Compared to conventional treatment alone, combining Gusongbao preparation with standard care is demonstrably more effective in boosting lumbar spine (L2-L4) and femoral neck bone density, reducing low back pain, and enhancing clinical outcomes, according to the available data. Gusongbao preparation's adverse reactions consisted mainly of mild gastrointestinal discomfort.
The tissue distribution of Qingfei Paidu Decoction, in live animals, was quantitatively determined using HPLC-MS/MS. The Hypersil GOLD C (18) column (21 mm × 50 mm, 19 m) facilitated gradient elution, using acetonitrile as mobile phase A and 0.1% formic acid solution as mobile phase B. A comprehensive analysis revealed the presence of 19, 9, 17, 14, 22, 19, 24, and 2 compounds in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. In the prescription, 8 groups of compounds contained 14 herbs. The compounds, following administration of Qingfei Paidu Decoction, were rapidly disseminated throughout the body's tissues, showing significant concentrations within the lung, liver, large intestine, and kidneys. The overwhelming number of compounds showed a secondary distribution. A detailed study of the distribution rules governing the major active components within Qingfei Paidu Decoction was conducted, offering a solid basis for clinical application.
The present study sought to determine how Wenyang Zhenshuai Granules (WYZSG) influence autophagy and apoptosis of myocardial cells in rats with sepsis, specifically by investigating changes in microRNA-132-3p (miR-132-3p)/uncoupling protein 2 (UCP2) expression levels. The sixty SD rats were randomly distributed into a modeling group (comprising 50 rats) and a sham operation group (containing 10). The modeling group created the sepsis rat model by means of cecal ligation and perforation. The modeled rats, having achieved success, were divided randomly into WYZSG low-, medium-, and high-dose groups, along with a model group and a positive control group. Rats in the control group, which underwent a sham procedure, had their cecum's opening divided, avoiding any perforation or ligation. Utilizing hematoxylin-eosin (HE) staining, the pathological changes of the rat's heart muscle tissue were observed. The TdT-mediated dUTP nick-end labeling (TUNEL) assay provided evidence of apoptosis in the myocardial cells. To quantify the expression of miR-132-3p and the mRNA levels of UCP2, microtubule-associated protein light chain 3 (LC3-/LC3-), Beclin-1, and caspase-3, real-time quantitative polymerase chain reaction (RT-qPCR) was performed on rat myocardial tissue. The expression of UCP2, LC3-/LC3-, Beclin-1, and caspase-3 proteins in myocardial tissue samples was measured through Western blot analysis. Bortezomib price A dual luciferase reporter assay was applied to demonstrate the regulatory relationship between miR-132-3p and UCP2. A disorder of myocardial fibers was observed in sepsis model rats, accompanied by pronounced inflammatory cell infiltration and the presence of myocardial cell edema and necrosis. Progressive increases in WYZSG administration correlated with a range of enhancements in the myocardial histopathological presentation. Rats in the model, positive control, and WYZSG low-, medium-, and high-dose groups demonstrated reduced survival rates and left ventricular ejection fractions (LVEF), in contrast to the sham group. These groups also displayed heightened myocardial injury scores and apoptosis rates. Relative to the model group, the positive control group and the WYZSG low-, medium-, and high-dose groups experienced increased survival rates and LVEF, and correspondingly decreased myocardial injury scores and apoptosis rates. In the model group, the positive control group, and the WYZSG low-, medium-, and high-dose groups, the expression of miR-132-3p and the mRNA and protein levels of UCP2 in myocardial tissue were lower; meanwhile, the mRNA and protein levels of LC3-/LC3-, Beclin-1, and caspase-3 were higher when compared to the values in the sham operation group. In the context of the model group, the positive control group and the varying WYZSG low-, medium-, and high-dose groups saw an upregulation of miR-132-3p expression, coupled with an elevation in UCP2 mRNA and protein expression, whereas LC3-/LC3-, Beclin-1, and caspase-3 mRNA and protein expression were down-regulated. Excessive autophagy and apoptosis in septic rat myocardial cells were suppressed by WYZSG, ameliorating myocardial injury, potentially through modulation of miR-132-3p/UCP2 expression.
