Tissue clearing and three-dimensional imaging of intact tissues: a review on FACT protocol.

FACT is a developed technique for clearing tissues that does not use acrylamide. Since the removal of lipids is crucial for transparency and efficient antibody staining throughout the tissue, especially for microscopy and imaging, it is a harmful process that can cause the loss of important biological molecules such as proteins. The FACT technique overcomes this by chemically bonding the membrane and intracellular proteins with the extracellular matrix, creating a massive 3D hydrogel matrix and providing structural support to fortify the tissue during processing. Compared to other acrylamide-based techniques, the FACT technique requires less labor and harmful chemicals and is therefore considered a more suitable option. In this study, we describe the complete FACT protocol for antibody staining and imaging of whole-cleared tissues while preserving structure and improving image quality. The protocol includes tissue perfusion, fixation, clearing, antibody staining, refractive index matching (RIM) (), microscopy, and imaging. The timing for each step varies depending on the size, weight, and type of tissue, as well as the type of immunostaining. We provide an example of the FACT protocol using mouse brain tissue, which demonstrates its suitability for molecular interrogation analysis of large tissues. The FACT technique has been successfully performed on different types of tissues, making it a favorable choice for a variety of applications.

A Bibliometric Analysis of Study of Associations of Certain Genotypes with the Cardiovascular Form of Diabetic Neuropathy.

This bibliometric analysis explores the landscape of research on the associations between specific genotypes and the cardiovascular form of diabetic neuropathy. Diabetes mellitus (DM) is a major contributor to premature mortality, primarily due to increased susceptibility to cardiovascular diseases. The global prevalence of DM is rising, with projections indicating further increases. Diabetic neuropathy, a complication of DM, includes the cardiovascular subtype, posing challenges in diagnosis and management. Understanding the genetic basis of cardiovascular diabetic neuropathy is crucial for targeted therapeutic interventions. The study utilizes bibliometric analysis to synthesize existing literature, identify trends, and guide future research. The Scopus database was searched, applying inclusion criteria for English articles related to genotypes and cardiovascular diabetic neuropathy. The analysis reveals a dynamic field with a notable impact, collaborative efforts, and multidimensional aspects. Publication trends over 1997-2023 demonstrate fluctuating research intensity. Top journals, authors, and affiliations are highlighted, emphasizing global contributions. Keyword analysis reveals thematic trends, and citation analysis identifies influential documents. Limitations include database biases, incomplete metadata, and search query specificity. The urgent need to explore genetic factors in cardiovascular diabetic neuropathy aligns with the increasing global diabetes burden. This analysis provides a comprehensive overview, contributing to the broader discourse on diabetic neuropathy research.

Reconstructing Critical-Sized Mandibular Defects in a Rabbit Model: Enhancing Angiogenesis and Facilitating Bone Regeneration via a Cell-Loaded 3D-Printed Hydrogel-Ceramic Scaffold Application.

In this study, we propose a spatially patterned 3D-printed nanohydroxyapatite (nHA)/beta-tricalcium phosphate (ß-TCP)/collagen composite scaffold incorporating human dental pulp-derived mesenchymal stem cells (hDP-MSCs) for bone regeneration in critical-sized defects. We investigated angiogenesis and osteogenesis in a rabbit critical-sized mandibular defect model treated with this engineered construct. The critical and synergistic role of collagen coating and incorporation of stem cells in the regeneration process was confirmed by including a cell-free uncoated 3D-printed nHA/ß-TCP scaffold, a stem cell-loaded 3D-printed nHA/ß-TCP scaffold, and a cell-free collagen-coated 3D-printed nHA/ß-TCP scaffold in the experimental design, in addition to an empty defect. Posteuthanasia evaluations through X-ray analysis, histological assessments, immunohistochemistry staining, histomorphometry, and reverse transcription-polymerase chain reaction (RT-PCR) suggest the formation of substantial woven and lamellar bone in the cell-loaded collagen-coated 3D-printed nHA/ß-TCP scaffolds. Histomorphometric analysis demonstrated a significant increase in osteoblasts, osteocytes, osteoclasts, bone area, and vascularization compared to that observed in the control group. Conversely, a significant decrease in fibroblasts/fibrocytes and connective tissue was observed in this group compared to that in the control group. RT-PCR indicated a significant upregulation in the expression of osteogenesis-related genes, including BMP2, ALPL, SOX9, Runx2, and SPP1. The findings suggest that the hDP-MSC-loaded 3D-printed nHA/ß-TCP/collagen composite scaffold is promising for bone regeneration in critical-sized defects.

