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Background:: Hepatocellular Carcinoma (HCC) is the fifth most frequent cancer worldwide with a low overall survival due to high metastasis and recurrence rates. The aim of this study is to assess and compare the possible anti-neoplastic effect of capsaicin and nanoformulated capsaicin on in vitro HCC human cell line HepG2. The source of the cell line, including when and from where it was obtained. Whether the cell line has recently been authenticated and by what method. Whether the cell line has recently been tested for mycoplasma contamination. Materials and Methods:: Capsaicin-loaded Trimethyl Chitosan Nanoparticles (CL TMCS NPs) were synthesized by ionotropic gelation of cationic TMCS with capsaicin. The synthesized nanoparticles were characterized through TEM, and zeta analyzer. Human hepatocarcinoma HepG2 cell lines were cultured and treated with 50, 75 & 100 μM of Capsaicin (CAP), plain TMCS NPs and CL-NPs as well as ethanol (control) for 24h and 48h. The induced effects were investigated by flow cytometry, immunocytochemistry assay for Bcl-2, Bax, and caspase proteins and evaluating gene expression levels of Bcl-2, Bax, and MDR-1 mRNA by real-time PCR. Results:: Our results demonstrated that capsaicin- loaded NPs had the potential to significantly increase capsaicin bioactivity compared with the plain capsaicin formulation either in inducing apoptosis through altering expression of apoptotic regulators or modifying MDR-1 expression. Conclusions:: TMCs nanoparticles investigated in this study may be a good drug delivery vehicle for capsaicin. Application of capsaicin-loaded NPs in HCC management as an adjunct therapeutic approach may be a novel strategy to improve the treatment efficacy and resistance of the conventionally used chemotherapy.

Background Human glucagon-like peptide-1 analogue, Liraglutide, has shown cardioprotective effects in animal and clinical studies of type 2 diabetes mellitus. This study was conducted to assess the effect of Liraglutide on diabetes-induced myocardial electrical remodeling. Materials and Methods A rat model of type 2 diabetes mellitus was induced by high-fat diet and low dose Streptozotocin (35 mg/kg). Diabetic rats were randomized into 4 subgroups (n=6–7): diabetic-untreated, diabetics treated with Liraglutide, diabetics treated with Ramipril, and diabetics treated with Metformin in addition to a control group. Changes in serum glucose, insulin, lipid profile and revised quantitative insulin sensitivity check index (QUICKI index) were assessed. QT and QTc intervals were measured and the degree of cardiac interstitial and perivascular fibrosis was examined. The expression of myocardial Ito channel α subunits, gap junction protein; Kv 4.2/4.3 and connexin 43 (Cx43) respectively, were assessed by western blotting and immunohistochemistry. Results Similar to Ramipril, both Liraglutide and Metformin effectively inhibited the diabetes-induced myocardial hypertrophy and fibrosis. However, Liraglutide treatment significantly improved Kv 4.2/4.3 and Cx43 expression/distribution and prevented diabetes-related QTc interval prolongation. Conclusions We have shown that pathological alterations in myocardial Cx43 expression and distribution, in addition to reduced Ito channel expression, may underlie the QTc interval prolongation in high-fat diet/STZ rat model of type 2 diabetes mellitus. The beneficial effects of Liraglutide, as those of Ramipril, on cardiac electrophysiology could be at least attributed to its direct ability to normalize expression and distribution of Cx43 and Ito channels in the diabetic rat heart.

