In light of the liver injury risk associated with the oral administration of Xianlin Gubao oral preparation, this study compared the differences in liver injury induced by two different extraction processes in rats and explored the correlation between hepatotoxicity and extraction process from the perspective of the differences in the content of the relevant components. Thirty male Sprague-Dawley(SD) rats were randomly divided into a normal group, tablet extract groups of different doses, and capsule extract groups of different doses, with 6 rats in each group. Each group received continuous oral administration for 4 weeks. The assessment of liver injury caused by different extracts was conducted by examining rat body weight, liver function blood biochemical indicators, liver coefficient, and liver pathological changes. In addition, a high-performance liquid chromatography(HPLC) method was established to simultaneously determine the content of icariin, baohuoside I, and bakuchiol in the extracts to compare the differences in the content of these three components under the two extraction processes. The results showed that both extracts caused liver injury in rats. Compared with the normal group, the tablet extract groups, at the studied dose, led to slow growth in body weight, a significant increase in triglyceride levels(P<0.05), a significant decrease in liver-to-brain ratio(P<0.05), and the appearance of hepatic steatosis. The capsule extract groups, at the studied dose, resulted in slow growth in body weight, a significant increase in aspartate aminotransferase levels(P<0.05), a significant decrease in body weight, liver weight, and liver-to-brain ratio(P<0.05), and the presence of hepatic steatosis and inflammatory cell infiltration. In comparison, the capsule extraction process had a higher risk of liver injury. Furthermore, based on the completion of the liquid chromatography method, the content of icariin and baohuoside Ⅰ in the capsule extract groups was 0.83 and 0.81 times that in the tablet extract groups, respectively, while the bakuchiol content in the capsule extract group was 29.80 times that in the tablet extract groups, suggesting that the higher risk of liver injury associated with the capsule extraction process may be due to its higher bakuchiol content. In summary, the differences in rat liver injury caused by the two extracts are closely related to the extraction process. This should be taken into consideration in the formulation production and clinical application.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Liver/pathology* ; Chemical and Drug Induced Liver Injury/pathology* ; Fatty Liver ; Tablets ; Body Weight ; Plant Extracts ; Phenols

OBJECTIVE: To explore the genetic basis for a child featuring global developmental disorder with epilepsy. METHODS: A child who had presented at Guangzhou Women and Children's Medical Center in July 2022 was selected as the study subject. Clinical data was collected. Potential variant was detected by whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a three-year-old ethnic Zhuang Chinese girl, had presented with global developmental disorder and epilepsy, for which rehabilitation therapy was ineffective. Genetic testing revealed that she has harbored a homozygous c.821T>C (p.Leu274Pro) missense variant of the PIGW gene, for which both of her parents and sister were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of uncertain significance. CONCLUSION The homozygous c.821T>C (p.Leu274Pro) variant of the PIGW gene probably underlay the onset of disease in this child. Above finding has enriched the mutational spectrum of the PIGW gene.
Child, Preschool ; Female ; Humans ; Computational Biology ; Developmental Disabilities ; Epilepsy/genetics* ; Genetic Testing ; Homozygote

OBJECTIVE: To quantify phytochemicals using liquid chromatography and mass spectroscopy (LCMS) analysis and explore the therapeutic effect of Aesculus hippocastanum L. (AH) seeds ethanolic extract against gastric ulcers in rats. METHODS: Preliminary phytochemical testing and LCMS analysis were performed according to standard methods. For treatment, the animals were divided into 7 groups including normal control, ulcer control, self-healing, AH seeds low and high doses, ranitidine and per se groups. Rats were orally administered with 10 mg/kg of indomethacin, excluding the normal control group (which received 1% carboxy methyl cellulose) and the per se group (received 200 mg/kg AH seeds extract). The test group rats were then given 2 doses of AH seeds extract (100 and 200 mg/kg, respectively), while the standard group was given ranitidine (50 mg/kg). On the 11th day, rats in all groups were sacrificed, and their stomach was isolated to calculate the ulcer index, and other parameters such as blood prostaglandin (PGE₂), tissue superoxide dismutase (SOD), catalase (CAT), malonyldialdehyde (MDA), and glutathione (GSH). All isolated stomach tissues were analyzed for histopathological findings. RESULTS: The phytochemical examination shows that the AH seeds contain alkaloids, flavonoids, saponins, phenolic components, and glycosides. LCMS analysis confirms the presence of quercetin and rutin. The AH seeds extract showed significant improvement in gastric mucosa conditions after indomethacin-induced gastric lesions (P<0.01). Further marked improvement in blood PGE₂ and antioxidant enzymes, SOD, CAT, MDA and GSH, were observed compared with self-healing and untreated ulcer-induced groups (P<0.01). Histopathology results confirmed that AH seeds extract improved the mucosal layer and gastric epithelial membrane in treated groups compared to untreated ulcer-induced groups. CONCLUSIONS LCMS report confirms the presence of quercetin and rutin in AH seeds ethanolic extract. The therapeutic effect of AH seeds extract against indomethacin-induced ulcer in rat model indicated the regenerated membrane integrity, with improved cellular functions and mucus thickness. Further, improved antioxidant enzyme level would help to reduce PGE₂ biosynthesis.
Rats ; Animals ; Stomach Ulcer/pathology* ; Antioxidants/therapeutic use* ; Ranitidine/adverse effects* ; Aesculus ; Ulcer/drug therapy* ; Quercetin ; Plant Extracts/chemistry* ; Indomethacin/therapeutic use* ; Glutathione ; Superoxide Dismutase ; Rutin/adverse effects* ; Prostaglandins/adverse effects* ; Phytochemicals/therapeutic use*