General movement assessment efficacy for assessment of nervous system integrity in children after hypoxic-ischemic encephalopathy in middle income countries.

BACKGROUND: Many infants who survive hypoxic-ischemic encephalopathy (HIE) face long-term complications like epilepsy, cerebral palsy, and developmental delays. Detecting and forecasting developmental issues in high-risk infants is critical. AIM: This study aims to assess the effectiveness of standardized General Movements Assessment (GMA) and Hammersmith Infant Neurological Examinations (HINE) in identifying nervous system damage and predicting neurological outcomes in infants with HIE. DESIGN: Prospective. SUBJECTS AND MEASURES: We examined full-term newborns with perinatal asphyxia, classifying them as Grade 2 HIE according to Sarnat and Sarnat. The study included 31 infants, with 14 (45.2 %) receiving therapeutic hypothermia (Group 1) and 17 (54.8 %) not (Group 2). We evaluated general movements during writhing and fidgety phases and conducted neurological assessments using the HINE. RESULTS: All infants exhibited cramped-synchronized - like movements, leading to cerebral palsy (CP) diagnosis. Three children in Group 1 and four in Group 2 lacked fidgety movements. During active movements, HINE and GMA showed high sensitivity and specificity, reaching 96 % and 100 % for all children. The ROC curve's area under the curve (AUC) was 0.978. CONCLUSION: Our study affirms HINE and GMA as effective tools for predicting CP in HIE-affected children. GMA exhibits higher sensitivity and specificity during fidgety movements. However, study limitations include a small sample size and data from a single medical institution, necessitating further research.

Comprehensive Overview of Innovative Strategies in Preventing Renal Ischemia-reperfusion Injury: Insights from Bibliometric and In Silico Analyses.

BACKGROUND: Ischemia-Reperfusion Injury (IRI) is a complex pathophysiological process with severe consequences, including irreversible loss of renal function. Various intraoperative prevention methods have been proposed to mitigate the harmful effects of warm ischemia and kidney reperfusion. AIM: This comprehensive analysis provides an overview of pharmacological agents and intraoperative methods for preventing and treating renal IRI. METHODS: Our analysis revealed that eplerenone exhibited the highest binding affinity to crucial targets, including Aldehyde Dehydrogenase (AD), Estrogen Receptor (ER), Klotho protein, Mineralocorticoid Receptor (MR), and Toll-Like Receptor 4 (TLR4). This finding indicates eplerenone's potential as a potent preventive agent against IRI, surpassing other available therapeutics like Benzodioxole, Hydrocortisone, Indoles, Nicotinamide adenine dinucleotide, and Niacinamide. In preventing kidney IRI, our comprehensive analysis emphasizes the significance of eplerenone due to its strong binding affinity to key targets involved in the pathogenesis of IRI. RESULTS: This finding positions eplerenone as a promising candidate for further clinical investigation and consideration for future clinical practice. CONCLUSION: The insights provided in this analysis will assist clinicians and researchers in selecting effective preventive approaches for renal IRI in surgical settings, potentially improving patient outcomes.

Photodynamic therapy of cervical cancer: a scoping review on the efficacy of various molecules.

