Ganoderic acid is a class of lanostane-type triterpenoids found in Ganoderma species, and is one of the most important pharmacologically active components in G. lucidum, exhibiting antioxidant, anti-neuropsychiatric, anti-tumor, and immune-enhancing properties. The content of ganoderic acid in G. lucidum is very low, and the traditional extraction process is complex, yielding minimal amounts at high cost. The biosynthetic pathway of G. lucidum triterpenoids(GLTs), including the synthesis of different structural forms of ganoderic acid from lanosterol, as well as the molecular regulatory mechanisms involving key regulatory enzyme genes and their functions, are not yet fully understood. With the continuous development of synthetic biology technologies, there has been a deeper understanding of the biosynthesis and metabolic regulation pathways of ganoderic acid and its derivatives at the molecular level. Research has explored the key regulatory enzyme genes related to ganoderic acid biosynthesis and their functions. Moreover, through the optimization of synthetic biology and culture conditions, large-scale production and preparation of GLTs at the cellular level have been achieved. This paper reviews and analyzes the latest research progress on the biosynthesis pathways and metabolic regulation of GLTs, focusing on the configuration of ganoderic acid and its derivatives, the biosynthetic pathways, key enzyme genes, transcription factors related to ganoderic acid biosynthesis, signal transduction mechanisms, and factors affecting triterpenoid biotransformation. This review is expected to provide a theoretical basis and technical reference for improving the efficient production of triterpenoid pharmacological components and the exploitation and utilization of G. lucidum resources.
Triterpenes/chemistry* ; Reishi/chemistry* ; Biosynthetic Pathways ; Lanosterol

OBJECTIVE: To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia (AML) cells. METHODS: Juglone and AML targets were collected from public databases, and the intersecting target clusters were taken for functional enrichment analysis to explore the potential mechanism of juglone in the treatment of AML. Then wet experiments were performed to verify. AML cell lines including KG-1a, MV-411, THP-1 and MOLM-13 were treated with different concentrations of juglone for 24 h. MTT assay was used to detect cell viability and determine the IC₅₀, and the most sensitive cell line was screened for subsequent experiments. Flow cytometry was used to detect the apoptosis of cells treated with different concentrations of juglone. Western blot was performed to check the expression of relevant proteins. RESULTS: Eleven targets were obtained as potential targets for juglone in the treatment of AML, and the top ten significantly enriched pathways were intrinsic pathway of apoptosis, programmed cell death, cytochrome c-mediated apoptotic response, apoptosis, apoptotic factor-mediated response, regulated necrosis, cytokine signaling in immune system, signaling by interleukins, oncogene induced senescence, and signal transduction. The cell viability of KG-1a, MV-411, THP-1 and MOLM-13 was decreased with increasing juglone concentration after 24 h of juglone treatment (r =-0.992, -0.886, -0.956, -0.910). Among them, MOLM-13 was the most sensitive to juglone. The results of flow cytometry showed that the apoptosis rate of MOLM-13 tended to significantly increase with the increasing concentration of juglone (r =0.99). At the same time point, p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLK were decreased in each juglone concentration group compared with control group. CONCLUSION Juglone inhibits the viability of KG-1a, MV-411, THP-1 and MOLM-13 cells, and induces apoptosis of MOLM-13 cells, the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.
Humans ; Naphthoquinones/pharmacology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Leukemia, Myeloid, Acute/pathology* ; Cell Line, Tumor ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Protein Kinases/metabolism* ; Signal Transduction ; Cell Survival/drug effects*

