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Because laparoscopic ovarian cystectomy of endometriomas is known to adversely impact patient ovarian reserve, the search for other techniques of surgical management is ongoing. The present study was undertaken to evaluate laparoscopic cyst deroofing as a feasible alternative.Prospective, randomized clinical trial (Canadian Task Force classification I).University maternity hospital.Women diagnosed with unilateral or bilateral ovarian endometriomas.Patients were managed with either laparoscopic ovarian cystectomy or cyst deroofing.A total of 122 women with endometriomas were randomized to either laparoscopic cystectomy (group 1) or laparoscopic cyst deroofing (group 2). The primary endpoint was the effect on ovarian reserve based on changes in anti-Müllerian hormone (AMH) values. At 1 month postsurgery, anti-Müllerian hormone values were significantly decreased (p.001) from preoperative values, from 4.25 ± 0.87 ng/mL to 1.66 ± 1.02 ng/mL in group 1 and from 4.2 ± 1.69 ng/mL to 2.15 ± 1.48 ng/mL in group 2. In addition, antral follicle count and ovarian volume decreased significantly (p.001) in both groups by 1 month postsurgery. The decreases in these 3 parameters were more significant (p.001) in group 1 than in group 2.Laparoscopic cyst deroofing of endometriomas appears to be a promising alternative to laparoscopic cystectomy, with less postoperative decrease in ovarian reserve; however, the higher rate of endometrioma recurrence warrants future clinical research to determine the optimal surgical management of endometriomas.

Background: Medical abortion, the termination of pregnancy through the use of a drug or a combination of drugs, has the potential to reduce complications and to expand access to abortion provided not only by specially trained clinicians but also by other health care providers who may or may not have training in surgical methods of abortion.Aim: This study aimed to elicit the safety and efficacy of intravenous injection of dexamethasone with vaginal misoprostol for shortening the induction abortion interval in the second trimester of pregnancy.Materials and Methods: This study was conducted in Ain-Shams Maternity University Hospital where 140 pregnant females were included for induction of second trimester abortion from June 2018 till December 2019.Results: There was significant statistical difference between the two groups as regard induction-expulsion interval (P >0.001) and length of hospital stay (P > 0.001), mean induction-expulsion interval in dexamethasone group was 10.5 hours; while in the control group was 17.5 hours, the mean length hospital stay was 16 hours in the dexamethasone group while it was 23 hours in the control group. There was significant statistical difference between the two groups as regard dose of misoprostol used (P>0.001), mean dose of misoprostol in the dexamethasone group was 800 mcg while it was 1600 mcg in the control group.Conclusion: It was suggested that use of intravenous injection of dexamethasone with misoprostol was effective in shortening the induction- abortion interval, the length of hospital stay and reducing the misoprostol doses

Background: There is a diverse community of micorganisms that supports the homeostasis of metabolic status and the balanced immune response in the host. Disturbed gut microbiome composition was found to be associated with multiple diseases in humans. Furthermore, there is an impaired balance between nutritional absorption and energy storage that is involved in the pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD) . Objectives: Investigate whether the gut bacterial microbiome could have a role in the inflammatory process leading to NAFLD development and decipher their effect on the immune response represented by Toll like receptor-4 levels. Methodology : One hundred and five adult participates were enrolled in the study, 70 patients diagnosed with NAFLD , they were further subdivided into 32 cases with pure steatosis (SS), and 38 cases with non alcoholic steatohepatitis (NASH), as well as 35 healthy subjects, all matched for age, gender. Full history and clinical examination, Body mass index (BMI), abdominal ultrasonography and l iver biopsy were done . Liver function tests, lipid profile, blood sugar, insulin and C-peptide, fasting insulin, and serum levels of Toll like receptor (TLR-4) were measured. Fresh stool samples were homogenized and either used for immediate aerobic and anaerobic cultures of bacteria, or for measurement of bacterial flora levels using quantitative real time PCR of genes e ncoding 16S rRNA. Results: BMI, Fasting glucose, LDL Cholesterol, HOMA-IR, AST, ALT and GGT were significantly increased in NAFLD group when compared to control group. The serum levels of TLR-4 were significantly increased in NAFLD groups compared to normal control group, with SS having the lowest level than that detected in NASH group. Levels of bacteroids and lactobacilli were significantly increased in NAFLD groups compared to control group and its level was significantly increased in NASH compared to simple steatosis. Clostridia, bifidobacteria, and E.coli showed no significant difference among groups. The increased copy numbers of bacteroids as well as lactobacilli were positively correlated with BMI, ALT, AST, fasting glucose, triglycerides and, TLR-4 serum levels. Conclusion: Gut microbiota play an important role in NAFLD-related pathophysiology . Further large-scale studies are recommended to understand the mechanism of such effect and to evaluate possible therapeutic targets for prevention and control of NAFLD.