Background: Cervical cancer poses a considerable worldwide health issue, where infection with the human papillomavirus (HPV) plays a vital role as a risk factor. Photodynamic therapy (PDT) is a minimally invasive treatment for HPV-related cervical lesions, which uses photosensitizers and light to selectively destroy abnormal cells. Objectives: Our objective is to present a comprehensive overview of the different types of molecules employed in PDT to reduce the occurrence and fatality rates associated with cervical cancer. Design: Scoping review and bibliometric analysis. Methods: The article explores clinical trials investigating the efficacy of PDT in treating low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion, as well as preclinical approaches utilizing various molecules for PDT in cervical cancer. Furthermore, the article sheds light on potential molecules for PDT enhancement, examining their properties through computer modeling simulations, molecular docking, and assessing their advantages and disadvantages. Results: Our findings demonstrate that PDT holds promise as a therapeutic approach for treating cervical lesions associated with HPV and cervical cancer. Additionally, we observe that the utilization of diverse dye classes enhances the anticancer effects of PDT. Conclusion: Among the various molecules employed in PDT, functionalized fullerene exhibits a notable inclination toward overexpressed receptors in cervical cancer cells, making it a potential candidate for intensified use in PDT. However, further research is needed to evaluate its long-term effectiveness and safety.

Using light to treat cervical cancer: what you need to know Cervical cancer is a significant global health concern, often linked to the human papillomavirus (HPV). There is a less invasive treatment called photodynamic therapy (PDT), which employs light and special substances to target and destroy abnormal cells related to HPV. In this review, we aim to give you a comprehensive look at the different substances used in PDT to reduce the occurrence and severity of cervical cancer. We have examined clinical trials focusing on treating specific types of cervical lesions and explored preclinical approaches using various substances. We have also delved into computer simulations and molecular docking to understand the strengths and weaknesses of these substances. Our findings show that PDT has potential as a treatment for HPV-related cervical lesions and cancer. Different dye classes used in this therapy enhance its effectiveness against cancer. Notably, a substance called functionalized fullerene stands out for its tendency to target receptors overexpressed in cervical cancer cells. It looks promising, but more research is necessary to ensure its long-term effectiveness and safety.

Sex differentials in the prevalence of behavioral risk factors and non-communicable diseases in adult populations of West Kazakhstan.

Introduction: The prevalence of non-communicable diseases (NCDs) is increasing worldwide. Several modifiable risk factors, such as smoking, alcohol drinking, physical inactivity, and obesity, have been linked to the development of NCDs in both genders. Understanding the prevalence of these risk factors and their associated factors is crucial for effective intervention planning in adult populations. This study aimed to provide an overview of the prevalence and associated factors of these risk behaviors among different genders of adults in West Kazakhstan. Methods: A cross-sectional study was conducted in four regions of West Kazakhstan. A stratified multistage sampling technique was utilized to obtain a representative sample size of 4,800 participants aged 18 -69 years. Trained researchers administered face-to-face interviews using validated questionnaires to gather information pertaining to sociodemographic characteristics, smoking habits, alcohol drinking, dietary patterns, physical activity levels, body mass index (BMI), and prevalent diseases. Results: This study, which included 4,800 participants from West Kazakhstan, revealed some striking numerical findings. The overall prevalence rates of behavioral risk factors and metabolic conditions were as follows: smoking was 13.6% (95%CI: 3.2-24.0%), alcohol drinking was 47.0% (27.7-66.3%), current obesity was 22.3% (9.0-35.6%), and physical inactivity was 80.7% (55.4-106.0%). In addition, the overall prevalence rates of metabolic conditions were 25.6% (11.3-39.9%) for hypertension, 7.5% (0.2-15.2%) for diabetes, 11.8% (2.1-21.5%) for high cholesterol, and 13.0% (2.8-23.2%) for cardiovascular diseases. Additionally, a higher prevalence of high cholesterol was observed in men, and a greater prevalence of heart disease was identified in women. Multinomial logistic regression revealed that physical inactivity was associated with hypertension, diabetes, and heart disease, while obesity was linked to hypertension, high cholesterol, and heart disease. Discussion: This study in West Kazakhstan identified variations in the prevalence of behavioral risk factors and NCDs, highlighting gender, age, and regional disparities. Notably, men showed higher rates of smoking and alcohol drinking, while women exhibited a greater prevalence of physical inactivity and obesity. Gender and regional differences were evident, with the West Kazakhstan region standing out for distinct patterns. Tailored interventions are crucial to address these disparities and enhance public health in the region.

