To investigate the preventive and therapeutic effects of Tanshinone ⅡA on radiation-induced heart disease (RIHD) through the regulation of the phosphoinositide 3-kinase/AKT/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway, and to elucidate its underlying mechanisms based on animal and cellular experiments, thereby providing a theoretical foundation for developing targeted clinical prevention and treatment strategies.

In animal experiments, SPF-grade rats and mice were respectively divided into blank control group, model group and experimental group. A single dose of X-ray irradiation (25 Gy for rats, 20 Gy for mice) was administered to establish the RIHD model. The blank control group received normal feeding. The model group received normal feeding after modeling. The experimental group received daily intraperitoneal injections of Tanshinone ⅡA sulfonate sodium injection (1 mg/10 g body weight) for one week following modeling. In cell experiments, H9C2 cardiomyocytes were divided into normal cell group, injury-induced group and a drug-treated group. A radiation-induced RIHD cell model was established. The normal cell group was cultured under standard conditions. The injury-induced group was cultured normally after modeling. The drug-treated group was administered Tanshinone ⅡA sulfonate sodium (1μL·mL^-1 culture medium) immediately after modeling. Body weight changes and myocardial histopathological characteristics were dynamically monitored. Transcriptome sequencing was performed on cardiac apex tissues from both rats and mice for joint analysis, aiming to screen for common differentially expressed genes and enriched pathways. Cell viability was assessed using the cell counting kit-8 (CCK-8) assay. Cell membrane damage was evaluated by the lactate dehydrogenase (LDH) release assay. The expression levels of key genes in PI3K/AKT/mTOR pathway, including angiopoietin-2 (ANGPT2) and cyclin D1 (CCND1), as well as the protein levels of phosphorylated phosphoinositide 3-kinase (P-PI3K) and phosphorylated AKT serine/threonine kinase (P-AKT) were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively.

Animal experiments showed that after the intervention, the body weights of rats in the blank control group, model group and experimental group were (434.37±8.52), (341.61±8.73) and (410.13±10.05) g, respectively; the body weights of mice were (30.97±0.89), (26.24±0.86) and (30.96±0.87) g, respectively; AST levels were (159.92±3.83), (171.04±2.63) and (149.63±10.55) U·L^-1, respectively; CK-MB levels were (219.00±5.83),(455.42±32.76) and (248.36±15.25) U·L^-1, respectively; LDH levels were (677.20±21.22),(864.63±6.39) and (635.77±22.72) U·L^-1, respectively; BNP levels were (29.37±6.04),(241.69±12.75) and (134.23±13.57) pg·mL^-1, respectively; GSH levels were (160.73±4.65), (330.38±9.41) and (116.71±11.29) U·L^-1, respectively. All the aforementioned indicators in model group showed statistically significant differences compared to blank control group, and all indicators in the experimental group showed statistically significant differences compared to model group (all P<0.001). In the cell experiments, joint transcriptome analysis revealed that 72% of homologous differentially expressed genes (624 in rats, 341 in mice) exhibited consistent expression trends in both species. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis indicated that ANGPT2, CCND1, THBS1, COL4A1, FN1 and COL4A2 were primarily enriched in the PI3K/AKT/mTOR pathway (all P<0.05), and PCR validation confirmed this consistent trend. In vitro experiments confirmed that the cell viabilities in normal cell group, injury-induced group and drug-treated group were (118.40±8.63)%, (73.10±6.12)% and (91.57±8.08)%, respectively. The differences between injury-induced group and normal cell group, as well as between drug-treated group and injury-induced group, were statistically significant (both P<0.001). The LDH release levels in injury-induced group and drug-treated group were (1.03±0.02) and (0.77±0.01)-fold that of normal cell group, respectively. The difference between the drug-treated group and the injury-induced group was statistically significant (P<0.001). The relative expression levels of P-PI3K in normal cell group, injury-induced group and drug-treated group were 0.92±0, 0.76±0.01 and 0.85±0.02, respectively; the relative expression levels of P-AKT were 0.79±0.01, 0.70±0.01 and 0.76±0.01, respectively. The differences between the injury-induced group and the normal cell group, as well as between the drug-treated group and the injury-induced group were statistically significant (all P<0.05).

