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Background: Colorectal cancer (CRC) is a common gastrointestinal cancer, and even though oxaliplatin chemotherapy is effective, there is a high likelihood of relapse, indicating the presence of oxaliplatin-resistant CRC. Therefore, it is crucial to comprehend the molecular mechanisms of oxaliplatin resistance and develop effective strategies to counter drug resistance. Numerous studies have demonstrated the close association between microRNAs (miRNAs) and drug resistance in CRC. In this study, we aimed to identify the essential exosomal and cellular miRNA related to oxaliplatin resistance in the CRC cell line HCT-116., Methods: The miRNA expression profile of CRC cells with resistance to oxaliplatin was analyzed. The effectiveness of diagnostics and biomarker potency of miRNAs were evaluated by receiver operating characteristic (ROC) analysis. Target miRNAs were identified, and the enrichment analysis was assessed based on Gene Ontology (GO), Reactome, and Human Disease Ontology (DO). In vitro experiments, oxaliplatin-resistant HCT-116 cells (HCT116-OXA) were developed, and the exosomes were isolated and characterized from HCT116-OXA and HCT116 cells. The expression of the selected miRNAs was evaluated in HCT116-OXA cells and their exosomes, and they were compared to HCT-116 cells using quantitative real-time PCR., Results: This study revealed that a combination of miR-4326, miR-3615, miR-7974, miR-130b-3p, and miR-454-3p exhibited the highest area under the curve (AUC), sensitivity, specificity, and superior diagnostic and predictive performance. In vitro experiments, HCT116-OXA cells displayed reduced early and late apoptosis, a bypass of S phase arrest, prolonged doubling time, and higher IC 50 compared to parental cells. The expression of miR-454-3p, miR-130b-3p, miR-7974, miR-3615, and miR-4326 was decreased in HCT116-OXA cells as compared to sensitive cells. However, a significantly higher expression of miR-130b-3p and miR-4326 was observed in the isolated exosomes of HCT116-OXA cells as compared to the sensitive cells., Conclusions: The low expression of miR-454-3p, miR-7974, and miR-3615 in CRC cells or high expression of miR-130b-3p and miR-4326 in isolated exosomes could predict the response to oxaliplatin therapy. This indicates the potential of these specific miRNAs to serve as predictive markers for the response to oxaliplatin therapy., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objectives: This review examines how food additives impact the central nervous system (CNS) focusing on the effects of sugars, artificial sweeteners, colorings, and preservatives., Methods: A literature search of PubMed, Scopus, and Web of Science was conducted for studies published since 2010. Key search terms included, food additives, neurotoxicity, cognition, and behavior., Results: It summarizes research findings on additives such as aspartame, stevia, methylene blue, azo dyes, sodium benzoate, and monosodium glutamate. It also covers mechanisms such as oxidative stress, neuroinflammation, and disruptions in neurotransmitter systems. Furthermore, it emphasizes the properties of natural compounds such as garlic ( Allium sativum ), tetramethylpyrazine, curcumin, licorice root extract (glycyrrhizin), and polyphenols in mitigating CNS damage caused by food additives., Discussion: Although ongoing studies are expanding our knowledge on the effects of these additives, future CNS research should focus on long-term investigations involving subjects to provide a more comprehensive understanding of the cumulative impacts of different additives and update regulatory standards based on new scientific findings.

Despite the unique properties of clay nanocomposites for cardiovascular applications, there are few data on the hemocompatibility of these nanomaterials. This study represents the first comprehensive investigation of the hemo/biocompatibility of clay nanocomposites in vitro . Nanocomposite coatings of polylactic acid (PLA)-polyethylene glycol (3 wt %)-Cloisite20A nanoclay (3 wt %) were produced using electrospraying technique as potential drug-eluting stent (DES) coatings. Pristine PLA coating served as a control. The coatings ' different structural and biological properties were assessed, including surface morphology, topography, hydrophobicity, mechanics, and the interaction of nanocomposites with blood components, endothelial cells (EC), and bacteria. Findings indicated that all of the coatings were highly hydrophobic with microbead/nanofiber morphology and had antifouling properties. The absorption profiles of plasma proteins were similar for all groups, and nanocomposites did not trigger the coagulation cascade and complement activation. The nanocomposites did not increase hemolysis or platelet and leukocyte adhesion and activation. Interestingly, the nanocomposites exhibited the lowest levels of interleukin-6 production. Cellular experiments showed that the nanocomposites did not reduce ECs survival compared to the control group, and a continuous layer of ECs covered the nanocomposite surfaces after 4 days. These results demonstrate the exceptional hemo/biocompatibility of as-prepared clay nanocomposites as promising biomaterials for implants such as DESs.

The 5,000 to 8,000 monogenic diseases are inherited disorders leading to mutations in a single gene. These diseases usually appear in childhood and sometimes lead to morbidity or premature death. Although treatments for such diseases exist, gene therapy is considered an effective and targeted method and has been used in clinics for monogenic diseases since 1989. Monogenic diseases are good candidates for novel therapeutic technologies like gene editing approaches to repair gene mutations. Clustered regularly interspaced short palindromic repeats (CRISPR)-based systems, the pioneer and effective gene editing tool, are utilized for ex vivo and in vivo treatment of monogenic diseases. The current review provides an overview of recent therapeutic applications of CRISPR-based gene editing in monogenic diseases in in vivo and ex vivo models. Furthermore, this review consolidates strategies aimed at providing new treatment options with gene therapy, thereby serving as a valuable reference for advancing the treatment landscape for patients with monogenic disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Heat-killed lactobacilli seem to have protective effects against oxidative stress and neurotoxicity. This study aimed to evaluate the antioxidant properties of specific heat-killed lactobacilli extracts and determine their neuroprotective effects against the neurotoxicity induced by blood plasma from people with multiple sclerosis (MS). The antioxidant activity of the three heat-killed lactobacilli was measured using the DPPH assay. For neuroprotective evaluations of lactobacilli, human neuroblastoma cells (SK-N-SH) were exposed to plasma from individuals with relapsing-remitting MS (RRMS) and healthy controls, with or without pre-treatment of heat-killed lactobacilli including Lactiplantibacillus plantarum (L. plantarum), Levilactobacillus brevis (L. brevis), and Lacticaseibacillus rhamnosus (L. rhamnosus). The morphological changes of SK-N-SH cells associated with plasma-induced apoptosis were observed using an inverted microscope. The neurotoxic effects of plasma samples were assessed using flow cytometry as the percentage of apoptosis in neuronal cells treated with plasma from RRMS patients and healthy controls. The neuroprotective effects of the lactobacilli were also evaluated using flow cytometry, which showed an increased viability percentage in cells pretreated with heat-killed lactobacilli extracts compared to those without pre-treatment. Compared to plasma from healthy controls, plasma from RRMS patients caused morphological changes characteristic of apoptosis such as rounding, detachment, and shrinkage in SK-N-SH cells on microscopy observations. Significant apoptosis in MS plasma-treated neuronal cells was identified by flow cytometry analysis compared to cells treated with plasma from healthy controls (p < 0.01). Heat-killed lactobacilli extracts showed antioxidant activity above 50% in the DPPH radical scavenging assay. Pre-treatment of cells with heat-killed lactobacilli significantly reduced the morphological changes and apoptosis percentage in neuronal cells induced by MS plasma samples. L. plantarum and L. rhamnosus had considerable neuroprotective effects (p < 0.001), followed by L. brevis (p < 0.05). These findings demonstrate that heat-killed lactobacilli extracts as bacterial fractions free of live microorganisms, are suitable safe candidates for adjunctive therapy with potential antioxidant and neuroprotective properties in MS., Competing Interests: Declarations. Ethics Approval and Consent to Participate: This study was performed with the approval of the Research Ethics Committee of the University of Isfahan, Iran, with the number: IR.UI.REC.1402.154 and the study procedures were in accordance with the Declaration of Helsinki. Competing Interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nowadays, extracellular vesicles (EVs) such as exosomes participate in cell-cell communication and gain attention as a new approach for cell-free therapies. Recently, various studies have demonstrated the therapeutic ability of exosomes, while the biological effect of human endometrial stem cell (hEnSC)-derived small EVs such as exosomes is still unclear. Herein, we obtained small EVs from hEnSC and indicated that these small EVs activate the vital cell signaling pathway and progress neurite outgrowth in PC-12 cell lines. For this purpose, hEnSC-derived small EVs were extracted by ultracentrifuge and characterized by DLS, SEM, TEM, and western blot. Also, dil-staining of hEnSC-derived small EVs was done to determine the penetration of hEnSC-derived small EVs into PC12 cells. The MTT assay, scratch assay, and western blot assay were applied to PC12 cells that were exposed to different concentrations of small EVs (0, 50, 100, and 150 µg/ml). Our results demonstrated that small EVs significantly increased neurite outgrowth, proliferation, and migration in PC12 cells in a dose-dependent manner. Moreover, the analysis of western blots showed increased expression of the PI3k/AKT signaling pathway in PC12 cells exposed to hEnSC-derived small EVs in a dose-dependent manner. Also, the results of this study indicated that hEnSC-derived small EVs can enhance cell proliferation and migration and promote neural outgrowth by activating the PI3k/AKT signaling pathway. Accordingly, hEnSC-derived small EVs became an effective strategy for cell-free therapies. Altogether, these positive effects make hEnSC-derived small EVs a new efficient approach in regenerative medicine, especially for the cure of neural injury., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent of publication: Not applicable. Competing interests: The authors declare that they have no competing interests with respect to the research, authorship, and/or publication of this article., (© 2025. The Author(s).)