General movements assessment: A bibliometric analysis.

This bibliometric analysis provides an in-depth exploration of the scholarly landscape in the field of Prechtl General Movement Assessment (GMA) research, spanning the period from 1961 to 2023. It offers valuable insights into the evolutionary trajectory and global impact of GMA. The study employs a longitudinal approach, meticulously tracking trends in scholarly output, international collaborations, and authorship patterns. Notably, our findings reveal a significant increase in GMA-related publications, highlighting the growing prominence of this field. The dominance of Australia and Austria in scholarly contributions underscores their pivotal roles. International collaborations are prominent, with active participation from European nations and the Americas. However, it is essential to acknowledge certain limitations, including potential data source biases and a reliance on English-language publications. This analysis serves as a valuable resource for stakeholders in the field, emphasizing the need for ongoing evaluation and collaborative efforts to enhance GMA applications and further our understanding of its clinical implications.

Role of Clinical Risk Factors and B-Type Natriuretic Peptide in Assessing the Risk of Asymptomatic Cardiotoxicity in Breast Cancer Patients in Kazakhstan.

The asymptomatic progression of chemotherapy-induced cardiotoxicity poses a significant risk to breast cancer patients. In the present single-center cohort study, a predictive model for evaluating the risk of cardiotoxicity during or by the end of chemotherapy was designed. The risk-prediction nomogram was delineated and assessed. In total, 34 patients out of 120 developed asymptomatic cardiotoxicity (28.3%). Of six explored biomarkers, only B-type natriuretic peptide showed a reliable pattern of incremental increase, revealing statistical significance between cardiotoxicity "+" and "-" groups by visit 4 or by the 9th month of monitoring (p 0.006). The following predictors were included in the model: age, hypertension, diabetes mellitus, baseline glomerular filtration rate, 6 min walk test measured at visit 4, BNP values at visit 4, left ventricular ejection fraction levels at visit 4, a total dose of radiotherapy received, and anthracycline cumulative doses. The model's AUC was 0.72 (95% CI 0.59; 0.86), evidencing the satisfactory predictive ability of the model; sensitivity 100% (95% CI 90.36; 100.0) at a specificity of 66.67% (95% CI 50.33; 79.79); PPV 54.1% [95% CI 47.13; 60.91]; PVN 100% [95% CI 94.64; 100.00]. The calibration plot showed satisfactory agreement between predicted and actual chances (p = 0.98). The designed model can be applied in settings lacking speckle tracking echocardiography.

Comparison the therapeutic effects of bone marrow CD144+ endothelial cells and CD146+ mesenchymal stem cells in POF rats.

Introduction: Premature ovarian insufficiency (POI) is a challenging issue in terms of reproduction biology. In this study, therapeutic properties of bone marrow CD146+ mesenchymal stem cells (MSCs) and CD144+ endothelial cells (ECs) were separately investigated in rats with POI. Methods: POI rats were classified into control POI, POI + CD146+ MSCs, and POI + CD144+ ECs groups. Enriched CD146+ MSCs and CD144+ ECs were directly injected into ovarian tissue (15 × 104 cells/10 µL) in relevant groups. After 4 weeks, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were measured in blood samples. Ovarian tissues were collected and subjected to Hematoxylin-Eosin and Masson's trichrome staining. The expression of angp-2, vegfr-2, smad-2, -4, -6, and tgf-ß1 was studied using qRT-PCR analysis. Histopathological examination indicated an increased pattern of atretic follicles in the POI group related to the control rats (P<0.0001). Results: Data indicated that injection of POI + CD146+ MSCs and CD144+ ECs in POI rats reduced atretic follicles and increased the number of normal follicles (P<0.01). Along with these changes, the content of blue-colored collagen fibers was diminished after cell transplantation. Besides, cell transplantation in POI rats had the potential to reduce increased FSH, and LH levels (P<0.05). In contrast, E2 content was increased in POI + CD146+ MSCs and POI + CD144+ ECs groups compared to control POI rats, indicating restoration of follicular function. CD144+ (smad-2, and -4) and CD146+ (smad-6) cells altered the activity of genes belonging TGF-ß signaling pathway. Unlike POI + CD146+ MSCs, aberrant angiogenesis properties were significantly down-regulated in POI + CD144+ ECs related to the control POI group (P<0.05). Conclusion: The transplantation of bone marrow CD146+ and CD144+ cells can lead to the restoration of ovarian tissue function in POI rats via modulating different mechanisms associated with angiogenesis and fibrosis.

