Experimental Animals Research Articles

Exploring the therapeutic potential: sinomenine and melatonin in alkali-induced corneal burns.

This study aimed to investigate the effects of sinomenine and melatonin on corneal alkali burns. Twenty-seven female Wistar albino rats, aged 3-6months and weighing 200-300g, were used in this study. After the induction of general anesthesia, 2mol/L sodium hydroxide (NaOH) solution was used to create corneal alkali burns in all experimental animals. The rats were divided into three groups: Group C, control group with no additional treatment; Group M, topical melatonin drop group; and Group S, topical sinomenine group. The rats were sacrificed under general anesthesia on the 7th day. Various parameters, including corneal inflammation, neovascularization, epithelialization, epithelial proliferating cell nuclear antigen (PCNA), epithelial inducible nitric oxide synthase (INOS), stromal INOS, and thickness, were evaluated. The experiment was completed with 27 rats distributed into three groups of nine rats each. Significant differences were observed between the groups in terms of stromal thickness, inflammation, epithelial iNOS, stromal iNOS, and epithelialization (p = 0.008, p = 0.005, p = 0.020, p = 0.037, and p = 0.000, respectively). The best stromal thickness was observed in Group M. Vascularization, inflammation, epithelial INOS, stromal iNOS, and epithelialization were most effectively reduced in Group S, followed by Group M. Group S outperformed Group C significantly in all these aspects (p = 0.049, p = 0.004, p = 0.015, p = 0.036, p = 0.000, respectively). There was no significant difference between the groups in terms of the epithelial PCNA levels (p = 0.259). The results suggest that topical sinomenine and melatonin have anti-inflammatory, anti-angiogenic, and reepithelialization effects when applied after alkali burns in rat corneas.

Oral Administration of Zinc Sulfate with Intramuscular Foot-and-Mouth Disease Vaccine Enhances Mucosal and Systemic Immunity

Background/Objectives: Foot-and-mouth disease (FMD) remains a significant global threat to livestock farming. Current commercial FMD vaccines present several challenges, including the risk of infection and adverse injection site reactions due to oil-based adjuvants. The complex immune environment of the gut-associated lymphoid tissue has the potential to induce broad and diverse immune responses. Therefore, we aimed to explore the potential of zinc sulfate as an oral adjuvant to enhance intestinal mucosal immunity and complement the effects of intramuscular (IM) FMD vaccination. Methods: We conducted serological analyses on mice and pigs, measuring secretory IgA (sIgA) levels and evaluating the expression of mucosal immunity-related genes in pigs. These assessments were used to investigate the systemic and mucosal immune responses induced by oral zinc sulfate administration in combination with an IM FMD vaccine. Results: This combination strategy significantly increased structural protein antibody titers and virus neutralization titers in experimental animals (mice) and target animals (pigs) across early, mid-, and long-term periods. Additionally, this approach enhanced the expression of key cytokines associated with mucosal immunity and increased sIgA levels, which are critical markers of mucosal immunity. Conclusions: Oral zinc sulfate administration may synergize with inactivated FMD vaccines, leading to sustained and enhanced long-term immune responses. This novel strategy could reduce the frequency of required vaccinations or allow for a lower antigen dose in vaccines, effectively stimulating the mucosal immune system and boosting systemic immunity. This approach has the potential to improve the overall efficacy of commercial FMD vaccines.

Biosafety Evaluation of a Chimeric Adenoviral Vector in Mini-Pigs: Insights into Immune Tolerance and Gene Therapy Potential

Background: The biosafety of gene therapy products remains a major challenge to their introduction into the clinic. In particular, the problem of immunogenicity of viral vectors is the focus of attention. Large animals such as pigs, whose anatomical and physiological characteristics are similar to those of humans, have an advantage in testing vector systems. Methods: We performed a comprehensive in vitro and in vivo study to evaluate the biosafety of a chimeric adenoviral vector carrying a green fluorescent protein gene (Ad5/35F-GFP) in a mini-pig model. Results: Transcriptome and secretome analyses of mini-pig leucocytes transduced with Ad5/35F-GFP revealed changes restraining pro-inflammatory processes and cytokine production. No adverse effects were revealed through the clinical, instrumental, laboratory, and histological examinations conducted within a week after the direct or autologous leucocyte-mediated administration of Ad5/35F-GFP to mini-pigs. The decrease in cytokine levels in the blood of experimental animals is also consistent with the in vitro data and confirms the immune tolerance of mini-pigs to Ad5/35F-GFP. Conclusions: Here, we show the safety of Ad5/35F in a mini-pig model and provide evidence that Ad5/35F is a promising vector for gene therapy. These results advance our understanding of vector–host interactions and offer a solid foundation for the clinical application of this vector.