There are a limited number of chemotherapeutic agents for the treatment canine visceral leishmaniasis (CVL). This study aimed to formulate and assess micellar formulation of miltefosine (MTF) to increase antileishmanial therapeutic effects in dogs naturally infected by Leishmania (L) infantum for the first time. MTF loaded pluronic F127 (PF/MTF) micelles were formulated and coated with chitosan (Cs/PF/MTF). Toxicity of compounds was evaluated. The in vitro and in vivo antileishmanial effect of Cs/PF/MTF was examined in L. infantum promastigotes and amastigotes as well as naturally infected dogs by L. infantum. In-vitro efficacy studies in promastigotes and amastigotes demonstrated that inhibitory concentration (IC50) of Cs/PF/MTF was significantly lower in comparison to miltefosine. In vivo data showed that Cs/PF/MTF is more effective against CVL compared with miltefosine alone. The result of this study indicated that intravenous injection of new formulation of Cs/PF/MTF was tolerated and treated on L. infantum naturally infected dogs with the dosages of 170 μg/kg daily for 28 days., 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. Published by Elsevier Ltd.)

Understanding the complex activation patterns of brain regions during motor tasks is crucial. Integrated functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS) offers advanced insights into how brain activity fluctuates with motor activities. This study explores neuronal activation patterns in the cerebral cortex during active, passive, and imagined wrist movements using these functional imaging techniques. Data were collected from 10 right-handed volunteers performing a motor task using fMRI and fNIRS. fMRI utilized a 3T scanner and a 20-channel head coil, while fNIRS recorded data with a 48-channel device at 765 nm and 855 nm. Analysis focused on key motor and sensory cortices using NIRS-SPM and SPM12, applying a significance threshold of p < 0.05 and a minimum cluster size of 10 voxels for group analysis. Super-threshold voxels were identified with FWE thresholding in SPM12. For activation map extraction we focused on the primary motor cortex, primary somatosensory cortex, somatosensory association cortex, premotor cortex, and supplementary motor cortex. Both fMRI and fNIRS detected activation in the primary motor cortex (M1). The primary somatosensory cortex was found to influence movement direction coding, with smaller activation sizes for upward movements. Combining fNIRS with fMRI provided clearer differentiation of brain activation patterns for wrist movements in various directions and conditions (p < 0.05). This study highlights variations in left motor cortex activity across different movement states. fNIRS proved effective in detecting brain function and showed strong correlation with fMRI results, suggesting it as a viable alternative for those unable to undergo fMRI., Competing Interests: Declarations. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Interleukin-2 (IL-2) is a well-known cytokine that plays a crucial role in stimulating immune cells, including natural killer (NK) cells and cytotoxic T cells. It has been studied as an immunotherapy for a variety of diseases, including cancer. However, due to its short serum half-life, high doses of IL-2 are required which can result in systemic toxicities like capillary leak syndrome., Objective: To demonstrate the enhanced antitumor efficacy of Albumin Binding Domain-conjugated IL-2 (ABD-IL-2) at a lower dose compared to IL-2., Methods: IL-2 and ABD-IL-2 were purified using Ni-NTA resin with a histidine sequence added to their C-terminal region for purification purpose. Peripheral blood lymphocytes were stimulated with IL-2 and ABD-IL-2 to assess their function. 4T1 cells were injected into BALB/c mice to establish a breast cancer model with metastasis evaluated in the lungs., Results: Both recombinant proteins significantly stimulated T lymphocyte proliferation compared to the negative control (P=0.000, P=0.001). Administration of both proteins reduced the size of isolated tumors in the breast cancer mouse model. The control group had more nodules and larger lung metastatic centers (P=0.000). Metastasis to secondary lymphoid organs occurred only in the control group., Conclusion: By using ABD-IL-2 at a one-third concentration compared to IL-2, we aimed to reduce administration toxicity associated with high doses of IL-2 in immunotherapy. This approach shows potential for improving IL-2-based treatments while minimizing adverse effects.

Objective(s): Some forms of breast cancer such as triple-negative phenotype, are serious challenge because of high metastatic cases, high mortality and resistance to conventional therapy motivated the search for alternative treatment approaches. Nanomaterials are promising candidates and suitable alternatives for improving tumor and cancer cell treatments., Materials and Methods: Biosynthesis of ZnO NPs by help of Berberis integerrima fruit extract, has been done. Analysis of Zinc Oxide NPs using DLS, FTIR, SEM, and EDS techniques have been performed. Moreover, biological activities of ZnO NPs evaluated through MTT method, Flow cytometry, and real time PCR methods. Biocatalytic and apoptotic activity of ZnO NPs on healthy HFF (human fibroblast cell line), MDA-MB 231, and MDA-MB 468 (triple negative breast cancer cell lines, (TNBC)) evaluated. Furthermore, Bax, Bcl-2 and caspase-3 apoptotic genes expression changes in cancer cells assessed in compare to GAPDH as a house keeping gene., Results: Physico-chemical investigation demonstrated ZnO NPs were confirmed by Berberis integerrima fruit extract for the first time. The MTT assay and Flow cytometry results indicated biocompatibility of the ZnO NPs in normal cell line and high anticancer potential against TNBC MDA-MB-231 and MDA-MB-468 cell lines. The IC50 of ZnO NPs were 104.4 and 44.86, 20.96 after 24 hours for HFF, MDA-MB-231 and MDA-MB-468 cells, respectively., Conclusion: The current research showed a fast, cost effective and ecofriendly method for ZnO NPs nanoparticle synthesis. Furthermore, In vitro data analysis demonstrated biocompatibility and highly anticancer effects of biosynthesized ZnO NPs against TNBC cancerous cells., Competing Interests: Declarations. Conflict of interest: The authors have no conflicts of interest in this research., (© 2024. The Author(s), under exclusive licence to Tehran University of Medical Sciences.)

Vascularization of bone tissue constructs plays a pivotal role in facilitating nutrient transport and metabolic waste removal during the processes of osteogenesis and bone regeneration in vivo. In this study, a sildenafil (Sil)-loaded nanofibrous scaffold of keratin/Soluplus/merwinite (KS.Me.Sil) was fabricated through electrospinning and the effectiveness of the scaffold was assessed for bone tissue engineering applications. The KS.Me.Sil nanofibrous scaffold exhibited notably enhanced ultimate tensile strength (3.38 vs 2.61 MPa) and elastic modulus (69.83 vs 46.27 MPa) compared to the KS scaffold. The in vitro release of Ca 2+ , Si 4+ and Mg 2+ ions and the release of Sil from the nanofibers as well as biodegradability and bioactivity were evaluated for 14 days. Protein adsorption capability and cytocompatibility of the scaffolds were tested. Alkaline phosphatase activity test, Alizarin red staining and qRT-PCR analysis demonstrated that the KS.Me.Sil nanofibers had the best osteogenic activity among other samples. Also, the results of the chorioallantoic membrane assay showed an almost threefold increase in blood vessel density in the group treated with the KS.Me.Sil nanofibers extract compared to the KS. In conclusion, our findings suggest that the electrospun KS.Me.Sil nanofibrous scaffold offers a robust structure with exceptional osteogenic and angiogenic characteristics, making it a promising candidate for bone tissue engineering applications., 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.)

