Research status of pathogenesis of anxiety or depression after percutaneous coronary intervention and Traditional Chinese Medicine intervention.

ETHNIC PHARMACOLOGICAL RELEVANCE: Anxiety or depression after percutaneous coronary intervention (PCI) is a common clinical disease. Currently, conventional pharmacotherapy primarily involves the administration of anxiolytic or antidepressant medications in conjunction with anticoagulants, antiplatelet agents, and other cardiovascular drugs. However, challenges such as drug dependence, adverse reactions and related concerns persist in the treatment of this disease. Numerous pertinent studies have demonstrated that Traditional Chinese Medicine (TCM) exhibits significant therapeutic efficacy and distinctive advantages in managing post-PCI anxiety or depression. AIM OF THIS REVIEW: This review attempted to summarize the characteristics of TCM for treating anxiety or depression after PCI, including single Chinese herbs, Chinese medicine monomers, compound TCM prescriptions, TCM patented drugs, and other TCM-related treatment methods, focusing on the analysis of the relevant mechanism of TCM treatment of this disease. METHODS: By searching the literature on treating anxiety or depression after PCI with TCM in PubMed, Web of Science, CNKI, and other relevant databases, this review focuses on the latest research progress of TCM treatment of this disease. RESULTS: In the treatment of anxiety or depression after PCI, TCM exerts significant pharmacological effects such as anti-inflammatory, antioxidant, anti-anxiety or anti-depression, cardiovascular and cerebrovascular protection, and neuroprotection, mainly by regulating the levels of related inflammatory factors, oxidative stress markers, neurotransmitter levels, and related signaling pathways. TCM has a good clinical effect in treating anxiety or depression after PCI with individualized treatment. CONCLUSIONS: TCM has terrific potential and good prospects in the treatment of anxiety or depression after PCI. The main direction of future exploration is the study of the mechanism related to Chinese medicine monomers and the large sample clinical study related to compound TCM prescriptions.

Metal ion assistant transformation strategy to synthesize catechol-based metal-organic frameworks from Ti3C2Tx precursors.

Chemical transformation strategy is capable of fabricating nanomaterials with well-defined structures and fascinating performance via controllable crystallization kinetics in the phase transformation. V2CTx MXene has been used as precursors to fabricate vanadium porphyrin metal-organic frameworks (V-PMOFs) via the coordination of deprotonated carboxylic acid ligands. However, the rational and in-depth exploration of synthesis mechanism with the aim of enriching the variety of MXene (i.e., Ti3C2Tx) and organic ligands (i.e., catechol-based) to design new MOFs is rarely reported. Herein, we have first developed a metal ion assistant transformation strategy to synthesize three-dimensional catechol-based TiCu-HHTP (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) MOFs with a non-interpenetrating SrSi2 (srs) framework using two-dimensional Ti3C2Tx as precursors. The unique synergetic transformation mechanism involves the electron transfer from Ti3C2Tx to electrostatically adsorbed Cu2+ ion for redox reaction, the subsequent Ti-C bond rupture for Ti4+ ion release, and the continuous chelation coordination between Ti4+/Cu2+ and HHTP. Ti3C2Tx precursors and auxiliary metal ion could be rationally substituted by V2CTx and Mn+ (e.g., Ni2+, Co2+, Mn2+, and Zn2+), respectively. This strategy lays the foundation for the design and synthesis of innovative and multifarious MOFs derived from MXene or other unconventional metal precursors.

NIR-Triggered On-Demand Nitric Oxide Release for Enhanced Synergistic Phototherapy of Hypoxic Tumor.

