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Parkinson’s disease (PD) is a common neurodegenerative disorder in middle-aged and elderly people. This study aimed to elucidate the role of mesenchymal stem cells (MSCs) in management of PD in ovariectomized rat model. MSCs were excised from adipose tissue of both the omentum and the inguinal fat pad of male rats, grown, and propagated in culture; then characterized morphologically; and by the detection of surface markers gene expression. In this study, 40 ovariectomized animals were classified into 5 groups; group 1 was ovariectomized control, groups 2 to 5 were subcutaneously administered with rotenone for 14 days after 1 month of ovariectomy for induction of PD. Group 2 was left untreated; groups 3, 4, and 5 were treated with Sinemet®, Cerebrolysin®, and a single dose of adipose tissue-derived MSCs (ADMSCs), respectively. Y-chromosome gene (sry) was assessed by polymerase chain reaction (PCR) in brain tissue of the female rats. Serum transforming growth factor β (TGF-β), monocyte chemoattractant protein 1 (MCP-1), and brain-derived neurotrophic factor (BDNF) levels were assayed using enzyme-linked immunosorbent assay technique. Brain dopamine level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) gene expression was detected by semiquantitative real-time PCR. The PD group showed significant increase in serum TGF-β and MCP-1 levels associated with significant decrease in serum BDNF, brain dopamine, and brain TH gene expression levels. In contrast, all treatments produce significant decrease in serum TGF-β and MCP-1 levels in concomitant with significant increase in serum BDNF, brain dopamine, and brain TH gene expression levels. In conclusion, the observed improvements in the studied biomarkers due to ADMSCs infusion might be attributed to their immunomodulatory, anti-inflammatory, and neurotrophic effects. [ABSTRACT FROM PUBLISHER]

Among the most challenging diseases to treat is lung cancer (LC). While immunotherapy has a checkered history, it has lately shown great promise in the treatment of LC, and interest in this promising new approach is on the rise around the globe. Immunotherapy using mesenchymal stem cells (MSCs) is gaining popularity. Regenerative medicine, cell therapy, and immune modulation are three areas that have shown significant interest in MSCs. More than that, MSCs have recently attracted attention as potential anti-cancer drug delivery vehicles due to their inherent ability to go home to tumor locations. Making MSCs a double-edged sword in the fight against neoplastic illnesses, they are also known to impart pro-oncogenic properties. Additionally, multiple studies have proposed extracellular vesicles (EVs) secreted by MSCs as a potential therapeutic agent or method for delivering anti-cancer drugs. However, there has been conflicting evidence regarding the impact of MSCs or MSC-EV on the behavior of cancer cells, and the exact mechanism for this effect is still unknown. Our research has focused on MSCs and their key characteristics, such as their immunomodulatory capabilities for cancer therapy. Our research has also explored the potential of MSCs and their derivatives to treat small-cell and non-small-cell lung cancers (NSCLC and SCLC, respectively) by leveraging MSCs' immunomodulatory characteristics. At the end of this article, we covered the pros and cons of this therapy procedure, as well as what researchers want to do in the future to make it more suitable for clinical application in LC treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cyclooxygenase-2 (COX-2), a key enzyme in the inflammatory pathway, is the target for various nonsteroidal anti-inflammatory drugs (NSAIDs) and selective inhibitors known as coxibs. This study focuses on the development of novel imidazole derivatives as COX-2 inhibitors, utilizing a Structure-Activity Relationship (SAR) approach to enhance binding affinity and selectivity. Molecular docking was performed using Autodock Vina, revealing binding energies of -6.928, -7.187, and -7.244 kJ/mol for compounds 5b, 5d, and 5e, respectively. Molecular dynamics simulations using GROMACS provided insights into the stability and conformational changes of the protein-ligand complexes. Key metrics such as RMSD, RMSF, Rg, SASA, and hydrogen bond analysis were employed to assess the interactions. The binding free energy of the inhibitors was estimated using the MMPBSA method, highlighting compound 5b (N-[(3-benzyl-2-methylsulfonylimidazol-4-yl)methyl]-4-methoxyaniline) with the lowest binding energy of -162.014 kcal/mol. ADMET analysis revealed that compound 5b exhibited the most favorable pharmacokinetic properties and safety profile. Overall, this investigation underscores the potential of these novel imidazole derivatives as effective COX-2 inhibitors, with compound 5b emerging as the most promising candidate for further development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

Polysaccharides, the most abundant biopolymers in nature, have attracted the attention of researchers and clinicians due to its practicality in biomedical and pharmaceutical sciences. These biomaterials have high bioavailability and play structural and functional roles in living organisms. Polysaccharides are classified into several groups based on their origin, including plant polysaccharides and marine polysaccharides (like chitosan, hyaluronic acid, dextran, alginates, etc.) with specific applications. These biopolymers possess unique physicochemical (such as surface functional groups, solubility, and stability), mechanical (like mechanical strength and tensile), and biomedical (such as antioxidant activity, biocompatibility, biodegradability, renewability, and non-immunogenicity) characteristics which have made them excellent platforms for a wide variety of biomedical and pharmaceutical applications. Ease of extraction and different preparation approaches are mentioned as other potential properties of polysaccharides that further improved their practicality in biomedical sciences. They have high drug/bioactive encapsulation capacity and sustained/controlled release manner in in vivo microenvironments. The anti-inflammatory and immunomodulation, stimuli-responsive drug/bioactive release, and passive and active drug/bioactive delivery are considered the potential features of these biopolymers in pharmaceutical sciences. Polysaccharides have indicated practical applications in biomedical sciences, including biosensors, tissue engineering, implantation, wound healing, vascular grafting, and vaccines. This review highlights the advances of polysaccharide-based materials in biomedical and pharmaceutical sciences., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Background: Ulcerative colitis is an inflammatory bowel disease (IBD) that involves inflammation of the colon lining and rectum. Although a definitive cure for IBD has not been identified, various therapeutic approaches have been proposed to mitigate the symptomatic presentation of this disease, primarily focusing on reducing inflammation. The aim of the present study was to evaluate the therapeutic potential of combining dental pulp stem cells (DPSCs) with sulfasalazine in an acetic acid-induced ulcerative colitis rat model and to assess the impact of this combination on the suppression of inflammatory cytokines and the regulation of oxidative stress in vivo., Methods: Ulcerative colitis was induced in rats through transrectal administration of 3% acetic acid. The therapeutic effect of combining DPSCs and sulfasalazine on UC was evaluated by measuring the colonic weight/length ratio and edema markers; performing histopathological investigations of colon tissue; performing immunohistochemical staining for NF-κB-P65 and IL-1β; and evaluating oxidative stress and antioxidant indices via ELISA. Moreover, the proinflammatory markers NF-κB-P65, TNF-α and TLR-4 were assessed in colon tissue via ELISA. Furthermore, qRT‒PCR was used to estimate the expression levels of the TLR-4, NF-κB-P65, and MYD88 genes in colon tissue., Results: The investigated macroscopic and microscopic signs of inflammation were markedly improved after the combined administration of sulfasalazine and DPSCs, where a noticeable improvement in histological structure, with an intact mucosal epithelium and mild inflammatory infiltration in the mucosa and submucosa, with slight hemorrhage. The administration of either DPSCs or sulfasalazine, either individually or in combination, significantly reduced ROS levels and significantly increased XOD activity. The immunohistochemical results demonstrated that the combined administration of DPSCs and sulfasalazine attenuated NFκB-p65 and IL-1β expression. Finally, the combined administration of DPSCs and sulfasalazine significantly downregulated MyD88, NF-κB and TLR4 gene expression., Conclusions: Cotreatment with DPSCs and sulfasalazine had synergistic effects on ulcerative colitis, and these effects were relieved., (© 2024. The Author(s).)