Objective: Spinal cord injury (SCI) is a severe and permanent nerve damage condition that poses significant burdens on individuals and society. Various therapeutic approaches have been explored to mitigate the consequences of SCI. Tissue engineering and regenerative medicine have emerged as a promising avenue for addressing this issue. This study aims to investigate the potential of a nanochitosan/polypyrrole-alginate conductive scaffold, loaded with the Noggin growth factor, an inhibitor of BMP-4 signaling, and human amniotic epithelial cells (hAECs), in promoting the regeneration of SCI in animal models., Methods: The attachment and distribution of isolated hAECs on a fabricated nanochitosan/polypyrrole-alginate conductive scaffold were assessed using SEM. Additionally, the neural differentiation of hAECs on the scaffold was investigated by analyzing the expression of specific neuronal (Calca, Fox3), oligodendrocyte (MBP), and astrocyte (GFAP) genes in vitro. To evaluate the combined effect of the scaffold and Noggin growth factor in animal models, a Noggin-loaded scaffold was designed using bioinformatics, and the loading and release capacity of Noggin were measured. For in vivo studies, rats underwent laminectomy and were transplanted with the scaffold, either alone or with Noggin and DII labeled- hAECs, at the T10-T11 level. Motor functions of the animal were evaluated using BBB scoring weekly in an open field for four weeks. Furthermore, the expression of neural genes and immunohistochemical tests were evaluated after four weeks., Results: hAECs exhibited uniform distribution and attachment to the scaffold. In vitro differentiation analyses showed increased expression of Calca, Fox3, MBP, and GFAP genes. Docking results indicated that Noggin could interact with chitosan nanoparticles through hydrogen bonds. The chitosan nanoparticles effectively loaded 22.6% of exposed Noggin, and the scaffold released 28.5% of the total incorporated Noggin. In vivo studies demonstrated that transplanting nanochitosan/polypyrrole-alginate conductive scaffolds with DII labeled-hAECs, with or without Noggin, improved motor functions in animal models. The assessment of gene expression patterns in transplanted hAECs revealed that neuronal (Calca, Fox3) and oligodendrocyte (MBP) genes in the injured spinal cord of the animal models were upregulated. Histopathological analysis showed a reduction in inflammation and glial scar formation, while neural fiber regeneration increased in the treated animals. Also, DII labeled-hAECs in the lesion site were alive after a period of four weeks., Conclusion: Based on these findings, it can be inferred that the integrative therapeutic effects of human amniotic epithelial cells, nanochitosan/polypyrrole-Alginate conductive scaffold, and Noggin (as BMP-4 signaling inhibitor) represents a promising and innovative approach in the field of translational medicine., Competing Interests: Declarations. Ethics approval and consent to participate: All experimental procedures were done after approval of proposal entitled “The effect of BMP signaling inhibition in Human Amniotic Epithelial Stem cells Seeded on Conductive nanochitosan/polypyrrole-alginate Scaffold for Directional Growth of axon in Spinal cord-Injured Rats” by the ethics committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.MSP.REC.1401.001) in 2022/04/12. Besides, the informed consent of the participation was obtained from individuals. Consent for publication: The Authors grant the Publisher the sole and exclusive license of the full copyright in the Contribution, which licenses the Publisher hereby accepts. Consequently, the Publisher shall have the exclusive right throughout the world to publish and sell the Contribution in all languages. Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Declarations of generative AI and AI-assisted technologies in the writing process: During the preparation of this work the authors used GPT-4 in order to improve readability and language. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication., (© 2024. The Author(s).)

Numerous conduits have been developed to improve peripheral nerve regeneration. However, challenges remain, including remote control of conduit function, and programmed cell behaviors like orientation. We synthesized Fe 3 O 4 -MnO 2 @Zirconium-based Metal-organic frameworks@Retinoic acid (FMZMR) core-shell and assessed their impact on Schwann cell function and behavior within conduits made from decellularized human umbilical arteries (DHUCA) under magnetic field (MF). FMZMR core-shell, featuring a spherical porous structure and catalytic properties, effectively scavenges radicals and facilitates controlled drug release under MF. The histology of the DHUCA indicates effective decellularization with adequate tensile strength and Young's modulus for sciatic nerve regeneration. In-vitro results demonstrate that FMZMR core-shell is biocompatible and promotes Schwann cell proliferation through remotely controlled drug release. Furthermore, its synergy with MF enhances cell orientation and increases neurite length by ~ 1.93-fold. Functional and histological evaluations indicate that the FMZMR core-shell combined with MF promotes nerve regeneration, decreases muscle atrophy, and enhances new neuron growth and myelin formation, without negatively affecting vital tissues. This study suggests that the synergistic effect of FMZMR core-shell with MF can alleviate some of the treatment challenges., Competing Interests: Declarations. Ethical approval: This research was carried out with the ethical code of IR.SHMU.AEC.1402.008. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: In soft tissue regeneration, the clinical efficacy of fibrin membranes has been a pressing concern. The key to this efficacy lies in the stability of membrane and its controlled absorption. Human serum albumin, with its influence on the formation and stability of fibrin networks, could hold the key to developing a more stable alternative. This study investigates the ultrastructure and biodegradability of plasma albumin-activated gel, a potential game-changer in the field., Methods: Blood samples were collected from the participants and centrifuged to obtain the concentrated growth factor. The poor platelet plasma syringe was placed inside the activated plasma albumin gel device. The ultrastructure of the membrane was examined using a scanning electron microscope (SEM). The weight difference was measured over 21 days to investigate the biodegradability of the samples., Results: Twenty-two samples were prepared from six individuals (three males and three females). Based on SEM images, activated albumin gel after 21 days in Hank's solution exhibited a significant decrease in density and evident signs of surface degradation. The weight was significantly reduced after 21 days (p < 0.05)., Conclusion: In the present study, the investigation of the ultrastructure and biodegradability of activated albumin gel showed that, based on the observed weight difference, the amount of biodegradation is high, and it may be necessary to use a thicker membrane compared to the conventional thickness of the connective tissue graft., Key Points: Enhanced stability and biocompatibility: The study highlights plasma albumin-activated gel's potential as a soft tissue scaffold, demonstrating significant biodegradation and structural changes that support cell infiltration and nutrient exchange, essential for tissue regeneration. Controlled degradation profile: Plasma albumin gel offers a prolonged biodegradation period compared to conventional fibrin membranes, making it suitable for applications requiring stable, long-lasting scaffolds in soft tissue regeneration. Future clinical applications: Findings suggest that thicker plasma albumin membranes may be needed for optimal effectiveness, paving the way for further exploration in clinical trials and animal models to validate this approach in soft tissue grafting., Plain Language Summary: This study investigates plasma albumin-activated gel as a promising material for supporting soft tissue repair, particularly in periodontal regeneration. Traditional materials, such as fibrin membranes, are often used to aid healing, but their rapid breakdown can limit effectiveness in the body. Plasma albumin, a protein naturally found in human blood, might offer a more stable alternative by forming a longer-lasting structure. In this study, researchers processed blood samples from participants to create the gel, examining its structure under a powerful microscope and tracking changes in weight over 21 days to assess its breakdown. Results showed that the gel gradually became less dense and more porous, allowing for cell movement and nutrient flow-both critical for tissue repair. Additionally, a significant reduction in weight indicated a controlled breakdown over time. These findings suggest that plasma albumin-activated gel may serve as a more durable scaffold for soft tissue regeneration, potentially improving healing outcomes in periodontal applications where a stable, longer-lasting material is needed., (© 2024 The Author(s). Clinical Advances in Periodontics published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

The coronavirus disease 2019 (COVID-19) has resulted in approximately 7.0 million fatalities between 2019 and 2022, underscoring a pressing need for comprehensive research into its underlying mechanisms and therapeutic avenues. A distinctive feature of severe COVID-19 is the dysregulated immune response characterized by excessive activation of immune cells and the consequent cytokine storms. Recent advancements in our understanding of cellular signaling pathways have illuminated the role of Transforming Growth Factor Beta (TGF-β) as a pivotal signaling molecule with significant implications for the pathogenesis of infectious diseases, including COVID-19. Emerging evidence reveals that TGF-β signaling, when activated by viral components or secondary pathways, adversely affects diverse cell types, particularly immune cells, and lung tissue, leading to complications such as pulmonary fibrosis. In our review article, we critically evaluate recent literature on the involvement of TGF-β signaling in the progression of COVID-19. We discuss a range of pharmacological interventions, including nintedanib, pirfenidone, corticosteroids, proton pump inhibitors, and histone deacetylase inhibitors, and their potential to modulate the TGF-β pathway in the context of COVID-19 treatment. Additionally, we explore ongoing clinical trials involving mesenchymal stem cells, low-dose radiation therapy, and artemisinin derivatives to assess their impact on TGF-β levels and subsequent clinical outcomes in COVID-19 patients. This review is particularly relevant at this juncture as the global health community continues to grapple with the ramifications of the COVID-19 pandemic, highlighting the urgent need for targeted therapeutic strategies aimed at TGF-β modulation to mitigate disease severity and improve patient 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 Ltd. All rights reserved.)

