Rare Case of a 20p13 Duplication Trisomy With Craniostenosis.

Duplication 20p or partial trisomy 20 is a rare chromosomal anomaly characterized by duplication of the short arm of chromosome 20, with various clinical abnormalities. Despite complete trisomy 20, which usually leads to prenatal death, partial trisomy 20 can manifest with variable phenotypes, from mild to severe manifestations. Here, we present a rare case of an 8-year-old boy diagnosed with trisomy 20, epilepsy with focal seizures of genetic origin, craniosynostosis, type 1 diabetes, and autism spectrum disorder. Duplication 20p is a complex diagnostic and presents a therapeutic challenge due to its diverse clinical manifestations. To succeed in the intricacy of such a unique and challenging case, a comprehensive clinical and genetic assessment must be performed.

Aloe vera gel confers therapeutic effect by reducing pyroptosis in ethanol-induced gastric ulcer rat model: Role of NLRP3/GSDMD signaling pathway.

BACKGROUND: Gastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved. METHODS: An ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done. RESULTS: The ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group. CONCLUSIONS: Aloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.

Fast skin healing chitosan/PEO hydrogels: In vitro and in vivo studies.

Due to its outstanding qualities, particularly when it takes the shape of hydrogels, chitosan is a well-known biological macromolecule with many applications. When chitosan hydrogels are modified with other polymers, the desirable function as skin regeneration hydrogels is compromised; nevertheless, the mechanical properties can be improved, which is crucial for commercialization. In this study, for the first time, bimetallic zinc silver metal-organic frameworks (ZAg MOF) loaded with ascorbic acid were added to chitosan/polyethylene oxide (PEO) based interpenetrating polymer network (IPN) hydrogels that were crosslinked with biotin to improve their antimicrobial activity, mechanical characteristics, and sustainable treatment of wounds. Significant changes in the microstructure, hydrophilicity level, and mechanical properties were noticed. Ascorbic acid release patterns were upregulated in an acidic environment pH (5.5) that mimics the initial wound pH. Impressive cell viability (98 %), antimicrobial properties, and almost full skin healing in a short time were achieved for the non-replaceable chitosan/PEO developed hydrogels. Enhancing the wound healing of the treated animals using the prepared CS/PEO hydrogel dressing was found to be a result of the inhibition of dermal inflammation via decreasing IL-1ß, suppressing ECM degradation (MMP9), stimulating proliferation through upregulation of TGF-ß and increasing ECM synthesis as it elevates collagen 1 and α-SMA contents. The findings support the implementation of developed hydrogels as antimicrobial hydrogels dressing for fast skin regeneration.

Acetylated oligopeptide and N-acetylcysteine protect against iron overload-induced dentate gyrus hippocampal degeneration through upregulation of Nestin and Nrf2/HO-1 and downregulation of MMP-9/TIMP-1 and GFAP.

Iron accumulation in the brain causes oxidative stress, blood-brain barrier (BBB) breakdown, and neurodegeneration. We examined the preventive effects of acetylated oligopeptides (AOP) from whey protein on iron-induced hippocampal damage compared to N-acetyl cysteine (NAC). This 5-week study used 40 male albino rats. At the start, all rats received 150 mg/kg/day of oral NAC for a week. The 40 animals were then randomly divided into four groups: Group I (control) received a normal diet; Group II (iron overload) received 60 mg/kg/day intraperitoneal iron dextran 5 days a week for 4 weeks; Group III (NAC group) received 150 mg/kg/day NAC and iron dextran; and Group IV (AOP group) received 150 mg/kg/day AOP and iron dextran. Enzyme-linked immunosorbent assay, spectrophotometry, and qRT-PCR were used to measure MMP-9, tissue inhibitor metalloproteinase-1 (TIMP-1), MDA, reduced glutathione (GSH) levels, and nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) gene expression. Histopathological and immunohistochemical detection of nestin, claudin, caspase, and GFAP was also done. MMP-9, TIMP-1, MDA, caspase, and GFAP rose in the iron overload group, while GSH, Nrf2, HO-1, nestin, and claudin decreased. The NAC and AOP administrations improved iron overload-induced biochemical and histological alterations. We found that AOP and NAC can protect the brain hippocampus from iron overload, improve BBB disruption, and provide neuroprotection with mostly no significant difference from healthy controls.

