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Yasamin Davatgaran Taghipour,1–3 Marziyeh Hajialyani,4 Rozita Naseri,5 Mahvash Hesari,6 Pantea Mohammadi,6 Azzurra Stefanucci,7 Adriano Mollica,7 Mohammad Hosein Farzaei,4,6 Mohammad Abdollahi81Department of Medical Nanotechnology, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; 2Phytopharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; 3Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; 4Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 5Internal Medicine Department, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran; 6Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; 7Department of Pharmacy, G. d’Annunzio University of Chieti-pescara, Chieti 66100, Italy; 8Toxicology and Diseases Group, the Institute of Pharmaceutical Sciences (TIPS) and Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, IranAbstract: Metabolic syndrome is a common metabolic disorder which has become a public health challenge worldwide. There has been growing interest in medications including natural products as complementary or alternative choices for common chemical therapeutics regarding their limited side effects and ease of access. Nanosizing these compounds may help to increase their solubility, bioavailability, and promisingly enhance their efficacy. This study, for the first time, provides a comprehensive overview of the application of natural-products-based nanoformulations in the management of metabolic syndrome. Different phytochemicals including curcumin, berberine, Capsicum oleoresin, naringenin, emodin, gymnemic acid, resveratrol, quercetin, scutellarin, stevioside, silybin, baicalin, and others have been nanosized hitherto, and their nanosizing method and effect in treatment and alleviating metabolic syndrome have been reviewed and discussed in this study. It has been discovered that there are several pathways or molecular targets relevant to metabolic disorders which are affected by these compounds. Various natural-based nanoformulations have shown promising effect in treatment of metabolic syndrome, and therefore can be considered as future candidates instead of or in conjunction with pharmaceutical drugs if they pass clinical trials successfully.Keywords: nanoformulation, natural products, metabolic syndrome, diabetes

"n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Cyclosporine is one of the main immunosuppressors used for renal transplant recipients, and is given to prevent transplant rejection. Although the drug increases the survival of patients and grafted organs, it has some side effects independent of its effect on the immune system that are usually ignored. In this study, we evaluate the effect of cyclosporine on serum Mg levels and metabolic side effects in renal graft patients."n"n Methods: In this study, we followed 157 renal transplant recipients (62 females and 95 males) who were being treated with cyclosporine at a private clinic to prevent transplant rejection. The patients were first physically examined and then blood samples were obtained in order to measure levels of cyclosporine, Mg, creatinine, fasting blood sugar, lipids, calcium, phosphorus, and uric acid levels. We then analyzed the data for correlations between serum Mg levels, cyclosporine and other metabolic complications."n"n Results: The mean levels of Mg and cyclosporine were 196±0.31mg/dl and 371±192 μg/dl, respectively. Hypomagnesemia was detected in 16 patients (10.2%).There was a significant negative correlation (p0.05) between levels of Mg and calcium (r=0.2), phosphorus (r=-0.01), triglycerides (r=0.06) and HDL (r=-0.08). Mean levels of cyclosporine, creatinine, LDL, fasting blood sugar and uric acid in patients with hypomagnesemia were significantly different from those patients with normal serum Mg levels (p0.05)."n"n Conclusion: According to the results of this and previous studies, there is a significant correlation between cyclosporine levels and hypomagnesemia as well as other biomedical complications secondary to hypomagnesemia. Therefore, we recommend routine serum Mg determination and greater attention to hypomagnesemic patients to prevent further complications. "nKeywords: Cyclosporine, hypomagnesaemia, renal transplantation, hyperlipidemia, hyperuricemia.

