Shengxian decoction improves lung function in rats with bleomycin-induced idiopathic pulmonary fibrosis through the inhibition of PANoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Shengxian decoction (SXD) is a classic Chinese medicinal formula that can effectively improve clinical symptoms and quality of life and delay disease progression in idiopathic pulmonary fibrosis (IPF) patients; however, the underlying mechanisms remain unclear. AIM OF THE STUDY: This study aimed to observe PANoptosis in bleomycin-induced IPF and to assess the efficacy and mechanism of action of SXD in the treatment of IPF. MATERIALS AND METHODS: Fifty SD rats were randomly divided into the sham, IPF, IPF + pirfenidone (PFD), IPF + SXD-medium dose (SXD-M), and IPF + SXD-low dose (SXD-L) groups. Lung function analysis and microcomputed tomography imaging of the rats with IPF treated with oral pirfenidone or oral SXD for 28 days were performed. Hematoxylin and eosin (HE) staining and Masson's trichrome staining were used to observe pathological lung damage. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum levels of IL-1ß, IL-18, TNF-α, and IFN-γ. Pyroptosis, apoptosis, and necroptosis were assessed using TUNEL, TUNEL/caspase-1, and PI fluorescence staining, respectively. GSDMD, caspase-3, and MLKL were examined by immunohistochemistry. The expression of fibrin-, ZBP1-, pyroptosis-, apoptosis-, and necroptosis-related proteins in the lung tissue was determined by western blotting. RESULTS: SXD normalized lung function in rats with bleomycin-induced IPF and reduced serum inflammatory factor levels and lung tissue fibrosis. The underlying mechanism of action involves the inhibition of pyroptosis pathway proteins, such as NLRP3, caspase-1, cleaved caspase-1, and GSDMD; apoptotic pathway proteins, such as Bax, Bcl-2, cleaved caspase-3, and caspase-3; and necroptosis pathway proteins, such as RIPK1, RIPK3, p-MLKL and MLKL. These pathways are modulated by the PANoptosis initiator ZBP1. Notably, the efficacy of SXD is concentration dependent, with a medium dose exhibiting superior effectiveness compared to a low dose. CONCLUSION: Bleomycin induced PANoptosis in the lung tissue of rats with IPF. Additionally, SXD effectively delayed or reversed the early pathological changes in bleomycin-induced pulmonary fibrosis by inhibiting PANoptosis.

Electrode switch-an efficient induced approach for self-activation of an electrode toward water splitting.

In this paper, we provide a novel electrode switch (ES) method to improve the stability of the alkaline electrolyzer toward water splitting. The voltage of the alkaline electrolyzer consisting of commercial Ni mesh electrodes utilizing the ES mode exhibits extreme stability because highly active Ni oxide(hydroxide) with oxygen defects is in situ formed during the hydrogen evolution reaction (HER) polarization process.

Degradation and phosphorus immobilization treatment of organophosphate esters hazardous waste by Fe-Mn bimetallic oxide.

Organophosphate esters (OPEs) waste is difficult to dispose effectively because of its stability and the potential risk of P element. In this study, taking one typical organic extractant of tributyl phosphate (TBP) as an example, we proposed a strategy to treat OPEs inspired by chemical looping combustion (CLC) technology-oxygen carrier immobilization process (OCIP), aiming at efficient TBP degradation and simultaneous P immobilization. Adopting Fe-Mn bimetallic oxide (FMBO) as oxygen carrier, an almost 100% P immobilization efficiency was achieved under recommended conditions which were obtained by response surface methodology. Meanwhile, gaseous products released from TBP degradation, e.g., non-methane hydrocarbon, was lower than the maximum allowable emission concentration limit. Further characterizations implied that P-species released from reaction process were mainly immobilized as stable inorganic forms of metaphosphate, phosphate and pyrophosphate. On the basis of identifying degradation intermediates, we proposed a possible degradation pathways. FMBO as an oxygen carrier provided sufficient oxygen molecules for flameless combustion of OCIP process. Electron paramagnetic resonance measurement confirmed the existence of oxygen vacancies on FMBO surface, which contributed to the formation of •O2-. Oxidation by oxygen molecules and •O2- attack resulted in the degradation and mineralization of TBP, with simultaneously achieving P stabilization.

Tributyl phosphate degradation and phosphorus immobilization by MnO2: Reaction condition optimization and mechanism exploration.