Tanshinone ⅡA mitigates radiation-induced cardiac injury by activating the PI3K/AKT/mTOR signaling pathway, upregulating key phosphorylated proteins (p-PI3K and p-AKT), reducing radiation toxicity and enhancing cellular viability.

To investigate the impact of quercetin (Que) on myocardial ischemia-reperfusion injury in rats and to elucidate its underlying mechanisms.

A rat model of myocardial ischemia-reperfusion was created by occluding the left anterior descending artery. A total of 60 SD rats were randomly divided into sham group, model group, low-dose experimental group (20 mg·kg^-1 Que), high-dose experimental group (80 mg·kg^-1 Que) and inhibitor group (80 mg·kg^-1 Que+3 mg·kg^-1 MCC950), with 12 rats in each group. Echocardiography was conducted after 14 days of continuous administration to assess the relevant indicators of cardiac function. Rat serum was taken and the amounts of serum myocardial damage indicators and inflammatory factors were detected by kit method. Western blotting was used to determine the relative expression levels of Toll-like receptor 2 (TLR2)/ nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) - related proteins in the rat myocardial tissue.

The left ventricular ejection fraction of rats in sham group, model group, low-dose experimental group, high-dose experimental group and inhibitor group were (79.36±5.37)%, (42.85±3.96)%, (48.51±4.20)%, (71.66±5.14)% and (55.73±4.68)%, respectively; the troponin Ⅰ (cTnⅠ) levels were (0.07±0.01), (0.38±0.03), (0.25±0.03), (0.13±0.01) and (0.20±0.02) ng·mL^-1, respectively; the interleukin-1β (IL-1β) levels were (1.01±0.15), (3.43±0.22), (2.65±0.26), (1.39±0.23) and (1.61±0.13) ng·mL^-1, respectively; the relative expression levels of TLR2 protein were 0.33±0.05, 1.01±0.07, 0.73±0.05, 0.45±0.03 and 0.50±0.06, respectively; the relative expression levels of NLRP3 protein were 0.34±0.06, 1.05±0.09, 0.86±0.07, 0.39±0.06 and 0.56±0.05, respectively. Compared with sham group, the model group showed statistically significant differences in the above indicators (all P<0.05); compared with model group and high-dose experimental group, the low-dose experimental group also exhibited statistically significant differences in the above indicators (all P<0.05).

Quercetin can alleviate myocardial ischemia-reperfusion (I/R) injury in rats and improve cardiac function. The mechanism may be related to the inhibition of the TLR2/NLRP3 inflammatory signaling pathway. Quercetin may exert its cardioprotective effect by down-regulating the expression of TLR2, thereby blocking its activation of the downstream NLRP3 inflammasome, containing NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC) and ultimately reducing the release of pro-inflammatory factors such as IL-1β.

To investigate the effects of telmisartan tablets (Tel) on viral myocardialtis (VM) mice through microRNA-320 (miR-320) and its mechanism.

A total of 60 BALB/c mice were divided into control group, model group, experimental group, Tel+rAAV-NC group and Tel+rAAV-miR-320 group, with 12 mice in each group. Except for control group, VM mouse models were established by intraperitoneal injection of coxsackievirus B3 0.1 mL containing 100 TCID50. Experimental group was given 10 mg·kg^-1 Tel intragastrically for 7 days. Based on experimental group, rAAV-NC was injected into the tail vein (1×10¹¹ viral copy number, dissolved in PBS 100 μL) in Tel+rAAV-NC group; based on experimental group, rAAV-miR-320 was injected into the tail vein (1×10¹¹ viral copy number, dissolved in PBS 100 μL) in Tel+rAAV-miR-320 group. The relative expression levels of miR-320 were detected by quantitative real time polymerase chain reaction. Creatine kinase isoenzyme, myoglobin and troponin were detected by enzyme-linked immunosorbent assay. TdT-mediated dUTP nick end labeling was used to detect apoptosis. The relative expression levels of peroxiredoxin-like protein NOX1 (PKNOX1)/B-cell lymphoma 10 (BCL10)/mucosa associated lymphoid tissue lymphoma translocation gene 1 (MALT1) signaling pathway were detected by Western blot.