Background: As a crucial constituent of tissue microenvironment, extracellular matrix (ECM) proteins can modulate tissue microenvironment and regulate the behavior of the surrounding cells. Periostin is usually absent or expressed in low levels in most adult tissues; however, it is often highly expressed during inflammation, injury and in multiple tumors as recently reported. Alterations in glycosylation regulate the development and progression of cancer, serving as important biomarkers and providing a set of specific targets for therapeutic intervention. Results: In current study, evidence showed that Periostin is overexpressed in ovarian cancer in a tumor type specific glycosylated form that affects Notch levels and activation. Moreover, ovarian cancer cell lines that constantly express glycosylated periostin showed enhanced Notch 1, 3 levels as well as Notch downstream effectors; Hes1, and NRARP. Our experiments in mice xenograft models showed increased carcinogenicity and metastatic potential in tumors produced by cells expressing glycosylated periostin forms. Conclusions: These results indicate that glycosylated periostin overexpression can in turn alter the carcinogenic potential of tumor cancer stem cells (CSC).

Biomarkers capable of detecting and targeting epithelial ovarian cancer cells for diagnostics and therapeutics would be extremely valuable. Ovarian cancer is the deadliest reproductive malignancy among women in the U.S., killing over 14 000 women each year. Both the lack of presenting symptoms and high mortality rates illustrate the need for earlier diagnosis and improved treatment of this disease. The glycosyltransferase enzyme GnT-III encoded by the Mgat3 gene is responsible for the addition of GlcNAc (N-acetylglucosamine) to form bisecting N-linked glycan structures. GnT-III mRNA expression is amplified in ovarian cancer tissues compared with normal ovarian tissue. We use a lectin capture strategy coupled to nano-ESI-RPLC-MS/MS to isolate and identify the membrane glycoproteins and unique glycan structures associated with GnT-III amplification in human ovarian cancer tissues. Our data illustrate that the majority of membrane glycoproteins with bisecting glycosylation are common to both serous and endometrioid histological subtypes of ovarian cancer, and several have been reported to participate in signaling pathways such as Notch, Wnt, and TGFβ.

Glycosylation changes associated with cellular transformation can facilitate the growth and progression of tumors. Previously we discovered that the gene Mgat3 encoding the glycosyltransferase GnT-III is elevated in epithelial ovarian carcinomas (EOCs) and leads to the production of abnormal truncated N-linked glycan structures instead of the typical bisected forms. In this study, we are interested in discovering how these abnormal glycans impact the growth and progression of ovarian cancer. We have discovered using stable shRNA gene suppression that GnT-III expression controls the expansion of side-population cells, also known as cancer stem cells. More specifically, we found that GnT-III expression regulates the levels and activation of the heavily glycosylated Notch receptor involved in normal and malignant development. Suppression of GnT-III in EOC cell lines and primary tumor-derived cells resulted in an inhibition of Notch signaling that was more potent than pharmacologic blockage of Notch activation via γ-secretase inhibition. The inhibition resulted from the redirection of the Notch receptor to the lysosome, a novel mechanism. These findings demonstrate a new role for bisecting glycosylation in the control of Notch transport and demonstrate the therapeutic potential of inhibiting GnT-III as a treatment for controlling EOC growth and recurrence.