This study aimed to prepare defatted ethanol extract of Abelmoschus esculentus leaves, Morus nigra leaves and Punica granatum peel, to identify the chemical composition of these extracts and to explore their efficacy in counteracting diabetic neuropathy. LC-ESI-MS spectrometry was the hyphenated tool for component identification of these extracts. Behavioral, biochemical, and histopathological investigations were carried out after treatments of diabetic rats. The phenolic contents in the extracts are 16.38, 34.75 and 40.57 mg GAE/g extract regarding A. esculentus leaves, M. nigra leaves and P. granatum peel respectively. Chemodiversity of the phenolic contents was observed from the LC/Mass, where A. esculentus extract contained isoflavonoids and flavanones, M. nigra extract consisted of benzofurans, prenylated flavonoids, stilbenes, and xanthones, and P. granatum extract was rich in ellagitanins, condensed tannins, and anthocyanins. The extracts normalize of blood glucose levels, enhance the explorative behavior of the rats and their response time to thermal pain, restore the oxidant/antioxidant balance, attenuate inflammation, augment brain monoamines levels and modulate MAO-A and Ache enzyme activity. Furthermore, they recovered brain histopathological alterations. Conclusively, this study offers experimental evidence for the neuroprotective impact of studied defatted ethanol extracts against diabetic neuropathy via their hypoglycemic effect, antioxidant activity, and anti-inflammatory potential., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The human gut microbiome is a dynamic and intricate ecosystem, composed of trillions of microorganisms that play a pivotal role in maintaining overall health and well-being. However, the gut microbiome is constantly exposed to various environmental factors, including the bile produced by the liver, which can significantly impact its composition and function. Bile acids, secreted by the liver and stored in the gallbladder, modulate the gut microbiome, influencing its composition and function. This altered microbiome profile can, in turn, impact the tumor microenvironment (TME), promoting an immunosuppressive environment that favors tumor growth and metastasis. Furthermore, changes in the gut microbiome can also influence the production of bile acids and other metabolites that directly affect cancer cells and their behavior. Moreover, bile acids have been shown to shape the microbiome and increase antibiotic resistance, underscoring the need for targeted interventions. This review provides a comprehensive overview of the intricate relationships between bile, the gut microbiome, and the TME, highlighting the mechanisms by which this interplay drives cancer progression and resistance to therapy. Understanding these complex interactions is crucial for developing novel therapeutic strategies that target the gut-bile-TME axis and improve patient outcomes., Competing Interests: Declarations. Competing Interests: None declared. Ethical Approval: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study end to develop nanoemulsions of Panax ginseng dry extract and to evaluate the potential impact of these nanoemulsions versus free Panax ginseng dry extract and Vit.E in recovering male infertility induced in rats. Nanoemulsions of Panax ginseng dry extract were prepared by oil in water method. The designed samples were characterized by TEM, zeta sizer, FTIR, and TGA. The in vitro study included DPPH assay to estimate the free radical scavenging activity of the suggested treatments. The in vivo study included 100 adult male Wistar rats which were assigned into 10 equal groups; five groups of young rats weighting (150-200 g) and five groups of aged rats weighting (350-400 g). Group I, negative control. Group II, bisphenol-A (BPA). Group III, BPA+ Panax ginseng dry extract nanoemulsion. Group IV, BPA+ free Panax ginseng dry extract. Group V, BPA +Vit.E. After 40 days, serum total testosterone, free testosterone, MDA, 8-OHdG and AGEs were estimated. Besides, the histological investigation of testicular tissue sections was performed. TEM imaging of Panax ginseng dry extract nanoemulsions indicated spherical shape with diameter range from 2 to 50 nm, and the size distribution was in the range from 62 to 123 d.nm. The zeta potential of the designed nanoemulsions was -32.8 to -38.9 mV. FTIR spectra revealed the common active groups in the prepared nanoemulsions. The thermal stability of the nanoemulsions was up to 207 ºC. The in vitro results of DPPH assay showed % inhibition of DPPH free radical for Panax ginseng nanoemulsions samples was 49.38% (for young-treated group Sample A) and 72.28% (for aged-treated group Sample B), while for free Panax ginseng dry extract samples was 30.27% (for young-treated group Sample C) and 56.76% (for aged-treated group Sample D), for Vit.E samples was 32.36% (for young-treated group Sample E) and 36.39% (for aged-treated group Sample F).Thus the nanoemulsions exhibit free radicals scavenging activity more than free Panax ginseng dry extract and Vit.E. The in vivo findings elucidated that Panax ginseng dry extract nanoemulsions and Vit.E successfully revers the progressive insult of BPA on male fertility by significantly enhance total testosterone (2.87±0.318) and free testosterone (1.63±0.033) serum levels, and significantly decrease MDA (2.77±0.018), 8-OHdG (6.76±0.174) and AGEs (92.60±1.701) serum levels. Interestingly, the most promising outcomes were recorded upon the treatment with Panax ginseng dry extract nanoemulsions. In conclusion the developed Panax ginseng dry extract nanoemulsion could be used as a promising strategy in improving potential male infertility defects by rescuing male sex hormones, neutralizing oxidative stress and retrieving the structural organization of the testes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Ethical Committee for Medical Research of the NRC, Egypt has been granted the final approval for the study under registration number of 13104112022 and all methods were performed in accordance with relevant regulations and guidelines including the ARRIVE guideline., (© 2024. The Author(s).)