A Neurosurgical Perspective on Brain Metastases from Renal Cell Carcinoma: Multi-Institutional, Retrospective Analysis.

BACKGROUND: While acknowledging the generally poor prognostic features of brain metastases from renal cell carcinoma (BM RCC), it is important to be aware of the fact that neurosurgery still plays a vital role in managing this disease, even though we have entered an era of targeted therapies. Notwithstanding their initial high effectiveness, these agents often fail, as tumors develop resistance or relapse. METHODS: The authors of this study aimed to evaluate patients presenting with BM RCC and their outcomes after being treated in the Neurosurgical Department of Clinical Emergency Hospital "Bagdasar-Arseni", and the Neurosurgical Department of the National Institute of Neurology and Neurovascular Diseases, Bucharest, Romania. The study is based on a thorough appraisal of the patient's demographic and clinicopathological data and is focused on the strategic role of neurosurgery in BM RCC. RESULTS: A total of 24 patients were identified with BM RCC, of whom 91.6% had clear-cell RCC (ccRCC) and 37.5% had a prior nephrectomy. Only 29.1% of patients harbored extracranial metastases, while 83.3% had a single BM RCC. A total of 29.1% of patients were given systemic therapy. Neurosurgical resection of the BM was performed in 23 out of 24 patients. Survival rates were prolonged in patients who underwent nephrectomy, in patients who received systemic therapy, and in patients with a single BM RCC. Furthermore, higher levels of hemoglobin were associated in our study with a higher number of BMs. CONCLUSION: Neurosurgery is still a cornerstone in the treatment of symptomatic BM RCC. Among the numerous advantages of neurosurgical intervention, the most important is represented by the quick reversal of neurological manifestations, which in most cases can be life-saving.

An Overview of Systemic Targeted Therapy in Renal Cell Carcinoma, with a Focus on Metastatic Renal Cell Carcinoma and Brain Metastases.

The most commonly diagnosed malignancy of the urinary system is represented by renal cell carcinoma. Various subvariants of RCC were described, with a clear-cell type prevailing in about 85% of all RCC tumors. Patients with metastases from renal cell carcinoma did not have many effective therapies until the end of the 1980s, as long as hormonal therapy and chemotherapy were the only options available. The outcomes were unsatisfactory due to the poor effectiveness of the available therapeutic options, but then interferon-alpha and interleukin-2 showed treatment effectiveness, providing benefits but only for less than half of the patients. However, it was not until 2004 that targeted therapies emerged, prolonging the survival rate. Currently, new technologies and strategies are being developed to improve the actual efficacy of available treatments and their prognostic aspects. This article summarizes the mechanisms of action, importance, benefits, adverse events of special interest, and efficacy of immunotherapy in metastatic renal cell carcinoma, with a focus on brain metastases.

An Overview of EGFR Mechanisms and Their Implications in Targeted Therapies for Glioblastoma.

Despite all of the progress in understanding its molecular biology and pathogenesis, glioblastoma (GBM) is one of the most aggressive types of cancers, and without an efficient treatment modality at the moment, it remains largely incurable. Nowadays, one of the most frequently studied molecules with important implications in the pathogenesis of the classical subtype of GBM is the epidermal growth factor receptor (EGFR). Although many clinical trials aiming to study EGFR targeted therapies have been performed, none of them have reported promising clinical results when used in glioma patients. The resistance of GBM to these therapies was proven to be both acquired and innate, and it seems to be influenced by a cumulus of factors such as ineffective blood-brain barrier penetration, mutations, heterogeneity and compensatory signaling pathways. Recently, it was shown that EGFR possesses kinase-independent (KID) pro-survival functions in cancer cells. It seems imperative to understand how the EGFR signaling pathways function and how they interconnect with other pathways. Furthermore, it is important to identify the mechanisms of drug resistance and to develop better tailored therapeutic agents.

Impact of porous microsponges in minimizing myotoxic side effects of simvastatin.