Genetic and epigenetic factors of arterial hypertension: a bibliometric- and in-silico-based analyses.

Introduction: Arterial hypertension (AH) is a pervasive global health concern with multifaceted origins encompassing both genetic and environmental components. Previous research has firmly established the association between AH and diverse genetic factors. Consequently, scientists have conducted extensive genetic investigations in recent years to unravel the intricate pathophysiology of AH. Methods: In this study, we conducted a comprehensive bibliometric analysis employing VOSviewer software to identify the most noteworthy genetic factors that have been the focal point of numerous investigations within the AH field in recent years. Our analysis revealed genes and microRNAs intricately linked to AH, underscoring their pivotal roles in this condition. Additionally, we performed molecular docking analyses to ascertain microRNAs with the highest binding affinity to these identified genes. Furthermore, we constructed a network to elucidate the in-silico-based functional interactions between the identified microRNAs and genes, shedding light on their potential roles in AH pathogenesis. Results: Notably, this pioneering in silico examination of genetic factors associated with AH promises novel insights into our understanding of this complex condition. Our findings prominently highlight miR-7110-5p, miR-7110-3p, miR-663, miR-328-3p, and miR-140-5p as microRNAs exhibiting a remarkable affinity for target genes. These microRNAs hold promise as valuable diagnostic and therapeutic factors, offering new avenues for the diagnosis and treatment of AH in the foreseeable future. Conclusion: In summary, this research underscores the critical importance of genetic factors in AH and, through in silico analyses, identifies specific microRNAs with significant potential for further investigation and clinical applications in AH management.

Bibliometric Analysis of Global Research Output on Antimicrobial Resistance among Pneumonia Pathogens (2013-2023).

Antimicrobial resistance (AMR) is a pressing global concern, posing significant challenges to the effective treatment of infections, including pneumonia. This bibliometric analysis aims to investigate the research output on AMR among pneumonia pathogens from 2013 to 2023. Data were extracted from the Web of Science Core Collection (WOS-CC) using an inclusive search strategy. The analysis included 152 relevant studies published in 99 different sources, involving 988 authors and yielding an average of 16.33 citations per document over the past decade. The findings reveal a notable increase in research on AMR among pneumonia pathogens, indicating a growing awareness of this critical issue. Collaborative studies were prevalent, with the majority of authors engaging in joint research efforts. Bradford's Law identified twelve core journals that were instrumental in disseminating research in this field, with "Medicine" emerging as the most prolific journal. The USA and China emerged as the leading contributors, while Germany displayed a strong inclination towards collaborative research. Intermountain Medical Center, Saitama Medical University, and Udice-French Research Universities were the most productive institutions, and Yayan J. and Rasche K. were the top authors. Furthermore, the analysis identified commonly encountered microorganisms such as Acinetobacter baumanii and Klebsiella pneumoniae in the context of AMR. Time-based analysis of keywords highlighted the significance of terms like "community-acquired pneumonia" and "ventilator-associated pneumonia". Overall, this comprehensive study sheds light on the global research landscape of AMR among pneumonia pathogens. The insights gained from this analysis are essential for guiding future research priorities and collaborative efforts to combat AMR effectively and improve treatment outcomes for pneumonia and related infections. As the frequency of reports concerning resistance among pneumonia pathogens, notably A. baumannii and K. pneumoniae, continues to rise, there is an immediate requirement for pharmaceutical manufacturers and healthcare providers to respond proactively and ready themselves for the forthcoming implications of this matter. It also underscores the importance of knowledge dissemination and evidence-based interventions to address this growing public health challenge. However, the study acknowledges the limitations associated with using a single publication database and encourages the inclusion of data from other sources in future research.