Yersinia pestis is the perilous pandemics that occurred in Asia and Europe. The bacterium has shown drug resistance that can cause the future pandemic and destroy the drug treatment against plague. As known, effective therapeutics such as designing potent vaccine that can aid world to protect against plague. The immunoinformatics approaches was implemented via different server. The 4 potent antigens (F1 capsule, LcrV, OmpA, and PH6) were listed as essential protein target for creating the multi-epitope vaccine. These targets were selected for designing multi-epitope vaccine that predicted the CTL and HTL epitopes. The vaccine construct included different linkers such as EAAAK, AAY, GPGPG, and SSL that an adjuvant (Beta defensin-3) inserted at N-terminal of vaccine. The computational physiochemical properties and other immunological analysis showed stable, soluble, antigen, non-allergen, and non-toxin. The molecular docking confirmed the stable binding and good interaction and the iMODS server showed the stable binding. Furthermore, computational immune simulation of multi-epitope vaccine showed that vaccine can stimulate adaptive and innate responses after second doses. In this study, the vaccine designed for Y. pestis that in future require immunological examination to unveil real efficiency., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier B.V.)

Lymphoma is the sixth most prevalent cancer globally. Non-Hodgkin's lymphomas are the majority group of lymphomas, with B cells accounting for approximately 95% of these lymphomas. A key feature of B-cell lymphoma is the functional perturbations of essential biological pathways caused by genetic aberrations. These lead to atypical gene expression, providing cells with a selective growth advantage. Molecular analysis reveals that each lymphoma subtype has unique molecular mutations, which pose challenges in disease management and treatment. Substantial efforts over the last decade have led to the integration of this information into clinical applications, resulting in crucial insights into clinical diagnosis and targeted therapies. However, with the growing need for more effective medication development, we anticipate a deeper understanding of signaling pathways and their interactions to emerge. This review aims to demonstrate how the BCR, specific signaling pathways like PI3K/AKT/mTOR, NF-kB, and JAK/STAT are diverse in common types of B-cell lymphoma. Furthermore, it offers a detailed examination of each pathway and a synopsis of the approved or in-development targeted therapies. In conclusion, finding the activated signaling pathways is crucial for developing effective treatment plans to improve the prognosis of patients with relapsed or refractory lymphoma. Trial Registration: ClinicalTrials.gov identifier: NCT02180724, NCT02029443, NCT02477696, NCT03836261, NCT02343120, NCT04440059, NCT01882803, NCT01258998, NCT01742988, NCT02055820, NCT02285062, NCT01855750, NCT03422679, NCT01897571., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Abdullah Alfaifi et al.)

The review examined the potential of starch-based drug delivery systems for managing breast cancer efficiently. It covered the background of breast cancer and the significance of drug delivery systems in treatment enhancement. Starch, known for its versatile physicochemical properties, was explored as a promising biopolymer for drug delivery. The review detailed the properties of starch relevant to drug delivery, synthesis methods, and characterization approaches. It discussed the application of starch-based systems in breast cancer treatment, focusing on their role in improving chemotherapy delivery. The advantages and limitations of these systems, such as biocompatibility and drug loading capacity, were evaluated, along with future research directions in starch modification and emerging technologies. The review concluded by emphasizing the potential of starch-based drug delivery systems in improving breast cancer treatment outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to identify the suitable induction protocol to produce highly qualified insulin producing cells (IPCs) from human adipose tissue derived stem cells (ADSCs) and evaluate the efficacy of the most functionally IPCs in management of diabetes mellitus (DM) in rats. The ADSCs were isolated and characterized according to the standard guidelines. ADSCs were further induced to be IPCs in vitro using three different protocols. The success of trans-differentiation was assessed in vitro through analysis of pancreatic endocrine genes expression, and insulin release in response to glucose stimulation. Then, the functionalization of the generated IPCs was evaluated in vivo. The in vitro findings revealed that the laminin-coated plates in combination with insulin-transferrin-selenium, B27, N2, and nicotinamide could efficiently up-regulate the expression of pancreatic endocrine genes. The in vivo study indicated effectual homing of the PKH-26-labelled IPCs in the pancreas of treated animals. Moreover, IPCs infusion in diabetic rats induced significant improvement in the metabolic parameters and prompted considerable up-regulation in the expression of the pancreatic related genes. The regenerative effect of infused IPCs was determined through histological examination of pancreatic tissue. Conclusively, the utilization of laminin-coated plates in concomitant with extrinsic factors promoting proliferation and differentiation of ADSCs could efficiently generate functional IPCs., (© 2024. The Author(s).)

The "Enhanced Recovery After Surgery" (ERAS) strategy, a patient-centered, evidence-based approach, aims to reduce surgical stress, maintain physiological function, and expedite recovery. Initially developed for elective surgeries, particularly colorectal procedures, ERAS protocols are now being explored for their potential benefits in the more challenging context of emergency surgeries. The current investigation aims to identify the most useful ERAS components in emergency surgery scenarios by comparing postoperative recovery times, possible health outcomes of patients, and complication rates. Through August 2023, extensive searches were conducted in the Cochrane Library, MEDLINE, EMBASE, and PubMed databases. Data were taken from nine RCTs, which were prospective and retrospective cohort studies and were used to derive important outcomes. The Cochrane Risk of Bias tool was employed to measure the caliber of research. Effect pooling estimates were estimated using random-effects models. For the investigations, STATA version 16.0 and Review Manager (RevMan) version 5.4 were used. Nine studies that addressed the range of ERAS components and outcomes were included. Compared to standard treatment, ERAS procedures generally showed faster postoperative recovery durations. Studies' success or adherence rates differed. Subgroup analyses were necessary due to significant heterogeneity in order to determine potential sources. For emergency colorectal procedures, ERAS methods shorten postoperative recovery periods when appropriately modified and put into practice. However, varying success rates throughout studies showed that, in order to maximize and standardize ERAS protocols for comprehensive advantages, significant thought and further study are required. The meta-analysis suggests that ERAS protocols offer substantial benefits in emergency colorectal surgeries, particularly in reducing postoperative recovery times and complication rates., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ahmed et al.)

