Explore the vast range of titles available.

Major Histocompatibility Complex (MHC) class I molecules selectively bind peptides for presentation to cytotoxic T cells. The peptide-free state of these molecules is not well understood. Here, we characterize a disulfide-stabilized version of the human class I molecule HLA-A*02:01 that is stable in the absence of peptide and can readily exchange cognate peptides. We present X-ray crystal structures of the peptide-free state of HLA-A*02:01, together with structures that have dipeptides bound in the A and F pockets. These structural snapshots reveal that the amino acid side chains lining the binding pockets switch in a coordinated fashion between a peptide-free unlocked state and a peptide-bound locked state. Molecular dynamics simulations suggest that the opening and closing of the F pocket affects peptide ligand conformations in adjacent binding pockets. We propose that peptide binding is co-determined by synergy between the binding pockets of the MHC molecule. Major Histocompatibility Complex (MHC) class I molecules present tightly binding peptides on the cell surface for recognition by cytotoxic T cells. Here, the authors present the crystal structures of a disulfide-stabilized human MHC class I molecule in the peptide-free state and bound with dipeptides, and find that peptide binding is accompanied by concerted conformational switches of the amino acid side chains in the binding pockets.

Natural products and chemical analogues are widely used in drug discovery, notably in cancer and infectious disease pharmacotherapy. Sarcophyton convolutum (Alcyoniidae) a Red Sea–derived soft coral has been shown to be a rich source of macrocyclic diterpenes and cyclized derivatives. Two previously undescribed polyoxygenated cembrane-type diterpenoids, sarcoconvolutums F (1) and G (2), as well as four identified analogues (3–6) together with a furan derivate (7) were isolated from a solvent extract. Compounds were identified by spectroscopic techniques, including NMR, HREIMS, and CD, together with close spectral comparisons of previously published data. Sarcoconvolutum F (1) contains a rare 1-peroxid-15-hydroxy-10-ene functionality. Isolated metabolites (1–7) were screened against lung adenocarcinoma (A549), cervical cancer (HeLa) and oral cavity carcinoma (HSC-2) lines. Compound 4 exhibited an IC50 56 µM and 55 µM against A549 and HSC-2 cells, respectively.

AimThis study aimed to assess the presence of stigma in patients with chronic hepatitis C and to assess the relationship between socio-demographic characteristics and stigma.Subjects and methodsThis is a cross-sectional descriptive and analytic study. This study was carried out at the communicable diseases, research and training center affiliated with Suez Canal University, Suez Governorate, Egypt. The sample included 260 patients with hepatitis C who filled in a questionnaire asking about the socio-demographic characteristics and hepatitis C stigma scale.ResultsThere was at least one stigmatizing characteristic in 155 (59.6%) of the patients with HCV. Among them, 53 (20.4%) reported that he/she is not the same as the others, 54 (20.8%) feel dirty, and 112 (43.1%) feel he/she is a bad person. Participants also agreed that people with hepatitis C are repulsive and rejected, according to 55 (21.2%) and 64 (24.6%), respectively. Sixty-seven (25.8%) had been hurt by the reactions of others. Among them, 52 (20%) stopped “hanging out” with others because of their reactions, 53 (20.4%) lost friends, and 55 (21.2%) were worried that others would tell about their illness. The marital relationship was affected by the diagnosis of hepatitis in 134 (51.5%) of participants. Subjects with younger age and who were married had higher stigma scores (p = 0.018, 0.013). Smokers were more rejected (p = 0.007) and hurt by reactions of others than non-smoking patients (p = 0.013); they had lost more friends (p = 0.002) and were more worried that others would tell about their illness (p = 0.016).ConclusionPatients with hepatitis C feel stigmatized in different areas; there is a need for implementation of educational programs to raise the awareness of community and health care providers about the stigma of hepatitis C and its negative consequences to act as advocates for their patients.