OBJECTIVE: To explore the genetic basis for a child with congenital heart disease (CHD) and global developmental delay (GDD). METHODS: A child who was hospitalized at the Department of Cardiac Surgery of Fujian Children's Hospital on April 27, 2022 was selected as the study subject. Clinical data of the child was collected. Umbilical cord blood sample of the child and peripheral blood samples of his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 3-year-and-3-month-old boy, had manifested cardiac abnormalities and developmental delay. WES revealed that he had harbored a nonsense variant of c.457C>T (p.Arg153*) in the NONO gene. Sanger sequencing showed that neither of his parents has carried the same variant. The variant has been recorded by the OMIM, ClinVar and HGMD databases, but not in the normal population databases of 1000 Genomes, dbSNP and gnomAD. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as a pathogenic variant. CONCLUSION The c.457C>T (p.Arg153*) variant of the NONO gene probably underlay the CHD and GDD in this child. Above finding has expanded the phenotypic spectrum of the NONO gene and provided a reference for the clinical diagnosis and genetic counseling for this family.
Humans ; Male ; Computational Biology ; DNA-Binding Proteins ; Genetic Counseling ; Genomics ; Heart Defects, Congenital/genetics* ; Mutation ; Parents ; RNA-Binding Proteins ; Child, Preschool ; Developmental Disabilities/genetics*

Mechanical stimulus is critical to cardiovascular development during embryogenesis period.The mechanoreceptors of endocardial cells and cardiac myocytes may sense mechanical signals and initiate signal transduction that induce gene expression at a cellular level,and then translate molecular-level events into tissue-level deformations,thus guiding embryo development.This review summarizes the regulatory roles of mechanical signals in the early cardiac development including the formation of heart tube,looping,valve and septal morphogenesis,ventricular development and maturation.Further,we discuss the potential mechanical transduction mechanisms of platelet endothelial cell adhesion molecule 1-vascular endothelial-cadherin-vascular endothelial growth factor receptor 2 complex,primary cilia,ion channels,and other mechanical sensors that affect some cardiac malformations.
Animals ; Heart/embryology* ; Humans ; Mechanotransduction, Cellular ; Myocytes, Cardiac/physiology* ; Vascular Endothelial Growth Factor A/metabolism*

The present study investigated the effect of extract of Poria cocos polysaccharides(PCP) on cytochrome P450 2 E1(CYP2 E1) and nuclear factor κB(NF-κB) inflammatory signaling pathways in alcoholic liver disease(ALD) mice and explored its protective effect and mechanism. Sixty male C57 BL/6 N mice of SPF grade were randomly divided into a control group, a model group, a positive drug group(bifendate, 200 mg·kg~(-1)), and high-(200 mg·kg~(-1)) and low-dose(50 mg·kg~(-1)) PCP groups. Gao-binge mo-del was induced and the mice in each group were treated correspondingly. Liver morphological and pathological changes were observed and organ index was calculated. Serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected. Malondialdehyde(MDA) and superoxide dismutase(SOD) in liver tissues were detected by assay kits. The levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The activation of macrophages was observed by immunofluorescence staining and protein expression of CYP2 E1, Toll-like receptor 4(TLR4), NF-κB p65, and phosphorylated NF-κB p65(p-NF-κB p65) were analyzed by Western blot. The ALD model was properly induced. Compared with the model group, the PCP groups significantly improved the pathological injury of liver tissues. Immunofluorescence staining revealed that compared with the model group, the groups with drug intervention showed decreased macrophages in liver tissues. Additionally, the PCP groups showed reduced ALT, AST, MDA, IL-6, and TNF-α(P<0.05), and potentiated activity of SOD(P<0.01). PCP extract has the protective effect against alcoholic liver injury in mice, and the underlying mechanism may be related to the regulation of the expression of CYP2 E1 and inhibition of TLR4/NF-κB inflammatory signaling pathway to reduce oxidative stress and inflammatory injury, thereby inhibiting the development of ALD.
Animals ; Cytochrome P-450 CYP2E1/pharmacology* ; Liver ; Liver Diseases, Alcoholic/pathology* ; Male ; Mice ; NF-kappa B/metabolism* ; Plant Extracts/pharmacology* ; Polysaccharides/pharmacology* ; Wolfiporia