Simvastatin (SV) is a poorly soluble drug; its oral administration is associated with a significant problem: Myopathy. The present study aims to formulate SV microsponges that have the potential to minimize the myotoxicity accompanying the oral administration of the drug. SV microsponges were prepared by exploiting the emulsion solvent evaporation technique. The % entrapment efficiency (%EE) of the drug approached 82.54 ± 1.27%, the mean particle size of SV microsponges ranged from 53.80 ± 6.35 to 86.03 ± 4.79 µm in diameter, and the % cumulative drug release (%CDR) of SV from microsponges was significantly higher than that from free drug dispersion much more, the specific surface area of the optimized microsponges formulation was found to be 16.6 m2/g revealed the porosity of prepared microsponges. Histological and glycogen histochemical studies in the skeletal muscles of male albino rats revealed that microsponges were safer than free SV in minimizing myotoxicity. These findings were proven by Gene expression of Mitochondrial fusion and fission (Mfn1) & (Fis1) and (Peroxisome proliferator-activated receptor gamma co-activator 1α) PGC-1α. Finally, our study ascertained that SV microsponges significantly decreased the myotoxicity of SV.

Acetylated Oligopeptide and N-acetyl cysteine Protected Against Oxidative Stress, Inflammation, Testicular-Blood Barrier Damage, and Testicular Cell Death in Iron-Overload Rat Model.

Multiple organs, including the testes, are damaged by iron overload. It has been shown that N-acetyl cysteine (NAC) influences oxidative stress in iron overload. The present study aimed to evaluate the roles of acetylated peptide (AOP) and NAC in the inhibition of iron-overload induced-testicular damage. At the beginning of the experiment, NAC (150 mg /kg) was given for a week to all 40 rats. Then, four groups were formed by dividing the animals (10 rats/group). Group I included healthy control rats. Group II (iron overload) was given intraperitoneal iron dextran (60 mg/kg/day) 5 days a week for 4 weeks. Group III (NAC) was given NAC orally at a dose of 150 mg/kg/day for 4 weeks in addition to iron dextran. Group IV (AOP) was given AOP orally at a dose of 150 mg/kg/day for 4 weeks besides iron dextran. When the experiment time was over, testosterone serum level, testicular B cell lymphoma-2 (BCL-2) and protein kinase B (PKB) protein levels, nuclear factor kappa-B (NF-κB), and Beclin1 mRNA expression levels, and malondialdehyde (MDA), and reduced glutathione (GSH) were determined by ELISA, quantitative reverse transcription-PCR, and chemical methods. Finally, histopathological examinations and immunohistochemical detection of claudin-1 and CD68 were performed. The iron overload group exhibited decreased testosterone, BCL-2, PKB, claudin-1, and GSH and increased MDA, NF-κB, Beclin1, and CD68, while both NAC and AOP treatments protected against the biochemical and histopathological disturbances occurring in the iron overload model. We concluded that NAC and AOP can protect against testes damage by iron overload via their antioxidant, anti-inflammatory, antiapoptotic, and ant-autophagic properties. The NAC and AOP may be used as preventative measures against iron overload-induced testicular damage.

Biodegradable functionalized magnetite nanoparticles as binary-targeting carrier for breast carcinoma.

In this study, Superparamagnetic magnetite nanoparticles (SPMNPs) are used in a new way as direct nanocarrier for Doxorubicin hydrochloride (DOX) via the functionalization of their surface with tri-sodium citrate through ligand exchange to conjugate DOX with imine bond to form tri-sodium citrate functionalized magnetite loaded DOX nanoparticles (DOX/Cit-MNPs). The DOX/Cit-MNPs were coated with chitosan to form chitosan coated citrate functionalized magnetite loaded DOX nanoparticles (Cs/DOX/Cit-MNPs) to offer biodegradability and pH-sensitive drug release features. The Fourier transform infrared spectroscopy (FTIR) analysis confirmed functionalization of SPMNPs, DOX-conjugation, and chitosan coating. The trans electron microscopy (TEM) show spherical nanostructures with average size 40 nm for coated nanocarriers. The saturation magnetization value of carrier was 59 emu/g.The in-vitro release of DOX from the chitosan coated tri-sodium citrate functionalized magnetite loaded DOX nanoparticles (Cs/DOX/Cit-MNPs) was studied to be 75% at pH 5.5 and 28.6% at pH 7.4 which proves the pH sensitivity of encapsulated Cs/DOX/Cit-MNPs. The effect of Cs/DOX/Cit-MNPs toward Human Breast Cancer Cell lines (MCF7) was studied and found to be 76% without magnet and 98% with external magnet after 72 h. With increasing DOX concentration and treatment time, the cell inhibition (IR%) of DOX solution and Cs/DOX-Cit-MNPs suspension to all cells is increased. Cs/DOX/Cit-MNPs showed sustained release and good inhibition to cancer cells and offer a protective mode for normal cells (WISH) compared to the free DOX.