Hepatitis C virus (HCV)-induced alterations in lipid metabolism and cellular protein expression contribute to viral pathogenesis. The mechanism of pleiotropic actions of cholesterol-lowering drugs, statins, against HCV and multiple cancers are not well understood. We investigated effects of fluvastatin (FLV) on microtubule-associated and cancer stem cell marker (CSC), doublecortin-like kinase 1 (DCLK1) during HCV-induced hepatocarcinogenesis. HCV replication models, cancer cell lines and normal human hepatocytes were used to investigate the antiviral and antitumor effects of statins. FLV treatment resulted in induction of microtubule bundling, cell-cycle arrest and alterations in cellular DCLK1 distribution in HCV-expressing hepatoma cells. These events adversely affected the survival of liver-derived tumor cells without affecting normal human hepatocytes. FLV downregulated HCV replication in cell culture where the ATP pool and cell viability were not compromised. Pravastatin did not exhibit these effects on HCV replication, microtubules and cancer cells. The levels of miR-122 that regulates liver homeostasis and provides HCV genomic stability remained at steady state whereas DCLK1 mRNA levels were considerably reduced during FLV treatment. We further demonstrated that HCV replication was increased with DCLK1 overexpression. In conclusion, unique effects of FLV on microtubules and their binding partner DCLK1 are likely to contribute to its anti-HCV and antitumor activities in addition to its known inhibitory effects on 3-hydroxy-3-methylglutary-CoA reductase (HMGCR).

Hepatitis C virus (HCV) infection is a prominent risk factor for the development of hepatocellular carcinoma (HCC). Similar to most solid tumors, HCCs are believed to contain poorly differentiated cancer stem cell-like cells (CSCs) that initiate tumorigenesis and confer resistance to chemotherapy. In these studies, we demonstrate that the expression of an HCV subgenomic replicon in cultured cells results in the acquisition of CSC traits. These traits include enhanced expression of d oublecortin and CaM k inase- l ike-1 (DCAMKL-1), Lgr5, CD133, α-fetoprotein, cytokeratin-19 (CK19), Lin28, and c-Myc. Conversely, curing of the replicon from these cells results in diminished expression of these factors. The putative stem cell marker DCAMKL-1 is also elevated in response to the overexpression of a cassette of pluripotency factors. The DCAMKL-1-positive cells isolated from hepatoma cell lines by fluorescence-activated cell sorting (FACS) form spheroids in Matrigel. The HCV RNA abundance and NS5B levels are significantly reduced by the small interfering RNA (siRNA)-led depletion of DCAMKL-1. We further demonstrate that HCV replicon-expressing cells initiate distinct tumor phenotypes compared to the tumors initiated by parent cells lacking the replicon. This HCV-induced phenotype is characterized by high-level expression/coexpression of DCAMKL-1, CK19, α-fetoprotein, and active c-Src. The results obtained by the analysis of liver tissues from HCV-positive patients and liver tissue microarrays reiterate these observations. In conclusion, chronic HCV infection appears to predispose cells toward the path of acquiring cancer stem cell-like traits by inducing DCAMKL-1 and hepatic progenitor and stem cell-related factors. DCAMKL-1 also represents a novel cellular target for combating HCV-induced hepatocarcinogenesis.

Overexpression and activation of the c-Src protein have been linked to the development of a wide variety of cancers. The molecular mechanism(s) of c-Src overexpression in cancer cells is not clear. We report here an internal ribosome entry site (IRES) in the c-Src mRNA that is constituted by both 5'-noncoding and -coding regions. The inhibition of cap-dependent translation by m(7)GDP in the cell-free translation system or induction of endoplasmic reticulum stress in hepatoma-derived cells resulted in stimulation of the c-Src IRES activities. Sucrose density gradient analyses revealed formation of a stable binary complex between the c-Src IRES and purified HeLa 40 S ribosomal subunit in the absence of initiation factors. We further demonstrate eIF2-independent assembly of 80 S initiation complex on the c-Src IRES. These features of the c-Src IRES appear to be reminiscent of that of hepatitis C virus-like IRESs and translation initiation in prokaryotes. Transfection studies and genetic analysis revealed that the c-Src IRES permitted initiation at the authentic AUG351, which is also used for conventional translation initiation of the c-Src mRNA. Our studies unveiled a novel regulatory mechanism of c-Src synthesis mediated by an IRES element, which exhibits enhanced activity during cellular stress and is likely to cause c-Src overexpression during oncogenesis and metastasis.

