. Objective To assess immunohistochemical expression of LXR-α in psoriatic (perilesional and perilesional) skin compared with control and to correlate its expression with the clinical and histopathological parameters of that disease in the studied patients. Patients and methods This case–control study was carried out on 76 participants, including 38 patients having chronic plaque psoriasis, besides 38 age-matched and sex-matched apparently normal volunteers (control group). The severity of psoriasis was assessed by Psoriasis Area and Severity Index score. The skin biopsies were subjected to hematoxylin and eosin and immunohistochemical staining of LXR-α. Results There was a significant stepladder downregulation of LXR-α from control to perilesional psoriatic skin, ending with lesional psoriatic skin, regarding its expression and H score in epidermis and dermal elements (P

Background Chronic renal failure (CRF) is a major public health problem worldwide. The pathophysiological basis of the disease and its complication include inflammation and oxidative stress, which are similar in humans and animals. In this study, we seek to develop new therapeutic modalities for CRF. Objective This study aimed to investigate the nephroprotective effects of curcumin (CUR) and/or sildenafil in adenine (AD) model of CRF. Materials and methods Rats were divided into five groups as follows: control naive group, AD group received AD 200 mg/kg/day orally to induce CRF, CUR group received CUR 200 mg/kg/day in addition to AD, sildenafil group received sildenafil 0.5 mg/kg/day in addition to AD, and combination group received combination of CUR 200 mg/kg/day and sildenafil 0.5 mg/kg/day in addition to AD. After consecutive 28 days of treatment, body weight, kidney index, and Doppler on renal artery assessments were done for all groups. In addition, kidney function tests and markers of oxidative stress were evaluated. Histopathological assessment of renal tissues and immunohistochemical staining for tumor necrosis factor-α were performed. Results CUR, sildenafil, and their combination significantly decreased body weight loss and urine volume and improved renal hemodynamic changes caused by AD. In addition, they significantly improved kidney function tests and biomarkers of oxidative stress. A significant down-regulation of tumor necrosis factor-α immunohistochemical expression was noted. They also brought histopathological changes induced by AD toward normal. Conclusion CUR and sildenafil may play a role in renal protection in AD-induced nephrotoxicity. The combined treatment showed better nephroprotective effect than either treatment alone did.

Carbonic anhydrase IX (CAIX) is an enzyme whose expression is very limited in normal tissues and it is highly expressed in various cancers. Therefore, inhibition of CAIX is considered as a promising therapeutic target for the treatment of solid tumors where hypoxic environment has developed. The aim of the current work is to evaluate the immunohistochemical (IHC) expression of CAIX in breast cancer (BC) of Egyptian patients and to investigate the associations of CAIX expression with the standard clinicopathologic features, IHC subtypes of BC, and overall survival. This retrospective study was conducted on 56 archival cases of Egyptian BC patients. Fifty-one of 56 cases (91.1%) showed positive expression of CAIX with cytoplasmic localization, whereas 5 cases (8.9%) showed negative expression. CAIX IHC overexpression is significantly associated with advanced stage and presence of coagulative tumor cell necrosis (P=0.03 and 0.02, respectively). Multivariate analysis revealed Ki67 labeling index and CAIX H-score grouping (P=0.03 and 0.02, respectively) as independent prognostic factors affecting BC patients' overall survival. We concluded that CAIX could play a role in the progression of the studied BC cases. CAIX is a good candidate for target therapy.

