Acetazolamide loaded-silver nanoparticles: A potential treatment for murine trichinellosis.

Trichinellosis is a global food-borne disease caused by viviparous parasitic nematodes of the genus Trichinella. Due to the lack of effective, safe therapy and the documented adverse effects of traditional therapy, this study aimed to evaluate the therapeutic effect of acetazolamide-loaded silver nanoparticles (AgNPs) on murine trichinellosis. Fifty male Swiss albino mice were divided into five groups of ten mice each: Group I, normal control group; Group II, infected with T. spiralis and not treated; Group III, infected and given AgNPs; Group IV, infected and treated with acetazolamide; and Group V, infected and treated with acetazolamide-loaded AgNPs. Mice were infected orally with 250 larvae. The efficacy was assessed by counting T. spiralis adults and larvae, measuring serum total antioxidant capacity, and observing the histopathological and ultrastructural alterations. Acetazolamide-loaded AgNPs treatment exhibited the highest percentage of reduction (84.72% and 80.74%) for the intestinal adults and the muscular larvae of T. spiralis-infected animals, respectively. Furthermore, during the intestinal and muscular phases, the serum of the same group had the best free-radical scavenging capacity (antioxidant capacity), which reduced tissue damage induced by oxidative stress. Histopathologically, the normal intestinal and muscular architecture was restored in the group treated with acetazolamide-loaded AgNPs, in addition to the reduced inflammatory infiltrate that alleviated inflammation compared to infected animals. Our results confirmed the marked destruction of the ultrastructural features of T. spiralis adults and larvae. Acetazolamide-loaded AgNPs are a promising therapy against T. spiralis infection.

Vorinostat induces G2/M cell cycle arrest in breast cancer cells via upregulation of PTEN.

OBJECTIVE: Breast cancer (BC) is the most common type of cancer in females worldwide. Various approaches were proposed to treat the disease, with no sole agent proved efficient. Thus, understanding the molecular mechanisms of different drugs became mandatory. The present study aimed at evaluating the role of erlotinib (ERL) and vorinostat (SAHA) in inducing apoptosis in breast cancer cells. The role of these drugs was assessed also on the expression profile of some cancer-related genes; PTEN, P21, TGF, and CDH1. MATERIALS AND METHODS: In the present study, breast cancer cells (MCF-7) and MDA-MB-231 along with human amniotic cells (WISH) were treated with two concentrations (50, and 100 µM) of erlotinib (ERL) and vorinostat (as known as SAHA) for 24 h. Cells were harvested for downstream analysis. DNA content and apoptosis were analyzed by flow cytometer, and qPCR was performed to assess the expression of different cancer-related genes. RESULTS: The results indicated that ERL and SAHA arrested both breast cancer cells at the G2/M phase after 24 h compared to normal cells and control. For apoptosis, BC cells showed an elevated level of total apoptosis (early and late) increasing the concentrations of the two applied drugs, with the most effective concentration of ERL at 100 µM in the 24-h treatment. In the control cells, SAHA was proved to be the most effective drug at a concentration of 100 µM with a percentage of apoptosis ranging from 1.7-12% in the 24-h treatment. Necrosis also was dose-dependent in the two breast cancer cell lines used. We further evaluated the expression profiles of PTEN, P21, TGF-ß, and CDH1. In MCF-7, data indicated that for TGF-ß, PTEN, and P21, the most effective treatment was SAHA at a concentration of 100 µM, while for CDH1, the most effective concentration was ERL at 100 µM. A similar profile was observed in MDA-MB-232, where for TGF-ß, PTEN, and P21, the most effective treatment was SAHA at a concentration of 100 µM, while for CDH1, the most effective concentration was SAHA at 50 µM. CONCLUSIONS: Our results shed some light on the role of ERL and SAHA in regulating the expression of cancer-related genes, though these data need further investigation.

Glutathione and its related enzymes in the gonad of Nile Tilapia (Oreochromis niloticus).