Significant Interrelations among Serum Annexin A1, Soluble Receptor for Advanced Glycation End Products (sRAGE) and rs2070600 in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a major cause of death and morbidity; it may be accompanied by oxidative stress and inflammation with or without underlying genetic etiology. Finding circulating biomarkers for COPD that can help early diagnosis and predict exacerbation and association with respiratory functions has been challenging. There were 40 healthy participants and 60 COPD patients in this research. The rs2070600 gene variant was examined by PCR-RFLP. Circulating sRAGE and annexin A1 levels were determined by ELISA. GSH and MDA were determined by spectrophotometry. In COPD patients, sRAGE serum levels were substantially lower, but conversely, annexin A1 levels were much greater than in controls. The rs2070600 gene polymorphism's strong association with COPD was demonstrated by genotyping and allelic frequency distribution. The GA genotype was most distributed in COPD, and it was strongly linked to lower serum sRAGE levels. The interrelation between annexin A1, sRAGE, and COPD could be explained through effects on inflammatory mediators' pathways. The rs2070600 gene polymorphism was found to significantly enhance the risk of COPD. Serum sRAGE and annexin A1 may be considered potential diagnostic tools for COPD. Through impacts on GSH and MDA levels that alter the release of inflammatory factors and, therefore, lung damage, it is possible to explain the relationship between annexin A1, sRAGE, and COPD.

Smart prototype for an electronic color sensor device for visual simultaneous detection of macrofuran based on a coated paper strip.

Nowadays, in the clinical, pharmaceutical, and environmental sectors, the development of facile and sensitive analytical methods and/or innovative devices for the follow-up and detection of antibiotics and pharmaceutical formulations, in general, are urgently needed and still challenging. This work declared three vital applications for broad-spectrum nitrofurantoin (macrofuran) antibiotic detection and quantification: A colorimetric method, a coated paper strip-based nano-lanthanum complex prototype and fabrication of smart electronic color sensor device-based coated paper strips. The colorimetric method showed a significant response upon increasing the concentration of the nitrofurantoin in a range between (1.0-100.0 ng/mL) via a visual color change from orange-yellow to red colors degree with detection and quantification limits of 0.175 and 0.53 ng/mL, respectively, whereas the nano-lanthanum complex coated paper strip prototype showed qualitative on-site sensing for nitrofurantoin via naked eye color changes which can be detected anywhere. Moreover, a smart prototype for detecting macrofuran in the means of paper color change in the RGB color component extraction algorithm and the grayscale projection value processing algorithm was fabricated. The change in RGB color on the coated paper strip was detected using an electronic color sensor device. The developed colorimetric method, coated paper strip, and the electronic color sensor device prototype exhibited fast, simple, costless, and selective towards macrofuran over the competing analyzed. As well as, showed good applicability in the different real samples spiked with different concentrations of macrofuran.

Detection of Epithelial-Mesenchymal Transition Markers in High Grade Bladder Cancer and Special Variants of Urothelial Carcinoma.

