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In this study isolates from Thymelaea hirsuta, a wild plant from the Sinai Peninsula of Egypt, were identified and their selective cytotoxicity levels were evaluated. Phytochemical examination of the ethyl acetate (EtOAc) fraction of the methanolic (MeOH) extract of the plant led to the isolation of a new triflavanone compound (1), in addition to the isolation of nine previously reported compounds. These included five dicoumarinyl ethers found in Thymelaea: daphnoretin methyl ether (2), rutamontine (3), neodaphnoretin (4), acetyldaphnoretin (5), and edgeworthin (6); two flavonoids: genkwanin (7) and trans-tiliroside (8); p-hydroxy benzoic acid (9) and β sitosterol glucoside (10). Eight of the isolated compounds were tested for in vitro cytotoxicity against Vero and HepG2 cell lines using a sulforhodamine-B (SRB) assay. Compounds 1, 2 and 5 exhibited remarkable cytotoxic activities against HepG2 cells, with IC50 values of 8.6, 12.3 and 9.4 μM, respectively, yet these compounds exhibited non-toxic activities against the Vero cells. Additionally, compound 1 further exhibited promising cytotoxic activity against both MCF-7 and HCT-116 cells, with IC50 values of 4.26 and 9.6 μM, respectively. Compound 1 significantly stimulated apoptotic breast cancer cell death, resulting in a 14.97-fold increase and arresting 40.57% of the cell population at the Pre-G1 stage of the cell cycle. Finally, its apoptosis-inducing activity was further validated through activation of BAX and caspase-9, and inhibition of BCL2 levels. In silico molecular docking experiments revealed a good binding mode profile of the isolates towards Ras activation/pathway mitogen-activated protein kinase (Ras/MAPK); a common molecular pathway in the development and progression of liver tumors.

Phytochemical study of Chiliadenus montanus aerial parts afforded six compounds; Intermedeol (1), 5α-hydroperoxy-β-eudesmol (2), 5,7-dihydroxy-3,3’,4’-trimethoxyflavone (3), 5,7,4’-trihydroxy-3,6,3’-trimethoxyflavone (jaceidin) (4), eudesm-11,13-ene-1β,4β,7α-triol (5) and 1β,4β,7β,11-tetrahydroxyeudesmane (6). These compounds were identified based on their NMR spectral data. The isolated compounds were tested for their cytotoxicity against liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). Jaceidin flavonoid (4) exhibited the highest cytotoxic effect in vitro. Therefore, both of jaceidin and C. montanus extract were evaluated for their in vivo anti-tumor activity against Ehrlich’s ascites carcinoma (EAC). Compared to control group, jaceidin and C. montanus extract decreased the tumor weight, improved the histological picture of tumor cells, lowered the levels of VEGF and ameliorate the oxidative stress. Molecular docking and in silico studies suggested that jaceidin was a selective inhibitor of VEGF-mediated angiogenesis with excellent membrane permeability and oral bioavailability.

Phytochemical study of Chiliadenus montanus aerial parts afforded six compounds; Intermedeol (1), 5α-hydroperoxy-β-eudesmol (2), 5,7-dihydroxy-3,3’,4’-trimethoxyflavone (3), 5,7,4’-trihydroxy-3,6,3’-trimethoxyflavone (jaceidin) (4), eudesm-11,13-ene-1β,4β,7α-triol (5) and 1β,4β,7β,11-tetrahydroxyeudesmane (6). These compounds were identified based on their NMR spectral data. The isolated compounds were tested for their cytotoxicity against liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). Jaceidin flavonoid (4) exhibited the highest cytotoxic effect in vitro. Therefore, both of jaceidin and C. montanus extract were evaluated for their in vivo anti-tumor activity against Ehrlich’s ascites carcinoma (EAC). Compared to control group, jaceidin and C. montanus extract decreased the tumor weight, improved the histological picture of tumor cells, lowered the levels of VEGF and ameliorate the oxidative stress. Molecular docking and in silico studies suggested that jaceidin was a selective inhibitor of VEGF-mediated angiogenesis with excellent membrane permeability and oral bioavailability.