Objective To analyze the ultrasonographic features of secondary squamous cell carcinoma of the thyroid(SSCC-T)and evaluate the diagnostic value of ultrasound.Methods A retrospective analysis was conducted on clinical and ultrasonographic data from 12 patients with pathologically confirmed SSCC-T treated at Beijing Friendship Hospital,Capital Medical University between January 2016 and January 2025.Evaluated parameters included lesion size,echogenicity,edge,vascularity,calcification,and cervical lymph node metastasis.Descriptive statistical analysis was performed to analyze the ultrasonographic features of SSCC-T,and Fisher's exact test was conducted to analyze the correlation between different ultrasound classifications and thyroid dysfunction.Results The 12 patients showed the following ultrasound classifications:nodular type(50.0%,6/12),diffuse type(33.3%,4/12),and mixed type(16.7%,2/12).All diffuse-type patients exhibited a characteristic cord-like hypoechoic pattern.Cervical lymph node metastasis was observed in all the patients,with 75.0%(9/12)showing lymph nodes >2 cm in maximum diameter.Thyroid dysfunction occurred in 66.7%(8/12)of patients,including 2 patients with dynamic shifts from hyperthyroidism to hypothyroidism.Diffuse and mixed types were associated with hypothyroidism(P=0.038).Conclusions SSCC-T demonstrates specific ultrasonographic features,particularly the cord-like hypoechoic pattern in the diffuse type.For patients with squamous cell carcinoma,regular ultrasound examinations of the thyroid and cervical lymph nodes combined with changes in thyroid function are conducive to the timely detection of thyroid metastasis of squamous cell carcinoma.
Humans ; Retrospective Studies ; Ultrasonography ; Carcinoma, Squamous Cell/diagnostic imaging* ; Thyroid Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Male ; Female ; Middle Aged ; Thyroid Gland/diagnostic imaging* ; Adult

Objective To investigate the therapeutic effects and mechanism of enalapril maleate tablet on doxorubicin-induced heart failure rats based on mitogen-activated protein kinase(MAPK)signaling pathway.Methods Eleven of the 40 male SD rats were randomly selected as the normal group(equivalent to 0.9％NaCl),and the remaining 29 were prepared with intraperitoneal injection of 3 mg·kg-1·w-1 doxorubicin to prepare heart failure model.After successful modeling,they were randomly divided into model group(n=15 cases)and experimental group(n=14 cases).Experimental group was given 1.8 mg·kg-1·d-1 enalapril maleate suspension for gavage;normal and model groups were given the same amount of 0.9％NaCl by gavage.After 8 weeks,the rats were subjected to cardiac ultrasound,the left ventricular ejection fractions(LVEF)of each group were recorded,the serum myocardial injury index level was detected by enzyme-linked immunosorbent assay,and the expression levels of mRNA and protein related to the MAPK signaling pathway were detected by real-time quantitative polymerase chain reaction and Western blot.Results The LVEF values of control,model and experimental groups were(77.85±3.34％)％,(41.39±2.87％)％and(60.10±6.53％)％;serum brain natriuretic peptide contents were(219.30±10.59),(333.90±61.19)and(260.00±16.10)pg·mL-1;the relative expression levels of Mapk8ip2 were 1.00±0.01,2.60±0.12 and 2.00±0.08;the relative expression levels of Mapk8ip3 were 1.00±0.00,6.77±1.04 and 3.66±0.54;the relative expression levels of Mapk1 were 1.00±0.00,4.40±0.14 and 2.71±0.24;the relative expression levels of Mapk3 were 1.00±0.01,7.83±0.34 and 2.71±0.24;the relative expression levels of P38-MAPK were 1.00±0.05,1.14±0.02 and 1.02±0.03;the relative expression levels of extracellular regulated protein kinase 1/2 protein were 1.00±0.07,1.49±0.03 and 1.16±0.10;the relative expression levels of c-Jun N-terminal kinase 1/2 protein were 1.00±0.03,1.65±0.19 and 1.14±0.01,respectively.Compared with the model group,the differences of above indexes in the normal and experimental groups were statistically significant(all P＜0.01).Conclusion Enalapril maleate tablets have therapeutic effects on rats with heart failure,and the mechanism may be achieved by regulating the MAPK signaling pathway.