Wnt 3a-Modified Scaffolds Improve Nerve Regeneration by Boosting Schwann Cell Function.

A pivotal approach in engineering artificial peripheral nerve sheaths encompasses the augmentation of the regenerative microenvironment via the manipulation of Schwann cells (SCs). Our investigation employed single-cell sequencing analysis to elucidate the potential functions of Schwann cells and the Wnt pathway in facilitating peripheral nerve regeneration. In vitro studies showed that activating the Wnt signaling pathway promotes the transition to repair SCs, boosting their growth, movement, and immune functions. To better understand the peripheral nerve regeneration environment, we created a polymer scaffold using ammonization and electrospinning. The Wnt3a protein was incorporated into the polycaprolactone (PCL) electrospun fiber surface. In a rat sciatic nerve defect model, the Wnt3a-modified scaffold showed better nerve repair outcomes than traditional electrospun scaffolds. After a week, the test group showed better immune regulation and angiogenesis, with a significant increase in axon growth rate observed after 3 weeks. Three-month-long animal experiments revealed notable improvements in neuroelectrophysiology, reduced organ atrophy, and enhanced sciatic nerve recovery. In this nerve defect model, Wnt3a-modified neural scaffolds achieved repair effects.

Molecular mechanisms of ferroptosis in renal ischemia-reperfusion injury Investigated via bioinformatics analysis and animal experiments.

Kidney transplantation is a pivotal treatment for end-stage renal disease. However, renal ischemia-reperfusion injury (IRI) during surgery significantly impacts graft function. Despite unclear molecular mechanisms, no specific therapies or preventative measures are available. Gene expression profiles from renal biopsies before and after IRI were downloaded from public databases. Differentially expressed genes were identified using the Wilcoxon rank-sum test and weighted gene co-expression network analysis. Ferroptosis-associated genes were screened using the FerrDb database. The genes with the highest connectivity were identified via the protein-protein interaction (PPI) network and upstream regulatory miRNAs were found through the gene-miRNA network. A mouse renal IRI model was constructed for transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) validation to elucidate the relationship between key ferroptosis genes and regulatory miRNAs in renal IRI. Differential analysis identified 15 ferroptosis-associated genes (TNFAIP3, IL6, KLF2, EGR1, JUN, ZFP36, GDF15, CDKN1A, HSPB1, BRD2, PDK4, DUSP1, SLC2A3, DDIT3, and CXCL2) involved in renal IRI regulation. In animal experiments, ferroptosis-related genes were also upregulated in the model group. Enrichment analysis and hematoxylin-eosin pathological staining suggested these genes are primarily involved in renal inflammatory responses. PPI network analysis revealed IL6 as the gene with the highest connectivity, and the gene-miRNA network indicated IL6 might be regulated by miR-let-7a. Animal experiments revealed decreased miR-let-7a and increased IL6 levels in the model group, identifying potential therapeutic targets. MiR-let-7a regulates ferroptosis in renal IRI by targeting IL6, highlighting IL6 as a crucial gene in the ferroptosis process of renal IRI.

Global research hotspots and trends of Buyang huanwu decoction: A visual analysis of the literature based on CiteSpace.