The relative expression levels of miR-320 in control group, model group, experimental group, Tel+rAAV-NC group and Tel+rAAV-miR-320 group were 1.00±0.18, 4.06±0.73, 1.82±0.34, 1.95±0.36 and 3.47±0.61, respectively; creatine kinase isoenzyme were (36.09±4.82), (125.18±19.67), (49.73±8.04), (55.62±8.25) and (103.56±17.49) U·mL^-1, respectively; myoglobin were (72.35±11.46), (368.29±61.83), (93.62±15.27), (90.74±16.18) and (316.51±57.92) μg·L^-1, respectively; troponin were (17.42±2.53), (64.74±10.90), (28.59±4.16), (32.45±5.98) and (53.91±9.64) μg·L^-1, respectively; the apoptosis rates were (3.17±0.52)%, (28.46±5.39)%, (6.97±1.24)%, (8.01±1.53)% and (24.89±4.16)%, respectively; the relative expression levels of PKNOX1 protein were 1.00±0.15, 2.07±0.36, 1.43±0.19, 1.39±0.20 and 1.91±0.32, respectively; the relative expression levels of BCL10 protein were 1.00±0.18, 1.95±0.34, 1.48±0.22, 1.41±0.21 and 1.84±0.35, respectively; the relative expression levels of MALT1 protein were 1.00±0.13, 1.90±0.32, 1.26±0.15, 1.37±0.18 and 1.69±0.27, respectively. Statistical comparisons revealed significant differences between model group and control group, as well as between experimental group and model group, and between Tel+rAAV-miR-320 group and Tel+rAAV-NC group (all P<0.05).

By inhibiting the expression of miR-320, Tel alleviates myocardial injury and inhibits apoptosis in VM mice, which may be achieved by inhibiting PKNOX1/BCL10/MALT1 signaling pathway.

To analyze the potential mechanism of naringenin in improving diabetes-related intestinal inflammation.

In cell experiment, STC-1 cells were randomized into blank group, advanced glycation end products (AGEs) group, experimental-L group (AGEs+25 μg·mL^-1 naringenin) and experimental-H group (AGEs+50 μg·mL^-1 naringenin). In animal experiment, male C57BL/6J mice were randomly divided into control group, model group (to construct diabetes-related intestinal injury model), experimental-L group (modeling +25 mg·kg^-1 naringenin), experimental-H group (modeling +75 mg·kg^-1 naringenin) and metformin group (modeling +0.5 g·kg^-1 metformin). STC-1 cell necroptosis was detected using the Hoechst 33342/propidium iodide (PI) double staining method. Glycolipid metabolism indicators and pro-inflammatory factor levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of phosphorylated mixed lineage kinase domain-like (p-MLKL) protein and Occludin protein was assessed by Western blotting.

In cell experiment, PI-positive rates of blank, AGEs, experimental-L and experimental-H groups were (4.36±0.30)%, (19.37±1.58)%, (15.90±1.03)% and (12.85±1.51), respectively; IL-6 levels were (17.74±2.23), (71.46±6.54), (42.39±5.34) and (33.63±1.82) pg·mL^-1, respectively; p-MLKL relative expression levels were 0.39±0.05, 0.83±0.10, 0.74±0.07 and 0.58±0.04, respectively. All indicators showed significant differences between AGEs group and blank group, experimental-L group or experimental-H group and AGEs group (P<0.05, P<0.01). In animal experiment, post-intervention FBG levels of blank control group, model group, experimental-L group, experimental-H group and metformin group were (4.89±0.54), (26.88±1.96), (18.47±1.53), (14.96±1.67) and (13.91±1.16) mmol·L^-1, respectively; TG levels were (0.43±0.06), (1.70±0.15), (1.46±0.14), (1.13±0.10) and (0.81±0.09) mmol·L^-1, respectively; IL-6 levels were (13.59±1.06), (62.02±5.92), (50.19±4.44), (37.78±3.58) and (48.91±8.46) pg·mL^-1, respectively; the relative expression levels of p-MLKL were 0.38±0.05, 1.07±0.13, 0.79±0.08, 0.61±0.05 and 0.80±0.09, respectively; the relative expression levels of Occludin were 0.97±0.07, 0.35±0.04, 0.61±0.05, 0.83±0.07 and 0.43±0.06, respectively. Significant differences were observed between model group and blank control group, experimental-L group or experimental-H group or metformin groups and model group (P<0.05, P<0.01).