Photobleaching is the permanent loss of fluorescence after extended exposure to light and is a major limiting factor in super‐resolution microscopy (SRM) that restricts spatiotemporal resolution and observation time. Strategies for preventing or overcoming photobleaching in SRM are reviewed developing new probes and chemical environments. Photostabilization strategies are introduced first, which are borrowed from conventional fluorescence microscopy, that are employed in SRM. SRM‐specific strategies are then highlighted that exploit the on–off transitions of fluorescence, which is the key mechanism for achieving super‐resolution, which are becoming new routes to address photobleaching in SRM. Off states can serve as a shelter from excitation by light or an exit to release a damaged probe and replace it with a fresh one. Such efforts in overcoming the photobleaching limits are anticipated to enhance resolution to molecular scales and to extend the observation time to physiological lifespans. In super‐resolution fluorescence microscopy, photobleaching not only leads into gradual loss of fluorophores but also greatly influences on spatiotemporal resolution. Both conventional photostabilization strategies applied in super‐resolution imaging and specific approaches repurposing fluorescence‐off states as shelters, are reviewed. Off states, originally devised for overcoming the diffraction limit, can shelter fluorophores from excitation or for replacing to a new one.

Dual targeting of epidermal growth factor receptor (EGFR) and human EGFR-related receptor 2 (HER2) is a proven approach for the treatment of lung cancer. With the aim of discovering effective dual EGFR/HER2 inhibitors targeting non-small cell lung cancer cell line H1299, three series of thieno[2,3-d][1,2,3]triazine and acetamide derivatives were designed, synthesized, and biologically evaluated. The synthesized compounds displayed IC50 values ranging from 12 to 54 nM against H1299, which were superior to that of gefitinib (2) at 40 µM. Of the synthesized compounds, 2-(1H-pyrazolo[3,4-b]pyridin-3-ylamino)-N-(3-cyano4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)acetamide (21a) achieved the highest in vitro cytotoxic activity against H1299, with an IC50 value of 12.5 nM in situ, and 0.47 and 0.14 nM against EGFR and HER2, respectively, values comparable to the IC50 of the approved drug imatinib (1). Our synthesized compounds were promising, demonstrating high selectivity and affinity for EGFR/HER2, especially the hinge region forming a hydrophobic pocket, which was mediated by hydrogen bonding as well as hydrophobic and electrostatic interactions, as indicated by molecular modeling. Moreover, the designed compounds showed good affinity for T790M EGFR, one of the main mutants resulting in acquired drug resistance. Furthermore, both pharmacokinetic and physicochemical properties of the designed compounds were within the appropriate range for human usage as predicted by the in Silico ADME study. The designed compound (21a) might serve as an encouraging lead compound for the discovery of promising anti-lung cancer agents targeting EGFR/HER2.

Thoracolumbar interfascial plane (TLIP) block was recently described as a regional anesthetic technique to achieve analgesia for lumbar spine surgery by blocking the dorsal rami of spinal nerves. The study aims to test the hypothesis that TLIP block can offer pain control and reduce the perioperative analgesic requirement in patients undergoing spinal surgery. There were 60 patients scheduled for lumbar spine surgery who were randomly assigned into two equal groups, TLIP and control groups. Patients in the TLIP group received general anesthesia and TLIP block while patients in the control group received general anesthesia alone. The primary outcome was the analgesic consumption in the first postoperative 24 hours, while intraoperative additional analgesic needs, time to the first request of postoperative analgesia, and pain scores were the secondary outcomes. At 24 hours postoperatively, morphine consumption was lower in the TLIP group (5.13±1.55) versus the control group (14.33±2.58) mg. The intraoperative fentanyl consumption was lower in the TLIP group (15±35.11 mcgs) versus the control group (105±62.08 mcgs). Postoperative first request for analgesia was delayed in the TLIP group (7.30±2.69 h) compared to the control group (0.92±1.23 h). Postoperative Pain scores at rest were 2.53 ± 0.97 and 3.43 ± 0.50 at 24 hours in the TLIP group and the control group, respectively. Postoperative Pain scores at passive flexion of spine were 2.73 ±0.87 and 3.93 ±0.78 at 24 hours in the TLIP group and the control group, respectively. Patients in the TLIP group had lower perioperative hemodynamic responses to surgical stimulation in comparison to the control group. Combined TLIP block with general anesthesia in patients undergoing spinal surgery reduced both postoperative and intraoperative analgesic needs, reduced intra-operative hemodynamic response to surgery, and achieved good postoperative pain control.