Buyang huanwu decoction (BYHWD) has shown significant clinical efficacy in the treatment of several diseases, particularly stroke. However, bibliometric research has not been comprehensive. BYHWD articles were collected from literature databases published from January 1, 1915, to March 31, 2024, including the China National Knowledge Infrastructure, Weipu, Wanfang, Pubmed, Scopus, and Web of Science Core Collection. Knowledge network graphs of annual publication volume, authors, institutions, countries, keywords, and references were constructed. Nine thousand two hundred thirty-eight Chinese literature and 559 English articles published between 1915 and 2024 showed an overall upward trend. The countries, institutions, journals, and authors with the highest output were China, Hunan University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangxian Cai, and Changqing Deng, respectively. Research teams outside China were located at Daejeon University, Gachon University, Aga Khan University, Yale University, etc. The results of keyword co-occurrence and burst analysis included clinical applications, animal experiments, action mechanisms, clinical efficacy, and safety evaluations based on systematic reviews and meta-analyses. Literature co-citation analysis revealed that BYHWD was highly correlated with neuroprotection and reduction of cerebral ischemia/reperfusion injury. Both Chinese and English literature have shown overall growth trend since 1984 and 1989, respectively. Clinical applications, pharmacological effects, mechanisms, active ingredients, evaluation of clinical efficacy and safety, modified BYHWD, methods, and biological techniques may be hotspots and focus of future research on BYHWD. Hotspot analytical methods and biological techniques include systematic reviews, meta-analyses, data mining, network pharmacology, and molecular docking. Future valuable research fields may include studies on neuroprotection, anti-inflammatory activity, ischemic stroke, bioactive compounds, and their underlying mechanisms.

Construction and evaluation of a new rat reference genome assembly, GRCr8, from long reads and long-range scaffolding.

We report the construction and analysis of a new reference genome assembly for Rattus norvegicus, the laboratory rat, a widely used experimental animal model organism. The assembly has been adopted as the rat reference assembly by the Genome Reference Consortium and is named GRCr8. The assembly has employed 40× Pacific Biosciences (PacBio) HiFi sequencing coverage and scaffolding using optical mapping and Hi-C. We used genomic DNA from a male BN/NHsdMcwi (BN) rat of the same strain and from the same colony as the prior reference assembly, mRatBN7.2. The assembly is at chromosome level with 98.7% of the sequence assigned to chromosomes. All chromosomes have increased in size compared with the prior assembly and k-mer analysis indicates that the subject animal is fully inbred and that the genome is represented as a single haploid assembly. Notable increases are observed in Chromosomes 3, 11, and 12 in the prospective rDNA regions. In addition, Chr Y has increased threefold in size and is more consistent with the rat karyotype than previous assemblies. Several other chromosomes have grown by the incorporation of sizable discrete new blocks. These contain highly repetitive sequences and encode numerous previously unannotated genes. In addition, centromeric sequences are incorporated in most chromosomes. Genome annotation has been performed by NCBI RefSeq, which confirms improvement in assembly quality and adds more than 1100 new protein coding genes. PacBio Iso-Seq data have been acquired from multiple tissues of the subject animal and are released concurrently with the new assembly to aid further analyses.

Hypoxia-Preconditioned Human Umbilical Cord Mesenchymal Stem Cells Transplantation Ameliorates Inflammation and Bone Regeneration in Peri-Implantitis Rat Model.

The failure of dental implant treatments is predominantly attributed to peri-implantitis, which entails chronic inflammation within the peri-implant tissue, ultimately leading to tissue degradation. Addressing this condition, human umbilical cord mesenchymal stem cell (hUCMSC) transplantation serves as a regenerative therapy; however, concerns regarding the viability and efficacy of transplanted cells in inflamed regions persist. Hypoxic preconditioning of hUCMSCs has emerged as a potential strategy for augmenting their regenerative and immunomodulatory capacities. This study aimed to evaluate the expression of inflammatory (tumor necrosis factor [TNF]-α) and bone regenerative biomarkers (nuclear factor of activated T-cell [NFATc1], osteocalcin, collagen type I alpha 1 [COL1α1]) within peri-implantitis models subsequent to the transplantation of hypoxia-preconditioned hUCMSCs. Peri-implantitis models were established through the insertion of implants into the femur bone of 42 Wistar strain Rattus norvegicus, followed by intrasocket injection of lipopolysaccharide. The experimental animals were categorized into three groups (control, normoxia, and hypoxia) and underwent observation on days 14 and 28. The expression levels of TNF-α, NFATc1, COL1α1, and osteocalcin were evaluated using immunohistochemical staining, and the resulting data were subjected to one-way analysis of variance analysis (p < 0.05). Transplantation of hypoxia-preconditioned hUCMSCs significantly ameliorated inflammation and osteoclastogenesis, as evidenced by significant reductions in TNF-α and NFATc1 expression compared with the control group. Furthermore, hypoxic preconditioning of hUCMSCs demonstrated a significant elevation in the expression of osteocalcin and COL1α1 relative to the control group. The transplantation of hypoxia-preconditioned hUCMSCs exhibited a capacity to ameliorate inflammation and enhance bone regenerative processes in peri-implantitis rat models.