Enhancing differentiation of menstrual blood-derived stem cells into female germ cells using a bilayer amniotic membrane and nano-fibrous fibroin scaffold.

Three-dimensional nanofiber scaffolds offer a promising method for simulating in vivo conditions within the laboratory. This study aims to investigate the influence of a bilayer amniochorionic membrane/nanofibrous fibroin scaffold on the differentiation of human menstrual blood mesenchymal stromal/stem cells (MenSCs) into female germ cells. MenSCs were isolated and assigned to four culture groups: (i) MenSCs co-cultured with granulosa cells (GCs) using the scaffold (3D-T group), (ii) MenSCs using the scaffold alone (3D-C group), (iii) MenSCs co-cultured only with GCs (2D-T group), and (iv) MenSCs without co-culture or scaffold (2D-C group). Both MenSCs and GCs were independently cultured for two weeks before co-culturing was initiated. Flow cytometry was employed to characterize MenSCs based on positive markers (CD73, CD90, and CD105) and negative markers (CD45 and CD133). Additionally, flow cytometry and immunocytochemistry were used to characterize the GCs. Differentiated MenSCs were analyzed using real-time PCR and immunostaining. The real-time PCR results demonstrated significantly higher levels of VASA expression in the 3D-T group compared to the 3D-C, 2D-T, and 2D-C groups. Similarly, the SCP3 mRNA level in the 3D-T group was notably elevated compared to the 3D-C, 2D-T, and 2D-C groups. Moreover, the expression of GDF9 was significantly higher in the 3D-T group when compared to the 3D-C, 2D-T, and 2D-C groups. Immunostaining results revealed a lack of signal for VASA, SCP3, or GDF9 markers in the 2D-T group, while some cells in the 3D-T group exhibited positive staining for all these proteins. These findings suggest that the combination of a bilayer amniochorionic membrane/nanofibrous fibroin scaffold with co-culturing GCs facilitates the differentiation of MenSCs into female germ cells.

Dysregulated miRNAs in recurrent miscarriage: A systematic review.

Recurrent miscarriage (RM) is a complex reproductive medicine disease that affects many families. The cause of RM is unclear at this time; however, lifestyle and genetic variables may influence the process. The slight alteration in miRNA expression has enormous consequences for a variety of difficulties, one of which may be RM. The target of this systematic study was to provide a framework of the dysregulated miRNAs in RM. The Prisma guidelines were applied to perform current systematic review pertaining to articles in the seven databases. Thirty-nine papers out of 245 received fulfilled all inclusion requirements. From all the mentioned miRNAs, 40 were up-regulated (65.57 %), whereas 21 were down-regulated (34.43 %). These dysregulated miRNAs contributed to the pathophysiology of RM by influencing key pathways and processes such as apoptosis, angiogenesis, epithelial-mesenchymal transition, and the immune system. Understanding the dysregulation of miRNAs, as well as the pathways and processes that engage these miRNAs and impact disease pathogenesis, may aid in clarifying the unknown underlying mechanisms of RM and the development of novel molecular therapeutic targets and medical domains.

Tissue Extract from Brittle Star Undergoing Arm Regeneration Promotes Wound Healing in Rat.

