Advancing thyroid disease research: The role and potential of zebrafish model.

Thyroid disorders significantly affect human metabolism, cardiovascular function, skeletal health, and reproductive systems, presenting a complex challenge due to their multifactorial nature. Understanding the underlying mechanisms and developing novel therapeutic approaches require appropriate models. Zebrafish, with their genetic tractability, short life cycle, and physiological relevance, have emerged as a valuable model for investigating thyroid diseases. This review provides a comprehensive analysis of the zebrafish thyroid gland's structure and function, explores its application in modeling thyroid pathologies such as hypothyroidism, hyperthyroidism, and thyroid cancer, and discusses current limitations and possible improvements. Furthermore, it outlines future directions for zebrafish-based research, focusing on enhancing the model's relevance to human thyroid disease and its potential to expedite the development of clinical therapies.

Mrc1 regulates parental histone segregation and heterochromatin inheritance.

Chromatin-based epigenetic memory relies on the symmetric distribution of parental histones to newly synthesized daughter DNA strands, aided by histone chaperones within the DNA replication machinery. However, the mechanism of parental histone transfer remains elusive. Here, we reveal that in fission yeast, the replisome protein Mrc1 plays a crucial role in promoting the transfer of parental histone H3-H4 to the lagging strand, ensuring proper heterochromatin inheritance. In addition, Mrc1 facilitates the interaction between Mcm2 and DNA polymerase alpha, two histone-binding proteins critical for parental histone transfer. Furthermore, Mrc1's involvement in parental histone transfer and epigenetic inheritance is independent of its known functions in DNA replication checkpoint activation and replisome speed control. Instead, Mrc1 interacts with Mcm2 outside of its histone-binding region, creating a physical barrier to separate parental histone transfer pathways. These findings unveil Mrc1 as a key player within the replisome, coordinating parental histone segregation to regulate epigenetic inheritance.

A replisome-associated histone H3-H4 chaperone required for epigenetic inheritance.

Faithful transfer of parental histones to newly replicated daughter DNA strands is critical for inheritance of epigenetic states. Although replication proteins that facilitate parental histone transfer have been identified, how intact histone H3-H4 tetramers travel from the front to the back of the replication fork remains unknown. Here, we use AlphaFold-Multimer structural predictions combined with biochemical and genetic approaches to identify the Mrc1/CLASPIN subunit of the replisome as a histone chaperone. Mrc1 contains a conserved histone-binding domain that forms a brace around the H3-H4 tetramer mimicking nucleosomal DNA and H2A-H2B histones, is required for heterochromatin inheritance, and promotes parental histone recycling during replication. We further identify binding sites for the FACT histone chaperone in Swi1/TIMELESS and DNA polymerase α that are required for heterochromatin inheritance. We propose that Mrc1, in concert with FACT acting as a mobile co-chaperone, coordinates the distribution of parental histones to newly replicated DNA.

Association between sugar-sweetened beverages and pure fruit juice with risk of six cardiovascular diseases: a Mendelian randomization study.

BACKGROUND: In observational and prospective cohort studies, intake of sugar-sweetened beverages (SSBs) and pure fruit juice (PFJ) has been associated with cardiovascular disease (CVD). Still, the causality of the connection has not yet been determined. Our objective was to uncover the relationship between SSBs/PFJ and CVD. METHODS: Genetically predicted causal associations between SSBs/PFJ (obtained in a published genome-wide association study) and six common CVDs (atrial fibrillation (AF), angina, heart failure (HF), acute myocardial infarction, hypertension, and coronary atherosclerosis) were assessed using MR analytic modeling. The primary analysis method utilized was the inverse variance weighted (IVW) method, complemented by additional methods such as the weighted median method, MR Egger regression, Cochran's Q test, MR pleiotropy residual, funnel plot, Bonferroni correction, and others for MR analysis. To ensure the robustness of the findings, F-values were calculated as a complementary test to set looser thresholds for exposing genetic instrumental variables (P < 1e-5). RESULTS: The results of MR analysis suggested genetically causal associations between SSBs and AF (odds ratio (OR): 1.023; 95% confidence interval (CI) 1.007-1.038; P = 0.0039) as well as between PFJ and angina (OR: 0.968; 95% CI, 0.943-0.993; P = 0.0138) there was genetic causality. However, MR analysis showed no causal association between SSBs/PFJ and other CVD risks. CONCLUSION: This study suggests that there may be a potential causal relationship between SSBs intake and AF and a causal negative association between PFJ intake and angina.

Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms.

Rapid ascent to high-altitude areas above 2500 m often leads to acute high altitude illness (AHAI), posing significant health risks. Current models for AHAI research are limited in their ability to accurately simulate the high-altitude environment for drug screening. Addressing this gap, a novel static self-assembled water vacuum transparent chamber was developed to induce AHAI in zebrafish. This study identified 6000 m for 2 h as the optimal condition for AHAI induction in zebrafish. Under these conditions, notable behavioral changes including slow movement, abnormal exploration behavior and static behavior in the Novel tank test. Furthermore, this model demonstrated changes in oxidative stress-related markers included increased levels of malondialdehyde, decreased levels of glutathione, decreased activities of superoxide dismutase and catalase, and increased levels of inflammatory markers IL-6, IL-1ß and TNF-α, and inflammatory cell infiltration and mild edema in the gill tissue, mirroring the clinical pathophysiology observed in AHAI patients. This innovative zebrafish model not only offers a more accurate representation of the high-altitude environment but also provides a high-throughput platform for AHAI drug discovery and pathogenesis research.

Coordination of histone chaperones for parental histone segregation and epigenetic inheritance.

Chromatin-based epigenetic memory relies on the accurate distribution of parental histone H3-H4 tetramers to newly replicated DNA strands. Mcm2, a subunit of the replicative helicase, and Dpb3/4, subunits of DNA polymerase ε, govern parental histone H3-H4 deposition to the lagging and leading strands, respectively. However, their contribution to epigenetic inheritance remains controversial. Here, using fission yeast heterochromatin inheritance systems that eliminate interference from initiation pathways, we show that a Mcm2 histone binding mutation severely disrupts heterochromatin inheritance, while mutations in Dpb3/4 cause only moderate defects. Surprisingly, simultaneous mutations of Mcm2 and Dpb3/4 stabilize heterochromatin inheritance. eSPAN (enrichment and sequencing of protein-associated nascent DNA) analyses confirmed the conservation of Mcm2 and Dpb3/4 functions in parental histone H3-H4 segregation, with their combined absence showing a more symmetric distribution of parental histone H3-H4 than either single mutation alone. Furthermore, the FACT histone chaperone regulates parental histone transfer to both strands and collaborates with Mcm2 and Dpb3/4 to maintain parental histone H3-H4 density and faithful heterochromatin inheritance. These results underscore the importance of both symmetric distribution of parental histones and their density at daughter strands for epigenetic inheritance and unveil distinctive properties of parental histone chaperones during DNA replication.

Zebrafish in dermatology: a comprehensive review of their role in investigating abnormal skin pigmentation mechanisms.

Skin pigmentation abnormalities, ranging from aesthetic concerns to severe hyperpigmentation disease, have profound implications for individuals' psychological and economic wellbeing. The intricate etiology of hyperpigmentation and our evolving comprehension of its underlying mechanisms underscore the need for robust animal models. Zebrafish, renowned for their transparent embryos and genetic parallels to humans, have been spotlighted as a pivotal model for skin pigmentation studies. This review offers a concise overview of zebrafish skin attributes, highlighting the shared melanin production pathways with humans. We systematically dissect the diverse strategies to craft zebrafish models of abnormal skin pigmentation, spanning physical, chemical, and genetic interventions, while critically appraising the merits and constraints of each approach. Additionally, we elucidate the metrics employed to gauge the efficacy of these models. Concluding, we cast a visionary gaze on prospective breakthroughs in the domain, aiming to steer forthcoming efforts in refined zebrafish models for skin pigmentation research.

Microbiota-Gut-Brain Axis Dysregulation in Alzheimer's Disease: Multi-Pathway Effects and Therapeutic Potential.

An essential regulator of neurodegenerative conditions like Alzheimer's disease (AD) is the gut microbiota. Alterations in intestinal permeability brought on by gut microbiota dysregulation encourage neuroinflammation, central immune dysregulation, and peripheral immunological dysregulation in AD, as well as hasten aberrant protein aggregation and neuronal death in the brain. However, it is unclear how the gut microbiota transmits information to the brain and how it influences brain cognition and function. In this review, we summarized the multiple pathways involved in the gut microbiome in AD and provided detailed treatment strategies based on the gut microbiome. Based on these observations, this review also discusses the problems, challenges, and strategies to address current therapeutic strategies.