In silico formulation optimization and particle engineering of pharmaceutical products using a generative artificial intelligence structure synthesis method

Pharmaceutical drug dosage forms are critical for ensuring the effective and safe delivery of active pharmaceutical ingredients to patients. However, traditional formulation development often relies on extensive lab and animal experimentation, which can be time-consuming and costly. This manuscript presents a generative artificial intelligence method that creates digital versions of drug products from images of exemplar products. This approach employs an image generator guided by critical quality attributes, such as particle size and drug loading, to create realistic digital product variations that can be analyzed and optimized digitally. This paper shows how this method was validated through two case studies: one for the determination of the amount of material that will create a percolating network in an oral tablet product and another for the optimization of drug distribution in a long-acting HIV inhibitor implant. The results demonstrate that the generative AI method accurately predicts a percolation threshold of 4.2% weight of microcrystalline cellulose and generates implant formulations with controlled drug loading and particle size distributions. Comparisons with real samples reveal that the synthesized structures exhibit comparable particle size distributions and transport properties in release media.

Fecal microbiota transplantation for the treatment of intestinal and extra‐intestinal diseases: Mechanism basis, clinical application, and potential prospect

AbstractTo review the theoretical basis and therapeutic effects of fecal microbiota transplantation (FMT) in various diseases in animal experiments and clinical studies, as well as the limitations and current standards of FMT application. PubMed and Web of Science databases were searched for articles published only in English between 1975 and 2023 on reliable results of animal experiments and clinical treatment of FMT. The properties of the gut microbiota and its interactions with the host metabolism are critical to human health, and microbiome disturbance is closely associated with human intestinal and extra‐intestinal diseases. Therefore, therapeutic tools targeting on the modulation of gut microbiota have attracted increasing attention, among which FMT represents the most widely studied intervention strategy. This review gathered and summarized application of FMT in intestinal diseases, metabolic diseases, hypertension, cancer, nervous system diseases and arthritis, and elaborated the beneficial effects that can be achieved by altering the microbiota with FMT and the mechanisms of action. In addition, the potential risks and side effects of FMT approach are discussed, as well as current efforts to standardize the development of FMT. Through a systemic review of the outcome and mechanism of FMT in the treatment of intestinal diseases and extra‐intestinal diseases, we aimed to provide a theoretical basis for the construction of an optimized FMT framework, so as to better exert its application prospects.

Evaluation of toxicity of feed additive for highly productive animals

The study of new feed additives requires toxicological research to assess their safety for further use. This research presents the results of an acute toxicity study of the feed additive “Bodrivin,” developed for highly productive animals of dairy, meat-dairy, and meat breeds. The aim is to prevent stress of various etiologies, enhance the nutritional value of the diet, especially during periods of energy deficiency, and consequently improve productivity and profitability in production. Non-linear laboratory rats were used for the experiment. The first experimental group received a single oral dose of the feed additive via syringe and atraumatic needle with a bulbous end at a dosage of 2000 mg/kg. After obtaining the results of the experiment over a 14-day period, a similar experiment was conducted on the second experimental group. At the conclusion of the experiment, no signs indicating toxic effects of the studied feed additive were observed in the animals, and the body weight of the experimental animals remained unchanged in both the first and second series of the experiment. The acute toxicity study of the feed additive “Bodrivin” indicated that the evaluated feed additive belongs to Class V of danger according to GOST 32644-2014.

Borneol-Functionalized Macrophage Membrane-Encapsulated Mesoporous Selenium Nanoparticles Loaded with Resveratrol for the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) is a serious neurological disease that can result in paralysis. After SCI occurs, the blood-spinal cord barrier (BSCB) is disrupted, and permeability is transiently elevated. However, the permeability of the BSCB returns to normal over time, which prevents many drugs from being used in subsequent treatments. In this study, we designed a borneol-functionalized macrophage membrane encapsulating mesoporous selenium nanoparticles loaded with resveratrol (MSe-Res-BMMs) for SCI treatment. In vivo animal experiments and in vitro cell experiments demonstrated that MSe-Res-BMMs were able to protect neurons from ferroptosis by reducing ROS levels and increasing glutathione peroxidase-4 (GPx-4) activity. In addition, this treatment also reduced ROS-induced inflammation and apoptosis by decreasing the expression of inflammatory factor IL-1β and apoptotic factor Cleaved Caspase-3 at the site of injury. Therefore, MSe-Res-BMMs are expected to provide new therapeutic options for SCI treatment.