Hypoxia of tumor microenvironments is a major factor restricting tumor treatment, which causes progression and metastasis of tumor. The hypoxic tumor microenvironment not only makes the traditional treatment method, such as chemotherapy, ineffective but also hinders the O2-dependent treatments, such as photodynamic therapy (PDT). Recently, stimuli-responsive nitric oxide (NO) donors have attracted extensive research interest in hypoxic tumor treatment because the NO release process is O2-independent. Besides, NO can distribute more uniformly than drug molecules and more widely than the PDT-generated active species due to its strong diffusion ability (200 µm in cells) and long lifetime (2 s in cells). Encouraged by these advantages, a near infrared light-triggered NO release polymeric nanoplatform (P1-CapNO NPs) was constructed by a thermally sensitive NO release unit, a photothermal unit, and a hydrophilic polyethylene glycol unit. P1-CapNO NPs possess strong absorption in the NIR region (the wavelength of maximal absorption peak was 790 nm with a molar absorption coefficient of 2.4 × 105 M-1 cm-1), great photothermal conversion efficiency (23.8%), and NO release ability (the released NO concentration can reach 1.3 µM) under 808 nm laser irradiation. Owing to these advantages, the great synergistic antitumor effect can be achieved in vitro and in vivo even under the hypoxic environment. The synergistic therapeutic strategy in this work could bypass the obstacles caused by hypoxia in tumor treatment and provide a reference for building a NO-involved therapeutic platform.

Yi-Qi-Jian-Pi formula inhibits hepatocyte pyroptosis through the IDH2-driven tricarboxylic acid cycle to reduce liver injury in acute-on-chronic liver failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Yi-Qi-Jian-Pi formula (YQJPF) is a commonly used traditional Chinese medicine (TCM) compound used to treat acute-on-chronic liver failure (ACLF) in China, but its specific mechanism of action has not been fully clarified. AIM OF THE STUDY: The aim of this study was to determine the effect of YQJPF on liver injury and hepatocyte pyroptosis in rats and further explore its molecular mechanism of action. MATERIALS AND METHODS: This study established carbon tetrachloride (CCl4)-, lipopolysaccharide (LPS)- and D-galactose (D-Gal)-induced in vivo models of ACLF in rats and in vitro LPS-induced hepatocyte injury models. Animal experiments were divided into the following groups: control, ACLF model, groups with different doses of YQJPF (5.4, 10.8, and 21.6 g/kg), and western medicine (methylprednisolone). There were 7 rats in the control group and 11 in the other groups. Serological, immunohistochemical, and pathological analyses were used to observe the effect of YQJPF on the liver of ACLF rats. The protective effect of YQJPF on hepatocytes was further verified by RT-qPCR, western blotting, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and other methods. RESULTS: YQJPF significantly improved liver injury in vivo and in vitro, which depended on the regulation of hepatocyte NLRP3/GSDMD-induced pyroptosis. In addition, we found that mitochondrial membrane potential and ATP production decreased after LPS treatment of hepatocytes, which suggested that YQJPF may improve mitochondrial energy metabolism disorders in hepatocytes. We administered a hepatocyte mitochondrial uncoupling agent, FCCP, to determine whether mitochondrial metabolic disorders affected cell pyroptosis. The results showed that the expression of IL-18, IL-1ß, and NLRP3 proteins increased significantly, indicating that the effect of this drug on hepatocyte pyroptosis may be related to mitochondrial metabolism disorders. We found that YQJPF significantly restored the tricarboxylic acid (TCA) cycle rate-limiting enzyme activity and affected the content of TCA metabolites. Furthermore, we revealed that the IDH2 gene, which plays a unique role in ACLF, is a key factor in the regulation of the mitochondrial TCA cycle and can be upregulated under the action of YQJPF. CONCLUSIONS: YQJPF can inhibit classical pyroptosis in hepatocytes by regulating TCA cycle metabolism, thus alleviating liver injury, and IDH2 may be a potential upstream regulatory target of YQJPF.

