Hepatic-derived BMP9 is involved in hepatic fibrosis-induced kidney injury through inhibition of renal VEGFA.

Clinical observations suggest that acute kidney injury (AKI) occurs in approximately 20-50% of hospitalized cirrhotic patients, suggesting a link between the liver and kidney. Bone morphogenetic protein 9 (BMP9) is a protein produced primarily by the liver and can act on other tissues at circulating systemic levels. Previous studies have demonstrated that controlling abnormally elevated BMP9 in acute liver injury attenuates liver injury; however, reports on whether BMP9 plays a role in liver injury-induced AKI are lacking. By testing we found that liver injury in mice after bile duct ligation (BDL) was accompanied by a significant upregulation of the kidney injury marker kidney injury molecule (KIM-1). Interestingly, all these impairments were alleviated in the kidneys of hepatic BMP9 knockout (BMP9-KO) mice. Peritubular capillary injury is a key process leading to the progression of AKI, and previous studies have demonstrated that vascular endothelial growth factor A (VEGFA) plays a key role in maintaining the renal microvascular system. In animal experiments, we found that high levels of circulating BMP9 had an inhibitory effect on VEGFA expression, while renal tubular epithelial cell injury was effectively attenuated by VEGFA supplementation in the hypoxia-enriched-oxygen (H/R) constructs of the AKI cell model in both humans and mice. Overall, we found that elevated BMP9 in hepatic fibrosis can affect renal homeostasis by regulating VEGFA expression. Therefore, we believe that targeting BMP9 therapy may be a potential means to address the problem of clinical liver fibrosis combined with AKI.

Syringaresinol alleviates IgG immune complex induced acute lung injury via activating PPARγ and suppressing pyroptosis.

Acute lung injury (ALI) is a life-threatening condition characterized by severe lung inflammation and tissue damage. In this study, we investigate the potential therapeutic efficacy of (+)-Syringaresinol (SYG), a natural compound known for its antioxidant and anti-inflammatory properties, in alleviating ALI induced by IgG immune complexes (IgG-IC). Using MH-S cells as a model, we explore SYG's ability to target peroxisome proliferator-activated receptor gamma (PPARγ) and its anti-inflammatory properties. Our comprehensive investigation aims to elucidate the specific molecular mechanisms underlying SYG's effects against pyroptosis, as revealed through transcriptomic analysis. Validation in C57BL/6 mice provides in vivo support. Our findings indicate that SYG effectively mitigates IgG-IC-induced lung damage, as evidenced by a significant reduction in lung inflammation and tissue injury. SYG treatment notably decreases pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1ß) in both lung tissue and cells. Molecular docking analysis reveals SYG's robust binding to PPARγ, leading to the inhibition of IgG-IC-induced inflammatory signaling pathways. Additionally, transcriptomic analysis unveils SYG's potential in suppressing macrophage pyroptosis, potentially through the downregulation of key inflammatory mediators (NLRP3, GSDMD, Caspase-1). In summary, our study presents compelling evidence supporting SYG as an effective therapeutic agent for ALI. SYG's activation of PPARγ contributes to the suppression of NF-κB and C/EBPs expression, thereby mitigating inflammation. Moreover, SYG demonstrates the ability to inhibit macrophage pyroptosis by targeting the NLRP3/GSDMD/caspase-1 axis.

Clinical Role of Serum Interleukin-17A in the Prediction of Refractory Mycoplasma pneumoniae Pneumonia in Children.

BACKGROUND: Mycoplasma pneumoniae pneumonia (MPP) is a common community-acquired pneumonia (CAP) in children, which may become refractory MPP (RMPP) to treatment. OBJECTIVE: The purpose of this study was to evaluate the clinical utility of measuring serum interleukin (IL)-17A to predict RMPP. PATIENTS AND METHODS: A retrospective clinical study at a single pediatric center included a review of the medical records of all children hospitalized for CAP between November 2015 and October 2019. The diagnosis of MPP was based on clinical presentation, chest radiography, and measurement of serum anti-Mycoplasma immunoglobulin IgM antibody titer using the microparticle agglutination method or sputum samples for Mycoplasma pneumoniae by PCR. Serum levels of IL-18 and IL-17A were determined by ELISA. RESULTS: Of the 625 children diagnosed with CAP, there were 154 children with MPP and without underlying diseases who were divided into a non-refractory MPP (NRMPP) group (n = 109) and a RMPP group (n = 45). The RMPP group had a higher incidence of tachypnea, cyanosis, hypoxia, segmental or lobar pneumonia, pleural effusion, and a longer period of hospitalization compared with NRMPP group (all P-values < 0.05). A serum IL-17A level above 10.8 pg/mL was a predictor for RMPP: area under the curve (AUC) 0.822; standard error (SE) 0.039; 95% confidence interval (CI) 0.746-0.897; diagnostic sensitivity and specificity of 77.8% and 77.1%, respectively. An LDH level above 436.5 IU/L and an IL-18 level above 464.5 pg/mL were the second most useful markers for RMPP: AUC 0.775, 0.775; SE 0.038, 0.039; 95% CI 0.700-0.850, 0.698-0.852; sensitivity 77.8%, 82.2%; specificity 62.4%, 59.6%; respectively. CONCLUSION: This preliminary study of MPP in a pediatric population has shown that measurement of serum IL-17A may be a useful marker for the predictor of RMPP.

