Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Bladder has many important functions as a urine storage and voiding organ. Bladder injury caused by various pathological factors may need bladder reconstruction. Currently the standard procedure for bladder reconstruction is gastrointestinal replacement. However, due to the significant difference in their structure and function, intestinal segment replacement may lead to complications such as hematuria, dysuria, calculi and tumor. With the recent advance in tissue engineering and regenerative medicine, new techniques have emerged for the repair of bladder defects. This paper reviews the recent progress in three aspects of urinary bladder tissue engineering, i.e., seeding cells, scaffolds and growth factors.
Humans ; Intercellular Signaling Peptides and Proteins ; Regenerative Medicine ; trends ; Tissue Engineering ; trends ; Tissue Scaffolds ; Urinary Bladder

OBJECTIVE: To observe the effects of the combined therapy of the auricular-point pressure at the free position and the unprotected perineal delivery technique during the 2nd stage of labor in the primiparas so as to improve the clinical delivery quality. METHODS: A total of 146 primiparas who accepted the natural delivery willingly were collected. According to the visit sequence, they were divided into an observation group (72 cases) and a control group (74 cases). The free position and the unprotected perineal delivery were adopted in combination during the labor in both of the two groups. Additionally, in the observation group, the auricular-point pressure with semen vaccariae was intervened when entering the active phase. The points were pengqiang (TF), zigong (uterus), neishengzhiqi (TF), pizhixia (AT), shenmen (TF), jiaogan (AH), pi (CO) and wei (CO). Each point was pressed for 1 to 2 min each time, repeated once every 10 to 20 min until the end of the 2nd stage of labor. The episiotomy rate, perineal laceration degree, perineal pain degree, the duration of the 2nd labor stage, postpartum hemorrhage, postpartum urine retention and neonatal asphyxia rate were recorded and compared in the primiparas between the two groups. RESULTS: The perineal laceration of the degree Ⅲ and Ⅳ did not occur in the two groups. Compared with the control group, the effect on the perineal laceration was better in the observation group (<0.05). The episiotomy rate was 5.6% (4/72) in the observation group, lower than that in the control group (<0.05). The total perineal laceration rate was 68.1% (48/72) in the observation group, similar to the control group (>0.05). In the observation group, the neonatal asphyxia rate was 1.4% (1/72), the postpartum hemorrhage 6.9% (5/72) and the incidence of urine retention 5.6% (4/72), all lower than 10.8% (8/74), 18.9% (14/74) and 17.6% (13/74) in the control group respectively (all <0.05). In the observation group, on the 1st, 2nd and 3rd days after labor, the perineal pain degree and the duration of the 2nd stage of labor were superior to the control group (all <0.001). CONCLUSION The combined therapy of the auricular-point pressure intervention at the free position and the unprotected perineal delivery technique effectively reduces the episiotomy rate and perineal laceration degree, relieves the perineal pain, reduces the neonatal asphyxia rate and improves the delivery quality during the 2nd stage of labor in the primiparas.
Female ; Humans ; Labor, Obstetric ; Parity ; Perineum ; Pregnancy ; Pressure

ObjectiveTo investigate the incidence and gene mutation spectrum of childhood thalassemia in Sanya city. MethodsThere were 938 children in our hospital screened by routine blood test, C-reactive protein test and hemoglobinelectro-phoresis. Based on the screening results in children with thalassemia and its subtypes, the alpha thalassaemia children were diag-nosed by gap - polymerase chain reaction, while the beta thalassaemia ones were diagnosed by polymerase chain reaction-reverse dot blot, and all the results were retrospectively analyzed.ResultsScreening positive rate of thalassemia anemia was 13.65% (128/938), genetic diagnosis positive rate was 11.41% (107/938). In 107 cases diagnosed with thalassemia by genetic test, 59 were alpha thalassaemia, and 46 were beta thalassaemia, and 2 cases were alpha thalassaemia combined with beta thalassaemia. In 59 cases of alpha thalassaemia, 31 had genotype of - SEA/alpha alpha , 13 cases with genotype alpha 4.2 / alpha alpha, and 6 were of HbH disease. In the 46 cases of beta thalassaemia children, six gene locus mutations were found : CD41-42 (CTTT) in 21 cases, TATAbox - 28 (A - G) in 13 cases, CDs14/15 (G) in 5 cases, IVS - Int 654 (C - > T) in 4 cases, CD17 (A - > T) in 2 cases, and 27-28 (C) in 1 case.ConclusionHigh prevalence of thalassemia in children from Sanya city warrants genetic counseling, premarital check-up and prenatal diagnosis.