Leptin has been recognized as an important factor for promoting normal cutaneous wound healing. The aim of this work was to explore leptin expression in keloid and hypertrophic scars (HS) compared with surgical scars and normal skin. The relationship of this expression with clinicopathologic parameters of studied cases was also evaluated. Using immunohistochemical techniques, leptin was analyzed in skin biopsies of 60 nonobese subjects without metabolic syndrome who presented with keloids (20), HS (20), and surgical scars (20). Twenty normal skin samples, from age-matched, sex-matched, and body mass index-matched subjects, were enrolled as a control group. Leptin showed positive immunoreactivity in epidermis in all cases of surgical scars and keloids and in 75% of HS cases. Dermal expression in fibroblasts, inflammatory cells, and endothelial cells was positive in all cases of surgical scars and keloids and in 70% of HS cases. Leptin was overexpressed in keloids and HS compared with normal skin in epidermis (P

Objectives: Fibromatosis is a rare breast lesion that is considered locally aggressive tumor without metastasis. It doesn't need more than surgical excision with clean margins as a treatment but the recurrence is very common. Breast fibromatosis clinically mimics other lesions as fibromatosis like metaplastic tumor of breast. Therefore, recognition of breast fibromatosis is important for surgeons and histopathologists, in order to set a proper plan for management and avoid unnecessary extensive surgery. Comprehensive search revealed only 33 case reports as it's compromising less than 0.2% of all primary breast tumor. Case summary Methods and Materials: A 35 years old female patient complained of palpable left breast mass for four months. Her imaging belonged to BI-RAD (4) assessment category. The pathological examination of the core biopsy showed B3; spindle cell lesion. The patient underwent surgical excision of the mass and the histopathologic assessment revealed an infiltrative uncapsulated lesion composed of proliferated spindle shaped cells (mixed fibroblasts and myofibroblast like cells) arranged in sweeping fascicles with occasional extravasated RBCs. There was no mitosis, necrosis or atypia. There was no associated hyperplasia, atypical hyperplasia, insitu or invasive components. Results: Immunohistochemical studies showed positivity for SMA and B- Catenine and negativity for Pan CK and P63 that confirm our diagnosis. Conclusion: The conclusion of this case report is to stress upon keeping breast fibromatosis in mind as a potential differential diagnosis for fibromatosis like metaplastic carcinoma and other mimics of spindle cell lesions in breast.

The effect of tramadol addiction on epididymal structure was not investigated before. Therefore, this experimental study was carried out to investigate the effect of chronic tramadol use on the epididymal structure using light and electron microscopies. Thirty adult Wister Albino male rats were divided into two groups: control group (five rats) and tramadol-treated group (25 rats), which was further subdivided into five subgroups that received tramadol orally at 4.5, 9, 45, 90, and 135 mg/kg/day, respectively, for 18 weeks. Epididymal tissues were dissected and processed for histopathological examination. Morphometric analysis showed significantly reduced mean values of epididymal ducts' diameters and epithelial height in the tramadol-treated group compared with the control group. Light microscopic examination revealed degeneration and necrosis of epididymal cells in the tramadol-treated group. Electron microscopic (EM) examination showed ultrastructure alterations in a dose-dependent manner. In conclusion, tramadol can adversely affect all epididymal cells, which subsequently deteriorate epididymal function and may affect sperm maturation, leading to subfertility.

Objectives Acute rhinosinusitis (ARS) is a common pediatric problem. Our aim was to determine the efficacy of normal nasal saline irrigation (NSI) with or without amoxicillin in treatment of acute rhinosinusitis (ARS) in children. Methods It is a prospective randomized, blind placebo-controlled trial. Children with uncomplicated ARS were recruited. One group received (amoxacillin 100 mg/kg/day) and 0.9% NSI. The second group received placebo and 0.9% NSI. The primary outcome was the effect of treatment on clinical response. Secondary outcomes included: Rating of Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), middle meatus (MM) bacteriological and cytological cellular responses and adverse effects. Results Sixty two patients with ARS were eligible for the study. In amoxicillin group (31 patients); clinical cure was observed in 26 (83.9%) in comparison to 22 (71%) patients in NSI without antibiotics group (31 patients) (p = 0.22). No differences between both groups in the reported nasal symptom scores and total symptoms scores improvements at day 7 (p = 0.09 and 0.65) and day 14 (p = 0.29 and 0.14), respectively. The mean total PRQLQ values had no differences between both groups after the 2 weeks of treatment (p = 0.06). At day 7, MM neutrophils reduced significantly in amoxicillin group in comparison to placebo group (p = 0.004). At day 14, the MM cytological content had no differences between both groups (p = 0.07). Normal NSI with placebo has less reported adverse effects than amoxicillin and nasal saline irrigations (p = 0.005). Conclusions NSI can be used alone with the same clinical, bacteriological and cytological cellular changes efficacy and with higher safety profile than amoxicillin after 14 days of treatment in uncomplicated clinically diagnosed ARS in children.