Cell membrane nanomaterials composed of phospholipids and glycoproteins for drug delivery in inflammatory bowel disease: A review.

Inflammatory bowel disease (IBD) is a serious chronic intestinal disorder with an increasing global incidence. However, current treatment strategies, such as anti-inflammatory drugs and probiotics, have limitations in terms of safety, stability, and effectiveness. The emergence of targeted nanoparticles has revolutionized IBD treatment by enhancing the biological properties of drugs and promoting efficiency and safety. Unlike synthetic nanoparticles, cell membrane nanomaterials (CMNs) consist primarily of biological macromolecules, including phospholipids, proteins, and sugars. CMNs include red blood cell membranes, macrophage membranes, and leukocyte membranes, which possess abundant glycoprotein receptors and ligands on their surfaces, allowing for the formation of cell-to-cell connections with other biological macromolecules. Consequently, they exhibit superior cell affinity, evade immune responses, and target inflammation effectively, making them ideal material for targeted delivery of IBD therapies. This review explores various CMNs delivery systems for IBD treatment. However, due to the complexity and harsh nature of the intestinal microenvironment, the lack of flexibility or loss of selectivity poses challenges in designing single CMNs delivery strategies. Therefore, we propose a hierarchically programmed delivery modality that combines CMNs with pH, charge, ROS and ligand-modified responsive nanoparticles. This approach significantly improves delivery efficiency and points the way for future research in this area.

Escherichia coli Nissle 1917 ghosts alleviate inflammatory bowel disease in zebrafish.

Escherichia coli Nissle 1917 (EcN) has become a research hotspot in inflammatory bowel disease (IBD). It has a strong targeting effect on the colon, and has some therapeutic effect on inflammatory bowel disease. EcN is prepared into EcN ghosts, which also retain EcN's biological characteristics. Consequently, EcN ghosts are used for drug delivery. This study evaluated the safety and efficacy of EcN ghosts as carriers of drugs for treating IBD in zebrafish. Caco-2 cell adhesion experiments and zebrafish intestinal adhesion experiments demonstrated that EcN ghosts was highly adherent to the intestine. Additionally, oral administration of EcN ghosts attenuated dextran sulfate sodium-induced IBD symptoms by inhibiting neutrophil chemotaxis and reactive oxygen species production in larval zebrafish. Because of the unique biological functions of EcN ghosts, it may serve as a strategy for future targeted drug delivery in IBD treatment.

The potential of white-rot fungi for algal control: Mechanisms, Strategies, and Challenges.

As human society and industrialization have progressed, harmful algal blooms have contributed to global ecological pollution which makes the development of a novel and effective algal control strategy imminent. This is because existing physical and chemical methods for dealing with the problem have issues like cost and secondary pollution. Benefiting from their environmentally friendly and biocompatible properties, white-rot fungi (WRF) have been studied to control algal growth. WRF control algae by using algae for carbon or nitrogen, antagonism, and enhancing allelopathies. It can be better applied to practice by immobilization. This paper reviews the mechanism for WRF control of algae growth and its practical application. It demonstrates the limitations of WRF controlling algae growth and aids the further study of biological methods to regulate eutrophic water in algae growth research. In addition, it provides theoretical support for the fungi controlling algae growth.

Improvement in Zebrafish with Diabetes and Alzheimer's Disease Treated with Pasteurized Akkermansia muciniphila.