To investigate the microstructural integrity, tract volume analysis, and functional connectivity (FC) alterations of the left uncinate fasciculus (UF) in patients with amyotrophic lateral sclerosis (ALS) compared to healthy controls (HCs). Fourteen limb-onset ALS patients were recruited at baseline and ten at follow-up, along with 14 HCs. All participants underwent 3D T1-weighted, diffusion tensor imaging and kurtosis imaging (DTI/DKI), and resting-state functional MRI (rs-fMRI) using a 3 Tesla scanner with 64-channel coils. Eight metrics of diffusion, rs-FC of the left UF, and graph theory analyses were extracted. Statistical group comparisons and correlation analysis for significant diffusion metrics were also conducted. Significantly lower radial kurtosis (RK), mean kurtosis (MK), and higher DTI diffusivity metrics were observed in the left UF of ALS patients than in HCs. RK and MK were correlated with various cognitive scores, particularly executive function and visuospatial ability. The volume of the left UF was positively correlated only with RK and MK at follow-up. While rs-FC analysis did not reveal group differences, a negative functional link between the left UF and cerebellum was observed in HCs but not in patients. Graph theory analysis suggested decreased connectivity in baseline patients and potential compensatory effects during the follow-up. Our study reveals microstructural abnormalities and potential network changes in left UF. DKI metrics, especially RK and MK, may be more sensitive biomarkers than DTI metrics, particularly longitudinally. Diffusion changes appear to precede volume and functional connectivity alterations, suggesting diffusion as a potential early biomarker., Competing Interests: Declarations. Conflict of interests: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: The study was approved by the Ethics Committee of the Tehran University of Medical Sciences (Ethical Code: IR.TUMS.MEDICINE.REC.1400.1173). Written consent was obtained from all participants with potentially identifiable images or data. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: The authors affirm that human research participants provided informed consent for publication., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study aimed to evaluate the utility of arterial spin labeling (ASL) in assessing cerebral blood flow (CBF) changes in amyotrophic lateral sclerosis (ALS), and its potential as a biomarker for early diagnosis., Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that employed ASL to compare CBF between ALS patients and healthy controls were included., Results: Seven studies were included. A consistent finding across these studies was hypoperfusion in both the motor and non-motor regions, particularly in the frontotemporal cortex. Hypoperfusion in motor regions was correlated with functional impairment and was observed prior to structural changes, suggesting its potential as an early biomarker. There is limited evidence to suggest that monitoring changes in CBF patterns in the brain. Besides, limited findings showed initial hyperperfusion in regions not yet involved in the pathological process, and progressing hypoperfusion in regions with increasing pathological burden., Conclusions: This review highlights the potential of ASL as a valuable tool for understanding the neurovascular dysfunction in ALS. Further research is required to validate its clinical utility for diagnosing ALS and monitoring disease progression., Competing Interests: Declaration of Competing Interest The authors declare no financial or other conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Poly (β-amino Ester) nanocarriers show promise for gene therapy, but their effectiveness can be limited by the environment within the body. This study aims to understand how common cell culture media components affect optimized PBAE nanocarrier performance in gene delivery., Methods: Optimized PBAE was synthesized based on Michael addition reaction and characterized by different assays, this study employed techniques like DLS and TEM to characterize PBAE nanocarriers, followed by cellular uptake analysis (flow cytometry and confocal imaging) and evaluation of gene expression under different polymer/DNA ratio ratios and media conditions., Results: The nanocarriers exhibited size under 200 nm and surface positive charge, with high encapsulation efficiency (up to 95%). Cellular uptake, transfection efficiency, and cytotoxicity were evaluated. Flow cytometry analysis revealed high cellular uptake (over 77% at 1 hour and up to 95% after 3 hours) and good viability. Transfection efficiency reached up to 80% with 2 μg DNA, particularly at weight ratios of 60 and 90., Conclusion: The study also identified factors affecting transfection efficiency, including serum concentration and antibiotics in the culture medium, highlighting the importance of optimizing these conditions for future applications.

The burgeoning field of nano-bone regeneration is yet to establish a definitive optimal particle size for nanocarriers. This study investigated the impacts of nanocarrier's particle size on the bone regeneration efficacy of fingolimod (FTY720)-loaded nanoemulsions. Two distinct particle sizes (60 and 190 nm, designated as NF60 and NF190, respectively) were produced using low-energy and high-energy emulsion techniques, maintaining a consistent surfactant, co-surfactant, and oil. In vitro studies using rat mesenchymal stem cells revealed that both NF60 and NF190 exhibited cell viability and reduced lactate dehydrogenase. Interestingly, NF60 demonstrated superior antioxidant properties, significantly reducing nitric oxide and intracellular reactive oxygen species (ROS) levels compared to NF190. Furthermore, NF60 significantly enhanced ALP activity and calcium deposition during osteogenic differentiation, indicating its potential to promote the early stages of bone formation. In vivo studies using a rat calvarial bone defect model demonstrated that both NF60 and NF190 significantly upregulated the expression of key osteogenic genes, including Runx2, Col, ALP, OCN, and BMP2. Notably, NF60 induced significantly higher expression of Runx2 and BMP2. X-ray and histological investigations revealed significantly improved bone regeneration in the NF60 group, highlighting the superior bone healing potential of smaller FTY720 nanoemulsions, without infiltration of inflammatory cells. The smaller particle size demonstrated superior antioxidant properties, enhanced osteogenic differentiation, and improved bone regeneration, suggesting smaller nanoparticles, with their larger surface area, accelerated drug release rate, and lower viscosity, interact more effectively with cells, leading to increased and effective drug delivery and cellular uptake. Findings highlight the importance of nanocarrier size in optimizing drug delivery for bone tissue engineering applications.

Atopic dermatitis (AD) remains a challenging condition, with conventional treatments often leading to adverse effects and limited efficacy. This review explores the diverse landscape of AD treatments, encompassing conventional methods, novel topical and systemic therapies, and emerging bioengineered strategies. While conventional drug administration often requires high dosages or frequent administration, leading to adverse effects, targeted biologics have shown promise. Phototherapy and wet wrap therapy, while helpful, have limitations. Given these factors, the need for modern and effective therapeutic strategies for AD is pressing. Complementary or alternative therapies have garnered significant attention in recent years as a compelling treatment for AD. Among these, functionalized biomaterials and textiles with physicochemical, nanotechnology-based characteristics, or bioengineered features are some of the most common typical adjuvant therapies. The multifunctional-engineered biomaterials, as a new generation of biomedical materials, and stem cells, seem to hold tremendous promise for the treatment of dermatological diseases like AD. Biomaterials have seen great success, especially in various medical fields, due to their unique and adaptable characteristics. These materials, including collagen, PCL, and PLGA, offer unique advantages, such as biocompatibility, biodegradability, controlled drug release, and enhanced drug retention., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mohammad Ebrahim Astaneh reports financial support was provided by Fasa University of Medical Science. Mohammad Ebrahim Astaneh reports a relationship with Fasa University of Medical Science that includes: employment. Mohammad Ebrahim Astaneh has patent pending to No Patent. The authors have no conflicts of interest to report. 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 B.V. All rights reserved.)

Objective: To characterize the longitudinal metabolite profile of the left dorsolateral prefrontal cortex (DLPFC) in amyotrophic lateral sclerosis (ALS) using magnetic resonance spectroscopy (MRS) and to examine its correlation with cognitive assessments., Methods: Thirteen patients at baseline and ten at follow-up, along with 14 age-, sex-, and handedness-matched healthy controls (HCs), were recruited. Three Tesla with a 64-channel coil, Point-RESolved Spectroscopy (PRESS) sequence (TR=1500 ms and TE=140 ms) was used. Metabolites in the left DLPFC were quantified using LCModel. Cognitive performance and functional impairment were assessed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) and Revised ALS Functional Rating Scale (ALSFRS-R), respectively. Group comparisons were adjusted for multiple comparisons (p < 0.05, Bonferroni correction). The links between the brain metabolites and cognitive function were investigated using relevant correlation tests (Pearson's or Spearman's)., Results: Our analysis revealed a significant difference in the choline-to-creatine ratio (tCho/tCr) among the three groups. Baseline ALS patients showed a higher tCho/tCr ratio than HCs (p = 0.033, Bonferroni-corrected). Interestingly, the total N-acetyl aspartate (tNAA)/tCr ratio, a marker of neuronal health, was strongly positively correlated with visuospatial cognitive scores at baseline and follow-up. Furthermore, at follow-up, tNAA/tCr was positively correlated with the total scores and specific sub-scores on the ECAS, encompassing both ALS-specific and non-specific cognitive domains. At follow-up, positive correlations emerged between tNAA/tCr and the total language and executive function scores., Conclusions: Metabolite alterations and correlations with cognition were observed in the left DLPFC of ALS patients, supporting extra-motor involvement and its association with cognitive decline., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

There is an interplay between the gonadotropin-releasing hormone (GnRH) and melatoninergic systems. The key enzyme of melatonin synthesis (arylalkylamine N-acetyltransferase, AANAT), and GnRH receptors are expressed in the hippocampus. While it has been shown that hippocampal AANAT enzyme activity is necessary for proper hippocampal cognitive function, their role in long-term potentiation (LTP) induction is not fully understood. In current study, the impact of GnRH on LTP induction was investigated, while hippocampal melatonin synthesis had been inhibited. The melatonin synthesis was inhibited by AANAT-siRNA administration, and LTP was induced using in vivo field potential electrophysiological recording. Animals were divided into 5 groups: Intact, vehicle, siRNA, GnRH and siRNA+GnRH. All animals, except intact group, experienced the stereotaxic surgery and intra-hippocampal cannulation to receive vehicle agent, AANAT siRNA (0.5 μg/hip), GnRH (1 ng/rat), and AANAT siRNA+GnRH. The recognition memory was assessed by Novel object recognition test. The field potential electrophysiology experiment was conducted by stimulating the Schaffer collateral pathway, and LTP induction was carried out through high-frequency stimulation (HFS). After recording, animals' brain was isolated and quickly frozen for further hippocampal melatonin levels measurement by LC-MS and AANAT mRNA levels by qRT-PCR. GnRH injection in the hippocampus increased local AANAT-mRNA expression and melatonin levels. GnRH-treated animals displayed higher LTP amplitude compared to intact, vehicle and siRNA groups. While the reduction in hippocampal melatonin levels by AANAT-siRNA inhibited LTP and impaired recognition memory, the GnRH prevented these adverse effects. The data suggests that GnRH have protective effects against AANAT-siRNA-induced LTP decline. The protective mechanism at least partially, may be related to the increased expression of local AANAT-mRNA., 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 Ltd. All rights reserved.)