Aims Pleomorphic adenoma (PA) of the breast is a rare tumour seen usually in postmenopausal women. Although PA of the salivary glands (SG) is recognized to be a benign tumour, the nature and biology of similar tumours seen in the breast remains to be defined. The aim of this study was to describe PA of the breast that was reported on core biopsy as an invasive matrix-producing metaplastic breast carcinoma (MBC). Methods and results A core biopsy from a clinically malignant retroareolar mass showed mildly atypical polygonal cells with surrounding myxoid stroma. Immunohistochemistry showed expression of basal and luminal cytokeratins, but oestrogen receptor, human epidermal growth factor receptor 2 (HER2) and myoepithelial markers were negative. The excision specimen showed similar features, but in addition the stroma showed cartilage and bone. Also it was clear that the lesion was circumscribed and merged with a sclerosed papillary lesion consistent with what has been described as mammary PA. Conclusion This lesion shows an overlap of morphology and immunophenotype with SG-PA and with MBC. The majority of mammary PAs have a benign behaviour, but local recurrence and development of carcinoma occur. We propose a new terminology of pleomorphic adenoma-like tumour of the breast to reflect the uncertain nature of these tumours and help guide management decisions.

Glioma-associated oncogene homolog (GLI)1 is involved in controlling cell proliferation and angiogenesis. The aim of this work was to explore its possible role in non-melanoma skin cancer pathogenesis through its immunohistochemical (IHC) expression in skin biopsies of these diseases and correlating this expression with the clinico-pathological parameters of the studied cases. Seventy-six cutaneous specimens were studied; 30 cases with basal cell carcinoma (BCC), 30 cases with squamous cell carcinoma (SCC) and 16 normal skin samples, from age- and gender-matched subjects, as a control group. GLI1 was expressed in all BCC cases and in 60% of SCC cases. All SCC cases showed cytoplasmic, while 70% of BCC cases showed nucleocytoplasmic immunoreactivity. It was over expressed in BCC and SCC compared to normal skin (p = 0.01 and 0.0006, respectively). Higher Histo (H) score in BCC cases was significantly associated with female gender (p = 0.04), multiple lesions, desmoplastic stromal reaction and stromal angiogenesis (p 0.001 for all). Higher H score in SCC cases was significantly associated with scalp location, nodular type, recurrent lesions, high tumor grade, lymphovascular invasion (p = 0.004 for all), inflammatory stromal reaction (p = 0.01), lymph node involvement and absence of calcification (p = 0.001 for both). In conclusion, GLI1 may play a role in BCC pathogenesis through its role in cell proliferation, migration, and angiogenesis. Its upregulation and cytoplasmic localization in SCC may suggest that its role in tumor pathogenesis is through mechanisms other than Hedgehog pathway activation. Further studies are needed to clarify the exact molecular basis of its oncogenic action.