Transitional cell carcinoma is considered the most predominant type of bladder cancer. Bladder can cer can also be found as squamous cell carcinoma that accounts for 5% of the total bladder cancer due to its etiology. The biomarkers associated with grade, prognosis, and stage of the disease are not well proved and known however, many studies have pointed to the association between SNAL/SLUG and Twist2 to the overall survival in patients with bladder cancer. These biomarkers were found to have a crucial role in inhibiting cadherin mediators specifically E-cadherin which are found normally in high level to integrate cell adhesion and normal function of the bladder. This research aims to detect SNAL/SLUG and Twist2 biomarkers in specimens of patients with bladder cancer and to detect their impact on E-cadherin, a tumor suppressor mediator responsible for improving survival and prevent metastasis. MATERIALS AND METHODS: Using 150 archival tissue blocks from human bladder cancer cases to detect expression of SNAIL/SLUG and Twist2 in relation to loss of E-cadherin by immunohistochemical method. RESULTS: Our results have revealed that in squamous cell carcinoma 40 specimens showed marked Twist 2 expression, and 30 specimens showed marked snail/slug biomarkers expression while poorly differentiated cancer cases showed marked expression of Twist 2 in 60 specimens and marked expression of Snail/slug marked expression in 50 specimens. Both were associated with E-cadherin loss. Among the 100 specimens with transitional cell carcinoma, 70 specimens showed divergent differentiation with 7 subtypes each showed different medium to high expression of Snail/Slug and Twist 2 biomarkers with the loss of E-cadherin. E-cadherin was strongly associated with the inverse increase in SNAL/SLUG and Twist2 biomarkers in urothelial carcinoma. CONCLUSION: Detection of SNAIL/SLUG and Twist 2 biomarkers in urothelial cancer is an important predictor for the loss of E-cadherin, a cornerstone in urinary bladder cell adhesion and its loss in urothelial carcinoma may contribute to cancer invasion and poor prognosis. 
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Does interleukin-33 level correlate with the activity of Pemphigus vulgaris?: A case-control study.

Pemphigus is a group of immune-mediated blistering diseases of skin and mucus membrane caused by destruction of the intercellular junction (desmosomes) by autoantibodies. Pemphigus vulgaris (PV) is considered the most common type of all pemphigus family. Various cytokines play a major role in pemphigus pathogenesis. Interleukin-33 (IL-33) role has been studied in various autoimmune diseases as; psoriasis and rheumatoid arthritis, yet it has not been studied in Egyptian patients with PV. The study aimed to evaluate the possible role of IL-33 in PV by assessing its level in the serum using ELISA and to detect its correlation with activity score using Pemphigus Disease Area Index (PDAI). Forty-four patients with PV and 36 age and sex-matched healthy controls were enrolled in the study. After full history taking and complete dermatological examination, the severity score was calculated using PDAI, then serum samples were taken from each patient and control subjects and subjected to quantitative measurement of serum IL-33 using ELISA. Serum level of IL-33 is significantly raised in PV patients compared to control subjects (P-value = .007). The level of IL-33 was found to be strongly correlated with the activity of the disease measured by PDAI. IL-33 might have a role in PV pathogenesis as shown by its rising level in PV patients. In addition, serum level of IL-33 is strongly correlated with the activity of PV. Thus, we suspect that IL-33 can be used as marker for monitoring PV severity and measuring treatment efficacy.

Molecular docking and statistical optimization of taurocholate-stabilized galactose anchored bilosomes for the enhancement of sofosbuvir absorption and hepatic relative targeting efficiency.

The work aimed to improve both absorption and hepatic availability of sofosbuvir. Bilosomes and galactose-anchored bilosomes were investigated as potential nanocarriers for this purpose. Sofosbuvir is a class III drug with high solubility and low permeability. Thus, the drug entrapment into lipid-based galactose-anchored carriers would enhance drug permeability and improve its liver availability. The galactosylated taurocholate was designed and synthesized based on molecular docking studies, where both galactose and taurocholate molecules were connected in a way to avoid affecting crucial interactions and avoid steric clashes with their cellular uptake receptors. The suggested nano-carriers were prepared using a thin-film hydration technique with sodium taurocholate and span 60 as stabilizers. The prepared formulae were statistically optimized using a central composite design. The optimized plain and galactosylated formulae, composed of SAA to drug ratio of 1:1 w/w and sodium taurocholate to span ratio of 10:1 w/w, have a vesicular size, zeta potential and entrapment efficiency in the range of 140-150 nm, -50 mV and 85%, respectively. The optimized formulae were lyophilized to increase their physical stability and facilitate accurate drug dosing. In vivo results showed that Sofosbuvir availability in the liver was significantly increased after oral administration of the plain and the galactosylated bilosomal formulae when compared to the oral drug solution with relative targeting efficiencies (RTIs) of 1.51 and 3.66, respectively. These findings confirmed the hypothesis of considering the galactosylated bilosomes a promising nanocarrier to efficiently target sofosbuvir to the liver.

Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression.

Although regulatory B cells (Bregs) have been proven to play a suppressive role in autoimmune diseases, infections and different tumors, little is known regarding hepatocellular carcinoma (HCC), especially in hepatitis C-related settings. Herein, we analyzed the frequency of circulating Bregs, serum levels of IL-10, IL-35 and B-cell activating factor (BAFF) and investigated their association with regulatory T cells (Tregs) and disease progression in HCV-related HCC. For comparative purposes, four groups were enrolled; chronic HCV (CHC group, n = 35), HCV-related liver cirrhosis (HCV-LC group, n = 35), HCV-related HCC (HCV-HCC group, n = 60) and an apparently healthy control (Control-group, n = 20). HCC diagnosis and staging were in concordance with the Barcelona Clinic Liver Cancer (BCLC) staging system. Analysis of the percentage of Breg cells and peripheral lymphocyte subsets (Treg) was performed by flow cytometry. Serum cytokine levels of IL-10, IL-35 and B-cell activating factor (BAFF) were measured by ELISA. The frequency of Bregs was significantly higher in the HCV-HCC group compared to the other groups and controls. A significant increase was noted in late-HCC versus those in the early stages. The frequency of Bregs was positively correlated with Tregs, serum IL-10, IL-35 and BAFF. In conclusion, Peripheral Bregs were positively correlated with the frequency of Tregs, IL-10, IL-35 and BAFF, and may be associated with HCV-related HCC progression.

Tissue Profile of CDK4 and STAT3 as Possible Innovative Therapeutic Targets in Urinary Bladder Cancer.

Bladder cancer represents a global health problem. It ranks ninth in worldwide cancer incidence. In Egypt, carcinoma of the bladder is the most prevalent cancer, Bladder cancer has the highest recurrence rate of any malignancy. Certainly, suitable molecular diagnostic markers are required to improve the early detection of bladder cancer and then to prolong survival of patients. The present study was aimed to explore the expression of CDk4 and STAT3 in bladder cancer tissues as prospective for target therapy. Our studied groups showed higher values of CDK4 and STAT3 expression in malignant tissues (SCC andUC collectively) compared to cystitis, however, significantly higher values of CDK4 and STAT3 expression were detected in UC group compared to SCC group. Urothelial carcinomas with papillary patterns showed lower parameters of CDK4 and STAT3 expression compared to the non-papillary variant, with significant differences. Higher grades of UC showed significantly higher parameters of CDK4 and STAT3 expression compared to low grade ones. Muscle invasion increases the level of CDK4 and STAT3 expression parameters, compared to non-muscle invasive UC. Conclusion: Our results showed a good correlation of the expression patterns of both the cell cycle (CDK4) and inflammatory (STAT3) markers studied and might be helpful for suggesting more selective agents in the therapeutic scenario of bladder cancer in the near future. Potential biomarkers such as CDK4 andSTAT3 may be targets for molecular based therapeutic strategies in the prevention or management of bladder cancer. Future studies should explore molecular mechanisms of these proteins to define their roles in tumorigenesis.