Rheumatoid arthritis (RA) is a common autoimmune condition and chronic inflammatory disease, mostly affecting synovial joints. The complex pathogenesis of RA is supportive of high morbidity, disability, and mortality rates. Pathological changes a common characteristic in RA synovial tissue is attributed to the inadequacy of apoptotic pathways. In that regard, apoptotic pathways have been the center of attention in RA therapeutic approaches. As the regulators in the complex network of apoptosis, microRNAs (miRNAs) are found to be vital modulators in both intrinsic and extrinsic pathways through altering their regulatory genes. Indeed, miRNA, a member of the family of non-coding RNAs, are found to be an important player in not even apoptosis, but proliferation, gene expression, signaling pathways, and angiogenesis. Aberrant expression of miRNAs is implicated in attenuation and/or intensification of various apoptosis routes, resulting in culmination of human diseases including RA. Considering the need for more studies focused on the underlying mechanisms of RA in order to elevate the unsatisfactory clinical treatments, this study is aimed to delineate the importance of apoptosis in the pathophysiology of this disease. As well, this review is focused on the critical role of miRNAs in inducing or inhibiting apoptosis of RA-synovial fibroblasts and fibroblast-like synoviocytes and how this mechanism can be exerted for therapeutic purposes for RA., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fahad Alsaikhan reports financial support was provided by Prince Sattam bin Abdulaziz University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Male infertility is identified by the inability of a man to successfully impregnate his fertile female partner, even following a year of regular unprotected sexual intercourse. About half of all infertility cases are attributed to what is known as "male factor" infertility. The escalating prevalence of male infertility in the contemporary era across the globe can be largely attributed to environmental pollution, which is the common etiological factor due to the ubiquitous presence of the environmental contaminants. Bisphenol A is recognized as an endocrine-disrupting chemical that has adverse effects on both male and female reproductive systems. On the other hand, numerous studies have demonstrated that Panax ginseng possessed the potential to improve male infertility parameters; promote spermatogenesis, recover the quality and motility of sperm and enhance testicular functions as it acted as a natural androgen supplement. The objective of this review is to offer a summary of the findings obtained from the current research data on the insult of bisphenol A (BPA) on male infertility and its supposed mode of action, as well as shed light on the potent ameliorative role of Panax ginseng extract, with a special focus on the mechanism behind its action. This review delivers a clear understanding of BPA mechanism of action on male infertility and the presumed risks deriving from its exposure. Also, this review provides evidence for the functional role of Panax ginseng extract in restoring male fertility., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

This study aims to explore the efficacy of Copper/Tin (CuS/SnS) nanocomposites loaded into exosomes against skin cancer A431 cell line. CuS/SnS nanocomposites (S1, S2, S3) were synthesized and characterized, then loaded into exosomes (Exo) (S1-Exo, S2-Exo and S3-Exo) and characterized. After that, the loaded samples were investigated in vitro against A431 using cytotoxicity, apoptosis, and cell cycle assays. CuS/SnS nanocomposites were indexed to hexagonal CuS structure and orthorhombic α-SnS phase and showed nano-rode shape. The exosomes loaded with nanocomposites were regular and rounded within the size of 120 nm, with no signs of broken exosomes or leakage of their contents. The cytotoxicity assay indicated the enhanced cytotoxic of S1-Exo versus the free nano-form S1 on A431. Interestingly, S1-Exo recorded 1.109 times more than DOX in its anti-skin cancer capacity. Moreover, S1-Exo recorded 40.2 % for early apoptosis and 22.1 % for late apoptosis. Furthermore, it displayed impact in arresting the cancer cell cycle at G0/G1 phase and reducing G2/M phase. Noteworthy, loaded nanocomposites were safe against normal HSF skin cells. In conclusion, the loaded CuS/SnS nanocomposites into the exosomes could be of great potential as anti-skin cancer candidates through induction of apoptosis and promotion of the cell cycle arrest at G0/G1 phase., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The current study was constructed to fabricate polyamide based nanofibrous scaffolds (NS) and to define the most promising one for the generation of cardiomyocytes from adipose tissue derived mesenchymal stem cells (ADMSCs). This purpose was extended to assess the potentiality of the generated cardiomyocytes in relieving myocardial infarction (MI) in rats. Production and characterization of NSs were carried out. ADMSCs were cultured on NS and induced to differentiate into cardiomyocytes by specific growth factors. Molecular analysis for myocyte-specific enhancer factor 2 C (MEF2C) and alpha sarcomeric actin (α-SCA) expression was done to confirm the differentiation of ADMSCs into cardiomyocytes for further transplantation into MI induced rats. Implantation of cells in MI afflicted rats boosted heart rate, ST height and PR interval and lessened P duration, RR, QTc and QRS intervals. Also, this type of medication minified serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) enzymes activity as well as serum and cardiac troponin T (Tn-T) levels and upraised serum and cardiac α-SCA and cardiac connexin 43 (CX 43) levels. Microscopic feature of cardiac tissue sections of rats in the treated groups revealed great renovation in the cardiac microarchitecture. Conclusively, this attempt gains insight into a realistic strategy for recovery of MI through systemic employment of in vitro generated cardiomyocytes., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background Pediatric respiratory infections, mainly bronchiolitis, are a substantial clinical burden. The most common etiology is respiratory syncytial virus (RSV). Other viruses include human rhinovirus, human metapneumovirus, influenza, adenovirus, coronavirus, and parainfluenza viruses. Objective We aimed to study the epidemiology and clinical characteristics of children with confirmed viral bronchiolitis and flu after the COVID-19 pandemic season and compare the behavior of each virus. Methods This retrospective observation study was done over seven months, from October 2022 to April 2023. All children (0-14) were included in the study if they met the clinical diagnosis of bronchiolitis or flu. Viral etiology is confirmed by PCR, using the respiratory panel available in our center which included the detection of four viruses: COVID-19, RSV, influenza A, and B. Clinical data, lab results, and X-rays were collected and correlated with each viral infection for all admitted patients. Results We recruited 237 children with bronchiolitis and flu symptoms from October 2022 to April 2023. The peak of infections (41%) was in November. Seasonal variations for each virus showed distinct patterns across the year. RSV peaked at the beginning of the season, gradually declining after that. In contrast, influenza A and B maintained a relatively consistent presence throughout the season. Meanwhile, COVID-19 reached its peak during March and April. One hundred forty-four (60%) of the patients were under two years of age. RSV was predominant in 150 patients (63.3%). COVID-19 was only detected in 25 patients (10%), whereas influenza A and B were equally isolated in 31 (13%) patients each. Fifty-one children (21%) were initially sick and required pediatric intensive care unit (PICU) admission, with no deaths reported. Notably, COVID-19 had a milder disease course, a shorter length of stay (LOS) in the hospital (two days) and a shorter duration of illness (five days) compared to other viruses. RSV infection was linked to more profound hypoxia and more sick children with more extended hospital stays. Conclusion Our study showed that, following the pandemic and the release of lockdown measures, there was another peak of upper respiratory tract infections (URTI) and flu, which was more aggressive, primarily due to other viruses, especially RSV. This resurgence was associated with more severe respiratory symptoms and an increased need for hospitalization. Notably, children with COVID-19 were in better condition compared to those with RSV., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Prince Sultan Military Medical City Scientific Research Center issued approval E-2136. On the recommendation of the board of review in the ethical aspects of the proposal, the Institutional Review Board (IRB) is pleased to approve and grant permission to conduct your study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shahin et al.)

Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process., (© 2024. The Author(s).)

Doxorubicin (DOX) is the cornerstone of chemotherapy. However, it has dose-dependent cardiotoxic events that limit its clinical use. This study was intended to investigate the efficiency of DOX as an anti-cancer against the MCF-7 cell line in the presence of diosmin (DIO) and to appraise the protective impact of DIO against DOX cardiotoxicity in vivo. In vitro study was carried out to establish the conservation of DOX cytotoxicity in the presence of DIO. In vivo study was conducted on 42 adult female Wistar rats that were equally allocated into 6 groups; control, DIO (100 mg/kg), DIO (200 mg/kg), DOX (20 mg/kg, single dose i.p.), DIO (100 mg/kg) + DOX, received DIO orally (100 mg/kg) for 30 days, then administrated with a single dose of DOX and DIO (200 mg/kg) + DOX, received DIO orally (200 mg/kg) for 30 days, then administrated with DOX. In vitro study showed preservation of cytotoxic activity of DOX on MCF-7 in the presence of DIO. In vivo study indicated that DOX altered electrocardiograph (ECG) parameters. Also, it yielded a significant rise in CK-MB, cTnT and LDH serum levels and cardiac contents of MDA, IL-1β; paralleled by a significant drop in cardiac IL-10 and SOD. Moreover, significant upregulation of Bax, TNF-α, and HIF-1α, in concomitant with significant downregulation of Bcl-2 mRNA in cardiac tissue have been recorded in the DOX group. Furthermore, histopathological description of cardiac tissues showed that DOX alters normal cardiac histoarchitecture. On the opposite side, DIO pretreatment could ameliorate ECG parameters, suppress IL-1β and enhanceIL-10, promote activity of SOD and repress MDA. Additionally, downregulation of Bax, TNF-α, HIF-1α and upregulation of Bcl-2 have been demonstrated in DIO-pretreated rats. Furthermore, the histopathological examination of cardiac tissues illustrated that DIO had a favorable impact on the protection of heart histoarchitecture. DIO is suggested for protection against acute cardiotoxicity caused by DOX without affecting antitumor activity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this communication, the solubility of digitoxin drug in supercritical CO 2 was studied at different operating conditions (311 < T (K) < 343, 120 < P (bar) < 300). The results revealed digitoxin drug solubility (in mole fraction) was between 0.095 × 10 -5 to 1.12 × 10 -5 . In the case of thermodynamic solubility modeling, cubic and non-cubic equation of states i.e. SAFT (statistical associating fluid theory), SRK (Soave-Redlich-Kwong) and sPC-SAFT (simplified perturbed chain SAFT) EoSs and six density-based correlations (Chrastil, Kumar-Johnston (KJ), Mendez-Santiago-Teja (MST), Garlapati and Madras (GM), Bartle et al. and Sung-Shim models) were considered. All used equations indicated reasonable behavior with appropriate accuracy for the solubility of the digitoxin drug. Meanwhile, sPC-SAFT EoS and Kumar-Johnston correlation with AARD% set to 8.96 % and 6.25 %, respectively exhibited greater accuracy in fitting the solubility data. Moreover, total, solvation and vaporization enthalpies of the digitoxin/supercritical carbon dioxide binary mixture were calculated based on KJ, Chrastil and Bartle et al. models., (Copyright © 2024. Published by Elsevier B.V.)

This investigation aimed to establish the promising role of insulin-producing cells (IPCs) growing from bone marrow-mesenchymal stem cells (BM-MSCs) in relieving hyperglycemia induced in rats. BM-MSCs were differentiated into IPCs using three different protocols. The efficiency of BM-MSCs differentiation into IPCs in vitro was confirmed by detecting IPCs specific gene expression (Foxa-2, PDX-1 and Ngn-3) and insulin release assay. The in vivo study design included 3 groups of male Wistar rats; negative control group, diabetic group and IPCs-transfused group (5 ×10 6 cells of the most functional IPCs/rat). One month after IPCs infusion, serum glucose, insulin, c-peptide and visfatin levels as well as pancreatic glucagon level were quantified. Gene expression analysis of pancreatic Foxa-2 and Sox-17, IGF-1 and FGF-10 was done. Additionally, histological investigation of pancreatic tissue sections was performed. Our data clarified that, the most functional IPCs are those generated from BM-MSCs using differentiation protocol 3 as indicated by the significant up-regulation of Foxa-2, PDX-1 and Ngn-3 gene expression levels. These findings were further emphasized by releasing of a significant amount of insulin in response to glucose load. The transplantation of the IPCs in diabetic rats elicited significant decline in serum glucose, visfatin and pancreatic glucagon levels along with significant rise in serum insulin and c-peptide levels. Moreover, it triggered significant up-regulation in the expression levels of pancreatic Foxa-2, Sox-17, IGF-1 and FGF-10 genes versus the untreated diabetic counterpart. The histopathological examination of pancreatic tissue almost assisted the biochemical and molecular genetic analyses. These results disclose that the cell therapy holds potential to develop a new cure for DM based on the capability of BM-MSCs to generate β-cell phenotype using specific protocol., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Obese individuals have a higher risk of degenerative disc disease (DDD). Currently, body mass index is not sensitive enough to differentiate between muscle and fat distribution, and obesity-related health issues are linked to the way body fat is distributed. Therefore, this study aims to investigate the association between the dorsal subcutaneous fat thickness (DSFT) of the lumbar spine, an alternative measurement tool of body fat distribution, and DDD., Methods: A total of 301 patients with DDD and 123 participants without the disease were recruited. Using length functions of magnetic resonance imaging (MRI) console, the DSFT of L1 to S1 intervertebral disc levels was measured in mid-sagittal spin-echo T2 weighted image. The Mann-Whitney U test and Chi-squared test (X2) were utilized to examine any variations between the case and control groups. Logistic regression models were built to explore the association of the DSFT with DDD., Results: The logistical regression model showed a positive association between DDD and DSFT [OR: 1.30, 95% CI: 1.02-1.64, p = 0.03]. In the stratified logistic regression analysis, a positive association was found between DDD and DSFT among younger participants and females [OR young : 1.48; 95% CI (1.02-2.20); p = 0.04-OR female : 1.37; 95% CI (1-1.88); p = 0.05]., Conclusions: Younger females with thicker DSFT at the L1-L2 level are more likely to develop DDD. This suggests that increased DSFT may be a contributing factor to DDD.