Diabetes and Alzheimer's disease (AD) are associated with specific changes in the composition of the intestinal flora. Studies have shown that the supplementation with pasteurized Akkermansia muciniphila has therapeutic and preventive effects on diabetes. However, it is not clear whether there is any association with improvement in and prevention of Alzheimer's disease and diabetes with Alzheimer's disease. Here, we found that pasteurized Akkermansia muciniphila can significantly improve the blood glucose, body mass index, and diabetes indexes of zebrafish with diabetes mellitus complicated with Alzheimer's disease and also alleviate the related indexes of Alzheimer's disease. The memory, anxiety, aggression, and social preference behavior of zebrafish with combined type 2 diabetes mellitus (T2DM) and Alzheimer's disease (TA zebrafish) were significantly improved after pasteurized Akkermansia muciniphila treatment. Moreover, we examined the preventive effect of pasteurized Akkermansia muciniphila on diabetes mellitus complicated with Alzheimer's disease. The results showed that the zebrafish in the prevention group were better in terms of biochemical index and behavior than the zebrafish in the treatment group. These findings provide new ideas for the prevention and treatment of diabetes mellitus complicated with Alzheimer's disease. IMPORTANCE The interaction between intestinal microflora and host affects the progression of diabetes and Alzheimer's disease. As a recognized next-generation probiotic, Akkermansia muciniphila has been shown to play a key role in the progression of diabetes and Alzheimer's disease, but whether A. muciniphila can improve diabetes complicated with Alzheimer's disease and its potential mechanism are unclear. In this study, a new zebrafish model of diabetes mellitus complicated with Alzheimer's disease was established, and the effect of Akkermansia muciniphila on diabetes mellitus complicated with Alzheimer's disease is discussed. The results showed that Akkermansia muciniphila after pasteurization significantly improved and prevented diabetes mellitus complicated with Alzheimer's disease. Treatment with pasteurized Akkermansia muciniphila improved the memory, social preference, and aggressive and anxiety behavior of TA zebrafish and alleviated the pathological characteristics of T2DM and AD. These results provide a new prospect for probiotics in the treatment of diabetes and Alzheimer's disease.

Advances in the Utilization of Zebrafish for Assessing and Understanding the Mechanisms of Nano-/Microparticles Toxicity in Water.

A large amount of nano-/microparticles (MNPs) are released into water, not only causing severe water pollution, but also negatively affecting organisms. Therefore, it is crucial to evaluate MNP toxicity and mechanisms in water. There is a significant degree of similarity between the genes, the central nervous system, the liver, the kidney, and the intestines of zebrafish and the human body. It has been shown that zebrafish are exceptionally suitable for evaluating the toxicity and action mechanisms of MNPs in water on reproduction, the central nervous system, and metabolism. Providing ideas and methods for studying MNP toxicity, this article discusses the toxicity and mechanisms of MNPs from zebrafish.

Advances in Zebrafish for Diabetes Mellitus with Wound Model.

Diabetic foot ulcers cause great suffering and are costly for the healthcare system. Normal wound healing involves hemostasis, inflammation, proliferation, and remodeling. However, the negative factors associated with diabetes, such as bacterial biofilms, persistent inflammation, impaired angiogenesis, inhibited cell proliferation, and pathological scarring, greatly interfere with the smooth progress of the entire healing process. It is this impaired wound healing that leads to diabetic foot ulcers and even amputations. Therefore, drug screening is challenging due to the complexity of damaged healing mechanisms. The establishment of a scientific and reasonable animal experimental model contributes significantly to the in-depth research of diabetic wound pathology, prevention, diagnosis, and treatment. In addition to the low cost and transparency of the embryo (for imaging transgene applications), zebrafish have a discrete wound healing process for the separate study of each stage, resulting in their potential as the ideal model animal for diabetic wound healing in the future. In this review, we examine the reasons behind the delayed healing of diabetic wounds, systematically review various studies using zebrafish as a diabetic wound model by different induction methods, as well as summarize the challenges and improvement strategies which provide references for establishing a more reasonable diabetic wound zebrafish model.

Konjac Glucomannan: An Emerging Specialty Medical Food to Aid in the Treatment of Type 2 Diabetes Mellitus.

There are many factors causing T2DM; thus, it is difficult to prevent and cure it with conventional treatment. In order to realize the continuous intervention of T2DM, the treatment strategy of combining diet therapy and traditional medication came into being. As a natural product with the concept of being healthy, konjac flour and its derivatives are popular with the public. Its main component, Konjac glucomannan (KGM), can not only be applied as a food additive, which greatly improves the taste and flavor of food and extends the shelf life of food but also occupies an important role in T2DM. KGM can extend gastric emptying time, increase satiety, and promote liver glycogen synthesis, and also has the potential to improve intestinal flora and the metabolic system through a variety of molecular pathways in order to positively regulate oxidative stress and immune inflammation, and protect the liver and kidneys. In order to establish the theoretical justification for the adjunctive treatment of T2DM, we have outlined the physicochemical features of KGM in this article, emphasizing the advantages of KGM as a meal for special medical purposes of T2DM.

Advances in Escherichia coli Nissle 1917 as a customizable drug delivery system for disease treatment and diagnosis strategies.