Protective Role of Anthraquinone Purpurin Against Cardiotoxicity Induced by Isoproterenol in Adult Wistar Rats

Background Purpurin are naturally occurring anthraquinones derived from the roots of Rubia species. Purpurin is a red-colored bioactive compound commonly used as a food colorant. In ancient times, Rubia species plants were used in Chinese medicine to treat rheumatoid arthritis. Research studies have proven purpurin exerts antimicrobial, neuromodulatory, antigenotoxic, anti-inflammatory, anticancer, and antioxidant effects. The present investigation was proposed to evaluate the efficacy of purpurin against myocardial infarction in rats. Materials and Methods Purpurin was pretreated in healthy adult male rats and subjected to a myocardial infarction with isoproterenol to assess the cardioprotective effect of purpurin. CRP, total protein, and uric acid levels were quantified to analyze the efficacy against myocardial infarction. Cardiac functional markers and antioxidant levels were measured to evaluate the role of purpurin on isoproterenol-induced myocardial infarction. Further to prove the cardioprotective efficacy of purpurin cardiac tissue ATPases and electrolytes were assessed in the experimental animals. The anti-inflammatory property of purpurin was analyzed by quantifying proinflammatory cytokines. Histopathological analysis of cardiac tissue was to confirm the protective effect of purpurin against isoproterenol-induced myocardial infarction. Results The present investigation demonstrated the significant protective effect of purpurin by decreasing the levels of CRP, uric acid levels, and total protein levels in myocardial infarction-induced rats. It restored the cardiac functional markers and glutathione system in the cardiac tissue of myocardial infarction-induced rats. It increased the levels of cardiac ATPases and reinstated the electrolytes in the cardiac tissue of myocardial infarction-induced rats. Purpurin significantly demonstrated an anti-inflammatory and cardioprotective effect that was evidenced with histopathological analysis. Conclusion Our findings prove purpurin suppresses the proinflammatory response of isoproterenol treatment and exerts a cardioprotective effect in myocardial infarction-induced rats.

Anti- psoriatic effect and phytochemical evaluation of Iraqi Scabiosa palaestina ethyl acetate extract

The purpose of this study was to confirm the antipsoriasis activity of Scabiosa palaestina (S. palaestina) ariel component extract and identify the active compound(s) responsible for this activity using a developed RP-HPLC technology. The active ethyl acetate extract of S. palaestina was extracted and fractionated by the hot continuous Soxhlet apparatus method. Psoriasis was induced in experimental animals after 4 days of imiquimod (IMQ) cream application on dorsal skin rats of 3 treated groups (6 rats for each) and the normal group (6 rats) left without treatment. Two of the psoriatic-induced groups were treated with ethyl acetate (EA) extract or methotrexate (MTX) for 12 days, starting from day 4 of the IMQ application. Assessment of psoriatic lesions was done during the experiment, depending on the psoriasis area severity index (PASI). At the end of the study (day 15), animals were sacrificed and 2 skin specimens were collected for histopathological examination and cytokine measurement. Compared with the positive control group, ethyl acetate extract shows significant improvement in PASI (p-value &lt; 0.05) and histopathological changes exerted by IMQ. On the other hand, no significant reduction has been seen in the psoriatic and angiogenic mediator (IL-17 and VEGF) with a P-value &gt; 0.05 compared with the positive control group, which may be attributed to other cytokines that could be affected by the ethyl acetate extract of S. palaestina. These results suggest that the antipsoriasis properties of ethyl acetate extract may possibly be due to the presence of flavonoid compounds (luteolin, apigenin, quercetin, vitexin and kaempferol).