Shifted Legendre orthonormal polynomials (SLOPs) are used to approximate the numerical solutions of fractional optimal control problems. To do so, first, the operational matrix of the Caputo fractional derivative, the SLOPs, and Lagrange multipliers are used to convert such problems into algebraic equations. Also, the method is proposed for solving multidimensional problems, and its convergence is proved. This method is tested on some nonlinear examples. The results indicate that the technique can efficiently solve multidimensional problems. [ABSTRACT FROM AUTHOR]

During the excavations of the graveyard at the site of Deh Dumen in south-western Iran, 15 graves from the Early/Middle Bronze Age were uncovered that contained a variety of metallic artefacts. This paper reports on the analysis of nine metal artefacts, including eight broken vessels and a decorative strip that covered the handle of a dagger. The ICP-MS results showed that the bodies of the vessels are made of tin bronze alloy with variable amounts of tin, while the internal piece of the base of one vessel is made from an arsenical copper alloy. Further, the metallic strip is a thin sheet manufactured with partially pure silver. Microanalytical and microstructural information yielded by SEM-EDS revealed elongated Cu-S inclusions and lead globules as various phases formed in bronze solid solution. This study presents some information about the transition from arsenical copper to bronze metallurgy in the third millennium bc in south-western Iran. [ABSTRACT FROM AUTHOR]

A numerical algorithm for solving optimization problems with stochastic diffusion equation as a constraint is proposed. First, separation of random and deterministic variables is done via Karhunen-Loeve expansion. Then, the problem is discretized, in spatial part, using the finite element method and the polynomial chaos expansion in the stochastic part of the problem. This process leads to the optimal control problem with a large scale system in its constraint. To overcome these difficulties the adjoint technique for derivative computation to implementation of the optimal control issue in preconditioned Newton's conjugate gradient method is used. By some numerical simulation, it is shown that this hybrid approach is efficient and simple to implement. [ABSTRACT FROM AUTHOR]

Anthrax, a zoonotic disease caused by Bacillus anthracis, has affected humans since ancient times. For genomic characterization of Razi B. anthracis Sterne 34F2 substrain, single nucleotide polymorphism (SNP) genotyping method developed by Van Erth, variable-number tandem-repeat (VNTR)-8 analysis proposed by Keim, and multiple-locus VNTR analysis (MLVA)-3 introduced by Levy were employed. In the SNPs typing system, where the nucleotide content of the genome at 13 evolutionary canonical loci was collectively analyzed, the originally South African 34F2 substrain was categorized in the A.Br.001/002 subgroup. In the VNTR-8 analysis, fragments with lengths of 314, 229, 162, 580, 532, 158, and 137 bp were identified at the following loci: vrrA, vrrB1, vrrB2, vrrC1, vrrC2, CG3, and pxO1, respectively. In addition, application of Levy's MLVA-3 genotyping method revealed that the genome of this strain carried 941, 451, and 864 bp fragments at AA03, AJ03, and AA07 loci, respectively. The present findings are undoubtedly helpful in meeting the requirements set by the World Organization for Animal Health (OIE) and World Health Organization (WHO) for anthrax vaccine manufacturers including Razi Institute. However, further similar studies are required to promote the current epidemiological knowledge of anthrax in Iran.

Cyclosporine is the main immunosuppressive drug used for renal transplant reci-pients in order to prevent transplant rejection. Although the drug has increased the survival of patients and grafted organ, it has some side effects independent of its effect on the immune system. This study was done to evaluate the effect of cyclosporine on serum Mg level and its metabolic side effects in renal allograft patients. 157 (62 female and 95 male) renal transplant recipients treated with cyclosporine to prevent transplant rejection were included in the study. Clinical and biochemical data along with cyclosporine levels was documented. Mean serum Mg level was 196 ± 0.31 mg/dL and mean serum cyclosporine level was 371 ± 192 µg/dL. Hypomagnesemia was detected in 16 (10.2%) with a negative significant correlation with cyclosporine levels, serum creatinine, plasma LDL, fasting Blood sugar and uric acid. In conclusion according to the results of this study there is a significant correlation between cyclosporine and hypomagnesemia. Therefore, routine measurement of serum Mg and its treatment seems necessary to prevent its complications.

