Novel Insights in the Hypertension Treatment & Type 2 Diabetics Induced by Angiotensin Receptor Blockers: MD Simulation Studies & Molecular Docking of Some Promising Natural Therapies.

Angiotensin receptor blockers (ARBs) are commonly used to treat hypertension that target the hormonal system (renin-angiotensin system (RAS)), which regulates various physiological functions in the body. ARBs work by blocking the binding of angiotensin II to its receptor, thereby preventing a rise in blood pressure. These drugs not only normalize the overactivation of RAS but also provide protective effects against cardiovascular, renal, and type 2 diabetic patients. Inappropriate RAS activity has been linked to insulin resistance of type 2 diabetes. Olmesartan, as an ARB, was found to have a beneficial role in reducing postprandial glucose levels in type 2 diabetes. However, ARBs can cause side effects, prompting a search for new compounds that have fewer adverse effects. This study explores the potential of natural metabolites, specifically eugenol, gallic acid, myricetin, p-cymene, quercetin, and kaempferol, as ARB inhibitors compared to the current standard, olmesartan. Using in silico studies, the binding affinity of these natural substances to the ARB receptor was evaluated. The results showed that myricetin and kaempferol had affinities higher than those of olmesartan, suggesting that they could serve as promising ARB inhibitors for hypertension treatment. These natural compounds could provide an alternative approach to conventional antihypertensive drugs, which may have fewer side effects. However, more research is needed to validate the efficacy and safety of these natural compounds as antihypertensive drugs. Further in vitro and in vivo studies are needed to confirm their effectiveness and safety. This study provides a promising starting point for future investigations into the potential of natural metabolites as alternative treatments for hypertension. The findings also highlight the importance of exploring natural alternative treatments for hypertension and the protective effects of ARBs on early stage type-2 diabetics.

Effect of high intensity interval training on arterial stiffness in obese hypertensive women: a randomized controlled trial.

OBJECTIVE: High-intensity interval training (HIIT) has been linked to a lower risk of cardiovascular disease and mortality. The study's overarching goal is to evaluate the impact of HIIT on arterial stiffness in obese hypertensive women. PATIENTS AND METHODS: Sixty obese hypertensive women aged between 40-50 years were randomized to group A (Intervention group, n = 30) or group B (Control group, n = 30). Intervention group received HIIT (4 minutes of cycling at 85-90% of peak HR interspersed with 3-minute active recovery time at 60 - 70% of peak HR, three times per week). Arteriovenous stiffness indicators, the augmentation index corrected for heart rate 75 (AIx@75HR), and oscillometric pulse wave velocity (o-PWV), as well as cardio-metabolic parameters, were assessed before and after 12 weeks of treatment. RESULTS: Finding between-group analysis showed a significant difference in AIx@75HR (95% CI: -8.45 to 0.30) , o-PWV ( 95% CI: -1.14 to 0.15), total cholesterol, (95% CI: -31.25 to -1.12), HDL-cholesterol (95% CI: 8.92 to 0.94), LDL-cholesterol (95% CI: -25.35 to -0.06) , and triglycerides (95% CI: -53.58 to -2.51). CONCLUSIONS: High-intensity interval training for 12 weeks has a favorable effect on arterial stiffness in obese hypertensive women and lowers associated cardio-metabolic risk factors.

Retraction Note: Combined effect of Schroth method and Gensingen brace on Cobb's angle and pulmonary functions in adolescent idiopathic scoliosis: a prospective, single blinded randomized controlled trial.

The article "Combined effect of Schroth method and Gensingen brace on Cobb's angle and pulmonary functions in adolescent idiopathic scoliosis: a prospective, single blinded randomized controlled trial", by S.A. Moawd, G. Nambi, A.E. El-Bagalaty, S.M. Hassan, S.E.B. Elsayed, F.M. Aboelmagd, N.A. Alhwoaimel, H.A. Abdeen, published in Eur Rev Med Pharmacol Sci 2023; 27 (2): 601-610-DOI: 10.26355/eurrev_202301_31061-PMID: 36734703 has been retracted by the Editor in Chief for the following reasons: After publication, concerns were raised about the use of copyright and trademark protected terms "Gensingen Brace" and "the Schroth Method" by the authors of the paper without permission for referring to results of a study with treatment of patients with a "Gensingen Brace". The owner of the copyright expressly denies the use of his trademark for scientific statements that are neither authorized by him nor correspond to the product's characteristics and qualities of his well-known products sold under the trademark. After being informed about the copyright and trademark issue, the corresponding author has been acknowledged and affirmed that the authors were not aware of the possible copyright and trademark infringement at the time of submission. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/31061.