Hippocampus under pressure: molecular mechanisms of cognitive impairment in shr rats

In clinical studies and in animal experiments, data have been obtained indicating the association of chronic hypertension with the development of cognitive impairment. The review examines structural and biochemical changes in the hippocampus of SHR rats with genetic hypertension, which are used as a model of essential hypertension, as well as vascular dementia. The dysfunction of the hypothalamic-pituitary-adrenocortical system, observed in SHR rats at an early age, may, along with the development of hypertension, be a key factor in the damage to the hippocampus at the structural and molecular levels. Global changes at the body level (hypertension, neurohumoral dysfunction) are associated with the development of vascular pathology and destruction of the blood-brain barrier. Changes in multiple biochemical glucocorticoid-dependent processes in the hippocampus (dysfunction of steroid hormone receptors, disorders of neurotransmitter systems, BDNF deficiency, oxidative stress, neuroinflammation) are accompanied by structural changes including cellular processes of neuroinflammation (microgliosis, astrogliosis), disorders of neurogenesis in the subgranular neurogenic niche, neurodegenerative processes at the level of synapses, axons and dendrites up to neuronal cell death. The consequence of this is dysfunction of the hippocampus, a key structure of the limbic system necessary for the realization of cognitive functions. Summarizing of the available results at various levels, from the level of the organism and the structure of the brain (hippocampus) to the molecular one, allows us to confirm the translational validity of SHR rats for modeling the mechanisms of vascular dementia.

Effect of Structure on Osteogenesis of Bone Scaffold: Simulation Analysis Based on Mechanobiology and Animal Experiment Verification

Porous scaffolds, whose mechanical and biological properties are greatly affected by structure, are new treatments for bone defects. Since bone repair is related to biomechanics, analyzing the osteogenesis in scaffolds based on mechanical stimulation may become a more effective method than traditional biological experiments. A tissue regeneration algorithm based on mechanical regulation theory was implemented in this study to evaluate the osteogenesis of classical scaffolds (Gyroid, I-WP, and Diamond). In vivo experiments were used to verify and supplement the simulation results. Different approaches to describing osteogenesis were discussed. Bone formation was more obvious inside the Gyroid scaffold and outside the I-WP scaffold, while the new bone was more sufficient and evenly distributed in the Diamond scaffold. The osteogenesis pattern of the bone scaffold in the simulation analysis was consistent with the results of animal experiments, and the bone volume calculated by the tissue fraction threshold method and the elastic modulus threshold method was very similar to the in vivo experiment. The mechanical responses mediated by structure affect the osteogenesis of bone scaffolds. This study provided and confirmed a simulation analysis method based on mechanical regulation theory, which is more efficient and economical for analyzing tissue healing in bioengineering.

Public attitudes toward the use of human induced pluripotent stem cells: insights from an Italian adult population

IntroductionHuman induced pluripotent stem cells (hiPSCs), derived from reprogrammed adult somatic cells, hold significant promise for disease modelling, personalized medicine, drug discovery, and regenerative therapies. Public awareness and understanding of hiPSCs are crucial for advancing research in this field. However, limited data exists on the general population’s knowledge and attitudes toward their use.MethodsThis study aimed to assess the awareness and perceptions of hiPSCs among Italian adults through a web-based survey conducted via the EUSurvey platform, using a snowball sampling approach. The survey included demographic information and mandatory questions on knowledge, awareness, and concerns regarding hiPSC technology, with responses collected on a 3-point scale. Statistical analysis was performed using chi-squared tests, with significance set at p ≤ 0.05.ResultsOut of 1874 respondents, the majority were aged 18–35 years (40.5%), female (63.4%), and university-educated (67.2%). Among those familiar with hiPSCs (54.1%, n = 1,201), 95.3% expressed willingness to donate blood samples for hiPSC generation to treat individuals with incurable diseases. Concerns about current research and therapeutic applications were low (less than 20%), but nearly half of the respondents were hesitant or opposed to the use of hiPSCs in animal experiments and their commercialization by pharmaceutical companies. Increased skepticism was observed in older, less educated, religious individuals, and those who were not blood donors. Overall, the Italian public shows strong support for hiPSC-based therapies, though reservations exist around specific ethical and economic issues.DiscussionThese findings underscore the importance of addressing public concerns through targeted educational campaigns, not only in Italy but globally, to foster a more informed and supportive environment for advancing stem cell research and its clinical applications worldwide. Similar studies have been conducted in Japan, the United States, and Sweden, but there remains a need for all countries to engage with their citizens to better understand how stem cell research is perceived locally. Such engagement is crucial for guiding international strategies in personalized medicine and regenerative therapies, ensuring that emerging technologies are met with both ethical integrity and public trust.