Depression is a widespread neuropsychiatric illness whose etiology is yet mysterious. Lactoferrin (LF), an iron-binding glycoprotein, is reported to promote neuroprotection through its role in the modulation of oxidative stress and inflammation. The objective of the present research was to evaluate the efficacy of LF against chronic restraint stress (CRS)-induced depressive behavior in rats. Depression was evidenced by a reduced grooming time in the splash test and an increased immobility time in the tail suspension test (TST) and forced swimming test (FST). This effect was also accompanied by reduced GSH and serotonin levels and elevated lipid peroxidation and corticosterone levels in the hippocampus. Additionally, an exaggerated hippocampal inflammatory response was also shown by a rise in NF-κB (p65) and TNF-α levels and a reduced IL-10 level. Moreover, CRS substantially reduced the BDNF content as well as the protein levels of PI3K, Akt, and mTOR while boosting the GSK3β content. Interestingly, LF therapy significantly improved CRS-induced behavioral and biochemical aberrations, an effect which was suppressed upon pretreatment with LY294002 (PI3K inhibitor). This suggests that the antidepressant potential of LF may be mediated through the modulation of the PI3K/Akt/mTOR signaling pathway. Furthermore, LF succeeded in restoring 5-HT and corticosterone levels, diminishing oxidative stress and ameliorating the inflammatory cascades. Therefore, and for the first time, LF might serve as a promising antidepressant drug through targeting the PI3K/Akt/mTOR pathway.

Viral infections in humans are responsible for fatalities worldwide and contribute to the incidence of various human ailments. Controllable targeted medicine delivery against many illnesses, including viral infection, may be significantly aided by using bacteria and bacteria-derived products. They may accumulate in diseased tissues despite physical obstacles, where they can launch antiviral immunity. The ability to genetically and chemically modify them means that vaccinations against viral infections may be manufactured and delivered to affected tissues more safely and effectively. The objective of this study is to provide an overview of the latest advancements in the field of utilizing bacteria and bacterial derivatives as carriers for administering medication to treat viral diseases such as SARS-CoV-2, hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human papillomavirus, influenza, and Ebola virus., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Human Cytomegalovirus (HCMV) is a leading healthcare problem associated with stillbirth and congenital abnormalities. Determining the seroprevalence and the possible risk factors related to HCMV infections may be a cornerstone in preventing its complications. This cross-sectional study was conducted in Kassala and River Nile States to determine the seroprevalence and risk factors associated with HCMV infection in pregnant women. One hundred eighty-four (n = 184) blood specimens were collected from pregnant women from February 2018 to January 2020. Enzyme-linked immunosorbent assay (ELISA) was used to detect HCMV-specific IgG and IgM antibodies. Socio-demographical characteristics of the women were collected using structured questionnaires. The results showed that HCMV IgG was detected in 170 (92.4%) of the blood specimens, and IgM was detected in 29/93 (31.2%). There was a significant relationship between the history of miscarriage and the presence of IgG and IgM with a p -value = 0.001 and between HCMV IgM and gestational stage ( p -value = 0.028). The study found a strikingly high seroprevalence of HCMV infections among pregnant women in the investigated States. This high percentage of illiterate housewives living in rural areas makes it possible to reduce the incidence of HCMV infection in pregnant women by improving their knowledge, attitude, and practice regarding the route of viral transmission, which may reflect in lowering the rate of congenital diseases in their infants., (© 2023 Ehssan H. Moglad et al., published by Sciendo.)

Obesity is one of the major metabolic syndrome risk factors upon which altered metabolic pathways follow. This study aimed to discern altered metabolic pathways associated with obesity and to pinpoint metabolite biomarkers in serum of obese rats fed on high fructose diet using metabolomics. Further, the effect of standardized green versus black caffeinated aqueous extracts (tea and coffee) in controlling obesity and its comorbidities through monitoring relevant serum biomarkers viz. Leptin, adiponectin, spexin, malondialdehyde, total antioxidant capacity. Liver tissue oxidative stress (catalase, super oxide dismutase and glutathione) and inflammation (IL-1β and IL-6) markers were assessed for green coffee and its mixture with green tea. Results revealed improvement of all parameters upon treatments with more prominence for those treated with green caffeinated extract (coffee and tea) especially in mixture. Upon comparing with obese rat group, the green mixture of coffee and tea exhibited anti-hyperlipidemic action through lowering serum triglycerides by 35.0% and elevating high density lipoprotein by 71.0%. Black tea was likewise effective in lowering serum cholesterol and low density lipoprotein by 28.0 and 50.6%, respectively. GC-MS- based metabolomics of rat serum led to the identification of 34 metabolites with obese rat serum enriched in fatty acids (oleamide)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect that affects more than 500 million people worldwide. Individuals affected with G6PD deficiency may occasionally suffer mild-to-severe chronic hemolytic anemia. Chronic non-spherocytic hemolytic anemia (CNSHA) is a potential result of the Class I G6PD variants. This comparative computational study attempted to correct the defect in variants structure by docking the AG1 molecule to selected Class I G6PD variants [G6PD Nashville (Arg393His), G6PD Alhambra (Val394Leu), and G6PD Durham (Lys238Arg)] at the dimer interface and structural NADP + binding site. It was followed by an analysis of the enzyme conformations before and after binding to the AG1 molecule using the molecular dynamics simulation (MDS) approach, while the severity of CNSHA was determined via root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), hydrogen bonds, salt bridges, radius of gyration (Rg), solvent accessible surface area analysis (SASA), and principal component analysis (PCA). The results revealed that G6PD Nashville (Arg393His) and G6PD Durham (Lys238Arg) had lost the direct contact with structural NADP + and salt bridges at Glu419 - Arg427 and Glu206 - Lys407 were disrupted in all selected variants. Furthermore, the AG1 molecule re-stabilized the enzyme structure by restoring the missing interactions. Bioinformatics approaches were also used to conduct a detailed structural analysis of the G6PD enzyme at a molecular level to understand the implications of these variants toward enzyme function. Our findings suggest that despite the lack of treatment for G6PDD to date, AG1 remains a novel molecule that promotes activation in a variety of G6PD variants., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is a neurodegenerative disorder that jeopardizes the lives of diagnosed patients at late stages. This study aimed to assess, for the first time, the efficiency of germanium dioxide nanoparticles (GeO 2 NPs) in mitigating AD at the in vivo level compared to cerium dioxide nanoparticles (CeO 2 NPs). Nanoparticles were synthesized using the co-precipitation method. Their antioxidant activity was tested. For the bio-assessment, rats were randomly assigned into four groups: AD + GeO 2 NPs, AD + CeO 2 NPs, AD, and control. Serum and brain tau protein, phosphorylated tau, neurogranin, amyloid β peptide 1-42, acetylcholinesterase, and monoamine oxidase levels were measured. Brain histopathological evaluation was conducted. Furthermore, nine AD-related microRNAs were quantified. Nanoparticles were spherical with diameters ranging from 12-27 nm. GeO 2 NPs exhibited a stronger antioxidant activity than CeO 2 NPs. Serum and tissue analyses revealed the regression of AD biomarkers to almost control values upon treatment using GeO 2 NPs. Histopathological observations strongly supported the biochemical outcomes. Then, miR-29a-3p was down-regulated in the GeO 2 NPs-treated group. This pre-clinical study substantiated the scientific evidence favoring the pharmacological application of GeO 2 NPs and CeO 2 NPs in AD treatment. Our study is the first report on the efficiency of GeO 2 NPs in managing AD. Further studies are needed to fully understand their mechanism of action.