Skin tags (STs) are benign connective tissue tumors of the dermis. Several clinical observations suggested the involvement of sex steroids in their development. This study aimed at investigating the possible role of androgen receptor (AR) and estrogen receptors (ERs) in STs pathogenesis through their immunohistochemical (IHC) localization in skin biopsies of this disease and to correlate their expression with different clinical and histopathological parameters. Using IHC techniques, we examined 62 cases with STs and 30 gender- and age-matched, healthy subjects, representing the control group. ERα, ERβ, and AR were upregulated in STs compared to normal skin in epidermis and dermis (p .001 for all). Higher AR H score was significantly associated with axillary STs (p = .02), skin colored tags (p = .03), acanthosis, and papillomatosis (p = .04 for both). Higher ERα H score was significantly associated with hyperpigmented tags (p .001) and positive family history (p = .003). Higher ERβ H score was significantly associated with female gender and obesity (p = .004 for both). Higher ERα and AR H scores were significantly associated with loose collagen arrangement (p = .02, p = .004, respectively). Higher AR, ERα, and ERβ H scores were significantly associated with the presence of mast cells (p = .01, p = .04, p = .002, respectively) and dilated blood vessels (p = .006, p = .04, p = .04, respectively). In conclusion, AR and ERs may share in STs pathogenesis through their effect on keratinocytes, fibroblasts, and mast cells.

Background: Hirschsprung disease (HD) is diagnosed by absence of ganglion cells in rectal biopsy. In some cases, standard methods fail to diagnose agangliosis. The aim of this study is to assess the diagnostic value of immunohistochemistry (IHC) of calretinin and synaptophysin compared to standard methods.Methods: This prospective cross section study was conducted in Menoufia University hospitals, Egypt spanning the period between October 2017 to December 2018. Rectal biopsies of the clinically suspected HD patients stained with calretinin and synaptophysin and their results compared to the standard hematoxylin and eosin (H&E) stained sections.Results: A total of 30 patients aged from 3 days to 2 years with a male to female ratio 11:4 were examined for rectal biopsies. Sections of 9 cases were diagnosed HD. In inadequate specimens, sensitivity and specificity of calretinin and synpatophysin (100%, 80%) and (100%, 85.71%) respectively were superior to the sensitivity (40%) and specificity (14%) of H&E. However, in adequate specimens, results of H&E, calretinin and synaptophysin were the same.Conclusions: Immunohistochemical expression of calretinin and synaptophysin were conclusive, diagnostic and superior to the results of H&E stained section in inadequate. However, in adequate specimens calretinin and synaptophysin were consistent and confirmatory to the results of H&E sections.

Background: Second to fourth digit (2D:4D) ratio is the ratio of index to ring fingers length. It reflects prenatal androgen exposure and sensitivity. Androgens are important in the pathogenesis of acne vulgaris, This ratio may therefore be of significance in determining the expression of androgen receptors. Aim: To investigate the relationship between second to fourth digit ratio and androgen receptor expression in female patients with acne vulgaris and to assess its association with clinical aspects of acne vulgaris. Methods: Females patients (n = 352) with different degrees of acne vulgaris severity and 168 age-matched females were enrolled. Right, left and total second to fourth digit ratios were calculated. Biopsies from all participants were processed for androgen receptor expression by immunohistochemical method. Results: Right, left and total second to fourth digit ratios were significantly lower in acne vulgaris patients than controls (P < 0.001 for all), and each of them had a significant negative correlation with duration of acne vulgaris (P < 0.001; P = 0.013; P < 0.001, respectively). Androgen receptors were detected in epidermal keratinocytes, hair follicles, sebaceous glands and fibroblasts. Right second to fourth digit ratio showed a negative correlation with androgen receptor H score of keratinocytes (r = −0.28;P = 0.02), hair follicles (r = −0.22; P = 0.05) and fibroblasts (r= −0.37;P = 0.001), while left second to fourth digit ratio demonstrated negative correlation with androgen receptor H score of sebocytes (r = −0.397; P < 0.000) only. Limitations: Lack of follow-up and absence of male participants were the main limitations of this study. Conclusion: A masculine second to fourth digit ratio in female patients could anticipate acne vulgaris development, its duration and severity. Moreover, this ratio is associated with an upregulation of cutaneous androgen receptors. Taken together, second to fourth digit ratio could help in designing plans for treatment of acne vulgaris.