Background: Movement disorders such as Parkinson's disease are associated with structural and functional changes in specific brain regions. Advanced magnetic resonance imaging (MRI) techniques combined with machine learning (ML) are promising tools for identifying imaging biomarkers and patterns associated with these disorders., Purpose/hypothesis: We aimed to systematically identify the brain regions most commonly affected in movement disorders using ML approaches applied to structural and functional MRI data. We searched the PubMed and Scopus databases using relevant keywords up to June 2023 for studies that used ML approaches to detect brain regions associated with movement disorders using MRI data., Study Type: A systematic review and diagnostic meta-analysis., Population/subjects: Sixty-seven studies with 6,285 patients were included., Field Strength/sequence: Studies utilizing 1.5T or 3T MR scanners and the acquisition of diffusion tensor imaging (DTI), structural MRI (sMRI), functional MRI (fMRI), or a combination of these were included., Assessment: The authors independently assessed the study quality using the CLAIM and QUADAS-2 criteria and extracted data on diagnostic accuracy measures., Statistical Tests: Sensitivity, specificity, accuracy, and area under the curve were pooled using random-effects models. Q statistics and the I 2 index were used to evaluate heterogeneity, and Begg's funnel plot was used to identify publication bias., Results: sMRI showed the highest sensitivity (93%) and mixed modalities had the highest specificity (90%) for detecting regional abnormalities. sMRI had a 94% sensitivity for identifying subcortical changes. The support vector machine (93%) and logistic regression (91%) models exhibited high diagnostic accuracies., Data Conclusion: The combination of advanced MR neuroimaging techniques and ML is a promising approach for identifying brain biomarkers and affected regions in movement disorders with subcortical structures frequently implicated. Structural MRI, in particular, showed strong performance., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 2., (© 2024 International Society for Magnetic Resonance in Medicine.)

Background: Ubiquitin-specific peptidases (USPs), also known as deubiquitinating enzymes (DUBs), play a crucial role in maintaining cellular homeostasis by selectively removing ubiquitin molecules from targeted proteins. This process affects protein stability, subcellular localization, and activity, thereby influencing processes such as DNA repair, cell cycle regulation, and apoptosis. Abnormal USP activities have been linked to various diseases, including cancer. Emerging evidence in lymphoma studies highlights the significance of USPs in controlling signaling pathways related to cancer initiation and progression and presents them as potential therapeutic targets., Aim: This study aimed to elucidate the multifaceted roles of USPs in lymphoma., Methods: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published in English up to May 2023 were retrieved from PubMed, Web of Science, and Scopus. The inclusion criteria focused on studies investigating the role of USPs in lymphoma cancer, involving human subjects or relevant lymphoma cell lines, exploring molecular mechanisms and signaling pathways, and assessing diagnostic or prognostic value., Results: After the selection process, 23 studies were selected for analysis. USPs were found to affect various aspects of lymphoma development and progression. Specific USPs were identified with roles in cell-cycle regulation, apoptosis modulation, drug resistance, DNA repair, and influence of key oncogenic pathways, such as B cell receptor (BCR) signaling., Conclusion: This systematic review underscores the emerging role of USPs in lymphoma and their potential as therapeutic targets. Inhibitors of USPs, such as USP14 inhibitors, show promise in overcoming drug resistance. The dynamic interplay between USPs and lymphoma biology presents an exciting opportunity for future research and the development of more effective treatments for patients with lymphoma. Understanding the intricate functions of USPs in lymphoma offers new insights into potential therapeutic strategies, emphasizing the significance of these enzymes in the context of cancer biology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Samareh Salavatipour, Tavakoli, Halimi, Tavoosi, Baghsheikhi, Talebi-Taheri, Niloufari, Salehi, Verdi, Rahgozar, Mosavi-Jarrahi and Ahmadvand.)

Background: Cutibacterium acnes(C. acnes), a Gram-positive anaerobe and a dominant bacterium species in the sebaceous follicles of the face was detected in the brain of Alzheimer's disease (AD) patients. It has been found that C. acnes activates non-specifically the innate immune system by producing proinflammatory cytokines and can participate in brain inflammation. We hypothesise that C. acnes could influence the brain through the structural alteration in axons and dendrites of neurons., Methods: In this regard, the hippocampus of rats was infected with C. acnes, and memory retention, amyloid-β (Aβ 1-42 ) deposition, hyperphosphorylated tau protein (p-Tau) formation, and expression levels of MAP2 and β-tubulin proteins in the hippocampus tissues were investigated., Results: C. acnes-infected rats displayed memory deficits and Aβ 1-42 deposits were detected in their hippocampus tissue up to 7 days post-infection. C. acnes was neurotoxic and exerted detrimental effects on MAP2 and β-tubulin proteins, which are required for normal neuronal function. An elevated level of p-Tau was also identified in infected animals., Conclusion: Based on these results, we propose that C. acnes infection of the brain participates in the initiation of the pathogenesis of sporadic AD through degeneration of axons and dendrites., Competing Interests: Declarations. Ethics approval: All methods were performed in accordance with the relevant guidelines and regulations )IR.SBMU.AEC.1401.022(. Consent for publication: Not applicable. Competing interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024. The Author(s).)

This study aimed to assess nano-pumice (NP) from pumice mining waste as a local, cost-effective anode catalyst in microbial fuel cells (MFCs) for treating edible vegetable oil refinery wastewater (EVORW) and generating bioenergy. Pumice mining waste was converted into nano in three stages: crushing up to ≤3 cm, reducing the size of the previous step particles to 150 μm and converting the previous step particles to <100 nm. Nano-pumice prepared was coated on the carbon cloth (CC) to increase anode surface area of MFC. Two MFCs were utilized, with MFC-1 serving as a control and MFC-2 incorporating a CC electrode coated with nano-pumice. The surface morphology, elemental and chemical composition, and textural characterization of CC, pumice, NP, and CC coated with NP were analyzed using FE-SEM, EDX, XRF, and BET techniques. MFC-2 achieved a maximum power density of 30±4W/m³ at a current density of 55±5A/m³. The MFC-1 reached a maximum power density of 18±4W/m³ at a current density of 35±6A/m³. In MFC-2, the EVORW treatment achieved maximum removals of COD (94 ± 2 %), NH 4 + (68 ± 6 %), TSS (81 ± 2 %), and TDS (73 ± 1 %). MFC-1 achieved removal efficiencies of 66 ± 3 % for COD, 57 ± 6 % for NH 4 2- (68 ± 6 %), TSS (81 ± 2 %), and TDS (73 ± 1 %). MFC-1 achieved removal efficiencies of 66 ± 3 % for COD, 57 ± 6 % for NH 4 + -N, 48 ± 3 % for TP, 45 ± 3 % for SO 4 2- , 65 ± 3 % for TSS, and 61 ± 1 % for TDS. MFC-2 power density rose significantly, reaching 61 ± 3 % (1.6 times) higher than MFC-1and it also demonstrated a superior ability to improve raw wastewater quality compared to MFC-1. The MFC with the CC/NP anode exhibited both excellent power production and high COD removal efficiency, making nano-pumice a suitable anode catalyst for MFC applications., 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 The Author(s).)