Background: Corrosive substance ingestion is rare but can cause severe injury, especially to the upper gastrointestinal tract, and can be a potentially fatal event. Various surgical procedures have been advocated for gastroesophageal reconstruction, but especially those using the right colon, when the ileocecal valve is preserved for gastric reconstruction, are briefly exposed in literature and have not been studied in humans by controlled studies. Using the right colon is believed to be beneficial because of the anti-reflux mechanism of the ileocecal valve. This study aims to report our experience in the use of right colon interposition for gastric reconstruction in the management of caustic injury, and to assess its influence on patient outcomes., Case Presentation: We describe five cases, all of which included corrosive substances ingested by patients referred to a local tertiary center institution undergoing right colon interposition for esophageal and gastric reconstruction. We evaluated five Iranian patients undergoing ileocolic segment interposition for gastric reconstruction. Of these, two were male patients (patient 1 was 51 years old, patient 2 was 32 years old), and three were female patients (patient 3 was 49 years old, patient 4 was 32 year old, patient 5 was 59 year old), with an age from 32 to 59 years (mean: 57 ± 10.95). The operating surgeon's first to fifth procedures proceeded uneventfully, with only one case of cervical leakage as a complication with spontaneous closure; relative mean operative time of 5.95 ± 1.17 hours, hospital stays of 25 ± 15.29 days for all five patients. No excess morbidity rate was observed., Conclusion: In this case series, a novel technique for post-gastrectomy reconstruction using right colon interposition along with an ileocecal reservoir with identical advantages in improving eating capacity, and avoiding biliary reflux thanks to the presence of the ileocecal valve, is introduced., Competing Interests: Declarations. Ethics approval and consent to participate: All protocols performed in studies involving human participants were in accordance with the ethical standards of the local Medical the Ethics Committee of the Shiraz University of Medical Science (Ethical code: IR.SUMS.MED.REC.1401.074). In addition, the study was carried out in accordance with the relevant guidelines and regulations and the Declaration of Helsinki. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Moldable hydrogel-based techniques loaded with osteoinductive agents such as metformin have become a promising field for reconstructing critical-sized bone defects, particularly in those with irregular shapes. Here, we used metformin incorporated in an alginate/hydroxyapatite hydrogel to accelerate the repair of the rabbit critical-sized mandibular defect., Methods: Cytotoxicity and osteoinduction of the metformin-loaded alginate/hydroxyapatite hydrogel were evaluated by culturing the osteosarcoma cell line (MG63). Moreover, in vivo bone formation was assessed in a rabbit bone defect model using computed tomography and histomorphometric analysis to compare the effects of alginate/hydroxyapatite hydrogel with or without metformin., Results: The data showed that the scaffolds were not cytotoxic and enhanced osteogenic characteristics of the cells, as manifested by augmented alkaline phosphatase activity and calcium deposition . In vivo studies indicated that all the treated groups exhibited more osteogenesis with a significant increase in bone-specific cell population and less residual scaffold remnant at the defect sites compared with the control group, which was significantly prominent in the group treated with alginate/hydroxyapatite/metformin. Moreover, computed tomography scan analysis also confirmed better bone filling in all the treated groups, especially in the defects treated with alginate/hydroxyapatite/metformin hydrogel., Conclusions: Both In vitro and in vivo experiments revealed that locally loaded metformin with the easy size- and shape-adapted alginate/hydroxyapatite hydrogel has proper biocompatibility and osteogenesis properties. Moreover, our study highlighted the synergistic effect of metformin and hydroxyapatite on osteogenesis., Competing Interests: Conflict of interestThe authors have no conflict of interest to disclose., (© The Association of Oral and Maxillofacial Surgeons of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Tracheal diverticulum is a rare condition often linked to other malformations. This case study highlights the posterior tracheal diverticulum, covering its causes, symptoms, diagnosis, treatment, and prognosis. The report is significant due to the rarity of tracheal diverticulum and potential for misdiagnosis, which can result in complications such as respiratory infections. The case offers novel insights into the presentation and management of tracheal diverticulum, helping to guide future diagnosis and treatment., Case Presentation: A 73-year-old Iranian man with a history of cardiac surgery 15 years ago was admitted to the Loghman Hakim Hospital in Tehran, Iran, for retrosternal chest pain, shoulder radiation, and a persistent cough lasting 4 months. The patient underwent cardiac tests and a lung computed tomography scan, which showed a 16 × 18 mm air-filled outpouching connected to the trachea's right posterolateral side, leading to a diagnosis of tracheal diverticulum. The patient was treated with bronchodilators and antibiotics., Conclusions: Tracheal diverticulum is typically asymptomatic but can present with respiratory difficulties, dysphagia, and hoarseness. Diagnosis relies on imaging, and treatment ranges from conservative management to surgical intervention, particularly in symptomatic cases or those with complications. Recognizing tracheal diverticulum in surgical and anesthesia planning is crucial to prevent severe risks such as airway obstruction or trauma. This case report highlights the importance of early detection and personalized management, potentially improving patient outcomes and guiding clinical decision-making in similar cases., (© 2024. The Author(s).)