Yi-Qi-Jian-Pi formula ameliorates immune function in acute-on-chronic liver failure by upregulating autophagy and mitochondrial biogenesis in CD8+ T lymphocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: A key event in the pathogenesis of acute-on-chronic liver failure (ACLF) is the imbalance in the systemic immune response; immunosuppression in patients with ACLF contributes to poor prognosis. The Yi-Qi-Jian-Pi formula (YQJPF) may improve T lymphocyte immune function in patients with ACLF. AIM OF THE STUDY: To investigate the immune mechanism of YQJPF in vivo and in vitro. MATERIALS AND METHODS: An ACLF rat model was established by injection of CCl4, lipopolysaccharide, and D-galactosamine. We examined the effect of different doses of YQJPF (6.43, 12.87, 25.74 g/kg) on liver injury and immune function in the ACLF rat model. Magnetic-activated cell sorting was used to sort the CD8+ T lymphocytes in the spleen for lymphocyte function detection. In primary CD8+ T lymphocytes and Jurkat cell lines, the expression of mitochondrial function and biogenesis and autophagy related markers were detected using molecular biological methods and flow cytometry analysis. RESULTS: YQJPF improved the peripheral blood lymphocyte count and proportion of CD8+ T lymphocytes in ACLF rats, increased pro-inflammatory factors (IL-2, IFN-λ, and TNF-α), and reduced anti-inflammatory factors (IL-10 and TGF ß1). YQJPF also improved metabolism and mitochondrial homeostasis in CD8+ T lymphocytes, alleviated lymphocyte immune dysfunction by promoting autophagy, upregulated mitochondrial biogenesis by promoting PGC-1α, NRF-1, and TFAM expression, and regulated the relationship between autophagy and mitochondrial biogenesis via PGC-1α. CONCLUSIONS: Our results suggest that YQJPF could improve immune function in a rat model of ACLF, possibly via affecting the homeostasis of lymphatic mitochondria in CD8+ T lymphocytes. YQJPF may enhance lymphocyte mitochondrial biosynthesis and promote lymphocyte autophagy. PGC-1α is a possible upstream regulatory target of YQJPF.

In Vitro and In Vivo Metabolic Activation of Tolterodine Mediated by CYP3A.

Tolterodine (TOL) is an antimuscarinic drug used for the treatment of patients with overactive bladder presenting urinary frequency, urgency, and urge incontinence. During the clinical use of TOL, adverse events such as liver injury took place. The present study aimed at the investigation of the metabolic activation of TOL possibly associated with its hepatotoxicity. One GSH conjugate, two NAC conjugates, and two cysteine conjugates were found in both mouse and human liver microsomal incubations supplemented with TOL, GSH/NAC/cysteine, and NADPH. The detected conjugates suggest the production of a quinone methide intermediate. The same GSH conjugate was also observed in mouse primary hepatocytes and in the bile of rats receiving TOL. One of the urinary NAC conjugates was observed in rats administered TOL. One of the cysteine conjugates was found in a digestion mixture containing hepatic proteins from animals administered TOL. The observed protein modification was dose-dependent. CYP3A primarily catalyzes the metabolic activation of TOL. Ketoconazole (KTC) pretreatment reduced the generation of the GSH conjugate in mouse liver and cultured primary hepatocytes after TOL treatment. In addition, KTC reduced the susceptibility of primary hepatocytes to TOL cytotoxicity. The quinone methide metabolite may be involved in TOL-induced hepatotoxicity and cytotoxicity.

Molecular mechanism of the unusual biphasic effects of the natural compound hinokitiol on iron-induced cellular DNA damage.

Hinokitiol is a natural monoterpene compound found in the heartwood of cupressaceous plants that have anticancer and anti-inflammatory properties. However, few studies have focused on its effect on iron-mediated cellular DNA damage. Here we show that hinokitiol exhibited unusual biphasic effects on iron-induced DNA damage in a molar ratio (hinokitiol/iron) dependent manner in HeLa cells. Under low ratios (<3:1), hinokitiol markedly enhanced DNA damage induced by Fe(II) or Fe(II)-H2O2; However, when the ratios increased over 3:1, the DNA damage was progressively inhibited. We found that the total cytoplasmic and nuclear iron concentration increased as the ratios of hinokitiol/iron increased. However, the cellular level of labile iron pool (LIP) only increased at ratios lower than 3, and the ROS generation is consistent with LIP change. Hinokitiol was found to interact with iron to form lipophilic hinokitiol-iron complexes with different stoichiometry and redox-activity by complementary applications of various analytical methods. Taken together, we propose that the enhancement of iron-induced cellular DNA damage by hinokitiol at low ratios (<3:1) was due to formation of lipophilic and redox-active iron complexes which facilitated cellular iron uptake and •OH production, while the inhibition at ratios higher than 3 was due to formation of redox-inactive iron complexes. These new findings will help us to design more effective drugs for the prevention and treatment of a series of iron-related diseases via regulating the two critical physicochemical factors (lipophilicity and redox activity of iron complexes) by simple natural compounds with iron-chelating properties.