Background: The skin covers the surface of the body and acts as the first defense barrier against environmental damage. Exposure of the skin to environmental physical and chemical factors such as mechanical injuries, UV rays, air pollution, chemicals, etc. Leads to numerous damages to skin cells such as fibroblasts, keratinocytes, melanocytes, etc. The harmful effects of environmental factors on skin cells could lead to various skin diseases, chronic wounds, wrinkles, and skin aging. Hair is an essential part of the body, serving multiple functions such as regulating body temperature and protecting against external factors like dust (through eyelashes and eyebrows). It also reflects an individual's personality. Therefore, the need for new treatment methods for skin diseases and lesions and at the same time preserving the youth, freshness, and beauty of the skin has been highly noticed by experts. Exosomes are nanovesicles derived from cells that contain various biological compounds such as lipids, proteins, nucleic acids, and carbohydrates. They are secreted by a variety of mammalian cells and even different plants. Exosomes are of great interest as a new therapeutic approach due to their stability, ability to be transported throughout the body, paracrine and endocrine effects, as well as the ability to carry various compounds and drugs to target cells., Aim: In this review, we have discussed the characteristics of exosomes, their cellular sources, and their therapeutic effects on wrinkles, skin aging, and rejuvenation and hair regrowth., Competing Interests: None., (© 2024 The Author(s). Published by Elsevier BV on behalf of The Japanese Society for Regenerative Medicine.)

Breast cancer is a prominent cause of death among women and is distinguished by a high occurrence of metastasis. From this perspective, apart from conventional therapies, several alternative approaches have been researched and explored in recent years, including the utilization of nano-albumin and statin medications like simvastatin. The objective of this study was to prepare albumin nanoparticles incorporating simvastatin by the self-assembly method and evaluate their impact on breast cancer metastasis and apoptosis. The data showed the prepared nanoparticles have a diameter of 185 ± 24nm and a drug loading capacity of 8.85 %. The findings exhibit improved release in a lysosomal-like environment and under acidic pH conditions. MTT data showed that nanoparticles do not exhibit a dose-dependent effect on cells. Additionally, the results from MTT, flow cytometry, and qPCR analyses demonstrated that nanoparticles have a greater inhibitory and lethal effect on MDA-MB-231 cells compared to normal simvastatin. And cause cells to accumulate in the G0/G1 phase, initiating apoptotic pathways by inhibiting cell cycle progression. Nanoparticles containing simvastatin can prevent cell invasion and migration in both monolayer and spheroid models, as compared to simvastatin alone, at microscopic levels and in gene expression. The obtained data clearly showed that, compared to simvastatin, nanoparticles containing simvastatin demonstrated significant efficacy in suppressing the growth, proliferation, invasion, and migration of cancer cells in monolayer (2D) and spheroid (3D) models., 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 Inc. All rights reserved.)

Peripheral neuropathy (PN) is one of the most common disorders characterized by the dysfunction or degeneration of peripheral nerves and has many different causes. PN often causes weakness, numbness, and pain, usually in the hands and feet, which can cause physical disability and a reduced quality of life. The purpose of this study was to conduct a review of the potential neuroprotective properties of progesterone against PN. A comprehensive systematic search was performed in many electronic databases (Scopus, PubMed, and Web of Science) until January 2024, following the PRISMA principles. A total of 72 studies underwent screening based on predetermined criteria for inclusion and exclusion. Ultimately, the present systematic review comprised 18 publications that satisfied the inclusion criteria. The data indicate that progesterone medication decreases PN by inhibiting the biochemical and morphological abnormalities caused by aging, diabetes, chemotherapy, and physical injury to peripheral nerves. However, as compared to the PN groups alone, progesterone treatment demonstrated tendencies towards being anti-oxidant, anti-inflammatory, anti-nociceptive, and neurodegenerative. Other studies have shown that PN also induces substantial biochemical changes in neuronal cells and tissues. Furthermore, we observed histological changes in the peripheral nerve tissue after PN. Overall, progesterone administration reversed these biochemical and histological alterations induced by PN in the vast majority of instances. Notably, the PN is ameliorated through progesterone administration. Progesterone achieves these neuroprotective effects through the inhibition of multiple mechanisms that are implicated in PN., Competing Interests: Declarations Ethical approve The ethical committee of the Iran University of Medical Sciences approved the systematic review (IR.IUMS.REC.1401.696). Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dealing with spinal cord injuries presents problematic due to multiple secondary mechanisms. Beyond primary concerns like paralysis and disability, complications including urinary, gastrointestinal, cardiac, and respiratory disorders, along with substantial economic burdens may occur. Limited research focuses on modeling and treating contusion and compression injuries. Tissue engineering emerges as an innovative treatment, targeting lesion pathophysiology. This study was evaluated implanting injectable biomaterials into injury-induced cavity before glial scar formation, avoiding tissue incisions and minimizing further damage. The efficacy of injectable alginate/thiolated chitosan hydrogel was investigated for acute spinal cord injury induced by Vanický method in Wistar rats. Three days post-injury, hydrogel was administrated through microinjection after laminectomy. After 60 days, the hydrogel group demonstrated notable motor function enhancement compared to the control by the BBB locomotor test (P < 0.05). However, no statistically significant differences were observed in MRI assessment concerning lesion severity. Stereological and histopathological evaluations revealed a reduction in vacuole volume and the presence of axon profiles within the scaffold (P < 0.05), alongside reduced infiltration of inflammatory and Gitter cells in the hydrogel group, although the latter was not statistically significant compared to the control. Thiolated chitosan/ alginate hydrogel implantation may be regarded as a promising treatment to enhance motor function by restraining destructive processes post-acute spinal cord injury., (© 2024. The Author(s).)

The P-glycoprotein (ABCB1)-mediated multidrug resistance (MDR) has emerged as a significant impediment to the efficacy of cancer chemotherapy in clinical therapy, which could promote the development of effective agents for MDR reversal. In this work, we reported the exploration of novel pyrazolo [1,5-a]pyrimidine derivatives as potent reversal agents capable of enhancing the sensitivity of ABCB1-mediated MDR MCF-7/ADR cells to paclitaxel (PTX). Among them, compound 16q remarkably increased the sensitivity of MCF-7/ADR cells to PTX at 5 μM (IC 50  = 27.00 nM, RF = 247.40) and 10 μM (IC 50  = 10.07 nM, RF = 663.44). Compound 16q could effectively bind and stabilize ABCB1, and does not affect the expression and subcellular localization of ABCB1 in MCF-7/ADR cells. Compound 16q inhibited the function of ABCB1, thereby increasing PTX accumulation, and interrupting the accumulation and efflux of the ABCB1-mediated Rh123, thus resulting in exhibiting good reversal effects. In addition, due to the potent reversal effects of compound 16q, the abilities of PTX to inhibit tubulin depolymerization, and induce cell cycle arrest and apoptosis in MCF-7/ADR cells under low-dose conditions were restored. These results indicate that compound 16q might be a promising potent reversal agent capable of revising ABCB1-mediated MDR, and pyrazolo [1,5-a]pyrimidine might represent a novel scaffold for the discovery of new ABCB1-mediated MDR reversal agents., Competing Interests: Declaration of competing interest The authors declared that there was no conflict of interest about this work., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Identifying new compounds with minimal side effects to enhance patients' quality of life is the ultimate goal of drug discovery. Due to the expensive and time-consuming nature of experimental investigations and the scarcity of data in traditional QSAR studies, deep transfer learning models, such as the BERT model, have recently been suggested. This study evaluated the model's performance in predicting the anti-proliferative activity of five cancer cell lines (HeLa, MCF7, MDA-MB231, PC3, and MDA-MB) using over 3,000 synthesized molecules from PubChem. The results indicated that the model could predict the class of designed small molecules with acceptable accuracy for most cell lines, except for PC3 and MDA-MB. The model's performance was further tested on an in-house dataset of approximately 25 small molecules per cell line, based on IC50 values. The model accurately predicted the biological activity class for HeLa with an accuracy of 0.77 ± 0.4 and demonstrated acceptable performance for MCF7 and MDA-MB231, with accuracy between 0.56 and 0.66. However, the results were less reliable for PC3 and HepG2. In conclusion, the ChemBERTa fine-tuned model shows potential for predicting outcomes on in-house datasets.

Alzheimer's disease (AD) is a devastating kind of dementia that is becoming more common worldwide. Toxic amyloid-beta (Aβ) aggregates are the primary cause of AD onset and development. Superparamagnetic iron oxide nanoparticles (SPIONs) have received a lot of interest in AD therapy over the last decade because of their ability to redirect the Aβ fibrillation process and improve associated brain dysfunction. The potential diagnostic application of SPIONs in AD has dramatically increased this interest. Furthermore, surface-modified engineered SPIONs function as drug carriers to improve the efficacy of current therapies. Various preclinical and clinical studies on the role of SPIONs in AD pathology have produced encouraging results. However, due to their physicochemical properties (e.g., size, surface charge, and particle concentration) in the biological milieu, SPIONs may play the role of a preventive or accelerative agent in AD. Even though SPIONs are potential therapeutic and diagnostic options in AD, significant efforts are still needed to overcome the inconsistencies and safety concerns. This review evaluated the current understanding of how various SPIONs interact with AD models and explored the discrepancies in their efficacy and safety., 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 Ltd. All rights reserved.)

