Synthesis and biological evaluation of some heterocyclic compounds

Cancer is one of the most striking diseases that has a potential impact on human health with high mortality rate. During the last century many anticancer agents have emerged but unfortunately, these agents could not provide effective solutions for cancer treatment due to side effects and resistance. All over the world, asking for new anticancer agents is still a major goal for medicinal chemists. Pyrrole and pyrrolo[2,3-d]pyrimidine scaffolds are very interesting bioactive core exhibiting several biological activities as anticancer, anti-inflammatory, antimicrobial activities. Herein, we highlighted on the anticancer activity of the pyrrole and pyrrolo[2,3-d]pyrimidine derivatives which are reported to possess anticancer activity and many of them are in market or still in clinical trials. This work deals with design and synthesis of new pyrrole and pyrrolopyrimidine derivatives. The new compounds were screened for their cytotoxic activity against HepG2 and MCF7in vitro. The most active compounds were evaluated for their VEGFR-2 inhibition in vitr

Advanced intra-tumoural structural characterisation of hepatocellular carcinoma utilising FDG-PET/CT : a comparative study of radiomics and metabolic features in 3D and 2D

Purpose: The aim of our work is to evaluate the correlation of two-dimensional (2D) and three-dimensional (3D) radiomics and metabolic features of hepatocellular carcinoma (HCC) with tumour diameter, staging, and metabolic tumour volume (MTV). Material and methods: Thirty-three patients with HCC were studied using 18F-fluorodeoxyglucose positron-emission tomography with computed tomography (18F [FDG] PET/CT). The tumours were segmented from the PET images after CT correction. Metabolic parameters and 35 radiomics features were compared using 2D and 3D modes. The metabolic parameters and tumour morphology were compared using 2 different types of software. Tumour heterogeneity was studied in both metabolic parameters and radiomics features. Finally, the correlation between the metabolic and radiomics features in 3D mode, as well as tumour morphology and staging according to the American Joint Committee on Cancer (AJCC) staging were studied. Results: Most of the metabolic parameters and radiomics features are statically stable through the 2D and 3D modes. Most of the 3D mode features show a correlation with metabolic parameters; the total lesion glycolysis (TLG) shows the highest correlation, with a Spearman correlation coefficient (rs) of 0.9776. Also, the grey level run length matrix/ run length non-uniformity (GLRLM_RLNU) from radiomics features exhibits a correlation with a Spearman correlation coefficient of 0.9733. Maximum tumour diameter is correlated with TLG and GLRLM_RLNU, with rs equal to 0.7461 and 0.7143, respectively. Regarding AJCC staging, some features show a medium but prognostic correlation. In the case of 2D-mode features, all metabolic and radiomics features show no significant correlation with MTV, AJCC staging, and tumour maximum diameter. Conclusions: Most of the normal metabolic parameters and radiomics features are statistically stable through the 3D and 2D modes. 3D radiomics features are significantly correlated with tumour volume, maximum diameter, and staging. Conversely, 2D features have negligible correlation with the same parameters. Therefore, 3D mode features are preferable and can accurately evaluate tumour heterogeneity

Relay Selection Schemes for FSO Communications over Turbulent Channels

Free Space Optics (FSO) Communication has attracted the attention of the researchers in the last decade due to its high data rate, security, and low cost. Relay-assisted techniques are used to divide the distance to shorter hops in order to mitigate the effects of turbulence, weather attenuation, pointing error, and geometric loss. Choosing an active relay per time slot has been proven to enhance the performance of the system and decrease the loading effect on the system when compared to all active relays. This paper investigates the best relay that can be selected according to the source to relay (S-R) channel coefficient, relay to destination (R-D) channel coefficient, and source to destination (S-D) channel coefficient. A comprehensive comparison is applied to the three following cases: (a) Broadcast phase from source to relay to select the best (Proactive-Relay); (b) Broadcast phase from relay to destination after broadcasting to all relays then select (Reactive-relays); and, (c) Direct link from source-to-best relay-to-destination to conclude which method is better for different scenarios, such as turbulence regime, number of relays, different pointing error effect, and severity of S-R as compared to R-D and vice versa. The selection methods regard to four aspects: (1) Number of relays (two or three relays); (2) Distance between Source-Relay and Relay-Destination (D = 400–600 m, 500–500 m, and 600–400 m); (3) The different turbulence of Log-normal channel and Gamma-Gamma channel (with a refractive index coefficient( C n 2 = 0.5 × 10−14, 2 × 10−14 and 5 × 10−14)); and finally, (4) Beam waist ω z (pointing error)