Objective To compare the pharmacokinetics of crushed posaconazole enteric-coated tablets and oral suspension after intragastric administration in rabbits.Methods The experiment was designed in a randomized cross-over study.Six New Zealand rabbits were intragastrically administrated with crushed posaconazole enteric-coated tablets or suspension,and blood was collected at specific time points.The concentration of posaconazole in plasma was determined by high-performance liquid chromatography,and the pharmacokinetic parameters of both groups were calculated with DAS 2.0 software.Results The main pharmacokinetic parameters of posaconazole enteric-coated tablets and suspension were obtained as follows:AUC0-twere(40.03±5.04)and(49.92±16.09)μg·mL-1·h;AUC0-∞ were(44.00±4.50)and(51.10±16.80)μg·mL-1·h;t1/2 were(7.30±1.13)and(8.53±1.34)h;Cmrx were(3.12±0.57)and(2.78±0.60)μg·mL-1;apparent volume of distribution(Vd)were(2.40±0.34)and(2.59±0.76)L·kg-1;clearance rate(CL)were(0.23±0.02)and(0.22±0.08)L·h-1·kg.There were no statistic differences in AUC0-t,Cmax and Vd between posaconazole suspension and crushed enteric-coated tablets after intragastric administration(all P＞0.05).Conclusion There was no pharmacokinetic advantage for crushed enteric-coated tablets against oral suspension.

Objective:To build a systematic and standardized nutrition management plan for patients with chronic kidney disease.Methods:Based on the nutrition care procedure and model, a preliminary draft of a nutrition management plan for chronic kidney disease patients was developed through a literature search, quality evaluation, and group discussions. After two rounds of expert consultation and revision of the preliminary draft of the nutrition management plan, the final plan was formed.Results:A total of 32 experts were invited to complete two rounds of consultation. In two rounds of expert consultation, 32 questionnaires were distributed, and 32 and 31 valid questionnaires were collected, with valid response rates of 100.0% and 96.9%, respectively. The expert authority coefficients were 0.853 and 0.871, respectively. The final nutrition management plan for chronic kidney disease patients included six first-level items of nutrition management personnel: nutrition risk screening, nutrition assessment, nutrition treatment, nutrition monitoring, and nutrition health education, with 23 second-level and 52 third-level items.Conclusions:The constructed nutrition management plan for chronic kidney disease patients is scientific and can provide a reference for nutrition guidance.

AIM To analyze the constituents absorbed into blood and brain from Zhishe Tongluo Capsules.METHODS Sixteen rats were randomly assigned into four groups and given intragastric administration(3.1 g/kg),after which the cerebral ischemia-reperfusion injury(MACO)model was established,the blood and brain tissues were collected,and UHPLC-Q Exactive Focus MS/MS was adopted in the identification of prototype constituents.RESULTS Total 70 constituents were identified,20 of which were found in the blood,mainly including flavonoids,tanshinones and Ligusticum chuanxiong phthalides,and 7 of them could enter the brain through blood-brain barrier.Compared with the normal administration group,the MACO administration group demonstrated added constituents absorbed into blood containing 3-hydroxybenzoic acid,calycosin-7-glucoside,curcumenol,senkyunolide B,dihydrotanshinone I and cryptotanshinone;removed constituents absorbed into brain containing puerarin,elemicin,sedanolide,and added those containing salvianolic acid A,senkyunolide I,dihydrotanshinone I in the left brain tissues(infarcted side).CONCLUSION The constituents absorbed into blood and brain from Zhishe Tongluo Capsules,along with the enhanced absorptions of phthalides,quinones and phenols in MACO rats in vivo may be the active substances for treating cerebral infarction.

