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Background/Aim: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder characterized by sphingomyelin accumulation causing progressive lung disease, respiratory failure, and death. Patients and Methods: This retrospective observational study used the TriNetX database of electronic health records for 15,108 patients with ASMD from 2000-2020. After exclusions, 8,980 individuals were followed for 10 or 20 years. Outcomes included incidence and prevalence of respiratory disorders. Associations of age, sex and race were assessed. Results: Nearly all respiratory outcomes increased significantly over 20 versus 10 years. Other respiratory disorders, specified respiratory disorders and secondary pulmonary hypertension exhibited the greatest increases, reflecting progressive lung damage in ASMD. While outcomes were poor overall, older age, male sex, and racial minority status associated with greater risks, indicating differences in disease progression or care. Conclusion: This study confirms the progressive nature of ASMD and need for close monitoring and treatment of pulmonary complications to reduce long-term morbidity and mortality. Genetic testing enabling diagnosis even for milder, adult-onset forms is critical to optimize outcomes. [ABSTRACT FROM AUTHOR]

Context: Nephropathy is a severe complication of type 1 diabetes (T1DM). However, the interaction between the PDHA1-regulated mechanism and CD4+ T cells in the early stage of kidney tubular injury remains unknown. Objective: To evaluate the role of PDHA1 in the regulation of tubular cells and CD4+ T cells and further to study its interaction in tubular cell injury in T1DM. Methods: Plasma and total RNA were collected from T cells of T1DM patients (n = 35) and healthy donors (n = 33) and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, PDHA1, and biomarkers of CD4+ T cells including T helper 1 cells (Th1) and regulatory T cells (Treg) markers. HK-2 cells cocultured with CD4+ T cells from T1DM patients or healthy donors (HDs) to evaluate the interaction with CD4+ T cells. Results: Increased PDHA1 gene expression levels in CD4+ T cells were positively associated with the plasma level of NGAL in T1DM patients and HDs. Our data demonstrated that the Th1/Treg subsets skewed Th1 in T1DM. Knockdown of PDHA1 in kidney tubular cells decreased ATP/ ROS production, NAD/NADH ratio, mitochondrial respiration, and cell apoptosis. Furthermore, PDHA1 depletion induced impaired autophagic fux. Coculture of tubular cells and T1DM T cells showed impaired CPT1A, upregulated FASN, and induced kidney injury. Conclusion: Our fndings indicate that Th1 cells induced tubular cell injury through dysregulated metabolic reprogramming and autophagy, thereby indicating a new therapeutic approach for kidney tubular injury in T1DM. [ABSTRACT FROM AUTHOR]

Background: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a rare autosomal recessive disease. The incidence of citrin deficiency is estimated between 1/10,000 and 1/20,000 in Taiwan. Case report: This report describes a case of a 42 day old female infant who suffered from prolonged jaundice, poor weight gain, and anemia. The initial total/direct bilirubin levels were 8.1/3.11 mg/dL. Liver biopsy was performed at 47 days old. The pathology revealed lobules marked with macrovesicular and microvesicular fatty metamorphosis. The serum amino acid profile showed elevated levels of threonine, methionine, citrulline, and arginine. Newborn screening disclosed normal results, but the genetic study revealed SLC25A13 mutation 851–854 del and 615 + 5G > A. The genetic study of her parents showed that the father carried the SLC25A13 mutation 851–854 del and the mother carried the SLC25A13 mutation 615 + 5G > A. Treatment with ursodeoxycholic acid decreased the bilirubin levels to a normal range at the age of 5 months. Conclusion: This report illustrates that hepatic steatosis is a feature of NICCD. For every young infant patient who develops cholestasis, the pediatrician must consider NICCD as a differential diagnosis even if newborn screening shows normal findings. [ABSTRACT FROM AUTHOR]

Akebia Fructus has long been used for hepatocellular carcinoma (HCC) in China,while the molecularmechanism remains obscure. Our recent work found that Akebia trifoliate (Thunb.) Koidz seed extract (ATSE) suppressed proliferation and induced endoplasmic reticulum(ER) stress in SMMC-7721. The present study aimed to throwmore light on themechanism. ER stress occurred afterATSE treatment in HepG2, HuH7, and SMMC-7721 cells, manifested as ER expansion, and SMMC-7721 was the most sensitive kind in terms of morphology. Cell viability assay showed that ATSE significantly inhibited cells proliferation. Flow cytometry analysis indicated that ATSE leads to an upward tendency of G0/G1 phase and a reduced trend of the continuous peak after G2/M phase in HepG2; ATSE promoted apoptosis in HuH7 and a notable reduction in G0/G1 phase; ATSE does not quite influence cell cycles of SMMC-7721. Western blot analysis showed an increased trend of the chosen ER stress-related proteins after different treatments but nonsignificantly; only HYOU1 and GRP78 were decreased notably by ATSE in HuH7. Affymetrix array indicated that lots of ER stress-related genes' expressions were significantly altered, and downward is the main trend. These results suggest that ATSE have anticancer potency in HCC cells via partly inducing ER stress. [ABSTRACT FROM AUTHOR]