The treatment of tributyl phosphate (TBP) extractant waste from specific industry, eg., nuclear industry, is a great challenge due to its stability and high environmental risk of phosphorus-containing species releasing. Inspired by chemical looping combustion (CLC) technology, a MnO2-assisted thermal oxidation strategy is proposed for TBP degradation and simultaneously P immobilization. Under recommended reaction conditions of 220 °C, 10 g MnO2 mL-1 TBP and 3 h reaction duration, a high P immobilization efficiency of 93.99% is achieved. Material characterization results indicate that P is mainly immobilized in the form of Mn2P2O7, which greatly reduces the environmental risk of P-containing species. TBP degradation intermediates are further identified by thermogravimetric-gas chromatography-mass spectrometry (TG-GC-MS), liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), which facilitates understanding of reaction mechanisms as well as proposing possible pathways of TBP degradation. It is suggested that MnO2 provides essential oxygen as oxygen carrier for flameless combustion. Meantime, MnO2 reduction leads to the generation of Mn(III) species. The existence of oxygen vacancy in MnO2 also facilitates •O2- radical generation. Under flameless combustion and attacks of Mn(III) and •O2-, TBP is firstly degraded into intermediates and finally mineralized into CO2 and H2O, while P is mainly immobilized as pyrophosphate.

Astragaloside IV Prevents Memory Impairment in D-galactose-induced Aging Rats Via the AGEs/RAGE/ NF-κB Axis.

BACKGROUND: We investigated the effects of astragaloside IV (AS-IV) on memory function in aging rats mimicked by D-galactose administration and explored the potential molecular mechanisms. METHODS: Twenty-seven male rats were randomly divided into control group (N = 9), model group (N = 9), and AS-IV treated group (N = 9). Aging model was stimulated by D-galactose (400 mg/kg/d, i.p., dissolved in saline) for 8 weeks in rats. The general status of the rats was observed weekly. Learning and memory function was determined using the eight-arm radical maze and step-down test. Pathological changes in the hippocampal CA1 region were determined by hematoxylin and eosin staining. Organ indexes, superoxide dismutase (SOD) activity and malonaldehyde (MDA) content in the serum were measured. Expression of advanced glycation end products (AGEs), receptor for AGEs (RAGE), nuclear factor-κB (NF-κB), interleukin (IL)-6, IL-1ß and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay, real-time polymerase chain reaction or western blotting. RESULTS: AS-IV improved the general status of the aging rats induced by D-galactose, prevented the impairment of memory function, organ indexes, and the pathological damage of the hippocampus. From the prospective of oxidative stress, AS-IV increased sera SOD activity and decreased MDA content. Additionally, AS-IV also reduced the inflammatory response by reducing hippocampal IL-1ß, TNF-α, and IL-6 expression. Importantly, AS-IV prevented D-galactose-induced expression of AGEs, RAGE and NF-κB in the hippocampus. CONCLUSION: AS-IV could prevent D-galactose-induced aging and memory impairment in rats, likely via regulation of inflammatory response, which was modulated by AGEs/RAGE/NF-κB axis.

Danggui Buxue Tang Ameliorates Bleomycin-Induced Pulmonary Fibrosis by Suppressing the TLR4/NLRP3 Signaling Pathway in Rats.

OBJECTIVE: To investigate the effects of Danggui Buxue Tang (DBT) on rats with pulmonary fibrosis (PF) and the underlying mechanism. METHODS: Sixty specific pathogen-free (SPF) male Sprague-Dawley (SD) rats were randomly divided into 4 groups: control, PF, prednisone treatment, and DBT treatment. Intratracheal instillation of bleomycin (BLM) was performed to establish a PF rat model. DBT was administered to PF rats concurrently for 2 weeks. Lung samples were then collected for HE and Masson staining after pulmonary function testing, and semiquantitative analysis for the degree of alveolitis and fibrosis was performed using the Szapiel and Ashcroft score systems. Myeloperoxidase (MPO) activity, hydroxyproline (HYP), hyaluronic acid (HA), and inflammatory cytokine content were measured. Western blotting was performed to detect fibrotic marker and TLR4/NLRP3 signaling pathway changes. RESULTS: Oral administration of DBT attenuated weight loss, survival rate, and pulmonary index. Lung histopathologic lesions were also reduced. DBT inhibited PF by decreasing the secretion of inflammatory cytokines and collagen deposition. Specifically, DBT reduced tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), IL-6, HYP, alpha-smooth muscle actin (α-SMA), collagen I, and collagen III levels. Corollary experiments identified a potential mechanism involving suppression of TLR4/MyD88/NF-κB signaling pathway activation and the NLRP3/ASC/caspase-1 axis, the downstream regulatory pathway. CONCLUSION: DBT exhibited a potent effect on BLM-induced PF rats by inhibiting the TLR4/NLRP3 signaling pathway. Thus, DBT alleviates pulmonary inflammation to inhibit fibrotic pathology and should be considered as a candidate for the clinical treatment of PF.