To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology, thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills. The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then, by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP), High-throughput Experiment-and Reference-guided Database(HERB), PubChem, GeneCards, SuperPred, and other databases, the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted. The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database, and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out. Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network, and STRING database was used to construct the protein-protein interaction(PPI) network of intersection targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out on the target genes by the DAVID database. The active ingredient-target-pathway network was constructed, and the key ingredients and targets were screened out for molecular docking verification. The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills, including 13 possible prototype drug ingredients, and 70 potential targets for mercury toxicity in liver and kidney were identified. Through PPI network topology analysis, 12 key target genes(HSP90AA1, MAPK3, STAT3, EGFR, MAPK1, APP, MMP9, NOS3, PRKCA, TLR4, PTGS2, and PARP1) and 6 subnetworks were obtained. Through GO and KEGG analysis of 4 subnetworks containing key target genes, the interaction network diagram of active ingredient-action target-key pathway was constructed and verified by molecular docking. It was found that taurodeoxycholic acid, N-acetyl-L-leucine, D-pantothenic acid hemicalcium, and other active ingredients may regulate biological functions and pathways related to metabolism, immunity, inflammation, and oxidative stress by acting on major targets such as MAPK1, STAT3, and TLR4, so as to inhibit the potential mercury toxicity of zogta in Qishiwei Zhenzhu Pills. In conclusion, the active ingredients of Qishiwei Zhenzhu Pills may have a certain detoxification effect, thus inhibiting the potential mercury toxicity of zogta and playing a role of reducing toxicity and enhancing effect.
Animals ; Mice ; Medicine, Tibetan Traditional ; Network Pharmacology ; Molecular Docking Simulation ; Tandem Mass Spectrometry ; Toll-Like Receptor 4 ; Medicine, Chinese Traditional ; Mercury ; Drugs, Chinese Herbal/toxicity*

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

OBJECTIVES: Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to protect infection and inflammation-related diseases due to its role in antibiotic and immunoregulatory effect. Ozonated triglyceride is a key component of ozonated oil that is one of ozone therapy dosage form. However, the potential role of ozonated triglyceride in sepsis remains unclear. This study aims to explore the effect of ozonated triglyceride on septic mouse model and the molecular mechanism. METHODS: Intraperitoneal injection of lipopolysaccharide (LPS), cecal ligation and puncture (CLP) were applied to construct septic mouse model. The mouse serum was obtained for detection of cytokines, and lung tissues were collected for hematoxylin and eosin (HE) staining to evaluate the extent of lung injury in septic mouse with ozonated triglyceride treatment at different time and doses. The survival of septic mice was observed for 96 h and Kaplan-Meier analysis was used to analyze the survival rates. In addition, primary peritoneal macrophages and human acute monocytic-leukemia cell line (THP-1) were treated with inflammasome activators with or without ozonated triglyceride. The level of cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The cleavage of caspase-1 and gasdermin-D (GSDMD) was detected by Western blotting. RESULTS: Ozonated triglyceride at different time and doses reduced the release of inflammasome-related cytokines [interleukin (IL)-1β and IL-18] (all P<0.05) but not pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-α (TNF-α) in septic mice (all P>0.05). Ozonated triglyceride significantly improved the survival rate of septic mice and reduced sepsis-induced lung injury (all P<0.05). Ozonated triglyceride significantly suppressed the canonical and non-canonical activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome (all P<0.05) but not affected absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes in vitro (all P>0.05). Ozonated triglyceride reduced the cleavage of caspase-1 and the downstream GSDMD. CONCLUSIONS Ozonated triglyceride presents a protect effect on sepsis lethality via reducing cytokines release and sepsis-related organ injury. The mechanism is that ozonated triglyceride specifically suppresses the activation of NLRP3 inflammasome. Ozonated triglyceride is a promising candidate for sepsis treatment.
Animals ; Humans ; Mice ; Caspase 1 ; Cytokines ; Disease Models, Animal ; Inflammasomes ; Lung Injury ; NLR Family, Pyrin Domain-Containing 3 Protein ; Ozone/therapeutic use* ; Sepsis/drug therapy*