Hypoxia-Activatable Nanovesicles as In Situ Bombers for Combined Hydrogen-Sulfide-Mediated Respiration Inhibition and Photothermal Therapy.

Photothermal therapy (PTT) has emerged as a promising alternative or supplement to cancer treatments. While PTT induces the ablation of solid tumors, its efficiency is hampered by self-recovery within impaired cancer cells through glycolysis and respiration metabolism. Based on this, the introduction of hydrogen sulfide (H2S)-mediated respiration inhibition is a good choice to make up for the PTT limitation. Herein, nanovesicles (NP1) are integrated by a hypoxia-responsive conjugated polymer (P1), polymetric H2S donor (P2), and near-infrared (NIR) light-harvesting aza-BODIPY dye (B1) for the delivery of H2S and synergistic H2S gas therapy/PTT. The scaffold of NP1 undergoes disassembly in the hypoxic environments, thus triggering the hydrolysis of P2 to continuously long-term release H2S. Dependent on the superior photothermal ability of B1, NP1 elicits high photothermal conversion efficiency (η = 19.9%) under NIR light irradiation for PTT. Moreover, NP1 serves as in situ H2S bombers in the hypoxic tumor environment and suppresses the mitochondrial respiration through inhibiting expression of cytochrome c oxidase (COX IV) and cutting off the adenosine triphosphate (ATP) generation. Both in vitro and in vivo results demonstrate good antitumor efficacy of H2S gas therapy/PTT, which will be recommended as an advanced strategy for cancer therapeutics.

Interrelation between homocysteine metabolism and the development of autism spectrum disorder in children.

Evidence is emerging that dysregulation of circulating concentrations of homocysteine, an important intermediate in folate and vitamin B12 metabolism, is associated with autism spectrum disorder (ASD), but comprehensive assessments and correlations with disease characteristics have not been reported. Multivariate ordinal regression and restricted cubic spline (RCS) models were used to estimate independent correlations between serum homocysteine, folate, and vitamin B12 levels and clinical outcomes and severity of children with ASD. After adjusting for confounding factors, serum homocysteine levels were significantly higher in children with ASD than in healthy controls (ß: 0.370; 95% CI: 0.299~0.441, p < 0.001). Moreover, homocysteine had a good diagnostic ability for distinguishing children with ASD from healthy subjects (AUC: 0.899, p < 0.001). The RCS model indicated a positive and linear association between serum homocysteine and the risk of ASD. The lowest quartile of folate was positively associated with ASD severity (OR: 4.227, 95% CI: 1.022~17.488, p = 0.041) compared to the highest quartile, and serum folate showed a negative and linear association with ASD severity. In addition, decreased concentrations of folate and vitamin B12 were associated with poor adaptive behavior developmental quotients of the Gesell Developmental Schedules (p < 0.05). Overall, an increased homocysteine level was associated with ASD in a linear manner and is thus a novel diagnostic biomarker for ASD. Decreased concentrations of folate and vitamin B12 were associated with poor clinical profiles of children with ASD. These findings suggest that homocysteine-lowering interventions or folate and vitamin B12 supplementation might be a viable treatment strategy for ASD.

Effect of Pulmonary Function Training with a Respirator on Functional Recovery and Quality of Life of Patients with Stroke.

