[Ultrafiltration of Angelicae Sinensis Radix and Astragali Radix inhibits ferroptosis and improves pulmonary fibrosis in rats by regulating Nrf2/xCT/GPX4 signaling pathway].

This study aims to investigate the mechanism of ferroptosis mediated by the nuclear factor-E2-related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11, also known as xCT)/glutathione peroxidase 4(GPX4) signaling pathway in radiationinduced pulmonary fibrosis and the intervention effect of Angelicae Sinensis Radix(ASR) and Astragali Radix(AR) ultrafiltration extract. Fifty Wistar rats were randomly divided into five groups, with 10 rats in each group. Except for the blank group without radiation, the rats in each group were anesthetized and subjected to a single local chest irradiation of 40 Gy X-rays once to establish a rat model of radiation-induced pulmonary fibrosis. After radiation, the rats in the intervention groups were orally administered with ASR-AR ultrafiltration extract at doses of 0. 12, 0. 24, and 0. 48 g·kg~(-1), respectively, once a day for 30 days. After 30 days of continuous administration, the levels of oxidative stress indicators superoxide dismutase(SOD) activity, reduced glutathione(GSH),malondialdehyde(MDA), and ferrous ion(Fe~(2+)) in lung tissues of each group were detected by colorimetry. Immunofluorescence was used to detect reactive oxygen species(ROS) fluorescence expression in lung tissues. Hematoxylin-eosin(HE) and Masson staining were performed to observe pathological changes in lung tissues. Immunohistochemistry and Western blot were used to detect the expression levels of Nrf2/xCT/GPX4 signaling pathway and fibrotic proteins in lung tissues. The results showed that compared with the results in the blank group, the levels of Fe~(2+) and MDA in the model group increased, while SOD activity and GSH levels decreased,and ROS levels increased. HE and Masson staining results showed that the structure of lung tissue was seriously damaged, the pulmonary interstitium was significantly proliferated, the alveoli collapsed and consolidated severely, and there were more inflammatory cell aggregates and collagen fiber deposits. Transmission electron microscopy showed that the degree of lung tissue damage in the model group was relatively high, with increased, smaller, and disorganized damaged mitochondria, irregular morphology, shallow matrix,most mitochondria ruptured and shortened, mildly expanded, some mitochondria with increased electron density of the matrix, partial mitochondrial outer membrane rupture, and characteristic changes of ferroptosis-specific mitochondria. Immunohistochemistry showed that the expression of transferrin receptor protein 1(TFR1) in lung tissues was significantly increased, while the expression of GPX4,ferritin heavy chain 1(FTH1), Nrf2, and xCT was significantly decreased. Western blot showed that the expression of α-smooth muscle actin(α-SMA) and collagen Ⅰ protein increased. Compared with the model group, the intervention group with ASR-AR ultrafiltration extract significantly improved lipid peroxidation and antioxidant-related indicators, decreased Fe~(2+) levels, alleviated fibrosis, and decreased the expression of TFR1, α-SMA, and collagen Ⅰ proteins in lung tissues, while increased the expression of GPX4, FTH1, Nrf2, and xCT proteins. In summary, ASR-AR ultrafiltration extract has an ameliorative effect on radiation-induced pulmonary fibrosis, and its mechanism may involve the inhibition of ferroptosis by regulating the Nrf2/xCT/GPX4 signaling pathway.

Role and molecular mechanism of traditional Chinese medicine in preventing cardiotoxicity associated with chemoradiotherapy.

