Pharmacological evaluation of some novel synthesized compounds derived from spiro(cyclohexane-1,2′-thiazolidines)

A series of novel spiro(cyclohexane-1,2′-thiazolidine) derivatives 1–5 and spiro(cyclohexane1,2′-thiazolo-pyridine) derivatives 6–14 were synthesized. Arylidene thiazolidine derivative 2b was reacted with hydroxylamine hydrochloride, hydrogen peroxide or ethyl cyanoacetate to give spiro(cyclohexane-1,2′-thiazolidine), and spiro(cyclohexane-1,2′-thiazole) derivatives 15–17. Moreover, some of the newly prepared products were screened for their antibacterial, antioxidant, and anticancer activities, and some of them showed moderate to good biological activities. The results showed that the compounds 9, 7a, and 8 have the highest antioxidant activity (92.52, 85.00, and 84.61 %, respectively at 100 μg/mL) when compared with butylated hydroxyl toluene as a standard (93.6 %). Also, the compound 9 showed the highest anticancer activity against two cell lines (MCF-7 and HepG2).     

Design,synthesis, and molecular modeling of heterocyclic bioisostere as potent PDE4 inhibitors

A new hybrid template was designed by combining the structural features of phosphodiesterase 4 (PDE4) inhibitors with several heterocyclic moieties which present an integral part in the skeleton of many apoptotic agents. Thirteen compounds of the synthesized hybrids displayed higher inhibitory activity against PDE4B than the reference drug, roflumilast. Further investigation indicated that compounds 13b and 20 arrested the cell cycle at the G2/M phase and the pre‐G1 phase, and induced cell death by apoptosis of A549 cells in a caspase‐dependent manner.

     

Genotype analysis of T. gondii strains associated with human infection in Egypt

The distribution of Toxoplasma gondii genotypes varies from one geographic area to another. The present study aimed to determine T. gondii genotypes associated with human infection in Egypt. Individuals seropositive for anti-toxoplasma IgG and IgM (group I, n?=?50) or for specific IgG only (group II, n?=?50) were enrolled. Of the participants, 75 % were asymptomatic pregnant women. The others presented with lymphadenitis (n?=?21), chorioretinitis (n?=?3), and unexplained hepatomegaly (n?=?1). Using nested PCR, T. gondii GRA6-coding fragment was amplified from DNA extracted from blood samples of participants. Amplification was successful in 12 samples with nonsignificant difference between both groups but with a significant association with the presence of toxoplasmosis-related manifestations. Restriction fragment length polymorphism analysis of these samples revealed the presence of type I in seven samples and atypical types in five samples. Both typical and atypical strains were detected in individuals of both groups with no bias towards specific clinical presentation.     

Schistosomiasis Does Not Affect the Outcome of HCV Infection in Genotype 4-Infected Patients

Although reports suggest that Schistosoma mansoni increases hepatitis C virus (HCV) morbidity and chronicity, its impact on HCV spontaneous resolution is not clear. HCV genotype, viral load, abdominal ultrasonographic findings, and HCV-specific cell-mediated immunity (CMI) were examined among 141 healthcare workers infected with HCV (68 workers with and 73 workers without S. mansoni). HCV genotype 4 was dominate, and viral loads were 2.62 ± 0.69 × 10⁶ and 4.24 ± 1.4 × 10⁶ IU/mL among patients with and without coinfection, respectively (P = 0.309); 23.5% with and 32.9% without coinfection had spontaneously resolved HCV infection (P = 0.297). Interferon-γ spot-forming cells/10⁶ peripheral blood mononuclear cells among responding viremic patients with and without coinfection were 716 ± 194 and 587 ± 162, whereas among aviremic patients, it was 794 ± 272 and 365 ± 36 (P > 0.05), respectively. In conclusion, there was no statistical difference in HCV spontaneous resolution, viral load, liver pathology, or CMI in patients with or without S. mansoni coinfection, suggesting that it did not impact the outcome of HCV infection.     

Impacts of n-acetyl cysteine on gibberellic acid-induced testicular dysfunction through regulation of inflammatory cytokines,steroid and antioxidant activity

In agriculture, gibberellic acid (GA3) is commonly used with extreme dangers for public health. The current research evaluates the improving effects of n-acetyl cysteine (NAC, 150 mg/kg bw) co-administered with GA3 (55 mg/kg bw) mediated testicular injury. Twenty-four male albino rats were split into 4 groups: Negative control (CNT), NAC group, positive GA3 group and protective group, co-administered NAC plus GA3. On day 21, rats were anesthetised then euthanised by decapitation. Blood samples were collected; testicular samples were taken for semen analysis, serum chemistry, RNA extraction, histological and antioxidants markers examination. Our results revealed a significant decline p < .05 of catalase level and total antioxidant capacity. There was a substantial rise of MDA concentration in GA3-treated rats along with a considerable decrease of the antioxidant markers (SOD, GSH) and serum male reproductive hormones. In GA3-treated rats, an overexpression of the inflammatory cytokines (TNF-α, IL-1β) and anti-inflammatory cytokine IL-10 with boost mRNA expression of nuclear factor-kappa (NF_kB) were confirmed. There was downregulation of steroidogenesis genes and decrease in sperm quality and concentration with an increase in sperm abnormalities, all were reported in GA3-treated rats. NAC treatment significantly increased the antioxidant state, testicular function beside structural germ cell and seminiferous tubules histology accompanied by upsurge of steroidogenic mRNA expressions (P450scc and 3β-HSD) and downregulated the pro-inflammatory cytokines mRNA expression (TNF-α, IL-1β). These results confirm the antioxidant capability of NAC and afford robust evidence about the ameliorative effect of the NAC to attenuate the testicular injury induced by GA3 through modulation of the antioxidant defence system, steroidogenic and pro-inflammatory cytokines mRNA expression.