OBJECTIVE: To evaluate the effect of Shilajit, a medicine of Ayurveda, on the serum changes in cytokines and adipokines caused by non-alcoholic fatty liver disease (NAFLD). METHODS: After establishing fatty liver models by feeding a high-fat diet (HFD) for 12 weeks, 35 Wistar male rats were randomly divided into 5 groups, including control (standard diet), Veh (HFD + vehicle), high-dose Shilajit [H-Sh, HFD + 250 mg/(kg·d) Shilajit], low-dose Shilajit [L-Sh, HFD + 150 mg/(kg·d) Shilajit], and pioglitazone [HFD + 10 mg/(kg·d) pioglitazone] groups, 7 rats in each group. After 2-week of gavage administration, serum levels of glucose, insulin, interleukin 1beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), adiponectin, and resistin were measured, and insulin resistance index (HOMA-IR) was calculated. RESULTS: After NAFLD induction, the serum level of IL-10 significantly increased and serum IL-1β, TNF-α levels significantly decreased by injection of both doses of Shilajit and pioglitazone (P<0.05). Increases in serum glucose level and homeostasis model of HOMA-IR were reduced by L-Sh and H-Sh treatment in NAFLD rats (P<0.05). Both doses of Shilajit increased adiponectin and decreased serum resistin levels (P<0.05). CONCLUSION The probable protective role of Shilajit in NAFLD model rats may be via modulating the serum levels of IL-1β, TNF-α, IL-10, adipokine and resistin, and reducing of HOMA-IR.
Adiponectin ; Animals ; Cytokines ; Diet, High-Fat ; Glucose ; Insulin Resistance ; Interleukin-10 ; Liver ; Male ; Minerals ; Non-alcoholic Fatty Liver Disease/pathology* ; Pioglitazone/therapeutic use* ; Rats ; Rats, Wistar ; Resins, Plant ; Resistin/therapeutic use* ; Tumor Necrosis Factor-alpha

OBJECTIVE: To investigate the anti-inflammatory potential of Ampelopsis japonica on contact dermatitis (CD). METHODS: A total of 38 Balb/c mice were divided into 5 groups by using a random number table: normal mice (n=6), CD model mice (n=8), CD mice treated with 3 or 30 mg/kg of the ethanol extract of A. japonica (EEAJ, n=8) and 7.5 mg/kg dexamethasone treated CD mice (DEX, n=8). CD was induced using topical application of 1-fluoro-2,4-dinitrofluorobenzene in mice. EEAJ and DEX were topically applied to the shaved skin of each mouse for 6 days, and the effects of EEAJ and DEX on skin lesions and color, histopathological abnormalities such as epidermal hyperplasia and immune cell infiltration, and tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) production were investigated. The effects on changes in body weights and spleen/body weight ratio were also investigated. RESULTS: EEAJ at 30 mg/kg significantly prevented scaling, erythema and enlargement of skin weight compared to using carbon dioxide. EEAJ also prevented epithelial hyperplasia and immune cell infiltrations induced by repeated application of DNFB (P<0.01). In addition, EEAJ significantly lowered levels of TNF-α, IL-6 and MCP-1 (P<0.05 or P<0.01). The anti-inflammatory effects of EEAJ were similar to those of DEX. CONCLUSION A. japonica may be a new therapeutic agent with the potential to reduce or replace corticosteroids and its mechanisms are closely related to regulation of TNF-α production.
Ampelopsis ; Animals ; Anti-Inflammatory Agents/therapeutic use* ; Cytokines ; Dermatitis, Contact/pathology* ; Dinitrofluorobenzene/therapeutic use* ; Hyperplasia/drug therapy* ; Interleukin-6 ; Mice ; Mice, Inbred BALB C ; Plant Extracts/therapeutic use* ; Tumor Necrosis Factor-alpha