Reactive oxygen species (ROS) are common products of mitochondrial oxidative phosphorylation, xenobiotics metabolism and are generated in response to several environmental stress conditions. Some of them play important biochemical roles in cellular signal transduction and gene transcription. On the other hand, ROS are known to be involved in a wide range of human diseases, including cancer. The excessive production of such ROS together with disruption of homeostasis detoxifying mechanisms can mediate a series of cellular oxidative stresses. The oxidative stress of redundant free radicals production can lead to oxidative denaturation of cellular macromolecules including proteins, lipids and DNA. Moreover, oxidative damage is one of the major causes of DNA mutations, replication errors and genomic abnormalities which result in either inhibition or induction of transcription, and end with the disturbance of signal transduction pathways. Among affected signaling pathways are redox-sensitive kinases. The stimulation of these kinases induces several transcription factors through the phosphorylation of their module proteins. The activation of such pathways induces proliferation and cellular transformation. A diet rich in antioxidant compounds has potential health benefits, and there is a growing interest in the role of natural antioxidants in nutrition for prevention and cure of cancer diseases. A controversy has risen regarding the relation between antioxidants and the significant decrease in the risk of cancer incidence. In this review, we will focus on redox-sensitive kinases signaling pathways, highlighting the effects of dietary antioxidant on the prevention, incidence, prognosis or even treatment of human cancers. In addition, we will place emphasis on the chemical classes of pterocarpans as natural anti-oxidants/cancers as well as their underlying mechanisms of action, including their effects on MAPKs and topoisomerase activities.

Natural products and chemical analogues are widely used in drug discovery, notably in cancer and infectious disease pharmacotherapy. Sarcophyton convolutum (Alcyoniidae) a Red Sea–derived soft coral has been shown to be a rich source of macrocyclic diterpenes and cyclized derivatives. Two previously undescribed polyoxygenated cembrane-type diterpenoids, sarcoconvolutums F (1) and G (2), as well as four identified analogues (3–6) together with a furan derivate (7) were isolated from a solvent extract. Compounds were identified by spectroscopic techniques, including NMR, HREIMS, and CD, together with close spectral comparisons of previously published data. Sarcoconvolutum F (1) contains a rare 1-peroxid-15-hydroxy-10-ene functionality. Isolated metabolites (1–7) were screened against lung adenocarcinoma (A549), cervical cancer (HeLa) and oral cavity carcinoma (HSC-2) lines. Compound 4 exhibited an IC[sub.50] 56 µM and 55 µM against A549 and HSC-2 cells, respectively.

The methanol extract of T. arjuna leaves was evaluated as hepatoprotective and gastroprotective against Swiss albino rats. In hepatoprotective study, the liver damage induced by paracetamol while the gastric lesion induced by absolute ethanol in the gastro protective study. The extract was given orally (250 mg/kg,500 mg/kg and 1,000 mg/kg) in different experimental models in both studies. The extract at dose (500 mg/kg) showed significant reduction in ALT serum level by 19.9% while at dose (1,000 mg/kg) it reduced significantly serum ALT, AST and ALP levels by -26.15%, -25.46% and -23.69%, respectively as compared with paracetamol treated group. In the gastro protective study, the extract produced significant reduction in the number and severity of mucosal lesion by (-52.1% & -67.3%, -66.7% & -71.2 % and -68.8% & -77.6%), respectively.

One new, 10, 11-dioxo-6,7α-erythraline epoxide (A1) and four known erythrinan alkaloids 10, 11-dioxo-erythraline (A2), erysodine (A3), 8-oxo-erythraline (A4) and erythraline (A5) were isolated from the 70% methanolic extract of stems of E. Corallodendron (Fabaceae). The isolated compounds were elucidated by exploiting 1D/2D NMR, and HR-ESI-MS analysis. The absolute configuration of A1 was determined by electronic circular dichroism (ECD). Mono Amine Oxidase inhibitory activity of the isolated alkaloids was investigated in vitro using kynuramine deamination assay on recombinant human MAO-A and B enzymes. The binding modes were predicted by molecular docking and the structure activity relationships of erythrinans were then evaluated. All isolated alkaloids demonstrated preferential activity against MAO-B. A1 displayed the highest potency and selectivity against MAO-B with IC50 of 25.18 μM, (SI >3.97). The selective inhibition exhibited by erythrinan alkaloids against MAO-B is in line with the expected biological impact of Erythrina in the treatment of neurodegenerative diseases and presents this chemical class as promising leads for managing AD and PD diseases.