With the in-depth and comprehensive study of bacteria and their related ecosystems in the human body, bacterial-based drug delivery system has become an emerging biomimetic platform that can retain the innate biological functions. Benefiting from its good biocompatibility and ideal targeting ability as a biological carrier, Escherichia coli Nissle 1917 (ECN) has been focused on the treatment strategies of inflammatory bowel disease and tumor. The advantage of a bacterial carrier is that it can express exogenous protein while also acting as a natural capsule by releasing drug slowly as a result of its own colonization impact. In order to survive in harsh environments such as the digestive tract and tumor microenvironment, ECN can be modified or genetically engineered to enhance its function and host adaptability. The adoption of ECN carries or expresses drugs which are essential for accurate diagnosis and treatment. This review briefly describes the properties of ECN, the relationship between ECN and inflammation and tumor, and the strategy of using surface modification and genetic engineering to modify ECN as a delivery carrier for disease treatment.

Leaving histone unturned for epigenetic inheritance.

Post-translational modifications in histones play important roles in regulating chromatin structure and gene expression programs, and the modified histones can be passed on to subsequent generations as an epigenetic memory. The fission yeast has been a great model organism for studying histone modifications in heterochromatin assembly and epigenetic inheritance. Here, we review findings in this organism that cemented the idea of chromatin-based inheritance and highlight recent studies that reveal the role of histone turnover in regulating this process.

Advances in Biomedical Functions of Natural Whitening Substances in the Treatment of Skin Pigmentation Diseases.

Pigmentation diseases can lead to significant color differences between the affected part and the normal part, resulting in severe psychological and emotional distress among patients. The treatment of pigmentation diseases with good patient compliance is mainly in the form of topical drugs. However, conventional hydroquinone therapy contributes to several pathological conditions, such as erythema, dryness, and skin desquamation, and requires a longer treatment time to show significant results. To address these shortcomings, natural whitening substances represented by kojic acid and arbutin have gradually become the candidate ingredients of traditional local preparations due to their excellent biological safety. This review focuses on several natural whitening substances with potential therapeutic effects in pigmentation disease and their mechanisms, and a thorough discussion has been conducted into the solution methods for the challenges involved in the practical application of natural whitening substances.

Advances in microRNA from adipose-derived mesenchymal stem cell-derived exosome: focusing on wound healing.

Skin wounds are a common condition causing economic burden and they represent an urgent clinical need, especially chronic wounds. Numerous studies have been conducted on the applications of stem cell therapy in wound healing, with adipose-derived mesenchymal stem cells (ADMSCs) playing a major role since they can be isolated easily, yielding a high number of cells, the less invasive harvesting required, the longer life span and no ethical issues. However, the lack of standardized doses and protocols, the heterogeneity of clinical trials, as well as the incompatibility of the immune system limit its application. Recent studies have demonstrated that specific stem cell functions depend on paracrine factors, including extracellular vesicles, in which microRNAs in exosomes (Exo-miRNAs) are essential in controlling their functions. This paper describes the application and mechanism whereby ADMSC-Exo-miRNA regulates wound healing. ADMSC-Exo-miRNA is involved in various stages in wounds, including modulating the immune response and inflammation, accelerating skin cell proliferation and epithelialization, promoting vascular repair, and regulating collagen remodeling thereby reducing scar formation. In summary, this acellular therapy based on ADMSC-Exo-miRNA has considerable clinical potential, and provides reference values for developing new treatment strategies for wound healing.

Advances in lncRNAs from stem cell-derived exosome for the treatment of cardiovascular diseases.

Cardiovascular diseases (CVDs) are the leading cause of mortality globally. Benefiting from the advantages of early diagnosis and precision medicine, stem cell-based therapies have emerged as promising treatment options for CVDs. However, autologous or allogeneic stem cell transplantation imposes a potential risk of immunological rejection, infusion toxicity, and oncogenesis. Fortunately, exosome can override these limitations. Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) in exosome from stem cell paracrine factors play critical roles in stem cell therapy and participate in numerous regulatory processes, including transcriptional silencing, transcriptional activation, chromosome modification, and intranuclear transport. Accordingly, lncRNAs can treat CVDs by directly acting on specific signaling pathways. This mini review systematically summarizes the key regulatory actions of lncRNAs from different stem cells on myocardial aging and apoptosis, ischemia-reperfusion injury, retinopathy, atherosclerosis, and hypertension. In addition, the current challenges and future prospects of lncRNAs treatment for CVDs are discussed.