Naringenin can improve the function of intestinal endocrine cells and protect against diabetes-related intestinal injury, which may be related to the mechanism of necrotic apoptosis mediated by MLKL.

To investigate the potential mechanism of propofol in improving intestinal ischemia-reperfusion injury (IIRI).

SD rats were randomly divided into sham group, model group (the superior mesenteric artery was clamped for 45 min and reperfusion for 2 h), experimental-L group (injection of 30 mg·kg^-1 propofol before ischemia), experimental-M group (injection of 45 mg·kg^-1 propofol before ischemia), experimental-H group (injection of 60 mg·kg^-1 propofol before ischemia); after reperfusion, the rats were killed and intestinal tissues were taken for use. Hematoxylin-eosin (HE) staining was used to observe the intestinal histopathological changes, Western blot assay was used to detect the expression of Bcl-2 antagonist killer(BAK), Bcl-2 associated X(BAX) and other proteins, and real-time quantitative polymerase chain reaction (RT-qPCR) assay was used to detect the expression of cytoplasmic mitochondrial DNA (mtDNA). The enzyme activity and enzyme-linked immunosorbent assay was used to detect the expression of adenosine triphosphate (ATP) and interleukin (IL)-1β in intestinal tissue.

The pathological injury scores (Chiu’s methods) in sham group, model group, experimental-L group, experimental-M group and experimental-H group were (0±0), (4.20±0.60), (3.00±0.45), (2.20±0.40) and (1.00±0.77) points, respectively; the relative expression levels of BAK protein were 0.24±0.03, 0.66±0.08, 0.56±0.08, 0.40±0.05 and 0.34±0.03, respectively; the relative expression levels of BAX protein were 0.35±0.03, 0.79±0.11, 0.62±0.03, 0.51±0.05 and 0.40±0.04, respectively; the relative expression levels of NOD-like receptor pyrin domain-containing protein 3 (NLRP3) protein were 0.32±0.03, 1.05±0.12, 0.81±0.11, 0.64±0.08 and 0.49±0.08, respectively; the relative expression levels of Cyclic guanosine monophosphate adenosine synthase (cGAS) protein were 0.23±0.02, 0.97±0.10, 0.78±0.08, 0.63±0.07 and 0.45±0.07, respectively; the relative expression levels of the NADH dehydrogenase subunit (ND)1 mRNA were 1.00±0.08, 2.23±0.29, 1.79±0.13, 1.59±0.11 and 1.34±0.09, respectively; the levels of ATP production were 1.00±0.14, 0.47±0.03, 0.65±0.07, 0.80±0.06 and 0.81±0.12, respectively. Compared model group with the sham group and compared experimental-L, M, H group with model group, the differences of above indicators were all statistically significant (all P<0.05).

Propofol can dose-dependently improve intestinal injury in IIRI rats and this protective effect was accompanied by downregulation of BAK/BAX protein expression, reduction of mtDNA release, and decreased activity of the downstream cGAS/NLRP3 inflammatory pathway.

To evaluate the effects of itraconazole capsules on the pharmacokinetics of a single oral dose of ADC189 and its metabolite ADC189-I07 in Chinese healthy subjects, and to assess the safety of their co-administration.

This was a single-center, open-label, non-randomized, two-period, fixed-sequence trial, using itraconazole as an inhibitor of cytochrome P450 3A4 (CYP3A4), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Analyze the impact of repeated administration of itraconazole capsules on the pharmacokinetic characteristics of ADC189 and its major metabolite ADC189-I07.