Background Major hydrophilic region in genomic HBV extending from aa99 to aa169, clustered with a highly conformational epitope, is critical to the antigenicity of hepatitis B surface antigen (HBsAg) and may affect the diagnosis of HBV in HBV screening test. So, this study aimed to characterize variants of S gene product of hepatitis B virus (HBV) isolated from patients with overt or occult HBV infection in north-eastern Egypt. Methods The study included sera of two different groups of volunteer blood donors (VBDs), 82 with overt HBV that were positive for HBsAg and anti-HBc and 343 donors negative for HBsAg eligible for donation. Of the latter group, only 44 were positive for anti-HBc. All anti-HBc positive sera were subjected to HBV DNA detection and partial sequence analysis targeting the HBV S gene. Results HBV DNA was detected in 22.7 % of HBsAg-/anti-HBc + (10/44 patients) and in 90 % of HBsAg + donors (74/82 patients) with significant statistical difference ( P  = 0.0001). Phylogenetic analysis showed that HBV strains retrieved from both groups were of genotype D. Amino acid escape mutation T125M was detected in only 2 samples of the occult infection group and in none of the overt group ( P  = 0.01). Different amino acid substitutions were identified in overt infection group: S143L/T (16.2 %, 12/74) and P120T/S (2.7 %, 2/74). Q129R was significantly more frequent in cases with occult HBV infection (40 %, 4/10) than overt group (6.8 %, 5/74) ( P  = 0.01). Conclusions HBV genotype D predominated both in patients with overt and occult HBV infection. Different profiles of amino acid substitutions in the major hydrophilic region were seen in these two groups in Egypt.

Major hydrophilic region in genomic HBV extending from aa99 to aa169, clustered with a highly conformational epitope, is critical to the antigenicity of hepatitis B surface antigen (HBsAg) and may affect the diagnosis of HBV in HBV screening test. So, this study aimed to characterize variants of S gene product of hepatitis B virus (HBV) isolated from patients with overt or occult HBV infection in north-eastern Egypt. The study included sera of two different groups of volunteer blood donors (VBDs), 82 with overt HBV that were positive for HBsAg and anti-HBc and 343 donors negative for HBsAg eligible for donation. Of the latter group, only 44 were positive for anti-HBc. All anti-HBc positive sera were subjected to HBV DNA detection and partial sequence analysis targeting the HBV S gene. HBV DNA was detected in 22.7 % of HBsAg-/anti-HBc + (10/44 patients) and in 90 % of HBsAg + donors (74/82 patients) with significant statistical difference (P = 0.0001). Phylogenetic analysis showed that HBV strains retrieved from both groups were of genotype D. Amino acid escape mutation T125M was detected in only 2 samples of the occult infection group and in none of the overt group (P = 0.01). Different amino acid substitutions were identified in overt infection group: S143L/T (16.2 %, 12/74) and P120T/S (2.7 %, 2/74). Q129R was significantly more frequent in cases with occult HBV infection (40 %, 4/10) than overt group (6.8 %, 5/74) (P = 0.01). HBV genotype D predominated both in patients with overt and occult HBV infection. Different profiles of amino acid substitutions in the major hydrophilic region were seen in these two groups in Egypt.

The telecommunications sector has seen a significant surge in innovative advancements, particularly in wireless communication, driven by increasing connectivity demands. With wireless networks and Internet of Things (IoT) devices now pervasive across civilian, military, and medical sectors, security has become an imperative, constrained by the low power of IoT devices. In response, physical layer security (PLS) stood out as a tool for establishing keyless, secure communication, leveraging the physical layer parameters and other wireless communication techniques such as precoding, beamforming, and reconfigurable intelligent surfaces (RIS). RIS gained popularity for its efficiency in reflecting the legitimate signal with high power and low power for the illegitimate one. Yet, the optimal method of configuring its phase shift continues to require investigation.This work proposes three RIS phase shift configuration schemes in a RIS-and-jamming-aided network. The network consists of a transmitter and a multi-antenna receiver under the threat of several independent eavesdroppers. The proposed configuration schemes are a deep reinforcement learning-based (DRL-based) technique and two online model based configuration schemes. Numerical results simulating these configuration schemes and evaluating their performance are provided. Finally, the three methods are compared and assessed based on PLS analysis metric.