This study set out to evaluate the wound healing properties of brittle star extracts in vitro and in vivo. Due to the great arm regeneration potential of the brittle star, Ophiocoma cynthiae, the present study aimed to evaluate the wound healing effect of hydroalcoholic extracts of brittle star undergoing arm regeneration in wound healing models. The brittle star samples were collected from Nayband Bay, Bushehr, Iran. After wound induction in the arm of brittle stars, hydroalcoholic extracts relating to different times of arm regeneration were prepared. The GC-MS analysis, in vitro MTT cell viability and cell migration, Western blot, and computational analysis tests were performed. Based on the in vitro findings, two BSEs were chosen for in vivo testing. Macroscopic, histopathological and biochemical evaluations were performed after treatments. The results showed positive proliferative effects of BSEs. Specifically, forty-two compounds were detected in all groups of BSEs using GC-MS analysis, and their biological activities were assessed. The MTT assay showed that the 14 d BSE had a higher proliferative effect on HFF cells than 7 d BSE. The cell migration assay showed that the wound area in 7 d and 14 d BSEs was significantly lower than in the control group. Western blot analysis demonstrated an increase in the expression of proliferation-related proteins. Upon the computational analysis, a strong affinity of some compounds with proteins was observed. The in vivo analysis showed that the evaluation of wound changes and the percentage of wound healing in cell migration assay in the 7 d BSE group was better than in the other groups. Histopathological scores of the 7 d BSE and 14 d BSE groups were significantly higher than in the other groups. In conclusion, the hydroalcoholic extract of O. cynthiae undergoing arm regeneration after 7 and 14 days promoted the wound healing process in the cell and rat skin wound healing model due to their proliferative and migratory biological activity.

Amniotic fluid-derived exosomes attenuated fibrotic changes in POI rats through modulation of the TGF-ß/Smads signaling pathway.

In the current study, we investigated the regenerative effects of amniotic fluid exosomes (AF-Exos) in a rat model for premature ovarian insufficiency (POI). POI is a condition characterized by a decrease in ovarian function that can lead to infertility. We induced POI by administering cyclophosphamide (CTX) for 15 consecutive days, and then transplanted AF-Exos directly into both ovarian tissues. Four weeks later, we measured the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2), and performed histopathological evaluations using H & E and Masson's trichrome staining. We also monitored the expression of genes related to the TGF-ß signaling pathway using real-time PCR and examined the fertility rate of POI rats after AF-Exos therapy. Histological analysis showed an increase in atretic follicles and a decrease in healthy follicle count after POI induction. Four weeks post-AF-Exos intervention, the healthy follicle count increased (p < 0.01) while the atretic follicle count decreased (p < 0.001). In parallel, the deposition of collagen fibers also decreased following AF-Exos transplantation. The concentrations of FSH and LH hormones in sera remained unchanged after injection of AF-Exos, while E2 levels increased (p < 0.05). The expression of Smad-4 (p < 0.01) and Smad-6 (p < 0.05) was upregulated in POI rats that received AF-Exos, while Smad-2, TGF-ß1, TNF-α, and IL-10 remained statistically unchanged. Our records showed a notable increase in litter number after AF-Exos compared to the non-treated POI rats. These results suggest that AF-Exos transplantation has the potential to restore ovarian function through the TGF-ß/Smads signaling pathway in POI rats.

Proliferative Effect of Aqueous Extract of Sea Cucumber (Holothuria parva) Body Wall on Human Umbilical Cord Mesenchymal Stromal/Stem Cells.