Combined effect of Schroth method and Gensingen brace on Cobb's angle and pulmonary functions in adolescent idiopathic scoliosis: a prospective, single blinded randomized controlled trial.

OBJECTIVE: To detect the effect of the Schroth method added to the Gensingen brace for six months on Cobb's angle, axial rotation of the trunk, and pulmonary function in adolescent idiopathic scoliosis. PATIENTS AND METHODS: The study followed a prospective, single-blinded, randomized controlled trial design following the CONSORT guidelines. The study was conducted in Health and Rehabilitation Centre. 42 males aged 10-18 years old, diagnosed with adolescent idiopathic scoliosis (AIS) with curves of 35-40°, were recruited and then were allocated into three groups: Group A, Group B, and Group C. RESULTS: Significant improvement (p < 0.001) in Cobb's angle and the axial rotation of the trunk (ART) were noted after the treatment in the three groups, while pulmonary function showed better results in Group A (p < 0.001) when compared to the two other groups p ≥ 0.000). CONCLUSIONS: Six months of Schroth method added to Gensingen Brace demonstrate favorable results in Cobb's angle, thoracic trunk rotation angle, and pulmonary function in adolescent idiopathic scoliosis.

An investigation of susceptibility loci in benign, aggressive and primary progressive multiple sclerosis in Northern Irish population.

OBJECTIVE: To investigate the possibility that susceptibility loci in multiple sclerosis (MS) have a role in determining the disease outcome in Northern Ireland population. BACKGROUND: The Genetic Analysis of Multiple Sclerosis in Europeans (GAMES) initiative and follow-up refined analysis identified 15 candidate susceptibility loci within the Northern Irish population for MS. We aimed to investigate the 12 most significant markers for their role in disease outcome. METHODS: Cases with probable or definite MS (Poser criteria) were classified as benign onset (Kurtzke Expanded Disability Status Scale [EDSS]or=6.0 by 10 years), or primary progressive MS. All cases were Caucasian of Northern Irish origin. DNA was extracted from venous blood, microsatellite markers were amplified using polymerase chain reaction and typed using fluorescent fragment analysis. Allele frequencies were compared statistically using a chi-squared test with allowance for multiple comparisons (critical P<0.0042); significant markers were further analyzed by CLUMP (critical P<0.0014). RESULTS: Two microsatellite markers were significant: D3S1278 (Chr 3q13, P<0.001) and tumor necrosis factor (TNF)-alpha (Chr 6p21, P<0.001). A further three markers were significant in our preliminary analysis suggesting a trend toward impact on disease outcome; D4S432 (Chr 4p16, P=0.001), D2S347 (Chr 2q14, P=0.003), and D19S903 (Chr 19p13, P=0.003). CONCLUSIONS: This is the first study to suggest a role for TNF-alpha in the disease outcome in MS. Larger replication studies need to be performed to assess the role of markers D4S432, D2S347, and D19S903.

Identification of three novel alleles of HLA-DRB1 and HLA-A in the Brazilian population.

Two human leukocyte antigen (HLA)-DRB1 (HLA-DRB1*1376 and -DRB1*1465) and one HLA-A (HLA-A*2471) novel alleles have been identified in individuals from the Brazilian Bone Marrow Donor Registry. DNA sequencing of exon 2 for HLA-DRB1 alleles showed two and five nucleotide substitutions in -DRB1*1376 and -DRB1*1465, compared with closely related alleles, respectively. These substitutions result in a change of amino acid residues in HLA-DRB1*1376 at position 74 (Arg --> Glu) and in -DRB*1465 at positions 47 (Tyr --> Phe), 57 (Asp --> Ser) and 74 (Glu --> Ala). On the other hand, sequence analysis of exons 2 and 3 for HLA-A*2471 showed a single substitution, leading to a single amino acid change at position 151 (His --> Arg). These three novel alleles may have originated from other HLA alleles by gene conversion. However, it is also possible that HLA-A*2471 has evolved from one of the alleles of the HLA-A*2402 group through a point mutation.

Identification of two novel alleles HLA-B*3569 and -B*4450 and confirmation of HLA-A*2631 in the Brazilian population.

