Generation and characterization of PDGFRα-GFP knock-in mice for visualization of PDGFRα+ fibroblasts in vivo.

The platelet-derived growth factor (PDGF) and its receptor, PDGFRα, are critical for tissue development and injury repair. To track PDGFRα-expressing cells in vivo, we generated a knock-in mouse line that expresses green fluorescent protein (GFP) under the control of the PDGFRα promoter. This genetic tool enabled us to detect PDGFRα expression in various organs during both neonatal and adult stages. Additionally, we confirmed the correlation between endogenous PDGFRα and transgenic PDGFRα expression using mouse injury models, showing the potential of this genetic reporter for studying PDGFRα-mediated signaling pathways and developing therapeutic strategies. Overall, the PDGFRα-GFP knock-in mouse line serves as a valuable tool for investigating the biology of PDGFRα and its role in normal development and disease.

Spatial-temporal proliferation of hepatocytes during pregnancy revealed by genetic lineage tracing.

The maternal liver undergoes dramatic enlargement to adapt to the increased metabolic demands during pregnancy. However, the cellular sources for liver growth during pregnancy remain largely elusive. Here, we employed a proliferation recording system, ProTracer, to examine the spatial-temporal proliferation of hepatocytes during pregnancy. We discovered that during early to late pregnancy, hepatocyte proliferation initiated from zone 1, to zone 2, and lastly to zone 3, with the majority of new hepatocytes being generated in zone 2. Additionally, using single-cell RNA sequencing, we observed that Ccnd1 was highly enriched in zone 2 hepatocytes. We further applied dual-recombinase-mediated genetic lineage tracing to reveal that Ccnd1+ hepatocytes expanded preferentially during pregnancy. Moreover, we demonstrated that estrogen induces liver enlargement during pregnancy, which was abolished in Ccnd1 knockout mice. Our work revealed a unique spatial-temporal hepatocyte proliferation pattern during pregnancy, with Ccnd1+ hepatocytes in zone 2 serving as the major cellular source for hepatic enlargement.

RNA Epigenetics in Chronic Lung Diseases.

Chronic lung diseases are highly prevalent worldwide and cause significant mortality. Lung cancer is the end stage of many chronic lung diseases. RNA epigenetics can dynamically modulate gene expression and decide cell fate. Recently, studies have confirmed that RNA epigenetics plays a crucial role in the developing of chronic lung diseases. Further exploration of the underlying mechanisms of RNA epigenetics in chronic lung diseases, including lung cancer, may lead to a better understanding of the diseases and promote the development of new biomarkers and therapeutic strategies. This article reviews basic information on RNA modifications, including N6 methylation of adenosine (m6A), N1 methylation of adenosine (m1A), N7-methylguanosine (m7G), 5-methylcytosine (m5C), 2'O-methylation (2'-O-Me or Nm), pseudouridine (5-ribosyl uracil or Ψ), and adenosine to inosine RNA editing (A-to-I editing). We then show how they relate to different types of lung disease. This paper hopes to summarize the mechanisms of RNA modification in chronic lung disease and finds a new way to develop early diagnosis and treatment of chronic lung disease.

Potential of Mesenchymal Stem Cell-Based Therapies for Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is a common pathological feature of acute and chronic inflammatory lung diseases that currently has no effective clinical treatment. Mesenchymal stem cells (MSCs) are considered to be an ideal cell source for regenerating injured tissues, as they are easily extracted and expanded, have a limited risk of tumorigenicity, and lack immunogenicity. Recently, MSC-based therapies have been suggested as potential therapeutic strategies for attenuating PF. Although the administration of MSCs has been reported to have anti-inflammatory and anti-fibrotic effects in PF, further studies are required to optimize the MSC source and dose, delivery time, and route of administration to improve their protective effects. Moreover, the mechanisms underlying MSC-based therapies for PF remain elusive. Here, we review recently published data on MSC administration for the treatment of PF to provide insights into the therapeutic impact of MSC delivery procedures and sources. In addition, we discuss the potential mechanisms underlying the effects of MSC administration on PF and highlight promising strategies for improving the beneficial effects of MSCs.

Recombinant Lactobacillus casei expressing Clostridium perfringens toxoids α, ß2, ε and ß1 gives protection against Clostridium perfringens in rabbits.

The present study used Lactobacillus casei ATCC 393 as antigen delivery system to express C. perfringens toxoids α-ß2-ε-ß1 to construct the recombination Lactobacillus casei pPG-2-α-ß2-ε-ß1/L. casei 393. After being induced by 1% xylose, the specificity and integrity of recombinant strain were determined by Western-blotting. Rabbits as native animal model were immunized orally with pPG-2-α-ß2-ε-ß1/L. casei 393 and the titers of specific IgG and sIgA were determined by ELISA. The result showed that oral administration with the recombinants could elicit both local mucosal and systemic immune responses. The proliferation of spleen lymphocytes in rabbits immunized with pPG-2-α-ß2-ε-ß1/L. casei 393 was observed. Levels of IL-4 and IFN-γ produced were significantly higher in lymphocytes isolated from the vaccine group than those from the control groups. Flow cytometry assay showed that both the percentages of CD4+T cells and CD8+T cells from the vaccine group were significantly increased than the control groups. All these results showed that immunizing with recombinants can elicit both humoral immunity and cellular immunity. Besides, in order to determine the effectiveness of oral immunization with pPG-2-α-ß2-ε-ß1/L. casei 393, rabbits of vaccine group and control groups were challenged with 1×LD100 unit of culture filtrate of C. perfringens type C and type D toxins respectively. After challenge, 100% of the immunized rabbits survived, while the rabbits of the control group were killed within 48h. Observation on histopathology showed that histopathological changes were obviously found in heart, liver, spleen, lung, kidney, intestine and brain of rabbits from the control groups, while no apparent histopathological change was observed in the vaccine group. All the results show that pPG-2-α-ß2-ε-ß1/L. casei 393 can eliciteffective immunoprotection against C. perfringens. All of these suggest that the use of pPG-2-α-ß2-ε-ß1/L. casei 393 can be regarded as candidate for the development of a vaccine against C. perfringens.