Objective: Hepatocellular carcinoma (HCC) microenvironment has been recognized as a key contributor for cancer progression, metastasis, and drug resistance. The crosstalk between tumor cells, the vascular endothelial growth factor (VEGF), and the chemokine (C-C motif) ligand 2 (CCL2) signaling networks mediates immunoinhibitory impact and facilitates tumor angiogenesis. The current investigation aimed at exploring the potent anti-cancer activity of the newly designed nano-based anti-cancer therapy comprising anti-VEGF drug, avastin (AV), and CCR2 antagonist (CR) to counteract HCC and tracking its mode of action in vivo., Methods: The prepared AV, CR, and AVCR nanoprototypes were characterized by nanoscale characterization techniques in our previous work. Here, they are applied for unearthing their anti-cancer properties / mechanisms in hepatic cancer-induced rats via analyzing protein levels and genetic expression of the elements incorporated in the angiogenesis, apoptosis, and metastasis signalling pathways., Results: The present results revealed a significant down-regulation in the angiogenesis, survival and metastasis indices along with up-regulation in the pro-apoptotic mediators upon treatment of hepatic cancer-bearing rats with the novel synthesized nanomaterials when compared with the untreated counterparts. We showed across HCC model that anti-VEGF in combination with CCR2 antagonism therapy leads to sensitization and enhanced tumor response over anti-VEGF or CCR2 antagonism monotherapy, particularly in its nanoscale formulation., Conclusion: The present approach provides new mechanistic insights into the powerful anti-hepatic cancer advantage of the novel nanoprototypes which is correlated with modulating critical signal transduction pathways implicated in tumor microenviroment such as angiogenesis, apoptosis and metastasis. This research work presents a substantial foundation for future studies focused on prohibiting cancer progression and recovery by targeting tumor microenviroment.

A new series of nicotinonitrile derivatives 2 - 7 was designed and synthesized from the starting material ( E )-3-(4-chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one ( 1 ) to assess their molluscicidal activity. The newly synthesized nicotinonitrile compounds 2 - 7 were characterized based on FTIR, 1 H-NMR, and 13 C-APT NMR spectra as well as elemental microanalyses. The target compounds 2 - 7 were screened for their toxicity effect against M. cartusiana land snails and were compared to Acetamiprid as a reference compound. The results demonstrated that the nicotinonitrile-2-thiolate salts 4a and 4b had good mortality compared with that of Acetamiprid. The results of the in vivo effect of the prepared nicotinonitrile molecules 2 , 4a , and 4b on biochemical parameters, including AChE, ALT, AST, and TSP, indicated a reduction in the level of AChE and TSP as well as an increase in the concentration of transaminases (ALT and AST). A histopathological study of the digestive gland sections of the M. cartusiana land snails was carried out. The nicotinonitrile-2-thiolate salts 4a , b showed vacuolization, causing the digestive gland to lose its function. It could be concluded that the water-soluble nicotinonitrile-2-thiolate salts 4a , b could be adequate molluscicidal molecules against M. cartusiana land snails.

Hepatocellular carcinoma (HCC) is a global health problem with regional differences in epidemiological statistics. Co-assembling the drug nanoparticles and targeting moieties could improve the therapeutic delivery of anti-cancer drugs. In this attempt, we tracked the extrinsic and intrinsic apoptotic pathways in HCC cells using viramidine (VRM)-loaded aptamer (APT) nanoparticles. In these NPs, both APT and VRM act as targeted ligands/drugs to HCC cells. The NPs were characterized using TEM, ESI-MS, FTIR, and 1 H NMR. The results showed uniform particles with round and smooth shapes on the nano-scale. SRB-based cytotoxicity was performed and IC 50 values were measured for HCC versus normal cells upon the proposed treatments. The flow cytometry technique was applied to determine apoptosis, then confirmed using genetic and protein analyses. In addition, nitric oxide (NO) and its enzyme (iNOS) were analyzed to examine the effect of reactive nitrogen species (RNS) on apoptosis induction. The present findings indicated that Huh-7 cells were more sensitive to APT-VRM NPs than HepG2 cells, recording the lowest IC 50 values (11.23 ± 0.23 µM and 16.69 ± 1.12 µM), as well as the highest significant increase in the apoptotic cells (61.5% and 42%), respectively. Intriguingely, normal BHK-21 cells recorded undetectable IC 50 values in the applied NPs, confirming their targeted delivery ability. The genetic expression and protein levels of c-FLIP, Bcl-2, and TNF-α were down-regulated, while FADD, caspase 8, caspase 3, caspase 9, and Bax were up-regulated upon treatment with APT-VRM NPs. The prepared VRM NPs labeled with APT could significantly elevate NO via activation of iNOS. In conclusion, APT-VRM NPs bioconjugate interferes with HCC cells through NO-mediated extrinsic and intrinsic apoptosis., (© 2022. The Author(s).)