Danggui Buxue Tang ameliorates bleomycin-induced pulmonary fibrosis in rats through inhibiting transforming growth factor-ß1/Smad3/ plasminogen activator inhibitor-1 signaling pathway.

OBJECTIVE: To investigate the effect of Danggui Buxue Tang (DBT), a decoction from Traditional Chinese Medicine, on bleomycin-induced pulmonary fibrosis in rats, and to propose the possible underlying mechanism. METHODS: Forty male Sprague-Dawley rats were randomly divided into sham group, model group, prednisone group and DBT group. Pulmonary fibrosis rat model was established by intratracheal injection with bleomycin. Body weight and lung index were monitored. Histopathologic examination and collagen deposition were determined using Hematoxylin and eosin (HE) and Masson's trichrome staining. Immunohistochemistry staining was applied to observe the expression of alpha-smooth muscle actin (α-SMA). mRNA expression of α-SMA, collagen Ⅰ and collagen Ⅲ were measured by real-time fluorescence quantitative PCR (RT-qPCR). Inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and IL-1ß in serum were detected by Enzyme-linked immunosorbent assay. Alkali hydrolysis method was conducted to investigate the content of hydroxyproline (HYP). Transforming growth factor-ß1 (TGF-ß1), Smad3 and plasminogen activator inhibitor-1 (PAI-1) protein level were examined by Western blot assay. RESULTS: DBT significantly reduced the severity of bleomycin-induced pulmonary fibrosis and inflammation as indicated by minimizing the lost of weight, and by lowering the levels of lung index, inflammation score, Ashcroft score, collagen volume fraction (%), HYP, α-SMA, collagen Ⅰ, collagen Ⅲ, TNF-α, IL-6, IL-1ß, TGF-ß1, Smad3 and PAI-1, consistent with the effect of prednisone. CONCLUSION: Our findings suggest that DBT is able to ameliorate the pulmonary fibrosis, the possible mechanism may involve inhibition of pulmonary inflammation and collagen deposition, possibly via suppressing TGF-ß1/Smad3/PAI-1 signaling pathway.

[Optimization of high-cell-density fermentation process for S-adenosyl-L-methionine production].

Poor stability existed in the anaphase of the high-cell-density fermentation of Saccharomyces crevisiae for S-adenosyl-L-methionine (SAM) production in 5 L fermentor. To improve the fermentation stability, we studied the addition of diammonium hydrogen phosphate, sodium glutamate and adenosine disodium triphosphate into glucose feeding solution. Study of four fed-batch cultures showed that, after 34 h fermentation, when dry cell weight reached 100 g/L, the addition of 50 g pre-L-methionine and glucose feeding with 10 g/L adenosine disodium triphosphate was optimal for SAM production. Under this condition, after 65.7 h fermentation, both the dry cell weight and the yield of SAM reached the maximum, 180 g/L and 17.1 g/L respectively.

[Pre-L-methionine feeding strategy for S-adenosyl-L-methionine fermentative production].

The yield of S-adenosyl-L-methionine (SAM) on high-cell-density fermentation by saccharomyces cerevisiae is mostly affected by the feeding strategy of pre-L-methionine. The mutant strain SAM0801 that could accumulate more SAM was used in this study. Six high-cell-density fermentation experiments in 5 L fermentor were investigated to get the optimal feeding time and amount of L-methionine. The results showed that when 40 g L-methionine was added in the fermentor after 30 h fermentation, a dry cell weight of 100 g/L was achieved. Under this condition, after 58 h fermentation, both the dry cell weight and the yield of SAM reached the maximum, 168 g/L and 14.48 g/L respectively.