A stroke is a sudden onset cerebral blood circulation disorder. It occurs in patients with cerebrovascular disease due to various predisposing factors causing stenosis, occlusion, or rupture of intracerebral arteries, which, in turn, causes acute cerebral blood circulation disturbance and clinically manifests as symptoms and signs of excessive or permanent cerebral dysfunction. It can cause serious harm to patients' physical and mental health. This study aimed to evaluate the effect of Breathe-Link breathing trainers on lung function and the ability to perform activities of daily living in patients with stroke. Sixty patients with stroke were randomly divided into two groups. One group was set as the control group and received routine breathing training. The experimental group received a Breathe-Link trainer based on regular training, with rehabilitation training for 12 weeks as the time node. Respiratory muscle strength, respiratory velocity, respiratory capacity, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and rate in the first second (FEV1/FVC) were used to evaluate the respiratory function of patients, and the Barthel index was used to evaluate the ability to perform activities of daily living. Improvements in respiratory function and daily living ability were compared between the two groups. After 12 weeks of training, respiratory muscle strength, respiratory velocity, respiratory volume, FVC, FEV1, FEV1/FVC, and Barthel index of patients in the two groups improved compared with those before training (P < 0.05), and the improvement in the treatment group was better than that in the control group (P < 0.05). Breathe-Link breathing trainers can improve lung function and the ability to perform activities of daily living in patients with stroke, and its effect is acceptable. It can be recommended for clinical use.

Adverse Effects of Using Metallurgical Slags as Supplementary Cementitious Materials and Aggregate: A Review.

This paper discusses a sustainable way to prepare construction materials from metallurgical slags. Steel slag, copper slag, lead-zinc slag, and electric furnace ferronickel slag are the most common metallurgical slags that could be used as supplementary cementitious materials (SCMs) and aggregates. However, they have some adverse effects that could significantly limit their applications when used in cement-based materials. The setting time is significantly delayed when steel slag is utilized as an SCM. With the addition of 30% steel slag, the initial setting time and final setting time are delayed by approximately 60% and 40%, respectively. Because the specific gravity of metallurgical slags is 10-40% higher than that of natural aggregates, metallurgical slags tend to promote segregation when utilized as aggregates. Furthermore, some metallurgical slags deteriorate the microstructure of hardened pastes, resulting in higher porosity, lower mechanical properties, and decreased durability. In terms of safety, there are issues with the soundness of steel slag, the alkali-silica reaction involving cement and electric furnace ferronickel slag, and the environmental safety concerns, due to the leaching of heavy metals from copper slag and lead-zinc slag.

Exogenous Melatonin Modulates Physiological Response to Nitrogen and Improves Yield in Nitrogen-Deficient Soybean (Glycine max L. Merr.).

Melatonin (MT) is a key plant growth regulator. To investigate its effect at different growth stages on the yield of soybean under nitrogen deficiency, 100 µM MT was applied to soybean supplemented with zero nitrogen (0N), low nitrogen (LN), and control nitrogen (CK) levels, during the plant vegetative growth (V3) and filling (R5) stages. This study revealed that the application of MT mainly enhanced the nitrogen fixation of plants by increasing the root nodule number and provided more substrates for glutamine synthetase (GS) under 0N supply. However, under the LN supply, more ammonium was assimilated through the direct promotion of nitrate reductase (NR) activity by MT. MT enhanced the activity of ammonium-assimilation-related enzymes, such as GOGAT and GDH, and the expression of their coding genes, promoted the synthesis of chlorophyll and amino acids, and increased the photosynthetic capacity under nitrogen deficiency. Exogenous MT directly upregulated the expression of genes involved in the photosynthetic system and stimulated dry-matter accumulation. Thus, MT alleviated the inhibitory effect of nitrogen deficiency on soybean yield. This mitigation effect was better when MT was applied at the V3 stage, and the seed weight per plant increased by 16.69 and 12.20% at 0N and LN levels, respectively. The results of this study provide a new theoretical basis to apply MT in agriculture to improve the resilience of soybean plants to low nitrogen availability.

Reduction and removal of Cr(VI) in water using biosynthesized palladium nanoparticles loaded Shewanella oneidensis MR-1.