The effects of fipronil (FPN) on the liver of rats were studied. Rats ( n  = 6) were treated with 9.7 mg/kg (1/10 of FPN LD 50 ), and other rats ( n  = 6) received 120 mg/kg of 10% Uncaria tomentosa extract, while a mixture of 9.7 mg/kg FPN and 120 mg/kg of 10% Uncaria tomentosa extract were administered orally to the rats ( n  = 6) daily for 6 weeks. Body, hepatic weights, liver enzymes, and lipid profile were determined. Hepatic activities of MDA, TNO, TAC, TNF-α, and IL-6 in liver homogenate were measured. Immunohistochemistry of NF-kB and liver histopathology were performed. Fipronil-treated rats had a significant ( P  = 0.02) lower weight gain. Moreover, relative liver weight was significantly ( P  = 0.003) increased in FPN-treated rats. Rats administrated with FPN exhibited a significantly ( P  = 0.02) higher liver enzymes and promoted levels of MDA, TNO, TNF-α, and IL-6 ( P  < 0.0001) than that in the other groups. Immunostaining of NF-κB was increased ( P  < 0.0001) in FPN-treated rats. Interestingly, Uncaria tomentosa alone or with FPN decreased the liver immunostaining of NF-κB. In conclusion, FPN produced liver injury through lipid peroxidation and stimulation of NF-κB. However, Uncaria tomentosa combated the oxidative stress and liver damage induced by FPN via inhibition of NF-κB.

MR enterography (MRE) has been increased in the last decade as a modality of choice in diagnosis and evaluation of small bowel diseases in both children and adults. Lacking ionizing radiation, non-invasiveness, excellent soft tissue resolution, adequate luminal distension of small bowel loops are the advantages of this technique. Acquisition of images was used to be: T2WI, steady-state free precession, and T1WI, fat-suppressed gadolinium contrast-enhanced sequences. Multipoint Dixon sequence was added recently to the routine MR enterography protocol. The current study aimed to evaluate the added value of multipoint Dixon sequence as a valuable modification of MR enterography protocol for better assessment of small bowel lesions as activity of Crohn's disease, small bowel polyps, fibrotic strictures, with modification of MRE protocol in the future with less time consumption and better radiological evaluation. The current research was a prospective cross-sectional study. Data were collected prospectively after getting ethical approval from the ethical committee of the faculty of medicine, in our university. This study enrolled 69 patients with recurrent abdominal pain and/or bleeding in stool. The patients' age ranged from 18 to 50 years, with a mean of 32.6 ± 8.8. There is slightly higher female prevalence. The most common positive imaging findings in the studied patients were mucosal thickening in terms of submucosal fat deposition (36.23% of the MRE examination and 39.13% of the MRE with added Dixon sequence). Adding Dixon sequence yielded significantly higher AUC (97.2% vs. 90.5%, p = 0.047), higher sensitivity (100% vs. 92.16%), specificity (94.4% vs. 88.89%), accuracy (98.55% vs. 91.3%), positive predictive value (98.08% vs. 95.92%), and negative predictive value (100% vs. 80%). MRE is an excellent imaging modality in the assessment of small bowel diseases without the use of ionizing radiation. Developing MR-based sequences as multi-point Dixon sequence have the potential to improve the ability of MRE to image the subtle changes as Crohn's accompanying early inflammatory changes and fibrosis, as well as small intestinal polyps. Familiarity with MR enterography is essential for radiologists and gastroenterologists who participate in the clinical management of small intestinal diseases.

Targeting of cyclooxygenase-2 (COX-2) has emerged as a powerful tool for therapeutic intervention because the overexpression of this enzyme is synonymous with inflammation, cancer, and neurodegenerative diseases. Herein, a new series of 1,2,4-triazole Schiff bases scaffold with aryl and heteroaryl systems 9a–12d were designed, synthesized, structurally elucidated, and biologically evaluated as a potent COX-2 blocker. The rationale beyond the current study is to increase the molecule bulkiness allowing a selective binding to the unique hydrophobic pocket of COX-2. Among the triazole–thiazole hybrids, the one with the para-methoxy moiety linked to a phenyl ring 12d showed the highest In vitro selectivity by COX-2 inhibition assay (IC50 of 0.04 μM) and in situ anti-inflammatory activity when evaluated using the protein denaturation assay (IC50 of 0.88 μM) in comparison with commercially available selective COX-2 inhibitor, Celecoxib (IC50 of 0.05 μM). Towards the COX-2 selectivity, ligand-based three dimensional quantitative structures activity relationship (3D-QSAR) employing atomic-based and field-based approaches were performed and resulted in the necessity of triazole and thiazole/oxazole scaffolds for COX-2 blocking. Furthermore, the molecular modeling study indicated a high selectivity and promising affinity of our prepared compounds to COX-2, especially the hydrophobic pocket and the mouth of the active site holding hydrogen-bonding, hydrophobic, and electrostatic interactions. In Silico absorption, delivery, metabolism, and excretion (ADME) predictions showed that all the pharmacokinetic and physicochemical features are within the appropriate range for human use.