Objectives: This research aimed at uncovering the mechanisms behind obesity-related hypogonadism in adolescent boys and to investigate the association between anthropometric characteristics and testicular functions of these boys., Methods: This study included 60 adolescent boys (12-18 years) with exogenous obesity (BMI≥95th percentile) and 30 age matched lean controls (BMI=15th-85th percentile). Full clinical examination, anthropometric measurements and pubertal assessment were performed. Laboratory investigations included hemoglobin, hematocrit, lipid panel, LH, FSH, free and total testosterone, inhibin B and estradiol., Results: The results indicated the presence of positive family history of obesity in 85% of obese boys vs. 40% of the lean counterparts. Concerning SBP of obese boys, 7% were hypertensive (95th percentile), 25% were prehypertensive (between 90th and 95th percentiles) while, DBP findings showed that 33% are hypertensive and 33% are prehypertensive. Meanwhile, 13.3% of lean controls were prehypertensive. Anthropometric measurements and lipid profile values revealed a significant difference between obese and lean boys. Compared to obese boys the normal weight boys had higher levels of free testosterone (21.15 ± 2.90 pg/mL vs. 11.38 ± 3.96 pg/mL, p<0.001), total testosterone (10.59 ± 6.63 ng/dL vs. 3.23 ± 1.70 ng/dL, p<0.001), FSH (7.33 ± 3.75 mIU/mL vs. 5.63 ± 3.96 mIU/mL, p=0.026) and inhibin B (83.28 ± 27.66 pg/mL vs. 62.90 ± 17.85 pg/mL, p=0.001) and they registered lower level of estradiol (18.48 ± 7.33 pg/mL vs. 40.20 ± 7.91 pg/mL, p<0.001). In obese boys, BMI SDS significantly correlated with lipid profile and estradiol whereas, it showed significant negative correlation with LH, free and total testosterone and inhibin B. Penile length significantly correlated with LH while it revealed significant negative correlation with cholesterol., Conclusions: This study evidenced a close association between obesity and hypogonadism in adolescent boys which could be due to the increased estradiol level and decreased T/E2 ratio., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Despite the recent progress in the differentiation strategies of stem cells into pancreatic beta cell lineage, current protocols are not optimized for different cell types. The purpose of this study is to investigate and compare the ability of stem cells derived from dental pulp (DPSCs) and periodontal ligament (PDLSCs) as two anatomically different dental tissues to differentiate into pancreatic beta cells while assessing the most suitable protocol for each cell type., Methods: DPSCs & PDLSCs were isolated and characterized morphologically and phenotypically and then differentiated into pancreatic beta cells using two protocols. Differentiated cells were assessed by qRT-PCR for the expression of pancreatic related markers Foxa-2, Sox-17, PDX-1, Ngn-3, INS and Gcg. Functional assessment of differentiation was performed by quantification of Insulin release via ELISA., Results: Protocol 2 implementing Geltrex significantly enhanced the expression levels of all tested genes both in DPSCs & PDLSCs. Both DPSCs & PDLSCs illustrated improved response to increased glucose concentration in comparison to undifferentiated cells. Moreover, DPSCs demonstrated an advanced potency towards pancreatic lineage differentiation over PDLSCs under both protocols., Conclusion: In conclusion, the current study reports the promising potential of dental derived stem cells in differentiating into pancreatic lineage through selection of the right protocol., (© 2022. The Author(s).)

Aim: This study aimed to evaluate the efficacy of hypoxia-persistent insulin-producing cells (IPCs) against diabetes in vivo ., Materials & Methods: Mesenchymal stem cells (MSCs) differentiation into IPCs in the presence of Se/Ti (III) or CeO 2 nanomaterials. IPCs were subjected to hypoxia and hypoxia genes were analyzed. PKH-26-labeled IPCs were infused in diabetic rats to evaluate their anti-diabetic potential., Results: MSCs were differentiated into functional IPCs. IPCs exhibited overexpression of anti-apoptotic genes and down-expression of hypoxia and apoptotic genes. IPCs implantation elicited glucose depletion and elevated insulin, HK and G6PD levels. They provoked VEGF and PDX-1 upregulation and HIF-1α and Caspase-3 down-regulation. IPCs transplantation ameliorated the destabilization of pancreatic tissue architecture., Conclusion: The chosen nanomaterials were impressive in generating hypoxia-resistant IPCs that could be an inspirational strategy for curing diabetes., (© 2022 The Authors.)

Cardiac disease is the leading cause of mortality and disability worldwide. We investigated the role of undifferentiated adipose tissue-derived mesenchymal stem cells (ADMSC) alone and ADMSC seeded onto the electro-spun nanofibers (NF) for reconstructing damaged cardiac tissue in isoprenaline-induced myocardial infarction (MI) in rats. ADMSC were sorted by morphological appearance and by detection of cluster of differentiation (CD) surface antigens. The therapeutic potential of ADMSC for treating MI was evaluated by electrocardiogram (ECG), biochemical analysis, molecular genetic analysis and histological examination. Treatment of MI-challenged rats with ADMSC improved ECG findings, which were corroborated by significant decreases in serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) enzyme activities together with reduced serum troponin T (cTnT) and connexin 43 (Cx43) levels. MI model rats treated with ADMSC exhibited a significant increase in serum alpha sarcomeric actin (Actn) and GATA binding protein 4 (GATA4), and NK2 homeobox 5 ( NKX2.5) gene expression was decreased following treatment with ADMSC. ADMSC also ameliorated damage to cardiac tissue. The effects of ADMSC seeded onto NF were superior to those of ADMSC alone. ADMSC may be useful for mitigation of MI.

Background: This study was designed to generate functional insulin-producing cells (IPCs) from dental-derived mesenchymal stem cells (MSCs) and further explore their therapeutic potential against diabetes mellitus in vivo. MSCs were isolated from human dental pulp and periodontal ligament and were induced to differentiate into insulin-producing cells (IPCs) using laminin-based differentiation protocol for 14 days. Confirmation of IPCs was performed through real-time PCR analysis and insulin release assay. Then, the generated IPCs were labeled with PKH26 dye prior to transplantation in experimental animals. Twenty-eight days later, blood glucose, serum insulin (INS), c-peptide (CP), and visfatin (VF) levels and pancreatic glucagon (GC) level were estimated. Pancreatic forkhead box protein A2 (Foxa2) and SRY-box transcription factor 17 (Sox17), insulin-like growth factor I (IGF-1), and fibroblast growth factor10 (FGF 10) gene expression levels were analyzed., Results: Dental stem cells were successfully differentiated into IPCs that demonstrated increased expression of pancreatic endocrine genes. IPCs released insulin after being subjected to high levels of glucose. In vivo findings uncovered that the implanted IPCs triggered significant decrease in blood glucose, serum VF, and pancreatic GC levels with significant increase in serum INS and CP levels. Furthermore, the implanted IPCs provoked significant upregulation in the expression level of pancreatic genes. Histopathological description of the pancreas tissues revealed that transplantation of IPCs ameliorated the destabilization of pancreas tissue architecture., Conclusion: This study demonstrates the significant role of the implantation of IPCs generated from dental-derived stem cells in treatment of diabetes mellitus., (© 2022. The Author(s).)