Organogenesis最新文献

Fiber-photometric is a novel optogenetic method for recording neural activity in vivo, which allows the use of calcium indicators to observe and study the relationship between neural activity and behavior in free-ranging animals. Calcium indicators also convert changes in calcium concentration in cells or tissues into recordable fluorescent signals, which can then be observed using the system of fiber-photometric. To date, there is a paucity of relevant literature on the proper selection and application of fiber-photometric indicators. Therefore, this paper will detail how to correctly select and apply fiber-photometer indicators in four sections: the basic principle of optical fiber photometry, the selection of calcium fluorescent probes and viral vector systems, and the measurement of specific expression of fluorescent proteins in specific tissues. Therefore, the correct use of suitable fiber optic recording indicators will greatly assist researchers in exploring the link between neuronal activity and neuropsychiatric disorders.

Zinc ions play a pivotal role in facilitating the development of cartilage in mice. Nevertheless, the precise underlying mechanism remains elusive. Our investigation was centered on elucidating the impact of zinc deficiency on cartilage maturation by modulating SUMO1 and UBC9 at both the protein and mRNA levels. We administered a regimen inducing zinc deficiency to gravid mice from E0.5 until euthanasia. Subsequently, we subjected the embryos to scrutiny employing HE, Safranin O staining and IHC. Primary chondrocytes were isolated from fetal mouse femoral condyles and utilized for Western blot analysis to discern the expression profiles of SUMO1, SUMO2/3, UBC9, SOX9, MMP13, Collagen II, RUNX2, and aggrecan. Furthermore, ATDC5 murine chondrocytes were subjected to treatment with ZnCl₂, followed by RT-PCR assessment to scrutinize the expression levels of MMP13, Collagen II, RUNX2, and aggrecan. Additionally, we conducted Co-IP assays on ZnCl₂-treated ATDC5 cells to explore the interaction between SOX9 and SUMO1. Our investigation unveiled that zinc deficiency led to a reduction in cartilage development, as evidenced by the HE results in fetal murine femur. Moreover, diminished expression levels of SUMO1 and UBC9 were observed in the IHC and Western blot results. Furthermore, Western blot and Co-IP assays revealed an augmented interaction between SOX9 and SUMO1, which was potentiated by ZnCl₂ treatment. Significantly, mutations at the SUMOylation site of SOX9 resulted in alterations in the expression patterns of crucial chondrogenesis factors. This research underscores how zinc ions promote cartilage development through the modification of SOX9 by SUMO1.

Podocyte damage is a central feature of lupus nephritis (LN), making the identification of potential therapeutic targets to prevent podocyte injury and improve treatment outcomes essential. ORM1 has been suggested as a significant candidate gene in LN. In this study, mouse podocytes were induced using Immunoglobulin G (IgG) extracted from lupus patients. To investigate the role of ORM1, ORM1 knockdown was performed, and the effects on podocyte viability and apoptosis were assessed using the cell counting kit-8 (CCK-8) assay and flow cytometry. Additionally, autophagy markers LC3II/I and p62 were measured by western blotting and immunofluorescence, and the expression of the AMPK/mTOR signaling pathway was evaluated using western blotting. The results showed an upregulation of ORM1 in the LN model. Upon stimulation with IgG from LN patients, ORM1 knockdown reversed the reduction in podocyte viability, decreased the apoptosis rate, and reduced the elevated levels of autophagy, followed by an increase in AMPK phosphorylation and a decrease in mTOR phosphorylation. In conclusion, these results suggest that ORM1 modulates the expression of autophagy-related components in podocytes through the AMPK/mTOR signaling pathway, thereby influencing podocyte damage in the LN model in vitro.

This study delves into the rejuvenating effects of SS-31 on aged human Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs), focusing on its potential to restore their diminished osteogenic differentiation capacity, a critical issue in geriatric medicine and bone tissue engineering. SS-31 significantly improved mitochondrial function, increasing ATP production by 35% and reducing ROS levels by 40% in aged BM-MSCs. Osteogenic differentiation was enhanced, as evidenced by a 2.8-fold increase in ALP activity and a 3.5-fold increase in Alizarin Red S staining intensity. Additionally, SS-31 reduced NOS2 expression by 50%, highlighting its therapeutic potential in age-related bone loss. SS-31 intervention not only normalizes mitochondrial structure and function, reducing ROS levels and enhancing oxygen consumption rates, but also targets the NOS2 gene, a potential drug target, which upon knockdown, leads to a substantial upregulation of osteogenic markers and an improvement in mitochondrial function. In conclusion, the findings of this study highlight the therapeutic potential of SS-31 in reversing the age-related decline in BM-MSC function by specifically inhibiting NOS2 expression and restoring mitochondrial function. This research provides a scientific basis for the development of new treatments for osteoporosis and other age-related bone diseases, emphasizing the importance of targeting mitochondrial function and cellular senescence in regenerative therapies.

