Sacral Neural Crest-Independent Origin of the Enteric Nervous System in Mouse.

BACKGROUND & AIMS: The enteric nervous system (ENS), the gut's intrinsic nervous system critical for gastrointestinal function and gut-brain communication, is believed to mainly originate from vagal neural crest cells (vNCCs) and partially from sacral NCCs (sNCCs). Resolving the exact origins of the ENS is critical for understanding congenital ENS diseases but has been confounded by the inability to distinguish between both NCC populations in situ. Here, we aimed to resolve the exact origins of the mammalian ENS. METHODS: We genetically engineered mouse embryos facilitating comparative lineage-tracing of either all (pan-) NCCs including vNCCs or caudal trunk and sNCCs (s/tNCCs) excluding vNCCs. This was combined with dual-lineage tracing and 3-dimensional reconstruction of pelvic plexus and hindgut to precisely pinpoint sNCC and vNCC contributions. We further used coculture assays to determine the specificity of cell migration from different neural tissues into the hindgut. RESULTS: Both pan-NCCs and s/tNCCs contributed to established NCC derivatives but only pan-NCCs contributed to the ENS. Dual-lineage tracing combined with 3-dimensional reconstruction revealed that s/tNCCs settle in complex patterns in pelvic plexus and hindgut-surrounding tissues, explaining previous confusion regarding their contributions. Coculture experiments revealed unspecific cell migration from autonomic, sensory, and neural tube explants into the hindgut. Lineage tracing of ENS precursors lastly provided complimentary evidence for an exclusive vNCC origin of the murine ENS. CONCLUSIONS: sNCCs do not contribute to the murine ENS, suggesting that the mammalian ENS exclusively originates from vNCCs. These results have immediate implications for comprehending (and devising treatments for) congenital ENS disorders, including Hirschsprung's disease.

The role of SUMO specific peptidase 3 in secondary inflammation of ischemic stroke in mice.

Ischemic stroke is the main cause of death and disability, and microglia play a crucial role in the pathophysiology of hypoxic ischemic brain injury. We found that SENP3 is highly expressed in the early stages of ischemic stroke in both in vivo and in vitro mouse models, and may be related to the deSUMOylation of the key kinase MKK7 in the TLR4/p-JNK signaling pathway. Knocking down SENP3 can inhibit the deSUMOylation of MKK7, thereby inhibiting the activation of the TLR4/p-JNK signaling pathway in an in vitro stroke model. Proteomic analysis showed that SENP3 undergoes phosphorylation at the T429 site after ischemic stroke. Computer simulation predictions show a significant enhancement of the interaction between pT429-SENP3 and MKK7, which has been confirmed through experiments on the interaction of biological macromolecules (SPR). The mitochondrial metabolic abnormalities caused by energy abnormalities in the early stages of stroke provide a good explanation for the phosphorylation of SENP3. Therefore, we used the mitochondrial complex inhibitor TTFA to reverse demonstrate that the phosphorylation of SENP3 comes from the large amount of adenosine triphosphate produced by mitochondrial abnormal metabolism caused by early oxygen glucose deficiency. Finally, proteomic analysis indicates that a significant amount of oxidative phosphorylation does occur in the early stages of stroke. In summary, targeted regulation of SENP3 phosphorylation to affect the deSUMOylation of MKK7 may inhibit secondary inflammation in ischemic stroke.

Sanzi Yangqin Decoction Alleviates Allergic Asthma by Modulating Th1/Th2 Balance: Coupling Network Pharmacology with Biochemical Pharmacology.

This study aimed to verify that Sanzi Yangqin Decoction (SYD) can relieve asthma in mice and explore the effect on TH1/Th2 balance. The targets of SYD and asthma were explored from the public database using various methods. The potential targets and signaling pathways were identified by KEGG enrichment analysis from DAVID database. Mice asthma models were established using OVA and aluminum hydroxide. Lung tissues of mice were stained with HE and Masson. The contents of IFN-γ, IL-4, and TNF-α in BALF and IgE in mouse serum were detected using ELISA. In addition, the changes in Th1 and Th2 cells of the spleen were detected by flow cytometry. Fourteen core targets including IL4, IFNG, and MMP9 were identified for the treatment of asthma by SYD. The content of IL-4 in the lung tissue and BALF was gradually decreased with the increase in SYD concentration, while the IFN-γ was gradually increased. The drug significantly reduced IgE levels in serum and TNF-α in BALF. The number of Th1 cells in the spleen increased, while Th2 cells decreased in a concentration-dependent manner. SYD can alleviate pulmonary inflammation, restore Th1/Th2 balance, and relieve asthma.

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps.

The multiterritory perforator flap is one of the widest flap patterns used to repair tissue defects. However, flap necrosis of the distal part is still a challenging issue for plastic surgeons. Diallyl trisulfide (DATS) is an efficient ingredient extracted from garlic, exerting many important effects on different diseases. Our experiment aims to reveal whether DATS has a beneficial effect on the survival of perforator flaps and to explore its mechanism of action. The results showed that DATS enhanced angiogenesis and autophagy and reduced cell apoptosis and oxidative stress, thereby improving the survival rate of skin flaps. After co-administration with autophagy inhibitor 3-methyladenine (3MA), perforator flap survival was further improved. Mechanistically, we showed that PI3K/Akt and AMPK-HIF-1α signaling pathways in flap were activated under DATS treatment. All in all, DATS promoted the survival of multiterritory perforator flaps via the synergistic regulation of PI3K/Akt and AMPK-HIF-1α signaling pathways, and inhibition of DATS-induced autophagy further improves flap survival.

Diastasis recti abdominis in adult women based on abdominal computed tomography imaging: Prevalence, risk factors and its impact on life.

AIMS AND OBJECTIVES: This study aimed to obtain the incidence of diastasis recti abdominis (DRA) and analyse possible risk factors in adult females. Moreover, the relationships between DRA and lower back pain, pelvic floor function and quality of life were also analysed. BACKGROUND: Diastasis recti abdominis is a separation of the abdominal muscles at the linea alba. Currently, studies on the prevalence rates, risk factors and consequences of DRA are varied. In particular, reports on DRA among adult women are lacking. DESIGN: A one-sample questionnaire study design is used following the STROBE checklist. METHODS: The inter-rectus distance was measured by computed tomography in 644 women. Custom questionnaires, the Oswestry Disability Index, The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) were used to investigate personal information, the subjects' back pain, pelvic floor function and quality of life, respectively. RESULTS: The incidence of DRA was 28.4%. Age, the number of pregnancies, BMI and diabetes were influencing factors for DRA. After age stratification, pregnancy and diabetes were found to be risk factors for DRA in young women, and obesity and diabetes were risk factors for DRA in older women. This study showed that the association between DRA and low back pain was highly significant. CONCLUSIONS: Diastasis recti abdominis is common in adult women. Avoiding multiple pregnancies, preventing diabetes and controlling weight may prevent DRA, which may be beneficial for decreasing low back pain in women. RELEVANCE TO CLINICAL PRACTICE: The findings have important implications for the health of adult women which can provide the basis for appropriate nursing implementation for DRA patients. The application of specific prevention and intervention measures for the risk factors may reduce the severity of low back pain.