Sea cucumber extracts and their bioactive compounds have the potential for stem cell proliferation induction and for their beneficial therapeutic properties. In this study, human umbilical cord mesenchymal stromal/stem cells (hUC-MSCs) were exposed to an aqueous extract of Holothuria parva body walls. Proliferative molecules were detected using gas chromatography-mass spectrometry (GC-MS) analysis in an aqueous extract of H. parva. The aqueous extract concentrations of 5, 10, 20, 40, and 80 µg/mL and 10 and 20 ng/mL of human epidermal growth factor (EGF) as positive controls were treated on hUC-MSCs. MTT, cell count, viability, and cell cycle assays were performed. Using Western blot analysis, the effects of extracts of H. parva and EGF on cell proliferation markers were detected. Computational modeling was done to detect effective proliferative compounds in the aqueous extract of H. parva. A MTT assay showed that the 10, 20, and 40 µg/mL aqueous extract of H. parva had a proliferative effect on hUC-MSCs. The cell count, which was treated with a 20 µg/mL concentration, increased faster and higher than the control group (p < 0.05). This concentration of the extract did not have a significant effect on hUC-MSCs' viability. The cell cycle assay of hUC-MSCs showed that the percentage of cells in the G2 stage of the extract was biologically higher than the control group. Expression of cyclin D1, cyclin D3, cyclin E, HIF-1α, and TERT was increased compared with the control group. Moreover, expression of p21 and PCNA decreased after treating hUC-MSCs with the extract. However, CDC-2/cdk-1 and ERK1/2 had almost the same expression as the control group. The expression of CDK-4 and CDK-6 decreased after treatment. Between the detected compounds, 1-methyl-4-(1-methyl phenyl)-benzene showed better affinity to CDK-4 and p21 than tetradecanoic acid. The H. parva aqueous extract showed proliferative potential on hUC-MSCs.

A Bibliometric and In Silico-Based Analysis of Anti-Lung Cancer Compounds from Sea Cucumber.

Lung cancer is one of the most lethal malignancies in the world. However, current curative approaches for treating this type of cancer have some weaknesses. Therefore, scientists are attempting to discover new anti-lung cancer agents. Sea cucumber is a marine-derived source for discovering biologically active compounds with anti-lung cancer properties. To explore the anti-lung cancer properties of sea cucumber, we analyzed surveys using VOSviewer software and identified the most frequently used keywords. We then searched the Google Scholar database for compounds with anti-lung cancer properties within that keyword family. Finally, we used AutoDock 4 to identify the compounds with the highest affinity for apoptotic receptors in lung cancer cells. The results showed that triterpene glucosides were the most frequently identified compounds in studies examining the anti-cancer properties of sea cucumbers. Intercedenside C, Scabraside A, and Scabraside B were the three triterpene glycosides with the highest affinity for apoptotic receptors in lung cancer cells. To the best of our knowledge, this is the first time that anti-lung cancer properties of sea cucumber-derived compounds have been examined in in silico conditions. Ultimately, these three components displayed anti-lung cancer properties in in silico conditions and may be used for the manufacture of anti-lung cancer agents in the near future.

Chemical Compositions and Experimental and Computational Modeling of the Anticancer Effects of Cnidocyte Venoms of Jellyfish Cassiopea andromeda and Catostylus mosaicus on Human Adenocarcinoma A549 Cells.

Nowadays, major attention is being paid to curing different types of cancers and is focused on natural resources, including oceans and marine environments. Jellyfish are marine animals with the ability to utilize their venom in order to both feed and defend. Prior studies have displayed the anticancer capabilities of various jellyfish. Hence, we examined the anticancer features of the venom of Cassiopea andromeda and Catostylus mosaicus in an in vitro situation against the human pulmonary adenocarcinoma (A549) cancer cell line. The MTT assay demonstrated that both mentioned venoms have anti-tumoral ability in a dose-dependent manner. Western blot analysis proved that both venoms can increase some pro-apoptotic factors and reduce some anti-apoptotic molecules that lead to the inducing of apoptosis in A549 cells. GC/MS analysis demonstrated some compounds with biological effects, including anti-inflammatory, antioxidant and anti-cancer activities. Molecular docking and molecular dynamic showed the best position of each biologically active component on the different death receptors, which are involved in the process of apoptosis in A549 cells. Ultimately, this study has proven that both venoms of C. andromeda and C. mosaicus have the capability to suppress A549 cells in an in vitro condition and they might be utilized in order to design and develop brand new anticancer agents in the near future.