Background: Adipokines are demonstrated to be associated with multiple cutaneous diseases. Leptin is mainly produced by the adipocytes that stem from the obese gene. In addition, it was reported that, secretion of leptin is a response to increased lipid uptake, thus, it might be regarded as a link between improper diet and the development of inflammatory acne. Objective: The aim of the current work wasto estimate serum leptin and adiponectin in both obese and non-obese patients with acne vulgaris and to evaluate adiponectin/leptin ratio (A/L) rates as a biomarker of insulin resistance and hence their role in pathogenesis of acne vulgaris in correlation with body weight and disease severity. Patients and methods: This prospective case-controlled study included a total of 60 patients with acne vulgaris, attending at the Dermatology, Andrology & STD Outpatient Clinic, Mansoura University Hospitals. Forty healthy subjects matched with the patients in age, sex were included. This study was conducted between April 2019 to January 2020. Results: Cases with acne vulgaris demonstrated significant increase in serum leptin level as well as significant decrease in serum adiponectin level compared to controls. No significant correlation was reported between both serum leptin and adiponectin levels and disease severity. Leptin could be used as reliable predictor in terms of the differentiation between cases of acne vulgaris and controls with high sensitivity, specificity and accuracy. Adiponectin could be used as reliable predictor in terms of the differentiation between cases of acne vulgaris and controls with high sensitivity, specificity and accuracy. Conclusion: Acne vulgaris was associated with significant elevation in leptin level, significant reduction in adiponectin level and significant decrease in A/L ratio. Thus, leptin, adiponectin and insulin resistance may be pathogenic cofactors contributing to the development of the disease and could be used as reliable predictors for development of acne vulgaris but not for severity of disease.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a suggested genetic basis. The newly identified human programmed cell death 1 gene could be associated with SLE susceptibility. We aimed to investigate the association between programmed cell death 1 polymorphism (PD1.3G/A (rs11568821) and PD1.5C/T (rs2227981)) with the risk of SLE in the Egyptian female population. This retrospective case–control study included 150 Egyptian females; 70 patients diagnosed to have SLE and 80 age-matched healthy controls. The two single nucleotide polymorphisms of the pdcd1 gene were genotyped by allelic discrimination through TaqMan real-time polymerase chain reaction. The PD1.3GG genotype and G allele as well as the PD1.5CC genotype were significantly more frequent in SLE patients (67.1%; p = 0.023, 82.1%; p = 0.0021, 62.9%; p = 0.0287 respectively). The GC haplotype was the most common haplotype among SLE patients (70.77%) with a reported significant linkage disequilibrium between the two studied polymorphisms ( p = 0.0041). Although most of the studies showed significant association of SLE with the minor alleles, we reported a significant association between the dominant genotypes (PD1.3GG and PD1.5CC) as well as the major G allele with the risk of SLE among Egyptian females.

Background Androgenetic alopecia (AGA) is associated with a risk of coronary heart disease (CHD), although the causes underlying this association are not clear. Serum homocysteine (SH) is a known risk factor for CHD, and methylene tetrahydrofolate reductase enzyme (MTHFR) plays a crucial role in the remethylation of homocysteine to methionine. The polymorphism C677T that affects the catalytic domain of the MTHFR protein leads to a high levels of SH. Our hypothesis was that this polymorphism and SH level are risk factors for CHD in patients with AGA. Materials and methods A total of 106 patients with AGA and 100 well-matched healthy controls were enrolled in the study. SH levels were estimated. DNA was extracted and polymerase chain reaction amplification, followed by restriction enzyme digestion for MTHFR (C677T) gene, was conducted. Results SH levels were significantly higher in the patient group and highest in those with the TT genotype. The mutant T allele was associated with hyperhomocysteinemia and an increased risk of CHD in patients with AGA. Conclusions AGA is associated with a higher risk of developing CHD due to the associated higher level of SH that, in turn, depends on and is correlated with mutant MTHFR genotypes. Cardiac evaluation and follow-up of patients with AGA is recommended for early detection and treatment of CHD to avoid an overall detrimental course.

Introduction: Male factor is responsible for about half of infertility problems. However, the reasons for the decrease in male fertility are still broadly unclear. The mechanisms of how smoking may impact male fertility have not been established. However, with its influence on different semen parameters, it is regarded as a risk factor for infertility.Aim: To investigate the effect of chronic smoking on spermatozoa NRF2 expression and DNA fragmentation in infertile men with apparently normal seminogram and to determine if NRF2 expression and DNA fragmentation markers could be possible predictors of the impact of chronic cigarette smoking on male fertility.Methods: Semen samples were collected from 170 subjects; 65 nonsmokers (40 fertile and 25 infertile) and 105 smokers (25 fertile and 80 infertile). NRF2 gene expression, 8-OHdG and DNA fragmentation were assayed.Results: There were significant increases in 8-OHdG and %DNA fragmentation with a significant decrease in NRF2 gene expression in infertile smokers. ROC curve analysis of spermatozoa NRF2 gene expression showed 95% sensitivity 93.3% specificity at cutoff value ≤0. 931 (p 19.33 pg/ml predicting the detrimental effect of smoking on spermatozoa DNA.Conclusion: Chronic cigarette smoking may be a hidden causative mechanism of delayed fertility. Spermatozoa NRF2 gene expression and seminal 8-OHdG levels may serve as sensitive diagnostic indicators predicting smoking induced infertility. So, the presence of normal seminal parameters could not be an exclusion of potential effect of chronic smoking on male fertility.