Optimal glucose control is crucial for maintaining brain health and preventing metabolic and cognitive disorders in the general population. Glycosylated hemoglobin (HbA1c) serves as a key marker for assessing glucose intolerance and its impact on brain structure and function in healthy individuals. However, existing literature presents conflicting findings, necessitating a systematic review to consolidate current knowledge in this domain. This systematic review examines 26 English-language studies involving participants aged 15 years and above, investigating the relationship between HbA1c levels and brain health. Studies focusing on normal/general populations and utilizing magnetic resonance imaging (MRI) as the imaging modality were included. Exclusion criteria encompassed review articles, abstracts, letters, animal studies, and research involving neuropsychiatric or metabolic diseases. Data were gathered from PubMed, Scopus, and Web of Science databases up to November 2023. Analysis reveals significant associations between HbA1c levels and various brain metrics, including volume, cortical thickness, fractional anisotropy, mean diffusivity, activity, and connectivity. However, findings exhibit inconsistency, likely attributed to disparities in sample characteristics and study sizes. Notably, hippocampal volume, white matter hyperintensity, and ventral attention network connectivity emerge as frequently affected structures and functions, mirroring trends observed in diabetic populations. Despite inconclusive evidence, glucose intolerance appears to exert considerable influence on select brain structures and functions in individuals without diagnosed metabolic disorders. Understanding these associations is critical for mitigating the risk of cognitive decline and dementia in healthy populations. Future investigations should aim to elucidate the intricate relationship between HbA1c concentrations and brain health parameters in normoglycemic individuals., (© 2024 British Society for Neuroendocrinology.)

Multifunctional wound dressings have been applied for burn injuries to avoid complications and promote tissue regeneration. In the present study, we fabricated a natural alginate-chitosan hydrogel comprising silymarin and green-synthesized zinc ‎oxide ‎nanoparticles (ZnO NPs). Then, the physicochemical attributes of ZnO NPs and loaded hydrogels were analyzed. Afterward, wound healing efficacy was evaluated in a rat model of full-thickness dermal burn wounds. The findings indicated that ZnO NPs were synthesized via reduction with phytochemicals from Elettaria cardamomum seeds extract. The microscopic images exhibited fairly spherical ZnO NPs (35-45 nm), and elemental analysis verified the relevant composition. The hydrogel, containing silymarin and biosynthesized ZnO NPs, displayed a uniform appearance, smooth surfaces, and a porous structure. Moreover, infrared spectroscopy ‎identified functional groups, confirming the successful loading without adverse interactions. The obtained hydrogel exhibited great water absorption, high porosity, sustainable degradation for several days, and enhanced antioxidant capability of the combined loaded component. In vivo studies revealed faster and superior wound healing, achieving nearly complete closure by day 21. Histopathology confirmed improved cell growth, tissue regeneration, collagen deposition, and neovascularization. It is believed that this multifunctional hydrogel-based wound dressing can be applied for effective burn wound treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Background: Distinguishing high-grade gliomas (HGGs) from brain metastases (BMs) using perfusion-weighted imaging (PWI) remains challenging. PWI offers quantitative measurements of cerebral blood flow (CBF) and cerebral blood volume (CBV), but optimal PWI parameters for differentiation are unclear., Purpose: To compare CBF and CBV derived from PWIs in HGGs and BMs, and to identify the most effective PWI parameters and techniques for differentiation., Study Type: Systematic review and meta-analysis., Population: Twenty-four studies compared CBF and CBV between HGGs (n = 704) and BMs (n = 488)., Field Strength/sequence: Arterial spin labeling (ASL), dynamic susceptibility contrast (DSC), dynamic contrast-enhanced (DCE), and dynamic susceptibility contrast-enhanced (DSCE) sequences at 1.5 T and 3.0 T., Assessment: Following the PRISMA guidelines, four major databases were searched from 2000 to 2024 for studies evaluating CBF or CBV using PWI in HGGs and BMs., Statistical Tests: Standardized mean difference (SMD) with 95% CIs was used. Risk of bias (ROB) and publication bias were assessed, and I 2 statistic was used to assess statistical heterogeneity. A P-value<0.05 was considered significant., Results: HGGs showed a significant modest increase in CBF (SMD = 0.37, 95% CI: 0.05-0.69) and CBV (SMD = 0.26, 95% CI: 0.01-0.51) compared with BMs. Subgroup analysis based on region, sequence, ROB, and field strength for CBF (HGGs: 375 and BMs: 222) and CBV (HGGs: 493 and BMs: 378) values were conducted. ASL showed a considerable moderate increase (50% overlapping CI) in CBF for HGGs compared with BMs. However, no significant difference was found between ASL and DSC (P = 0.08)., Data Conclusion: ASL-derived CBF may be more useful than DSC-derived CBF in differentiating HGGs from BMs. This suggests that ASL may be used as an alternative to DSC when contrast medium is contraindicated or when intravenous injection is not feasible., Technical Efficacy: Stage 2., (© 2024 International Society for Magnetic Resonance in Medicine.)

Background: Colorectal cancer [CRC] is among the most fatal types of cancer. An active targeting delivery system that specifically interacts with CRC cells could improve the therapy's outcomes. Herein, Cetuximab single-chain fragment variable antibody [scFv] fragments were conjugated to the surface of 5-FU encapsulated chitosan nanoparticles [CS NPs] to develop an effective therapeutic platform [scFv-CS/5-FU NPs]., Method: CS/5-FU NPs were synthesized using a special fluidic system. Encapsulation efficiency [EE], loading capacity [LC], and the drug release profile of the particles were determined. scFv fragments were produced recombinantly and tailored on the surface of CS/5-FU NPs. The physicochemical features of scFv-CS/5-FU NPs were also characterized. MTT and flow cytometry assay investigated the toxicity effect of scFv-CS/5-FU NPs on the HCT116 cell line., Results: CS/5-FU NPs had a homogenous spherical shape. They possessed sustainable drugrelease behavior. The produced scFv-CS/5-FU NPs were also spherical. scFv-CS/5-FU NPs significantly decreased the viability of cancerous cells in a dose-dependent manner and induced apoptosis in 97.97% of targeted cells., Conclusion: scFv-CS/5-FU NPs showed remarkable anti-CRC activity. This novel targeting delivery system reduced the effective dose of 5-FU which is of vital importance to decrease the devastating side effects of chemotherapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by amyloid plaques, neurofibrillary tangles, and neuronal loss. Early cerebral and body iron dysregulation and accumulation interact with AD pathology, particularly in the precuneus, a crucial functional hub in cognitive functions. Quantitative susceptibility mapping (QSM), a novel post-processing approach, provides insights into tissue iron levels and cerebral oxygen metabolism and reveals abnormal iron accumulation early in AD. Increased iron deposition in the precuneus can lead to oxidative stress, neuroinflammation, and accelerated neurodegeneration. Metabolic disorders (diabetes, non-alcoholic fatty liver disease (NAFLD), and obesity), genetic factors, and small vessel pathology contribute to abnormal iron accumulation in the precuneus. Therefore, in line with the growing body of literature in the precuneus region of patients with AD, QSM as a neuroimaging method could serve as a non-invasive biomarker to track disease progression, complement other imaging modalities, and aid in early AD diagnosis and monitoring., Competing Interests: The authors declare that they have no conflicts of interest., (© 2024 The Author(s). Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Background: Prostate cancer is among prevalent cancers in men. Numerous strategies have been proposed to intervene with the important prostate cancer-related signaling pathways. Among the most promising strategies is CRISPR/Cas9 strategy. This strategy has been used to modify expression of a number of genes in prostate cancer cells., Aims: This review summarizes the most recent progresses in the application of CRISPR/Cas9 strategy in modification of prostate cancer-related phenotypes with an especial focus on pathways related to androgen receptor signaling., Conclusion: CRISPR/Cas9 technology has successfully targeted several genes in the prostate cancer cells. Moreover, the efficiency of this technique in reducing tumor burden has been tested in animal models of prostate cancer. Most of targeted genes have been related with the androgen receptor signaling. Targeted modulation of these genes have affected growth of castration-resistant prostate cancer. PI3K/AKT/mTOR signaling and immune response-related genes have been other targets that have been successfully modulated by CRISPR/Cas9 technology in prostate cancer. Based on the rapid translation of this technology into the clinical application, it is anticipated that novel treatments based on this technique change the outcome of this malignancy in future., (© 2024. The Author(s).)