Background and Aims: Sirtuin-1 (SIRT1) has antidiabetic effects through the regulation of insulin secretion and modulation of inflammation. The SIRT1 rs3758391 gene polymorphism affects the level of SIRT1. The current study aimed to investigate the possible influence of SIRT1 gene variants in relation to oxidative stress parameters on the susceptibility to type 2 diabetes mellitus (T2DM) and its microvascular complications., Methods: In this case-control study 398 individuals including 300 patients with T2DM (100 T2DM without complication, 100 diabetic neuropathy patients and 100 patients with diabetic retinopathy) and 98 healthy subjects were studied for SIRT1 rs3758391 T > C variants. Also, the glutathione peroxidase (GPx) activity and the levels of glutathione (GSH), malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative status (TOS) were determined by colorimetric methods. SIRT1 genotypes were detected using the polymerase chain reaction-restriction fragment length polymorphism method., Results: The C allele of SIRT1 reduced the risk of T2DM, diabetic neuropathy and diabetic retinopathy. Significantly lower levels of GSH, GPx, and TAC were found in diabetic patients compared to control group. However, the level of MDA was significantly higher in patients compared to healthy individuals. Considering all individuals, the GPx activity increased in the presence of the SIRT1 CC, and TC genotypes compared to the TT genotype. Among all studied individuals the activity of GPx was significantly higher in normal body mass index (BMI) subjects than overweight, and obese individuals. However, among overweight and obese diabetic, diabetic retinopathy and diabetic neuropathy patients the mean level of TOS was significantly higher compared to patients with normal BMI., Conclusions: Our findings suggest a protective role for SIRT1 C allele against T2DM and diabetic neuropathy and diabetic retinopathy. We found in the presence of this allele the GPx activity increased. Also, we detected an enhanced oxidative stress level among overweight and obese patients with diabetes and its complications that could be involved in the pathogenesis of the disease., Competing Interests: Zohreh Rahimi is an Editorial Board member of Health Science Reports and a coauthor of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication. The remaining authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Introduction: Tracheostomy decannulation is a routine procedure in airway management. There is no standard decannulation method; however, the two commonly practiced approaches are tracheostomy downsizing and intermittent capping, which are both accompanied by multiple visits to the clinic and increase patient discomfort. Herein, we explore fiberoptic bronchoscopy application in a novel single-stage decannulation protocol., Methods: We conducted a retrospective study on tracheostomy patients eligible for decannulation. Fiberoptic bronchoscopy was performed on patients with spontaneous ventilation for ≥48 h, age ≥18, hemodynamic stability, normal chest X-ray, adequate swallowing, effective cough, adequate consciousness, patent speaking valve, and absent history of recurrent aspiration. Tracheostomy removal occurred after evaluating the airway and ruling out tracheomalacia, tracheitis with stenosis, obstructive granulation tissue, and moderate-to-severe stenosis. We documented patients' demographic and clinical information, along with details of their post-decannulation course., Results: Out of 58 patients admitted for tracheostomy removal, we excluded six patients (10.3%) from the study because, despite clinical indications for successful weaning, they exhibited abnormalities that interrupted the decannulation process. Of the remaining 52 patients, 50 (96.1%) were successfully weaned off, while two needed reinsertion during their hospital course. Bronchoscopy findings were unremarkable in 33 (63.5%) patients, and the most frequently observed abnormalities were paucity of vocal cord movement in 5 (9.6%) patients and granulation tissue formation in 5 (9.6%) patients. No further airway management was necessary after discharge., Conclusions: Our study introduces the innovative approach of single-stage bronchoscopic decannulation as a potentially beneficial tool for immediate