Glutathione (GSH) concentration, the activity of its metabolizing enzymes, glutathione transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), and the antioxidant enzyme catalase (CAT) in O. niloticus ovary and testis were examined. GSH concentration of O. niloticus testis exhibited high concentration (129 ± 21 nmol/g tissue) compared with GSH concentration (49.2 ± 8.3 nmol/g tissue) in the ovary. GST, GPx, GR, and CAT activities of O. niloticus testis exhibited high values compared with their corresponding values in ovary homogenates. However, protein concentration in ovary homogenates exhibited higher values (175 ± 40.6 mg) compared with testis homogenates (27.1 ± 3.7 mg). O. niloticus ovary was less effective in excretion of xenobiotices compared with the testis, where its function is mainly in increasing the protein content of the eggs; however, in O. niloticus testis, the glutathione cycle operated in accelerated way in the direction of reduced GSH production in order to protect the maturation stages in a save way. A simple reproducible procedure for the purification of GST from O. niloticus ovary was established. The enzymes proved to be homogenous as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and its molecular weight was calculated to be 25.1 kDa. GST of O. niloticus ovary exhibited maximum activity at pH 7.5. The Michaelis-Menten constant (K(m)) of the purified ovary GST for GSH and CDNB was 0.076 mM and 1.0 mM, respectively. Cibacron blue was the most potent inhibitor of ovary GST activity (IC50 value, concentration of inhibitor that will give 50% inhibition, equal 0.002 µM). The specific activity of GST toward different electrophilic substrates was determined. GST activity toward benzyl isothiocyanate was the highest compared with phenethyl isothiocyanate and allyl isothiocyanate.

High prevalence of diabetes mellitus in a cohort of Trinidadian patients with chronic obstructive pulmonary disease

OBJECTIVE: To define the prevalence of diabetes mellitus (DM) in a cohort of Trinidadian chronic obstructive pulmonary disease (COPD) patients, and investigate its relationship to lung function, quality of life, and depression. DESIGN AND METHODS: Anthropometric and spirometric data were obtained from 108 COPD (91 males) patients from Trinidad chest clinics, who also had HbA1c test results. Questionnaires on quality of life St. George’s Respiratory questionnaire ({SGRQ} and COPD Assessment Test {CAT}) and depression (Center for Epidemiologic Studies Depression Scale {CES-D & CESD-R}) were administered, and an interview conducted. RESULTS: Mean (SD) age: 67.4 (11.0) years. Median (IQR) HbA1c: 6.1 (5.7, 6.7) %. HbA1c values were obtained for 105 patients of whom 40% had diabetes, and 40% pre-diabetes. Diabetics had a greater (p=0.001) median (IQR) BMI [27.3 (24.1, 30.4)] than non-diabetics [24.2 (21.2, 27.2)]. Patients with at least one chest infection/exacerbation in the past year had increasing CAT & SGRQ Total (p<0.001), and CES-D & CESD-R (p≤0.013) scores. CAT and SGRQ total scores were negatively related to lung function and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages (p<0.001). All lung function parameters, except Forced expiratory volume/Forced vital capacity (FEV1/FVC), decreased with increasing CES-D and CESD-R scores (p<0.05). CAT & SGRQ correlated well with CES-D & CESD-R scores (p<0.001). Intravenous corticosteroid use was positively associated with HbA1c (p=0.043). Dosage of inhaled corticosteroids was associated with lower FEV1 (p=0.034) and higher SGRQ & CAT (p≤0.048). FVC % predicted was negatively related to HbA1c (p=0.033). CONCLUSION: The prevalence of DM in the COPD patients was 40%; however no significant correlations of DM to outcome measures were observed. Patients with worse quality of life due poor lung function were more depressed.

A novel calcium/calmodulin-regulated kinesin-like protein is highly conserved between monocots and dicots.

Recently, a novel kinesin-like protein (KCBP) that is regulated by Ca2+/calmodulin was isolated from dicot plants. A homolog of KCBP has not been reported in monocots. To determine if this motor protein is present in phylogenetically divergent flowering plants, Arabidopsis KCBP cDNA was used as a probe to screen a genomic library of maize, an evolutionarily divergent species. This screening resulted in isolation of a KCBP homolog. Comparison of the predicted amino acid sequence of the KCBP from maize (ZmKCBP), a monocot, with the previously reported KCBP sequences from dicot species showed that the amino acid sequence, domain organization, and gene structure are highly conserved between monocots and dicots. The C-terminal region of ZmKCBP, containing the motor domain and the calmodulin-binding domain, and the N-terminal tail, with a myosin tail homology region (MyTH4) and talin-like region, showed strong sequence similarity to the KCBP homolog from dicots. However, the coiled-coil region is less conserved between monocots and dicots. The ZmKCBP gene contained 22 exons and 21 introns. The location of 19 of the 21 introns of ZmKCBP is also conserved. The ZmKCBP protein is encoded by a single gene and expressed in all tissues. Affinity-purified antibody to the calmodulin-binding domain of Arabidopsis KCBP detected a protein in both the soluble and the microsomal fractions. The C-terminal region of ZmKCBP, containing the motor and calmodulin-binding domains, bound calmodulin in the presence of calcium and failed to bind in the presence of EGTA. The ZmKCBP, along with other KCBPs from dicots, was grouped into a distinct group in the C-terminal subfamily of kinesin-like proteins. These data suggest that the KCBP is ubiquitous and highly conserved in all flowering plants and the origin of KCBP predated the divergence of monocots and dicots.