In materials science, "green" synthesis has gotten a lot of interest as a reliable, long-lasting, and ecofriendly way to make a variety of materials/nanomaterials, including metal/metal oxide nanomaterials. To accommodate various biological materials, green synthesis of metallic nanoparticles has been used (e.g., bacteria, fungi, algae, and plant extracts). In this work, Shewanella oneidensis MR-1 was used to biosynthesize palladium nanoparticles (bioPd) under aerobic conditions for the Cr(VI) bio-reduction. The size and distribution of bio-Pd are controlled by adjusting the ratio of microbial biomass and palladium precursors. The high cell: Pd ratio has the smallest average particle size of 6.33 ± 1.69 nm. And it has the lowest electrocatalytic potential (-0.132 V) for the oxidation of formic acid, which is 0.158 V lower than commercial Pd/C (5%). Our results revealed that the small size and uniformly distributed extracellular bio-Pd could achieve completely catalytic reduction of 200 mg/L Cr(VI) solution within 10 min, while the commercial Pd/C (5%) need at least 45 min. The bio-Pd materials maintain a high reduction during five cycles. Microorganisms play an important role in the whole process, which can fully disperse palladium nanoparticles, completely reduce Cr(VI), and effectively adsorb Cr(III). This work expands our understanding and provides a reference for the design and development of efficient and green bio-Pd catalysts for environmental pollution control under simple and mild conditions.

An all-in-one nanoplatform with near-infrared light promoted on-demand oxygen release and deep intratumoral penetration for synergistic photothermal/photodynamic therapy.

Hypoxia and high-density extracellular matrix within the tumor microenvironment (TME) strengthens tumor resistance to the oxygen-dependent cancer therapy. Herein, an on-demand oxygen released nanoplatform (MONs/IR780/PFC-O2@BSA, BMIPO) that was triggered by near-infrared (NIR) light combined with TME has been designed for achieving synergistic photothermal/photodynamic therapy with deep intratumoral penetration and oxygen self-sufficiency. Notably, the zeta potential and transmission electron microscope (TEM) results indicated that such "smart" BMIPO nanoplatform possessed good colloidal stability and on-demand TME-specific degradability. This characteristic of the BMIPO nanoplatform allows it to simultaneously achieve high tumor accumulation and deep intratumoral penetration. The results of the O2 loading and release measurements showed that the as- prepared BMIPO possessed excellent O2 reversibly bind/release performance. Furthermore, the photothermal effect of NIR dye (IR780) accelerated the dissociation of TME-responsive BMIPO, as a result, it achieved an on-demand, continuous and complete O2 release to relieve tumor hypoxia during phototherapy. In vitro and in vivo results demonstrated that the as-prepared all-in-one nanoplatform have successfully realized NIR-triggered on-demand O2 release, nanocarrier-mediated glutathione (GSH) reducing, hyperthermia-promoted deep intratumoral penetration and dual-model imaging-guided precise cancer therapy. This work would provide inspiration for the design of nanoplatforms with on-demand release and deep intratumoral penetration for achieving high-efficiency synergistic photothermal/photodynamic therapy in hypoxic tumors.

Improved yield of theaflavin-3,3'-digallate from Bacillus megaterium tyrosinase via directed evolution.

Theaflavin-3,3'-digallate (TFDG) in black tea possesses several health benefits. However, low TFDG yields limit its application. Herein, tyrosinases from Bacillus megaterium (Bmtyrc) were used to synthesize TFDG. To improve the catalytic efficiency of tyrosinase, a directed evolution strategy and a high-throughput screening method was employed. Compared with the wild type, mutant Bmtyrc-3 (N205D/D166E/D167G/F197W) showed 6.46 and 4.91-folds higher specific activity and 51.97- and 1.95-folds higher Vmax values towards epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), respectively. Moreover, Bmtyrc-3 displayed significantly enhanced catalytic efficiencies, and the space-time yield of TFDG was 35.35 g L-1d-1. Bmtyrc-3 presents a broader substrate binding area, caused by a mutation (N205D) encompassing the active site. Changes in the potential of the substrate binding site and hydrogen bonds, and the electrostatic effect on the protein surface resulted in an increased activity of the substrates EGCG and ECG.

Glutathione Protects against Paraquat-Induced Oxidative Stress by Regulating Intestinal Barrier, Antioxidant Capacity, and CAR Signaling Pathway in Weaned Piglets.