decannulation. Based on our experience, we achieved a relatively satisfactory outcome following single-stage tracheostomy decannulation with bronchoscopy. The approach shows promise in providing valuable airway insights and predicting possible decannulation failures. Further research is needed to evaluate its impact on stress reduction for patients and surgeons, its superiority compared to traditional techniques, its long-term effects on healthcare, and its potential cost-effectiveness., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Situs inversus totalis is a rare congenital anomaly characterized by a mirror-image orientation of abdominal, and in some cases, thoracic organs. Here, we report our situs inversus totalis transplantation experience and further review liver transplantations in adult recipients and donors with situs inversus totalis., Case Presentation: We describe three cases with situs inversus totalis. The first case was liver transplantation in a recipient (a 61-year-old Iranian man) with situs inversus totalis, the second was a liver transplantation from a donor (a 52-year-old Iranian woman) with situs inversus totalis, and finally, for the first time, a simultaneous pancreas and kidney transplantation in a recipient (a 26-year-old Iranian man) with situs inversus totalis. In patient one, hepatectomy could be performed according to the standard method and on the basis of preoperative studies. Hepatic vein and arterial anastomosis were performed as in every other patient without situs inversus totalis. To prevent biliary complications, a Roux-en-Y hepaticojejunostomy was performed. In patient two, implantation time, suprahepatic vein, portal vein, arterial, and biliary reconstruction could be done as in any other case without situs inversus totalis. Plication of the right-sided diaphragm and fixation of the falciform ligament was done for our patient. In patient three, systemic drainage was preferred to portal flow for establishing the outflow drainage of the pancreas compared with otherwise normal patients., Conclusion: Although situs inversus totalis is a rare condition, our reported techniques are suitable, considering advantages such as easier accessibility, more acceptable placement of the implanted organs regarding vascular variations, and the appropriate location of the allograft in the proximity of other organs., (© 2024. The Author(s).)

Abdominal vascular injuries, especially in the celiac trunk, are uncommon in blunt trauma, yet their life-threatening nature necessitates rapid surgical interventions to control possible massive bleedings. Damage control surgery principles may aid management. It is crucial to thoroughly assess all trauma patients, even in instances of initial normal physical examinations., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Postoperative intra-abdominal adhesions represent a significant post-surgical problem. Its complications can cause a considerable clinical and cost burden. Herein, our study aimed to investigate the effect of Everolimus on peritoneal adhesion formation after inducing adhesions in rats. In this experimental study, adhesion bands were induced by intraperitoneal injection of 3 ml of 10% sterile talc solution in 64 male albino rats. The first group served as the control group. The second one received oral Prednisolone (1 mg/kg/day), the third received Everolimus (0.1 mg/kg/day), and group four received both drugs with similar dosages for four consecutive weeks. The formation of adhesion bands was qualitatively graded according to the Nair classification. The rats in the control group had extensive adhesions between the abdominal wall and the organs. Regarding substantial adhesion formation, 50% (8/16) of animals in the control group had substantial adhesions, while this rate in the groups receiving Prednisolone, Everolimus, and combination treatment was 31%, 31%, and 31%, respectively. Also, 68.75% (5/11) of the Prednisolone recipients had insubstantial adhesions, the same as Everolimus recipients, while in the combination group, 66.66% (10/15) rats had insubstantial adhesions. Everolimus demonstrated satisfactory results in reducing the rates of induced peritoneal adhesion in an experimental model, similar to Prednisolone and superior to a combination regime., (© 2024. The Author(s).)