Two novel alleles, human leukocyte antigen (HLA)-B*3569, -B*4450 and a confirmatory sequence of HLA-A*2631 were identified during a routine typing for the Brazilian Bone Marrow Donor Registry. Sequence analysis of coding exons 2 and 3 revealed a single nucleotide substitution in HLA-B*3569 and two single nucleotide substitutions in HLA-B*4450, compared with closely related alleles. At the protein level, these substitutions result in a change of a single amino acid residue in each of HLA-B*3569 and -B*4450 at positions 74 (Arg > Pro) and 80 (Thr > Ile), respectively. These variations are located in the highly polymorphic region at the end of the alpha(1) domain of the HLA molecule. It appears that HLA-B*3569 arose from the analogous HLA-B*3510 through a point mutation. However, HLA-B*4450 may have arisen from HLA-B*440301 and -B*4425 by gene conversion.

Mapping candidate non-MHC susceptibility regions to multiple sclerosis.

Understanding the genetic basis of multiple sclerosis (MS) remains a major challenge, despite decades of intensive research. In order to identify candidate non-MHC susceptibility regions to MS, the results of whole genome screens for linkage or association and follow-up studies in 18 different populations were superimposed together in a combined genomic map. Analysis of this map led to the prediction of at least 38 potential susceptibility regions, each showing linkage and/or association in several populations. Among these, 17 regions were the most reproducibly reported in these studies, thus representing top predicted candidates for MS. This non-formal approach to meta-analysis demonstrated the ability to verify results and retrieve lost information in an association study. Assessment of the map in a Northern Irish refined screen (n=415 cases, n=490 controls) revealed association in 15 regions (P<0.05), including 10 promising candidates on chromosomes 1p13, 2p13, 2q14, 3p23, 7q21, 13q14, 15q13, 17p13, 18q21 and 20p12 (P<0.0025). Seven of these regions were previously overlooked in the Northern Irish whole genome association study. Collating results from numerous studies, this draft map represents a tool that should facilitate the analysis of the genetic backgrounds of MS in many populations.

Anti-miracidial effect of recombinant glutathione S-transferase 26 and soluble egg antigen on immune responses in murine schistosomiasis mansoni.

The anti-miracidial potential of recombinant Schistosoma mansoni glutathione S-transferase 26 (rSmGST26) or native crude soluble egg antigens (SEA) was assessed. The associated dynamics of granuloma formation and immune responses were evaluated. Naive C57BL/6 mice were injected intravenously with multiple doses of either SEA (SEA-group) or rSmGST26 (GST-group) 7 days before cercarial infection. The immunized groups and the respective controls were sacrificed 6, 8 and 16 weeks postinfection (p.i.). Acceleration of ova destruction and reduction of granuloma diameter were greater in the GST-group than the SEA-group, mainly at 8 weeks p.i. However, the amelioration of hepatic pathology and function was more evident in the SEA-group. Concurrently, serum-specific IgG1 levels were elevated throughout the course of infection in the immunized groups compared to the infected controls. Initial rise of all splenic cytokines and serum anti-SEA IgE levels at 6 weeks p.i. was observed, followed by a dramatic drop in the levels of the proinflammatory cytokines IL-2, IFNgamma, IL-4 and TNF-alpha and IgE at 8 weeks of infection. IL-10 level was lower at 8 weeks p.i. than at 6 weeks, but was higher in immunized groups than in infected controls. Several responses may be implicated as an outcome of the present immunization protocol, such as increased levels of blocking antibody (IgG1) and IL-10 with decreased levels of proinflammatory cytokines and IgE.

Molecular cloning and characterization of the polypeptide backbone of Schistosoma mansoni circulating cathodic antigen.

One of the candidate schistosome antigens for the development of a circulating antigen detection diagnostic assay is the circulating cathodic antigen (CCA). Detection of CCA in urine provides a non-invasive assay with high sensitivity. Previously we reported that CCA is secreted in patients' urine as a small molecular weight material which is probably of a proteinaceous nature. In an attempt to further characterize the secreted component of CCA, we used a monoclonal antibody (MAb) reactive with urine-CCA to isolate an adult worm cDNA clone (SmN3-1) that encodes the polypeptide backbone of CCA. The sequence, gene organization and expression of SmN3-1 were analyzed. The 1.6 kb nucleotide and 347 amino acid sequences of SmN3-1 showed no significant homology to any published sequence. The size and antigenic properties of the expression product of SmN3-1 in Escherichia coli greatly resembled the CCA molecule excreted in urine, suggesting that the latter is primarily composed of the protein element of CCA.