Endoscopic retrieval of gastric trichophytobezoar: Case report of a 12-year-old girl with trichophagia.

RATIONALE: Trichophytobezoars, which are composed of hair and plant fibers, are usually located in the stomach. They are often associated with trichophagia and trichotillomania. The most commonly reported methods of trichophytobezoar treatment are open surgery and laparoscopic retrieval; there are few reports of endoscopic removal of trichophytobezoars. PATIENT CONCERNS AND DIAGNOSES: Twelve-year-old girl presented with a 3-day history of increasing upper abdominal pain, anorexia, and postprandial emesis. She had a 3-year history of pulling out and eating her own hair. Endoscopic examination showed a large intragastric trichophytobezoar measuring 10.5 cm × 3.5 cm in size, with extension of a few hairs through the pylorus. INTERVENTIONS AND OUTCOMES: The trichophytobezoar was packed with hair fibers and contained a hard core of mixed hair and vegetable fibers. After the core was cut, the trichophytobezoar was fragmented into pieces with the alternating use of a polypectomy snare and argon plasma coagulation. A small amount of hair and nondigestible food fibers was removed with grasping forceps during the initial procedure. The remaining hairball was loosened with biopsy forceps and was injected with sodium bicarbonate solution. The trichophytobezoar was removed completely at repeat endoscopy 5 days later. After 6 months of psychological intervention, the patient had no recurrence of trichophagia or trichophytobezoar. LESSONS: Endoscopy with sodium bicarbonate injection is an effective and minimally invasive method of retrieving a gastric trichophytobezoar.

Relationships between Th1/Th2 cytokine profiles and chest radiographic manifestations in childhood Mycoplasma pneumoniae pneumonia.

BACKGROUND: Mycoplasma pneumoniae pneumonia (MPP) is one of the most common childhood community-acquired pneumonias, and the chest radiograph usually shows bronchial pneumonia, segmental/lobar pneumonia, or segmental/lobar pneumonia with pleural effusion. The imbalance of Th1/Th2 function after Mycoplasma pneumoniae infection is an important immunological mechanism of MPP. In this study, we aimed to evaluate the correlations between Th1/Th2 cytokine profiles and chest radiographic manifestations in MPP children. PATIENTS AND METHODS: A total of 87 children with MPP were retrospectively reviewed in this study. According to the chest radiographic manifestations, they were divided into the following three groups: bronchial MPP group, segmental/lobar MPP group, and segmental/lobar MPP with pleural effusion group. Clinical features and changes in Th1/Th2 cytokines were further analyzed. RESULTS: The incidence of tachypnea and cyanosis was higher in children with segmental/lobar MPP with pleural effusion than in those with segmental/lobar or bronchial MPP. The peak body temperature of segmental/lobar MPP was higher than that of bronchial MPP, and the duration of fever and hospitalization was positively correlated with the severity of MPP. MPP children's chest radiograph showed a relationship with the changes in Th1/Th2 cytokines. Serum interleukin-4, interleukin-10 (IL-10), interferon-γ, and tumor necrosis factor-α (TNF-α) of segmental/lobar MPP were significantly higher than those of bronchial MPP, and serum IL-10 (cutoff value: 27.25 pg/mL) can be used as a diagnostic predictor for segmental/lobar MPP. Serum TNF-α and interleukin-6 of segmental/lobar MPP with pleural effusion were significantly higher than those of segmental/lobar MPP without pleural effusion. Serum TNF-α (cutoff value: 60.25 pg/mL) can be used as a diagnostic predictor for segmental/lobar MPP with pleural effusion. CONCLUSION: There were significant correlations between Th1/Th2 cytokine profiles and chest radiographic manifestations in MPP children. Serum IL-10 and TNF-α can be used as an optimal predictor for segmental/lobar MPP and segmental/lobar MPP with pleural effusion, respectively.