A novel cell-penetrating peptide (CPP) called FAM -Y 4 R 4 , with FAM as a fluorescent probe, was developed. Initially, we aimed to use Y 4 as a supramolecular host for water-insoluble drugs, with R 4 driving the complex into cells. However, an unexpected hurdle was discovered; the peptide self-assembled into amorphous aggregates, rendering it ineffective for our intended purpose. Molecular dynamics simulations revealed that intermolecular cation-π interactions between arginine and tyrosine caused this aggregation. By decorating the R 4 sidechains with p -sulfonatocalix[4]arene (CX4), we successfully dissolved most of the aggregates, significantly improved the peptide's solubility and enhanced the cell uptake with MCF7 and A549 cells via both direct penetration and endocytosis. The binding strength between CX4 and R 4 , as well as the interaction between curcumin and tyrosines was quantified. Encouragingly, our results showed that FAM -Y 4 R 4 , with CX4, effectively delivered curcumin - as a model for poorly water-soluble drugs - into cells which exhibited potent anticancer activity. Using R 4 /CX4 instead of the conventional R 7-9 oligoarginine-based CPP simplifies peptide synthesis and offers higher yields. CX4 shows promise for addressing aggregation issues in other peptides that undergo a similar aggregation mechanism., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

One of the critical challenges in managing colorectal cancer (CRC) is the development of oxaliplatin (OXP) resistance. Long non-coding RNAs (lncRNAs) have a crucial role in CRC progression and chemotherapy resistance, with exosomal lncRNAs emerging as potential biomarkers. This study aimed to predict key lncRNAs involved in OXP-resistance using in-silico methods and validate them using RT-qPCR methods in CRC cells and their isolated exosomes. Two public datasets, GSE42387 and GSE119481, were downloaded from the GEO database to identify differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) associated with OXP-resistance in the HCT116 cell line. The analysis of GSE42387 revealed 210 DEGs, and GSE119481 identified 73 DEmiRNAs. A protein-protein interaction (PPI) network analysis of the DEGs identified 133 interconnected genes, from which the top ten genes with the highest degree scores were selected. By intersecting predicted miRNAs targeting these genes with the DEmiRNAs, 38 common miRNAs were found. Subsequently, 224 lncRNAs targeting these common miRNAs were predicted. LncRNA-miRNA-mRNA network were constructed and the top five lncRNAs with the highest degree scores were identified. Analysis using the Kaplan-Meier plotter database revealed that the key lncRNAs NEAT1, OIP5-AS1, and MALAT1 are significantly associated with the overall survival of CRC patients. To validate these lncRNAs, OXP-resistant HCT116 sub-cell line (HCT116/OXR) was developed by exposing parental HCT116 cells to gradually increasing concentrations of OXP. Exosomes derived from both HCT116 and HCT116/OXR cells were isolated and characterized utilizing dynamic light scattering (DLS), transmission electron microscopy (TEM), and Western blotting. RT-qPCR confirmed elevated levels of NEAT1, OIP5-AS1, and MALAT1 in HCT116/OXR cells and their exosomes compared to parental HCT116 cells and their exosomes. This study concludes that NEAT1, OIP5-AS1, and MALAT1 are associated with the OXP-resistance in CRC. The high levels of these lncRNAs in exosomes of resistant cells suggest their involvement in intercellular communication and resistance propagation. This positioning makes them promising biomarkers for OXP-resistance in CRC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sahebnasagh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Wound management is a critical aspect of healthcare, necessitating effective and innovative wound dressing materials. Many existing wound dressings lack effectiveness and exhibit limitations, including poor antimicrobial activity, toxicity, inadequate moisture regulation, and weak mechanical performance. The aim of this study is to develop a natural-based nanofibrous structure that possesses desirable characteristics for use as a wound dressing. The chemical analysis confirmed the successful creation of Zein (Ze) (25% w/v) /gelatin (Gel) (10% w/v) /chitosan (CS) (2% w/v) /Polyvinyl alcohol (PVA) (10% w/v) nanofibrous scaffolds loaded with vitamin E tocopheryl polyethylene glycol succinate (Vit E). The swelling percentages of nanofiber (NF), NF + Vit E, cross-linked nanofiber (CNF), and CNF + Vit E were 49%, 110%, 410%, and 676%, respectively; and the degradation rates of NF, NF + Vit E, CNF, and CNF + Vit E were 29.57 ± 5.06%, 33.78 ± 7.8%, 14.03 ± 7.52%, 43 ± 6.27%, respectively. The antibacterial properties demonstrated that CNF impregnated with antibiotics reduced Escherichia coli (E. coli) counts by approximately 27-28% and Staphylococcus aureus (S. aureus) counts by about 34-35% compared to negative control. In conclusion, cross-linked Ze/Gel/CS/PVA nanofibrous scaffolds loaded with Vit E have potential as suitable wound dressing materials because environmentally friendly materials contribute to sustainable wound care and controlled degradation ensures wound dressings breakdown harmlessly., (© 2024. The Author(s).)

Recently, the anti-tumor effects of cannabis extract on various cancers have attracted the attention of researchers. Here, we report a nanoemulsion (NE) composition designed to enhance the delivery of two active components in cannabis extracts (∆9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD)) in an animal model of glioblastoma. The efficacy of the NE containing the two drugs (NED) was compared with the bulk drugs and carrier (NE without the drugs) using the C6 tumor model in rats. Hemocompatibility factors (RBC, MCV, MCH, MCHC, RDW, PPP, PT and PTT) were studied to determine the potential in vivo toxicity of NED. The optimized NED with mean ± SD diameter 29 ± 6 nm was obtained. It was shown that by administering the drugs in the form of NED, the hemocompatibility increased. Cytotoxicity studies indicated that the NE without the active components (i.e. mixture of surfactants and oil) was the most cytotoxic group, while the bulk group had no toxicity. From the in vivo MRI and survival studies, the NED group had maximum efficacy (with ~4 times smaller tumor volume on day 7 of treatment, compared with the control. Also, survival time of the control, bulk drug, NE and NED were 9, 4, 12.5 and 51 days, respectively) with no important adverse effects. In conclusion, the NE containing cannabis extract could be introduced as an effective treatment in reducing brain glioblastoma tumor progression., (© 2024. The Author(s).)

Purpose: This research sought to ascertain the Minimal Clinically Important Difference (MCID) and Robust Clinically Important Difference (RCID) of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) and Chalder Fatigue Questionnaire-11 (CFQ-11) as two important concepts for the clinical interpretation of the results in chronic post-stroke population., Methods: A total of 128 subjects with chronic post-stroke completed the MFSI-SF and CFQ-11 before and after six weeks of intervention. The MCIDs were derived using both anchor- and distribution-based methods; however, only anchor-based methods were used to estimate RCIDs., Results: Anchor-based MCIDs for MFSI-SF and CFQ-11 were in the range of -5 to -6.28 and -2 to -4.56, respectively. Distribution-based MCIDs in MFSI-SF and CFQ-11 were calculated in the range of -4.17 to -24.05 and -1.72 to -7.68, respectively. RCID ranges of -10 to -15 were obtained for the MFSI-SF and -6 to -7.33 for the CFQ-11., Conclusion: These findings may have implications for clinical experts in the clinical interpretation of fatigue changes observed in MFSI-SF and CFQ-11 in individuals with chronic stroke.

Introduction: Although radiomics has revealed an intriguing perspective for quantitative radiology, the impact of scanning parameters on its outcomes must be considered. In this study, the effects of changes in the region of interest (ROI) sizes, Hounsfield Unit (HU), and resolution of computed tomography (CT) on feature reproducibility have been investigated., Methods: The GAMMEX 464 phantom was used to evaluate the reproducibility of radiomics features across different ROI sizes, HU, and resolution. Data were acquired using a consistent system setup, with the phantom repositioned for each scan. The first acquisition series examined the effects of different ROI sizes and resolutions (1, 3, and 5 mm) on feature reproducibility. The second series assessed the impact of different HU and resolution. Segmentation and feature extraction were performed using LIFEx 7.1.0 software, focusing on textural radiomics features. Statistical analysis involved calculating the coefficient of variation (COV) to categorize feature variability. COV <5 % was considered highly stable., Results: Out of the 32 textural features studied, the analysis of changes in ROI size with a resolution of 1 mm, 3 mm, and 5 mm revealed that 16, 17, and 18 features had high reproducibility, with a COV<5 %. Polyethylene, acrylic, and water also demonstrated stable textural features across changes in scan parameters and image resolutions, with 4 reproducible features in all resolutions. The grey-level run length matrix (GLRLM) and grey-level zone length matrix (GLZLM) radiomics groups were highly stable in the context of variations in scan parameters and different materials., Conclusion: The results of this study highlight the importance of standardizing radiomics studies to reduce the influence of pre-analysis steps on feature values. This standardization is crucial for guaranteeing the consistency of radiomics features under various imaging conditions. Additional research is required to enhance these results., Implications for Practice: To ensure the reproducibility and reliability of radiomics features, it is imperative to standardize scanning parameters and pre-analysis protocols. This standardization will enhance the consistency of radiomics applications in both clinical and research environments., Competing Interests: Conflicts of interest The authors have no conflicts of interest., (Copyright © 2024 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.)