After co-administration of ADC189 with itraconazole, there was no difference in the maximum plasma concentration (C_max) of the active metabolite ADC189-I07 in plasma compares with ADC189 alone; the geometric mean ratio was 106.64%, with a 90% confidence interval (CI) of 84.12%-135.16%. The area under the curve (AUC_0-t) and AUC_0-∞ increased by approximately 42.00% and 47.00%, respectively, with geometric mean ratios and 90% confidence intervals of 142.48% (120.84%-167.98%) and 147.25% (123.95%-174.91%), respectively. The 90% CIs for all three parameters did not fall entirely within the no-effect boundary of 80.00%-125.00%. The median time to peak drug concentration (t_max) of ADC189-I07 was 4.00 (3.00-4.00) after administration alone and 4.00 (3.00-12.00) h after co-administration; non-parametric tests showed no statistically significant difference in t_max (P>0.05). All adverse events (AEs) during the trial were grade 1 or 2, resolved spontaneously, and the safety risk was controllable.

When ADC189 tablets are used clinically with a strong CYP3A4 inhibitor, no dosage adjustment is required for concomitant use.

To systematically evaluate the efficacy and safety of dapagliflozin (Forxiga^TM) combined with metformin (MET) in the treatment of type 2 diabetes mellitus (T2DM).

Several databases such as China National Knowledge Infrastructure (CNKI) and PubMed were searched by computer. To collect a randomized controlled trial of dapagliflozin combined with metformin in the treatment of type 2 diabetes. Quality evaluation, data extraction and data analysis of the literature were condueted. Glycosylated hemoglobin level, fasting blood glucose, 2 h postprandial blood glucose, fasting insulin, islet β - cell function, insulin resistance index, the incidence of adverse events, hypoglycemia and urinary tract infection were analyzed by RevMan5.4 software.

A total of 9 eligible randomized controlled trials (RCTs) involving 867 type 2 diabetes mellitus patients were included in the final analysis. As it turns out, the efficacy of dapagliflozin combined with MET group was significantly better than that of metformin alone (P<0.05), and the safety of the combined group had no statistically significant differince (P>0.05).

Compared with metformin monotherapy, the combination therapy of dapagliflozin and metformin yields significantly improved clinical outcomes in T2DM patients without increasing the incidence of adverse drug reactions. These findings provide robust scientific evidence for the rational clinical application of this therapeutic regimen.

To investigate the potential mechanisms and related signaling pathways of mitophagy in the occurrence and development of autosomal dominant polycystic kidney disease (ADPKD) using bioinformatics techniques.

The gene expression omnibus (GEO) dataset GSE7869 was downloaded and processed. Differentially expressed genes (DEGs) were identified using the R limma package. Mitophagy-related genes were retrieved from the GeneCards database and intersected with the DEGs to obtain candidate genes. A protein-protein interaction (PPI) network was constructed using STRING, and core genes were identified in Cytoscape using the maximalclique centrality (MCC) algorithm. Gene set enrichment analysis (GSEA) was conducted based on albumin (ALB) expression levels, and R packages including clusterProfiler, ggplot2 and enrichplot were used to visualize and interpret the enrichment results.

A total of 248 DEGs were obtained, including 61 up-regulated and 187 down-regulated genes. After intersecting with mitophagy-related genes, 38 candidate DEGs were identified. ALB was identified as the core differentially expressed gene through PPI analysis and Cytoscape. GSEA results indicated that the mitophagy-related gene ALB may play a role in ADPKD by regulating pathways such as extracellular matrix (ECM)-receptor interaction and branched-chain amino acid (BCAA) metabolism, as well as biological processes including organic acid and amino acid metabolism and organization of collagen fibrils.

ALB expression levels were significantly associated with pathways including ECM-receptor interaction and branched-chain amino acid metabolism, as well as with biological processes such as organic acid and amino acid metabolism and organization of collagen fibrils. These findings suggest that ALB may be involved in the pathogenesis of ADPKD.