OBJECTIVE: To investigate the effect of seabuckthorn berries extract (SBE) on pulmonary vascular hyperpermeability in the mice model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: Sixty Kunming mice were allocated into 6 groups by a random number table, including control, LPS, dexamethasone (Dex, 1 mg/kg), and 120, 240 and 480 mg/kg SBE groups, 10 mice in each group. Except the control group, mice were pre-treated with Dex and SBE, respectively, for 7 days before LPS was intraperitoneally injected to induce ALI. Pulmonary vascular hyperpermeability was evaluated by histopathologic observation and transvascular leakage determination. Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels in serum were measured using enzyme-linked immunosorbent assay. The expression of nuclear factor-kappa B (NF-κB) p65 in lung cells was determined by immunofluorescence analysis. The contents of cytoplasmic inhibitor of nuclear factor-κB kinase (IKK) and nuclear p65, as well as downstream proteins of E-selectin (CD62E) and intercellular adhesion molecule-1 (ICAM-1), were determined using Western blot analysis. RESULTS: Histopathological observation confirmed SBE treatment alleviated morphological lesion induced by LPS. Compared with the LPS group, 480 mg/kg SBE significantly decreased the water content of lung, Evans blue accumulation in lung tissue, and protein concentration and neutrophils count in bronchoalveolar lavage fluid (P<0.01); moreover, 480 mg/kg SBE significantly suppressed release of TNF-α and IL-6, and down-regulated expressions of IKK, nuclear p65, ICAM-1 and CD62E (P<0.01). CONCLUSION SBE maintained alveolar-capillary barrier integrity under endotoxin challenge in mice by suppressing the key factors in the pathogenesis of ALI.
Animals ; Mice ; Acute Lung Injury/drug therapy* ; Fruit/chemistry* ; Hippophae/chemistry* ; Intercellular Adhesion Molecule-1/metabolism* ; Interleukin-6/metabolism* ; Lipopolysaccharides ; Lung/pathology* ; NF-kappa B/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Plant Extracts/therapeutic use*

To study the effect and mechanism of extract of Quzhou Aurantii Fructus(QAF) on liver inflammation in CCl_4-induced liver fibrosis mice. Totally 60 C57 BL/6 male mice were randomly divided into control group(distilled water, oral), model group(distilled water, oral), colchicines group(Col, colchicines 2 mg·kg~(-1)·d~(-1), oral), low-dose QAF group(QAF-L, QAF 100 mg·kg~(-1)·d~(-1), oral) and high-dose QAF group(QAF-H, QAF 300 mg·kg~(-1)·d~(-1), oral) by random number table method. The model group and each administration group were injected with carbon tetrachloride(CCl_4) 1 mL·kg~(-1)(CCl_4-olive oil 1∶4), twice a week, totally 6 weeks. After the last administration, the mice were sacrificed, and serum and liver tissue were collected. Serum ALT and AST levels were measured in each group to observe the liver function of mice. The pathological changes and inflammatory cell infiltration in liver were observed by HE staining and F4/80 immunohistochemical staining. The mRNA expressions of TNF-α, IL-18 and IL-1β were detected by RT-PCR. The protein expressions of IκBα, p-IKKα/β, p-p65, NLRP3, caspase-1 and cleaved caspase-1 were analyzed by Western blot. The results showed that QAF significantly reduced serum ALT and AST levels, and alleviated the degree of liver damage.The results of immunohistochemistry showed that QAF significantly reduced liver inflammatory cell infiltration in liver fibrosis mice. The results of RT-PCR and Western blot showed that QAF significantly inhibited mRNA expressions of TNF-α, IL-18 and IL-1β in liver of fibrosis mice. QAF also suppressed the degradation of IκBα protein and reduced p-IKKα/β, p-p65, NLRP3 and cleaved caspase-1 protein expressions. In conclusion, QAF improves CCl_4-induced liver fibrosis in mice. The mechanism may be related to the inhibition of NF-κB/NLRP3 inflammasome-mediated inflammation signaling pathway.
Animals ; Inflammasomes/genetics* ; Inflammation ; Liver/pathology* ; Liver Cirrhosis/genetics* ; Male ; Mice ; NF-kappa B/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Plant Extracts