Cardiotoxicity is a serious complication of cancer therapy. It is the second leading cause of morbidity and mortality in cancer survivors and is associated with a variety of factors, including oxidative stress, inflammation, apoptosis, autophagy, endoplasmic reticulum stress, and abnormal myocardial energy metabolism. A number of studies have shown that traditional Chinese medicine (TCM) can mitigate chemoradiotherapy-associated cardiotoxicity via these pathways. Therefore, this study reviews the effects and molecular mechanisms of TCM on chemoradiotherapy-related cardiotoxicity. In this study, we searched PubMed for basic studies on the anti-cardiotoxicity of TCM in the past 5 years and summarized their results. Angelica Sinensis, Astragalus membranaceus Bunge, Danshinone IIA sulfonate sodium (STS), Astragaloside (AS), Resveratrol, Ginsenoside, Quercetin, Danggui Buxue Decoction (DBD), Shengxian decoction (SXT), Compound Danshen Dripping Pill (CDDP), Qishen Huanwu Capsule (QSHWC), Angelica Sinensis and Astragalus membranaceus Bunge Ultrafiltration Extract (AS-AM),Shenmai injection (SMI), Xinmailong (XML), and nearly 60 other herbs, herbal monomers, herbal soups and herbal compound preparations were found to be effective as complementary or alternative treatments. These preparations reduced chemoradiotherapy-induced cardiotoxicity through various pathways such as anti-oxidative stress, anti-inflammation, alleviating endoplasmic reticulum stress, regulation of apoptosis and autophagy, and improvement of myocardial energy metabolism. However, few clinical trials have been conducted on these therapies, and these trials can provide stronger evidence-based support for TCM.

[Repair of peripheral nerve gap with the use of tissue engineering scaffold complex].

OBJECTIVE: To study the feasibility to repair the peripheral nerve gap with tissue engineering scaffold complex that is composed of medical biodegradable material agarose hydrogel and nerve growth factor (NGF). METHODS: Chitosan tube containing agarose hydrogel and NGF was transplanted to bridge a 10 mm gap of injured sciatic nerve in rat. Chitosan duct without agarose hydrogel and NGF was used as negative control, while autograft nerve as positive control. Sixteen weeks after operation, the regeneration of nerve fiber was observed with morphological and immunohistochemistrical methods. RESULT: The number and diameter of regenerating nerve fibers bridged by the scaffold complex of agarose hydrogel and NGF were better than negative control group (P < 0.01) and reached the level of autograft nerve group. CONCLUSIONS: The new type of tissue engineering scaffold complex of agarose hydrogel and NGF may provide a microenvironment, as well as autograft nerve, to promote nerve regeneration. This technique may benefit patients with nerve injury in the future.

Acetyl-L-carnitineameliorates mitochondrial damage and apoptosis following spinal cord injury in rats.

Acetyl-l-carnitine (ALC) facilitates the entry and exit of fatty acids from mitochondria and plays an essential role in energy metabolism. Although ALC is known to exert neuroprotective effects in multiple neurological diseases, its effects on spinal cord injury (SCI)-induced mitochondrial impairments and apoptosis remain unclear. In this study, we aimed to evaluate the putative effects of ALC on mitochondrial dysfunction and apoptosis induced by SCI in a rodent model. Our results indicate that SCI elicits dynamic alternations in the expression of mitochondria-related proteins. Transmission electron microscopy analysis showed that ALC administration abrogated key ultrastructural abnormalities in mitochondria at 24h after SCI by maintaining mitochondrial length, reducing the number of damaged mitochondria, and reversing mitochondrial score (P<0.05 compared with SCI group). In addition, ALC administration maintained the mitochondrial membrane potential and mitochondrial Na(+)-K(+)-ATPase activity following SCI (P<0.05 compared with SCI group). ALC administration reversed the downregulation of mitofusin 1 (Mfn1), Mfn2, Bcl-2, and the upregulation of dynamin-related protein 1 (Drp1), mitochondrial fission 1 (Fis1), Bcl-2-associated X protein (Bax) and cytosol cytochrome c (cyto-CytC) induced by SCI (P<0.05 compared with SCI group). Finally ALC administration greatly reduced the percentage of apoptotic cells compared with the SCI group (P<0.01). In conclusion, our findings demonstrated that ALC ameliorated SCI-induced mitochondrial structural alternations, mitochondrial dysfunction, and apoptosis.