This paper focused on examining the influence of high mobility group box 1 (HMGB1)-induced pulmonary artery smooth muscle cell pyroptosis and immune dysfunction on chronic obstructive pulmonary disease-associated pulmonary hypertension (COPD-PH) in rats, and the intervention approach of Compound Tinglizi Decoction. A random sampling of ninety rats was made for the creation of groups, including the normal group, the model group, the low-dose, medium-dose, and high-dose Compound Tinglizi Decoction groups, and a simvastatin group. A 60-day fumigation schedule, in conjunction with intravascular LPS infusion, was used for the development of the rat COPD-PH model. Rats in the different dosage groups—low, medium, and high—of Compound Tinglizi Decoction received 493, 987, and 1974 g/kg, respectively, by gavage. Simvastatin, at a dosage of 150 mg/kg, was administered orally to the rats in the simvastatin group. After 14 days of observation, the rats' lung function, mean pulmonary artery pressure, and arterial blood gases were measured and analyzed. Rat lung tissue procurement was followed by hematoxylin-eosin (H&E) staining to identify potential pathological changes. To gauge the expression of relevant messenger RNA (mRNA) in lung tissue samples, real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was applied. Western blot (WB) analysis was then undertaken to determine the expression of corresponding proteins in the lung tissues. Lastly, enzyme-linked immunosorbent assay (ELISA) was used to quantify inflammatory factor levels in the rat lung tissue. Lung cell ultrastructural features were studied with a transmission electron microscope. Rats with chronic obstructive pulmonary disease-related pulmonary hypertension (COPD-PH) treated with Compound Tinglizi Decoction had improvements in forced vital capacity (FVC), forced expiratory volume in 0.3 seconds (FEV0.3), FEV0.3/FVC ratio, peak expiratory flow (PEF), respiratory dynamic compliance (Cdyn), arterial oxygen pressure (PaO2), and arterial oxygen saturation (SaO2). This contrasted with diminished resistance of expiration (Re), mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVHI), and arterial carbon dioxide pressure (PaCO2). The protein expressions of HMGB1, the receptor for advanced glycation end products (RAGE), pro-caspase-8, cleaved caspase-8, and gasdermin D (GSDMD) were significantly decreased by the compound Tinglizi Decoction in the lungs of COPD-PH rats, along with the mRNA expression of HMGB1, RAGE, and caspase-8. Pulmonary artery smooth muscle cell pyroptosis processes were hampered by the administration of Compound Tinglizi Decoction. Compound Tinglizi Decoction led to decreased interferon-(IFN-) and interleukin-17(IL-17) levels, and increased interleukin-4(IL-4) and interleukin-10(IL-10) levels in the lung tissues of rats with COPD-PH. Compound Tinglizi Decoction helped ameliorate the degree of damage to the trachea, alveoli, and pulmonary arteries within the lung tissue of COPD-PH rats. gibberellin biosynthesis The influence of Compound Tinglizi Decoction was quantifiably linked to the dosage level. Following administration of Compound Tinglizi Decoction, observable enhancements were seen in lung capacity, pulmonary artery blood pressure, arterial blood gas composition, inflammatory conditions, trachea integrity, alveolar structure, and pulmonary artery disease status. This enhancement is thought to be a result of HMGB1-mediated pyroptosis in pulmonary artery smooth muscle cells and a subsequent disruption of the balance among helper T cells (Th1/Th2, Th17/Treg).
From a ferroptosis perspective, this study explores how ligustilide, the chief active component of Angelicae Sinensis Radix essential oils in traditional Chinese medicine, lessens OGD/R injury in PC12 cells. In vitro OGD/R induction was followed by a 12-hour period of ligustilide administration during reperfusion, after which cell viability was determined using the CCK-8 assay. Intracellular reactive oxygen species (ROS) levels were quantified using DCFH-DA staining. Emotional support from social media Western blotting served as the technique to assess the expression of ferroptosis-related proteins—glutathione peroxidase 4 (GPX4), transferrin receptor 1 (TFR1), and solute carrier family 7 member 11 (SLC7A11)—and ferritinophagy-related proteins—nuclear receptor coactivator 4 (NCOA4), ferritin heavy chain 1 (FTH1), and microtubule-associated protein 1 light chain 3 (LC3). The immunofluorescence staining method was used to analyze the fluorescence intensity of LC3 protein. Glutathione (GSH), malondialdehyde (MDA), and iron (Fe) were measured using a chemiluminescent immunoassay technique. The observation of ligustilide's impact on ferroptosis was achieved through the enhancement of NCOA4 gene expression. In PC12 cells subjected to OGD/R, treatment with ligustilide demonstrated enhanced viability, a reduction in ROS release, lower levels of iron and malondialdehyde, as well as decreased expression of TFR1, NCOA4, and LC3. This was accompanied by increased levels of glutathione and upregulated expression of GPX4, SLC7A11, and FTH1, contrasting the OGD/R-only group’s results. The enhanced expression of the key protein NCOA4 during ferritinophagy caused a partial reversal of ligustilide's inhibitory effect on ferroptosis, hinting that ligustilide might alleviate OGD/R injury to PC12 cells by suppressing ferritinophagy and subsequently inhibiting ferroptosis. The manner in which ligustilide alleviated OGD/R injury within PC12 cells was by curbing the ferroptosis process, which is contingent upon ferritinophagy.