Polycystic ovary syndrome (PCOS) is associated with oxidative stress (OS) and serum superoxide dismutase (SOD) activity has been reported with mixed results. The objective of this study was to examine the activity of SOD both in the serum and FF from women with PCOS undergoing ICSI, as well as the expression of Cu/Zn-SOD mRNA in the cells recovered from the FF.Forty women undergoing an ICSI trial were divided into: group I, included 20 PCOS cases, group II included 20 age-matched controls with tubal factor infertility. Both groups were similarly stimulated. A total of 204 metaphase II (MII) oocytes were aspirated; (108) from PCOS, and (96) from the control group. SOD activities in the serum and FF, as well as Cu/Zn-SOD (SOD1) mRNAs in follicular fluid (FF) cells were analyzed.There was a statistically highly significant decrease (p 0.001) both in the mean serum SOD (45.56 ± 18.06) and FF SOD activity (42.49 ± 11.46) in PCOS than the control group (77.38 ± 7.82), (74.37 ± 6.15) respectively. The mean relative levels of Cu, Zn SOD mRNAs was significantly lower (p 0.001) in cells isolated from the FF in PCOS (0.36 ± 0.14) than the control group (0.81 ± 0.15). SOD activity in FF had no effects on fertilization rate (p 0.05), or embryo quality after intracytoplasmic sperm injection (ICSI).Although decreased SOD activity in FF has no effect on fertilization rate and/or embryo quality, serum SOD activity could be a clinical parameter for determining systemic oxidative stress in PCOS.

Matrix metalloproteinase-9 is closely associated with the invasive and metastatic potential of most types of solid cancers. Our objective was to investigate the MMP-9 expression in lung cancer and to evaluate their relations to histopathologic types and prognosis.Bronchoscopic samples were obtained from tumor and normal bronchial mucosa in 25 patients with lung cancer. Total RNA was isolated from the tissues, and the relative expression as well as the activity of MMP-9 was evaluated.Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) showed significantly higher MMP-9 expression (P0.0001) compared with normal tissues. MMP-9 activity in tissue and serum samples from both cancer groups were significantly higher than normal tissue and serum controls (P0.0001). Also, MMP-9 expression and tissue and serum activity were significantly higher in NSCLC than in SCLC (P=0.0167, 0.0454, and 0.004, respectively). As regards the pathologic types of NSCLC, similar results were found for the adenocarcinoma subgroup versus squamous cell lung cancer (P=0.0015, 0.0052, and 0.0011, respectively). MMP-9 expression and tissue activity were higher in stage III-IV NSCLC cases compared with early tumor stages (P=0.0120 and 0.0271, respectively).The expression and activity of MMP-9 are upregulated in NSCLC and are related to the pathologic type and clinical stage of NSCLC. Significantly higher expression and activity of MMP-9 in tumor tissue than in the surrounding tissue supports the important role of this metalloproteinase in the growth of lung cancer, and it could be used as a suggested therapeutic target.

Seminal quality could be affected by metallosis caused by intramedullary nailing (IMN). Our objectives were to estimate metal ion levels in the seminal plasma of subjects with IMN, to determine their effects on semen parameters and on spermatozoal apoptotic gene expression, and to determine whether these expressed genes could be used as candidate biomarkers of seminal deterioration in individuals with IMN or not. Semen samples were collected from 60 subjects with IMN and 30 age-matched healthy controls. Seminal plasma contents of cobalt (Co), chromium (Cr), and molybdenum (Mo) were assayed. Spermatozoal Bcl-2 and Bax gene expressions were determined. Studied semen parameters were significantly lower in subjects with IMN for ≥5 years in relation to controls while the concentrations of Co, Cr, and Mo in the seminal plasma samples were significantly higher. There were significantly lower spermatozoal Bcl-2 expression, higher Bax expression, and lower Bcl-2/Bax ratio in subjects with IMN for ≥5 years than in controls. In subjects with IMN for ≥5 years, receiver operating characteristic (ROC) curve analysis of studied gene expressions and Bcl-2/Bax ratio were done showing priority of the ratio with 86.7 % sensitivity, 100 % specificity, 100 % positive predictive value, and 93.8 % negative predictive value at cutoff values ≤0.777. Co, Cr, and Mo metals are found at high concentrations in the seminal plasma of individuals with IMN leading to increased spermatozoal apoptotic activity. Spermatozoal Bcl-2/Bax ratio could be used as a candidate biomarker of reproductive disorders in individuals with intramedullary nailing.