Tetramethylpyrazine (TMP) has been confirmed to suppress inflammation in endometriosis (EMs). Herein, this study investigated whether and how TMP affected NLRP3 inflammasomes and oxidative stress in EMs. After establishment of an EMs rat model, rats were treated with different concentrations of TMP. The size of endometriotic lesions and the latency and frequency of torsion in rats were recorded, followed by the measurement of relevant indicators (TNF-α, IL-6, IL-2, IL-10, MDA, SOD, GSH, CAT, ROS, NLRP3, ASC, GSDMD, caspase-1, Nrf2, and HO-1). The study experimentally determined that TMP treatment markedly decreased the size of endometriotic lesions and improved torsion in rats with EMs. The levels of inflammatory proteins, oxidative stress markers, NLRP3 inflammasome, and pyroptotic proteins were elevated in rats with EMs, all of which were reversed upon TMP treatment. Additionally, the activities of SOD, GSH, and CAT were lowered in rats with EMs, which were partly abrogated by TMP treatment. Furthermore, the downregulation of Nrf2 and HO-1 was counteracted by TMP treatment. To sum up, TMP represses excessive oxidative stress, NLRP3 inflammasome activation, and pyroptosis in rats with EMs. Additionally, TMP may activate the Nrf2/HO-1 pathway.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality globally. HCC is highly heterogenous with diverse etiologies leading to different driver mutations potentiating unique tumor immune microenvironments. Current therapeutic options, including immune checkpoint inhibitors and combinations, have achieved limited objective response rates for the majority of patients. Thus, a precision medicine approach is needed to tailor specific treatment options for molecular subsets of HCC patients. Lipid nanovesicle platforms, either liposome- (synthetic) or extracellular vesicle (natural)-derived present are improved drug delivery vehicles which may be modified to contain specific cargos for targeting specific tumor sites, with a natural affinity for liver with limited toxicity. This mini-review provides updates on the applications of novel lipid nanovesicle-based therapeutics for HCC precision medicine and the challenges associated with translating this therapeutic subclass from preclinical models to the clinic.

Post-reperfusion syndrome (PRS) is a severe and highly lethal syndrome that occurs after declamping the portal vein forceps during liver transplantation. It is marked by severe hemodynamic disturbances manifested by decreased mean arterial pressure, increased heart rate and elevated pulmonary artery pressure. The complex pathogenesis of PRS remains understudied. It is generally believed to be related to the large amount of acidic, cold blood that enters the circulation after release of the portal clamp. This blood is rich in oxygen-free radicals and metabolic toxins, which not only aggravate the ischemia-reperfusion injury of the liver but also further attack the systemic organs indiscriminately. Considering the range of possible adverse prognoses including acute kidney injury, delirium and graft nonfunction, it is imperative that clinicians increase their awareness and prevention of PRS. The aim of this article is to review the current risk factors, pathophysiological mechanisms and prevention strategies for PRS.

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) exhibit considerable therapeutic potential for myocardial regeneration. In our investigation, we delved into their impact on various aspects of myocardial infarction (MI), including cardiac function, tissue damage, inflammation, and macrophage polarization in a murine model. We meticulously isolated the exosomes from TNF-α-treated BMSCs and evaluated their therapeutic efficacy in a mouse MI model induced by coronary artery ligation surgery. Our comprehensive analysis, incorporating ultrasound, serum assessment, Western blot, and qRT-PCR, revealed that exosomes from TNF-α-treated BMSCs demonstrated significant therapeutic potential in reducing MI-induced injury. Treatment with these exosomes resulted in improved cardiac function, reduced infarct area, and increased left ventricular wall thickness in MI mice. On a mechanistic level, exosome treatment fostered M2 macrophage polarization while concurrently suppressing M1 polarization. Hence, exosomes derived from TNF-α-treated BMSCs emerge as a promising therapeutic strategy for alleviating MI injury in a mouse model.

This study is to investigate the therapeutical effect and mechanisms of human-derived adipose mesenchymal stem cells (ADSC) in relieving adriamycin (ADR)-induced nephropathy (AN). SD rats were separated into normal group, ADR group, ADR+Losartan group (20 mg/kg), and ADR + ADSC group. AN rats were induced by intravenous injection with adriamycin (8 mg/kg), and 4 d later, ADSC (2 × 10⁵ cells/mouse) were administrated twice with 2 weeks interval time (i.v.). The rats were euthanized after the 6 weeks' treatment. Biochemical indicators reflecting renal injury, such as blood urea nitrogen (BUN), neutrophil gelatinase alpha (NGAL), serum creatinine (Scr), inflammation, oxidative stress, and pro-fibrosis molecules, were evaluated. Results demonstrated that we obtained high qualified ADSCs for treatment determined by flow cytometry, and ADSCs treatment significantly ameliorated renal injuries in DN rats by decreasing BUN, Scr and NGAL in peripheral blood, as well as renal histopathological injuries, especially protecting the integrity of podocytes by immunofluorescence. Furthermore, ADSCs treatment also remarkably reduced the renal inflammation, oxidative stress, and fibrosis in DN rats. Preliminary mechanism study suggested that the ADSCs treatment significantly increased renal neovascularization via enhancing proangiogenic VEGF production. Pharmacodynamics study using in vivo imaging confirmed that ADSCs via intravenous injection could accumulate into the kidneys and be alive at least 2 weeks. In a conclusion, ADSC can significantly alleviate ADR-induced nephropathy, and mainly through reducing oxidative stress, inflammation and fibrosis, as well as enhancing VEGF production.

With the rapid development of the field of life sciences, traditional 2D cell culture and animal models have long been unable to meet the urgent needs of modern biomedical research and new drug development. Establishing a new generation of experimental models and research models is of great significance for deeply understanding human health and disease processes, and developing effective treatment measures. As is well known, long research and development cycles, high risks, and high costs are the "three mountains" facing the development of new drugs today. Organoids and organ-on-chips technology can highly simulate and reproduce the human physiological environment and complex reactions in vitro, greatly improving the accuracy of drug clinical efficacy prediction, reducing drug development costs, and avoiding the defects of drug testing animal models. Therefore, organ-on-chips have enormous potential in medical diagnosis and treatment.