Efficacy and Safety of Microwave Ablation (MWA) for Hepatocellular Carcinoma (HCC) in Difficult Anatomical Sites in Egyptian Patients with Liver Cirrhosis

Background and aim: Imaging guided microwave ablation (MWA) for hepatocellular carcinoma (HCC) has become a widely used method over recent years. Tumors close to the diaphragm, gastrointestinal tract, gallbladder, pancreas, hepatic hilum and major bile duct or vessels are generally considered relative contraindications for microwave ablation. This study was conducted to assess the effectiveness and safety of ultrasonography-guided MWA in treating patients with HCC in difficult anatomical sites in comparison to those in conventional sites. Patients and methods: Eighty-eight patients were included and divided into two groups: the study group of 44 with 46 lesions lying <5mm from the diaphragm, hepatic capsule, gall bladder (GB) or large vessel; and the control group of 44 patients with 50 lesions in non-risky sites. Each lesion was ablated using an ultrasound guided microwave probe using a detailed protocol. Results: Most of the patients were males, with a mean age of 57.8 years. In the study group, two patients had lesions adjacent to the GB, twelve were perivascular and 32 were subcapsular. The overall successful ablation rates were 84.8% and 92% in the study and control groups, respectively. Within the study group, ablation rates were 100%, 75% and 87.5% for lesions close to the GB, perivascular lesions and subcapsular lesions, respectively. One patient developed a subcutaneous abscess, with good outcome after proper treatment. Fever, pain and asymptomatic pleural effusion were reported after ablation without statistically significant difference between the groups or among subgroups. In conclusion: MWA for HCC in difficult anatomical sites is as effective and safe as for ordinary sites.

Association of Treg and TH17 Cytokines with HCV Pathogenesis and Liver Pathology.

Chronic hepatitis C (CHC) infection is considered a high risk for development of end-stage liver diseases, particularly server hepatitis, decompensated liver cirrhosis, and hepatocellular carcinoma. Regulatory T cells (Treg) and T-helper 17 (TH17) associated cytokines presumed to play a pivotal role in the immune pathogenesis of HCV infection and stimulate autoimmune diseases. Herein, we tried to assess the association of Treg and TH 17 cytokines with HCV pathogenesis and liver pathology. Fifty CHC infected patients and twenty HCV free controls were included in this study, IL17, IL21, IL10, IL4, TGF- and IL35 serum levels were assessed in both groups using enzyme linked immunosorbent assay (ELISA). CHC infected patients had statistically significant higher values of all serum cytokine levels when compared to the control group (P < 0.0001) for each. Additionally, serum levels of IL17, IL10 and IL35 were positively correlated with viral load. Also, the serum level of IL17 IL21, IL10 and IL35 was positively correlated with ALT serum levels. Only IL21 and IL10 were positively correlated with AST levels. Serum IL17, IL10, TGF- and IL35 levels were significantly elevated in CHC patients with advanced fibrosis stages. We concluded that CHC infected patients displayed high serum levels of Treg and TH17 associated cytokines. Collectively, these results support the hypothesis that liver damage in CHC infection might be due to an immune-mediated destructive mechanism rather than to the direct cytopathic effect of the virus itself.

The adipokine Chemerin and Fetuin-A Serum Levels in Type 2 Diabetes Mellitus: Relation to Obesity and Inflammatory Markers.

Chemerin and fetuin-A are recently discovered as metabolic regulator hormone in obesity and type 2 diabetes mellitus. However, elevated levels of chemerin and fetuin-A have been associated with insulin resistance and systemic inflammation. The present study aimed to investigate the significance of serum chemerin and fetuin-A levels in obese diabetic patients. Also, to determine whether, chemerin and fetuin-A along with markers of inflammation (IL6 and CRP) and obesity-related parameters in T2DM patients. Serum levels of chemerin and fetuin-A were evaluated using ELISA in 71 T2DM patients and 14 apparently healthy controls. Both groups were subdivided into obese and lean. Serum chemerin and fetuin-A levels were significantly higher in T2DM patients compared to controls (P < 0.001, for both) and significantly higher in obese T2DM in comparison to obese control group (P < 0.01 & P < 0.05, respectively). Serum chemerin and fetuin-A levels correlated positively with HbA1c, HOMA-IR, FBG, IL6 and CRP. In obese patients, serum chemerin and fetuin-A levels correlated positively with BMI and waist circumference. In conclusion, the strong association of chemerin and fetuin-A with insulin resistance and some inflammatory markers may provide an interesting link between obesity, inflammation and diabetes mellitus in human.