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy characterized by its high resistance to chemotherapeutic agents leading to high morbidity and mortality rates. Capsaicin, the active ingredient of hot peppers, has been reported for its potential as an active anti-cancer agent. In this study, we hypothesized that incorporating capsaicin into nanocarriers might improve its pharmacokinetics. As a result, densely dispersed capsaicin-loaded trimethyl-chitosan nanoparticles (CL-NPs) were developed and their anti-tumor effect was investigated in comparison with capsaicin on human HepG2 cells. The CL-NPs were obtained via iontropic gelation of cationic trimethyl chitosan (TMCS). Both synthesized TMCS and TMCS-based nanoparticles were characterized using zeta analyzer, nanosizer, and TEM. Human hepatoma cell line (HepG2) were cultured then divided into 4 groups receiving ethanol, conventional capsaicin, plain nanoparticles (PNs), or CL-NPs in dose of 100 μM. The apoptotic activity in the cell line was evaluated by DNA fragmentation assay, immunocytochemistry for caspase-3 and BCL-2, in addition to gene expression studies of BCL-2, and Bax genes via RT-PCR. The capsaicin effect on HCC response to chemotherapy was also assessed by studying the level of MDR-1 (multidrug resistance) gene expression. CL-NPs in dose of 100 μM, 24 h after treatment, showed more upregulation of Bax and downregulation of both BCL-2 and MDR-1 genes in comparison with conventional capsaicin. In addition, immunocytochemistry assay revealed that both capsaicin and plain NPs show higher expression of caspase-3 and lower expression of BCL-2 than the control group, while the group treated with CL-NPs showed complete necrosis. This indicates that plain TMCS nanoparticles had a little anti-apoptotic effect by themselves. Our findings highlight the potential of the developed CL-NPs as an effective anti-cancer agent which efficiently induced apoptosis in human HepG2 hepatocarcinoma cells. Moreover, a possible role in improving response to chemotherapy has been observed through downregulation of MDR-1 gene.

CLU is a disulfide linked, heterodimeric protein associated with the clearance of cellular debris and apoptosis. We assessed the association of seminal CLU gene expression with seminal variables in fertile and infertile men.A total of 124 men were divided into healthy, fertile men with normozoospermia, and men with asthenozoospermia, asthenoteratozoospermia and oligoasthenoteratozoospermia. History was obtained, and clinical examination and semen analysis were done. In semen we assessed sperm acrosin activity, sperm DNA fragmentation and seminal CLU gene expression.CLU RNA and CLU protein gene expression were significantly increased in semen samples of infertile men with oligoasthenoteratozoospermiaasthenoteratozoospermiaasthenozoospermia compared with healthy, fertile controls. CLU gene expression significantly correlated negatively with sperm count, motility, acrosin activity index, linearity index and linear velocity, and significantly correlated positively with the percent of sperm abnormal forms and DNA fragmentation.CLU gene expression was significantly increased in the semen samples of infertile men. It correlated negatively with sperm count, motility, acrosin activity, linearity index and linear velocity, and positively with the percent of sperm abnormal forms and DNA fragmentation.

Background Use of cellular phones emitting radiofrequency electromagnetic field (RF-EMF) has been increased exponentially and become a part of everyday life. This study aimed to investigate the effects of in vitro RF-EMF exposure emitted from cellular phones on sperm motility index, sperm DNA fragmentation and seminal clusterin (CLU) gene expression. Materials and Methods In this prospective study, a total of 124 semen samples were grouped into the following main categories: i. normozoospermia (N, n=26), ii. asthenozoospermia (A, n=32), iii. asthenoteratozoospermia (AT, n=31) and iv. oligoasthenoteratozoospermia (OAT, n=35). The same semen samples were then divided into two portions non-exposed and exposed samples to cell phone radiation for 1 hour. Before and immediately after exposure, both aliquots were subjected to different assessments for sperm motility, acrosin activity, sperm DNA fragmentation and CLU gene expression. Statistical differences were analyzed using paired t student test for comparisons between two sub-groups where p < 0.05 was set as significant. Results There was a significant decrease in sperm motility, sperm linear velocity, sperm linearity index, and sperm acrosin activity, whereas there was a significant increase in sperm DNA fragmentation percent, CLU gene expression and CLU protein levels in the exposed semen samples to RF-EMF compared with non-exposed samples in OAT>AT>A>N groups, respectively (p < 0.05). Conclusion Cell phone emissions have a negative impact on exposed sperm motility index, sperm acrosin activity, sperm DNA fragmentation and seminal CLU gene expression, especially in OAT cases.