The global health community at international climate change negotiations

With 2023 shattering climate records across the world following decades of unprecedented warming,1 the United Nations Framework Convention on Climate Change Conference of Parties 28 (UNFCCC COP28) in Dubai was the first UN climate change conference to feature an official ‘Health Day’ and witnessed the largest-ever turnout of the global health community. The threat of climate change to human well-being and planetary health2 3 has previously received little attention at the annual COPs, despite ever-growing scientific evidence warning of the increasing health dangers.</p

Methanolic Phoenix dactylifera L. Extract Ameliorates Cisplatin-Induced Hepatic Injury in Male Rats

This study investigated the ameliorative potential of methanolic date flesh extract (MDFE) against cisplatin-induced hepatic injury. Twenty male rats (weighing 180&ndash;200 g) were allocated into four groups: control; date flesh (DF) group (oral 600 mg/kg MDFE for 21 days); Cis group (7.5 mg/kg i.p. at day 16); and date flesh/cisplatin (DF/Cis) group (oral 600 mg/kg MDFE for 21 days and 7.5 mg/kg i.p. at day 16). Hepatic biochemical parameters in sera, and inflammatory and oxidant/antioxidant hepatic biomarkers were estimated. Hepatic histological changes and the immunohistochemistry of cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-&kappa;B), and alpha smooth muscle actin (&alpha;-SMA) were assessed. Pretreatment with MDFE decreased Cis-triggered liver biochemical parameters, oxidative stress, inflammatory biomarkers, and histological damage. Moreover, MDFE treatment reduced Cis-induced hepatic NF-&kappa;B, COX-2, and &alpha;-SMA protein expression. MDFE exerted a hepatoprotective effect when used concomitantly with Cis. Its effect was mediated via its antioxidant and anti-inflammatory ingredients

Efficacy of Tocilizumab in Management of COVID-19 Patients Admitted to Intensive Care Units: A Multicenter Retrospective Cohort Study

Background and Objectives: Mortality and illness due to COVID-19 have been linked to a condition known as cytokine release syndrome (CRS) that is characterized by excessive production of inflammatory cytokines, particularly interleukin-6 (IL-6). Tocilizumab (TCZ), a recent IL-6 antagonist, has been redeployed as adjunctive treatment for CRS remission in COVID-19 patients. This study aimed to determine the efficacy of Tocilizumab on patients’ survival and the length of stay in hospitalized COVID-19 patients admitted to the intensive care unit. Methods: Between January 2021 and June 2021, a multicenter retrospective cohort study was carried out in six tertiary care hospitals in Egypt’s governorate of Giza. Based on the use of TCZ during ICU stay, eligible patients were divided into two groups (control vs. TCZ). In-hospital mortality was the main outcome. Results: A total of 740 patient data records were included in the analysis, where 630 patients followed the routine COVID-19 protocol, while 110 patients received TCZ, need to different respiratory support after hospitalization, and inflammatory mediators such as C-reactive protein (CRP), ferritin, and Lactate dehydrogenase (LDH) showed a statistically significant difference between the TCZ group and the control group. Regarding the primary outcome (discharged alive or death) and neither the secondary outcome (length of hospital stay), there is no statistically significant difference between patients treated with TCZ and the control group. Conclusions: Our cohort of patients with moderate to severe COVID-19 did not assert a reduction in the risk of mortality or the length of stay (LOS) after TCZ administration

Development of benzimidazole-based derivatives as antimicrobial agents and their synergistic effect with colistin against gram-negative bacteria

Gram-negative bacteria pose a distinctive risk worldwide, especially with the evolution of major resistance to carbapenems, fluoroquinolones and colistin. Therefore, development of new antibacterial agents to target Gram-negative infections is of utmost importance. Using phenotypic screening, we synthesized and tested thirty-one benzimidazole derivatives against E. coli JW55031 (TolC mutant strain). Compound 6c showed potent activity with MIC value of 2 μg/ml, however, it lacked activity against several Gram-negative microbes with intact efflux systems, including E. coli BW25113 (wild-type strain). Combination of 6c with colistin partially restored its antibacterial activity against wild strains (MIC range, 8–16 μg/ml against E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa). 6c exhibited no cytotoxicity against two mammalian cell lines. Therefore, compound 6c represents a promising lead for further optimization to overcome Gram-negative resistance alone or in combination therapy