Background: Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive genetic disorder with approximately 1000 known cases worldwide, in which calcium phosphate microliths deposit in the alveolar air spaces. As of writing this report, no definitive conventional therapy exists, and many PAM cases may progress to severe respiratory failure and potential death. Bilateral lung transplantation (BLx) seems to be the most optimal solution; however, this procedure is challenging along with limited reports regarding the outcome in PAM. We report a case of PAM successfully treated with BLx for the first time in Iran., Method: We present the case of a 42-year-old female with a longstanding history of cough, not responding to conventional antitussive medication, who was diagnosed as a case of PAM following a hospitalization due to coughing, dyspnea on exertion, and hemoptysis. Despite treatment with corticosteroid and medical treatment, no improvement was achieved and she subsequently developed respiratory and right ventricular failure, with oxygen ventilation dependence. Eventually, she was scheduled for BLx. The operation was successful and during her 2-year follow-up, no recurrence or significant postoperative complications has been reported., Conclusion: This case presentation and literature review confirm the effectiveness of BLx as a promising treatment for PAM-diagnosed patients, improving both life expectancy and quality of life., (© 2024 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Purpose: Oxidative stress in chronic hyperglycemia could injure the tissues and onset of diabetes-related complications like retinopathy and neuropathy. This study investigates the association between methylenetetrahydrofolate reductase (MTHFR) and glutathione peroxidase (GPx) genetic variants with these complications., Methods: In this case-control study, 400 individuals, including 100 healthy subjects and 300 patients with type 2 diabetes mellitus (T2DM) in three subgroups: with retinopathy(n = 100), with neuropathy(n = 100), and without complication (n = 100) from West Iran, were studied. MTHFR (rs1801133) and GPx-1 (rs1050450) variants were identified by the PCR-RFLP method. The plasma levels of GPx activity, glutathione, malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative stress (TOS) were measured by chemical methods., Results: Higher BMI, TOS and MDA levels were observed in patients with neuropathy compared to other patients and controls. Diabetic patients with neuropathy had lower levels of glutathione (7.8 ± 4.5; P < 0.001), GPx activity (39.5 ± 8.5; P < 0.001), and TAC (703.1 ± 129.1; P = 0.0001) in comparison with other groups. The patients without complication and retinopathic patients had higher plasma levels of glutathione (12.2 ± 2.4; p = 0.02) and TAC (793.4 ± 124.6; P < 0.001), respectively. MTHFR TT genotype significantly correlated with lower levels of TOS (3.5 ± 1.1; P < 0.001) and OSI (0.0050 ± 0.001; P < 0.001). Subjects with the GPx-1 TT genotype had higher levels of MDA (6.8 ± 2.5; P = 0.02) and lower levels of TOS (3.7 ± 1.6; P < 0.001), which is statistically significant. TT genotype of MTHFR was associated with 3.9 fold (95% CI 1.04-4.76; P = 0.0436) increased risk of neuropathy. Also, GPx-1 CT genotype increased the risk of retinopathy [OR = 2.7 (95% CI = 1.38-5.44; P = 0.0039)]., Conclusion: The MTHFR TT genotype increased the risk of neuropathy in diabetic patients significantly. The GPx-1 CT genotype is related to increased retinopathy risk among diabetic patients. Both MTHFR and Gpx-1 TT genotypes were associated with higher BMI levels., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Candidate cardiomyocyte (CM) mitogens such as those affecting the extracellular signal-regulated kinase (ERK) signaling pathway represent potential targets for functional heart regeneration. We explored whether activating ERK via a constitutively active mutant of B-raf proto-oncogene (BRAF), BRAF-V600E (caBRAF), can induce proproliferative effects in neonatal rat engineered cardiac tissues (ECTs). Sustained CM-specific caBRAF expression induced chronic ERK activation, substantial tissue growth, deficit in sarcomeres and contractile function, and tissue stiffening, all of which persisted for at least 4 weeks of culture. caBRAF-expressing CMs in ECTs exhibited broad transcriptomic changes, shift to glycolytic metabolism, loss of connexin-43, and a promigratory phenotype. Transient, doxycycline-controlled caBRAF expression revealed that the induction of CM cycling is rapid and precedes functional decline, and the effects are reversible only with short-lived ERK activation. Together, direct activation of the BRAF kinase is sufficient to modulate CM cycling and functional phenotype, offering mechanistic insights into roles of ERK signaling in the context of cardiac development and regeneration.