Objectives To perform a systematic review to summarize the role of autophagy-related gene 7 (ATG7) and autophagy in vitiligo. Background Vitiligo is an acquired autoimmune pigmentary disorder due to loss of functional melanocytes. Colocalization studies revealed that the autophagy-related gene 7 has a role in the pathogenesis of vitiligo. Materials and methods Medline databases (Google Scholar, Medscape, ScienceDirect) and all materials published in English language available on the internet from 2007 to 2018. The search was performed on March 2018. All the studies were independently assessed for inclusion. They were included if they fulfilled the following criteria: published in English language, published in peer-reviewed journals, focused on the role of ATG7 in vitiligo. The initial search presented 38 articles which studied the role of ATG7 in vitiligo. If the studies did not fulfill the inclusion criteria, they were excluded such as studies on ATG7 in systemic diseases or skin diseases other than vitiligo, report without peer review, not within the national research program, letters/comments/editorials/news. Comparisons were made by a structured review with the results tabulated. Results In total, four potentially relevant publications were included; there was an association between vitiligo and autophagy marker ATG7. This association was due to premature senescence of melanocytes due to the accumulation of products of oxidative damage leading to pigment dilution. Conclusion Autophagy marker-related gene 7 has a role in the pathogenesis of vitiligo.

Objective The aim of this work was to elucidate the efficacy and safety of microneedling in the treatment of striae distensae (SD). Background SD is a common form of dermal scarring that appears on the skin as violaceous, erythematous, or hypopigmented linear striations. Microneedling therapy or collagen induction therapy is a minimally invasive, nonsurgical, and nonablative procedure that involves the use of a microneedling device to create controlled skin injury. Data sources Medline databases such as PubMed, Medscape, Science Direct, and EMF-Portal and all materials available on the Internet from 2010 to 2017 were searched. Study selection The initial search presented seven articles that have studied the role of microneedling in the treatment of SD. Data extraction If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls mentioned, adequate information provided, and assessment measures defined. Data synthesis Comparisons were made by structured review with the results tabulated. Findings The use of skin microneedling is found to be effective in the treatment of SD. Conclusion This study concluded that the use of skin microneedling is effective as a new modality for the treatment of SD.

Most tumors contain a minor population of cancer stem cells that are responsible for tumor heterogeneity, resistance to therapy and recurrence. Oct-4 is a transcription factor responsible for self-renewal of stem cells, whereas the Notch family of receptors and ligands may play a pivotal role in the regulation of stem cell maintenance and differentiation. This study aimed at an evaluation of Oct-4 and Notch-1 expression in both carcinoma and stromal cells of 83 cases of primary bladder carcinoma and to study the relationship between them. Notch-1 was expressed in carcinoma and stromal cells of all malignant cases, where expression in both cell types was correlated with parameters indicating differentiation, such as low grade (p < 0.05) and less proliferation (p < 0.05). However, Notch-1 expression in stromal cells was associated with nodal metastasis (p = 0.016) and advanced stage (p = 0.030). 56.6 and 75.9% of carcinoma and stromal cells of malignant cases showed Oct-4 expression, respectively. Oct-4 expression in carcinoma cells or stromal cells was associated with aggressive features of bladder carcinoma, such as poor differentiation (p = 0.001), high proliferation (p < 0.001, 0.030), and liability for recurrence (p = 0.010, p < 0.001). There was an inverse relationship between Notch-1 and Oct-4 expression in carcinoma cells (p = 0.002), but stromal expression of Notch-1 was found to be associated with a nuclear pattern of Oct-4 expression in carcinoma cells (p = 0.030). Oct-4 as a stem cell marker is expressed in carcinoma cells and in stromal cells of bladder carcinoma, where they may cooperate in the progression of bladder carcinoma by acquiring aggressive features, such as a liability for recurrence and dissemination. Notch-1 is also expressed in both carcinoma cells and stromal cells of bladder carcinoma. Although they could share in enhancing differentiation, stromal expression of Notch-1 may have a bad impact, possibly through up-regulation of the active nuclear form of Oct-4 in carcinoma cells.