Role of IL-28B polymorphisms in virologic response to combined pegylated interferon and ribavirin therapy in genotype 4 chronic HCV infected patients with and without cirrhosis

Background: Chronic hepatitis C virus (HCV) represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. The rs12979860 CC genotype of the interleukin 28B (IL28B) polymorphisms is associated with high rates of sustained virological response to pegylated interferon and ribavirin in HCV genotype-1 patients. Data on other genotypes are more limited.Objective: We aim to evaluate the predictive power of the rs12979860 IL28B single nucleotide  polymorphisms for treatment response at 3 and 6 months in chronic HCV genotype 4 Egyptian patients in relation to other predictors.Patients and methods: The study included 60 chronic HCV Egyptian patients receiving pegylated interferon and ribavirin therapy. Patients were classified into 2 groups; 30 patients with compensated cirrhosis, and 30 patients without cirrhosis. We analyzed selected pretreatment factors such as age, sex, HCV viral load, anti-schistosomal antibodies, insulin resistance, alpha fetoprotein, low and high density lipoproteins and single nucleotide polymorphisms of IL28B and tried to find out which of them influence sustained virological response.Results: In univariate analysis, CC genotype showed a significant association with sustained virological response at 6 months among the cirrhotic patients (81.8% responders had the CC genotype, 58.3% had the CT/TT genotype) (p= 0.009). While in multivariate analysis, the presenceKEYWORDS: HCV; IL28B; Polymorphism; Interferon; Schistosomiasis; Respons

Selected morphological changes in nauplii of brine shrimp (Artemia salina) after tributyltin chloride (TBTCl) exposure

Early life stage of organisms is a critical period because it is very sensitive to changes that occur in the surrounding. The present study aimed to determine the lethal concentration 50 (LC) and identify 50 morphological changes of brine shrimp (Artemia salina) nauplii exposed to tributyltin chloride (TBTCl) after 24hr exposure. Results showed the LC of TBTCl for A. salina nauplii was 469.08 ng.L. Significant differences 50 1 were discovered in the morphology of nauplii in control and those exposed. The nauplii underwent prominent abnormal growth in total length, head width, abdominal width and tail width. Other abnormalities included improper development of mandibles, underdeveloped endopod and endite, as well as swimming site in the second pair of antenna. These results indicated that TBTCl is an environmentally toxic substance with negative effects on non-target organism. Therefore, further in-depth investigation should be conducted to establish A. salina as a bioindicator for TBTCl contamination

Median lethal concentration (LC50) and morphological effects of tributyltin chloride (TBTCl) on male and female Artemia salina

Elevation of tributyltin (TBT) compounds in marine environment could affect organisms at any life stages. The present study aimed to determine median lethal concentration (LC50) and morphological effects of tributyltin chloride (TBTCl) on adult males and females of brine shrimp (Artemia salina). Individuals of adult males and females of A. salina were exposed to different concentrations of TBTCl. Morphological conditions of every A. salina individuals were observed under a microscope. Results showed the LC50 of TBTCl toxicity in male A. salina was 146.99 ngL-1 and for the female was 94.72 ngL-1. The LC50 of TBTCl was significantly different among different sexes. There was also a significant difference in some morphological characters of males and females exposed to different TBTCl concentrations. These morphological changes include their total length, head width, abdominal width, and tail width after the 24 h exposure to TBTCl. These results suggested that suspensions of the TBTCl were toxic to Artemia, most likely due to the formation of benign TBTCl aggregates in water. However, the mortality increased with extended exposure to 24 h. Highest mortality occurred at 200 ngL-1 TBTCl; 43.33% for male and 90% for female (LC50 < 150 ngL-1) for both. Depended on these findings, the female was more sensitive for TBTCl toxicity test when compared to male. These effects were attributed to changes in morphological characteristics of the body A. salina

Mechanism of Dinitrochlorobenzene-Induced Dermatitis in Mice: Role of Specific Antibodies in Pathogenesis

Dinitrochlorobenzene-induced contact hypersensitivity is widely considered as a cell-mediated rather than antibody-mediated immune response. At present, very little is known about the role of antigen-specific antibodies and B cells in the development of dinitrochlorobenzene-induced hypersensitivity reactions, and this is the subject of the present investigation.Data obtained from multiple lines of experiments unequivocally showed that the formation of dinitrochlorobenzene-specific Abs played an important role in the development of dinitrochlorobenzene-induced contact hypersensitivity. The appearance of dinitrochlorobenzene-induced skin dermatitis matched in timing the appearance of the circulating dinitrochlorobenzene-specific antibodies. Adoptive transfer of sera containing dinitrochlorobenzene-specific antibodies from dinitrochlorobenzene-treated mice elicited a much stronger hypersensitivity reaction than the adoptive transfer of lymphocytes from the same donors. Moreover, dinitrochlorobenzene-induced contact hypersensitivity was strongly suppressed in B cell-deficient mice with no DNCB-specific antibodies. It was also observed that treatment of animals with dinitrochlorobenzene polarized Th cells into Th2 differentiation by increasing the production of Th2 cytokines while decreasing the production of Th1 cytokines.In striking contrast to the long-held belief that dinitrochlorobenzene-induced contact hypersensitivity is a cell-mediated immune response, the results of our present study demonstrated that the production of dinitrochlorobenzene-specific antibodies by activated B cells played an indispensible role in the pathogenesis of dinitrochlorobenzene-induced CHS. These findings may provide new possibilities in the treatment of human contact hypersensitivity conditions