Some hepatotropic viruses (HBV and HCV) are capable of triggering autoimmune phenomena and manifest the features of autoimmune hepatitis (AIH) in the course of the disease. Careful attention is required to differentiate between AIH and chronic viral hepatitis (CVH) before the selection of treatment. This study was performed to assess the prevalence of rheumatoid factor (RF), antinuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), anti-mitochondrial antibodies (AMA), anti-parietal cell antibodies (APCA), anti-liver/kidney microsomal antibodies type I (ALKMA1) and anti-neutrophil cytoplasmic antibodies (ANCA) among patients with chronic liver diseases (CLD), and to assess the diagnostic value of these autoantibodies and their relation to HCV viral load and genotype and treatment with interferon-alpha (IFN-alpha). Five groups of patients with CLD (HCV, HBV, HCC, AIH and schistosomal hepatic fibrosis {SHF}) as well as a group of age- and gender-matched healthy controls were enrolled in the study. All the studied persons were subjected to full clinical assessment and laboratory investigations, including liver function tests, hepatitis markers, and HCV RNA by PCR. Detection of ANA, ASMA, APCA, AMA and ALKMA-1 was done by indirect immunofluorescence technique, while ANCA and RF were detected by EIA and latex agglutination test respectively. Results showed a significantly higher prevalence of RF, ASMA and ANCA among patients with CHC, RF and ASMA among HCC patients and ASMA and ALKMA1, among AIH patients as compared to the control group. Patients with HBV and those with SHF had a non-significantly higher prevalence of RF, ASMA and ANCA compared to controls. However, AMA was not detected in this study, and APCA showed no significant difference between the studied groups. The occurrence of these autoantibodies was not significantly related to HCV viral load, HCV genotype or treatment with IFN-alpha. There was a significant association between the occurrence of RF, ANA, ASMA, and ALKMA1 and high ALT levels, and between the occurrence of ANA, ASMA and ALKMA-1 and high AST and ALP levels. In conclusion, autoantibodies are commonly found among patients with HCV infection. The co-existence of HCV infection and autoimmune hepatitis should be considered in patients who are positive for both viral markers and autoantibodies and thorough evaluation of patients must be performed before selection of treatment. Testing for RF, ASMA and ANCA may have a good diagnostic value, however, AMA is the least useful in diagnosis.

Background:Hepatitis C virus (HCV) infection is a prominent risk factor for the development of hepatocellular carcinoma (HCC). Most solid tumors, including HCC, are believed to contain a subpopulation of poorly differentiated cancer stem-like cells (CSCs) that can initiate tumor formation and are relatively insensitive to antineoplastic chemotherapy. Because the putative intestinal and pancreatic stem cell marker DCAMKL-1 possesses microtubulepolymerizing activity and because intact microtubule filaments are required for efficient HCV replication, we hypothesize that DCAMKL-1 may be involved in HCV-induced hepatocarcinogenesis. Aim: Our aim is to delineate the role(s) of DCAMKL-1 in the development of HCV-induced hepatocellular carcinoma. Methods: We investigated our hypothesis using a selectable subgenomic replicon-expressing hepatoma cell line (GS5) and a corresponding control cell line (Huh7.5), immunofluorescence, immunohistochemistry, Western blot analysis, real-time RT-PCR, fluorescence-activated cell sorting (FACS) and a mouse xenograft model. Results: We demonstrate that HCV enhances expression of DCAMKL-1 and colocalizes with the replication complex attached microtubules. The siRNA-mediated inhibition of DCAMKL-1 expression concomitantly reduced HCV replication (In Vitro). The HCV+DCAMKL-1+ cells isolated from GS5 or DCAMKL-1+ cells from Huh7.5 formed spheroid bodies in a matrigel-based culture assay. Furthermore, we demonstrate that HCV induces retrodifferentiation of the replicon-expressing cells that results in much higher expression of α-fetoprotein and cytokeratin-19 in the tumor xenografts of GS5 cells compared to the control Huh7.5 tumors. Conclusion: DCAMKL-1 may represent a novel cellular target for the treatment of HCV infection and for directly targeting CSCs in HCC. We further demonstrate that HCV exhibits intrinsic ability to induce CSC features in liver-derived cells.