Bioengineering the Junctional Epithelium in 3D Oral Mucosa Models

Two-dimensional (2D) culture models and animal experiments have been widely used to study the pathogenesis of periodontal and peri-implant diseases and to test new treatment approaches. However, neither of them can reproduce the complexity of human periodontal tissues, making the development of a successful 3D oral mucosal model a necessity. The soft-tissue attachment formed around a tooth or an implant function like a biologic seal, protecting the deeper tissues from bacterial infection. The aim of this review is to explore the advancements made so far in the biofabrication of a junctional epithelium around a tooth-like or an implant insert in vitro. This review focuses on the origin of cells and the variety of extracellular components and biomaterials that have been used for the biofabrication of 3D oral mucosa models. The existing 3D models recapitulate soft-tissue attachment around implant abutments and hydroxyapatite discs. Hereby, the qualitative and quantitative assessments performed for evidencing the soft-tissue attachment are critically reviewed. In perspective, the design of sophisticated 3D models should work together for oral immunology and microbiology biofilms to accurately reproduce periodontal and peri-implant diseases.

Neural Stem Cell Therapy for Alzheimer’s Disease: A-State-of-the-Art Review

Alzheimer’s disease (AD) is a brain disorder that is more prevalent in developed nations and remains one of most intractable conditions so far. It is characterized by a gradual onset, a prolonged progression, and an unclear pathophysiology. At the present time, there are no effective treatments available for the disease. However, human neural stem cells (hNSCs) have the capacity to substitute lost neurons in a functional manner, strengthen synaptic networks that have been compromised, and repair the damaged brain. Due to the unavailability of restorative therapeutics, there is a significant global burden on the economy. When it comes to the treatment of neurodegenerative diseases, NSCs provide a potentially game-changing approach to treating Alzheimer’s disease. Through the delivery of trophic factors that promote the viability and regeneration of lost neurons in experimental animals suffering from neurodegenerative disorders, these treatments have the potential to facilitate beneficial recuperation. Positive restorative outcomes may be achieved in a variety of ways, including the replacement of lost cells, the combining of cells, the secretion of neurotrophic factors, the formation of endogenous stem cells, and transdifferentiation. Conversely, there are obstacles that need to be overcome before NSC-based treatments can be used in clinical settings. This review article discusses current developments in the use of neural stem cells (NSCs) for the treatment of Alzheimer’s disease (AD). In addition, we highlight the difficulties and opportunities that are involved with the use of neural stem cell transplant treatment for Alzheimer’s disease.

Prickly Ash Seeds Improve the Ruminal Epithelial Development and Growth Performance of Hu Sheep by Modulating the Rumen Microbiota and Metabolome

It is known that the addition of feed rich in bioactive components to animal diets will affect rumen fermentation parameters and flora structure. However, research on the regulatory effects of prickly ash seeds (PASs) during rumen development or on the rumen microbiome and its metabolites in sheep is limited. The current study was designed to explore the effects of PASs on sheep rumen development and growth performance using metagenomics and metabolomics. Eighteen 3-month-old Hu lambs were randomly allotted to three different dietary treatment groups: 0% (basal diet, CK), 3% (CK with 3% PAS, low-dose PAS, LPS), and 6% (CK with 6% PAS, high-dose PAS, HPS) PASs. The lambs were slaughtered to evaluate production performance. Our results showed that dietary PAS addition improved the average daily gain and reduced the F/G ratio of the experimental animals. Additionally, the height and width of the rumen papilla in the treatment groups were significantly higher than those in the CK group. The fermentation parameters showed that the levels of acetate and butyrate were significantly higher in the LPS group than in the CK and HPS groups. The propionate levels in the HPS group were significantly higher than those in the CK and LPS groups. Metagenomics analysis revealed that PAS dietary supplementation improved the abundance of Clostridiales and Bacteroidales and reduced the abundance of Prevotella, Butyrivibrio, and Methanococcus. Metabolomic analyses revealed that increased metabolite levels, such as those of serotonin, L-isoleucine, and L-valine, were closely related to growth-related metabolic pathways. The correlations analyzed showed that papilla height and muscular thickness were positively and negatively correlated with serotonin and L-valine, respectively. Average daily gain (ADG) was positively and negatively correlated with L-valine and several Prevotella, respectively. In addition, muscular thickness was positively correlated with Sodaliphilus pleomorphus, four Prevotella strains, Sarcina_sp_DSM_11001, and Methanobrevibacter_thaueri. Overall, PAS addition improved sheep growth performance by regulating beneficial microorganism and metabolite abundances, facilitating bacterial and viral invasion resistance.