Marine Cyanobacteria Compounds with Anticancer Properties: Implication of Apoptosis

Marine cyanobacteria have been proved to be an important source of potential anticancer drugs. Although several compounds were found to be cytotoxic to cancer cells in culture, the pathways by which cells are affected are still poorly elucidated. For some compounds, cancer cell death was attributed to an implication of apoptosis through morphological apoptotic features, implication of caspases and proteins of the Bcl-2 family, and other mechanisms such as interference with microtubules dynamics, cell cycle arrest and inhibition of proteases other than caspases

Identification and Bioactivity of Compounds from the Fungus Penicillium sp. CYE-87 Isolated from a Marine Tunicate

In the course of our continuous interest in identifying bioactive compounds from marine microbes, we have investigated a tunicate-derived fungus, Penicillium sp. CYE-87. A new compound with the 1,4-diazepane skeleton, terretrione D (2), together with the known compounds, methyl-2-([2-(1H-indol-3-yl)ethyl]carbamoyl)acetate (1), tryptamine (3), indole-3-carbaldehyde (4), 3,6-diisobutylpyrazin-2(1H)-one (5) and terretrione C (6), were isolated from Penicillium sp. CYE-87. The structures of the isolated compounds were established by spectral analysis, including 1D (1H, 13C) and 2D (COSY, multiplicity edited-HSQC and HMBC) NMR and HRESIMS, as well as comparison of their NMR data with those in the literature. The compounds were evaluated for their antimigratory activity against the human breast cancer cell line (MDA-MB-231) and their antiproliferation activity against HeLa cells. Compounds 2 and 6 showed significant antimigratory activity against MDA-MB-231, as well as antifungal activity against C. albicans

Bioactive 2(1H)-Pyrazinones and Diketopiperazine Alkaloids from a Tunicate-Derived Actinomycete Streptomyces sp.

As a part of our ongoing effort to allocate marine microbial bioactive leads, a tunicate-derived actinomycete, Streptomyces sp. Did-27, was investigated. Three new 2(1H)-pyrazinones derivatives, (S)-6-(sec-butyl)-3-isopropylpyrazin-2(1H)-one (1), (S)-3-(sec-butyl)-6-isopropylpyrazin-2(1H)-one (2) and (S)-6-(sec-butyl)-3-isobutylpyrazin-2(1H)-one (3), together with the known (1H)-pyrazinones analogues deoxymutaaspergillic acid (4), 3,6-diisobutyl-2(1H)-pyrazinone (5) and 3,6-di-sec-butyl-2(1H)-pyrazinone (6), and the diketopiperazine alkaloids cyclo(6-OH-d-Pro-l-Phe) (7), bacillusamide B (8), cyclo(l-Pro-l-Leu) and cyclo(l-Pro-l-Ile) (10) were isolated from this strain. The structures of the compounds were determined by study of their one- and two-dimensional NMR spectra as well as high-resolution mass spectral determinations. Compound 4 was reported previously as a synthetic product, while compound 6 was reported as 2-hydroxy-3,6-di-sec-butylpyrazine. Herein, we report the complete NMR data for compounds 4 and 6. The compounds were evaluated for their cytotoxic activities against three cell lines. Compound 5 showed potent and selective activity against HCT-116 cell line with IC50 of 1.5 μg/mL, while 1–10 showed variable cytotoxic activities against these cancer cell lines. These results provide further understanding about the chemistry and bioactivities of the alkylated 2(1H)-pyrazinone derivatives

Identification and Bioactivity of Compounds from the Fungus Penicillium sp. CYE-87 Isolated from a Marine Tunicate

In the course of our continuous interest in identifying bioactive compounds from marine microbes, we have investigated a tunicate-derived fungus, Penicillium sp. CYE-87. A new compound with the 1,4-diazepane skeleton, terretrione D (2), together with the known compounds, methyl-2-([2-(1H-indol-3-yl)ethyl]carbamoyl)acetate (1), tryptamine (3), indole-3-carbaldehyde (4), 3,6-diisobutylpyrazin-2(1H)-one (5) and terretrione C (6), were isolated from Penicillium sp. CYE-87. The structures of the isolated compounds were established by spectral analysis, including 1D (1H, 13C) and 2D (COSY, multiplicity edited-HSQC and HMBC) NMR and HRESIMS, as well as comparison of their NMR data with those in the literature. The compounds were evaluated for their antimigratory activity against the human breast cancer cell line (MDA-MB-231) and their antiproliferation activity against HeLa cells. Compounds 2 and 6 showed significant antimigratory activity against MDA-MB-231, as well as antifungal activity against C. albicans