Endogenous glutathione (GSH) effectively regulates redox homeostasis in the body. This study aimed to investigate the regulatory mechanism of different dietary levels of GSH supplementation on the intestinal barrier and antioxidant function in a paraquat-induced stress-weaned piglet model. Our results showed that dietary 0.06% GSH supplementation improved the growth performance of weaned piglets under normal and stressful conditions to some degree and decreased the diarrhea rate throughout. Exogenous GSH improved paraquat-induced changes in intestinal morphology, organelle, and permeability and reduced intestinal epithelial cell apoptosis. Moreover, GSH treatment alleviated intestinal oxidative stress damage by upregulating antioxidant (GPX4, CnZnSOD, GCLC, and GCLM) and anti-inflammatory (IL-10) gene expression and downregulating inflammatory cytokines (IFN-γ and IL-12) gene expression. Furthermore, GSH significantly reduced the expression levels of constitutive androstane receptor (CAR), RXRα, HSP90, PP2Ac, CYP2B22, and CYP3A29, and increased the expression levels of GSTA1 and GSTA2 in the jejunum and ileum of paraquat-induced piglets. We conclude that exogenous GSH protects against oxidative stress damage by regulating the intestinal barrier, antioxidant capacity, and CAR signaling pathway.

Photothermal Responsive Singlet Oxygen Nanocarriers for Hypoxic Cancer Cell Ablation.

Hypoxia in aggressively proliferating tumor cells has been demonstrated to restrict the efficiency of photodynamic therapy owing to its oxygen (O2 )-dependent generation of singlet oxygen (1 O2 ) from photosensitizers under light irradiation. To address this problem, we propose a small-molecule dye-based 1 O2 capturing agent, B1. B1 not only bears a near-infrared absorbing azo-boron dipyrromethene backbone, but also has 1,4-dimethylnaphthalene, which facilitates the capture of 1 O2 to form endoperoxide (B1-SO). B1-SO undergoes a reversible reaction via near-infrared photothermal stimulation, thus allowing 1 O2 release. Based on this mechanism, stable B1-SO containing micelles (B1-SO NPs) were prepared and employed as 1 O2 nanocarriers to ablate cancer cells in vitro. Taking advantage of this O2 -independent 1 O2 releasing ability, B1-SO NPs were demonstrated to have efficient cytotoxicity under near-infrared irradiation, especially in a hypoxic environment. The unique O2 -independent 1 O2 generation process of B1-SO NPs suggests they can be used as novel cancer phototherapy agents.

Rational Design of Near-Infrared-Absorbing Pt(II)-Chelated Azadipyrromethene Dyes as a New Generation of Photosensitizers for Synergistic Phototherapy.

Pt(II) photosensitizers are emerging as novel Pt anticancer agents for cancer photodynamic therapy (PDT) to avoid uncontrollable toxicity of cisplatin. However, the application of Pt(II) photosensitizers is limited by tumor hypoxia and the poor penetration depth of excitation light. To overcome these drawbacks, exploiting the next generation of Pt anticancer agents is of urgent need. According to theoretical calculations, novel near-infrared (NIR)-absorbing Pt(II)-chelated azadipyrromethene dyes (PtDP-X, where X = N, C, and S) were designed. Importantly, spin-orbit coupling of the Pt atom could promote the intersystem crossing of a singlet-to-triplet transition for converting oxygen to singlet oxygen (1O2), and the azadipyrromethene skeleton could provide a strong photothermal effect. As expected, PtDP-X exhibited intense NIR absorption and synergistic PDT and photothermal effects with low dark cytotoxicity. Furthermore, water-soluble and biocompatible PtDP-N nanoparticles (PtDP-N NPs) were prepared that achieved effective tumor cell elimination with low side effects under 730 nm light irradiation in vitro and in vivo. This pioneering work could push the exploitation of NIR-absorbing metal-chelated azadipyrromethene dyes, so as to promote the positive evolution of phototherapy agents.

[Astragalus injection mediates autophagy and myocardial remodeling in rats with ischemic cardiomyopathy through calumenin].

OBJECTIVE: To study the effects of astragalus injection on myocardial remodeling, calumenin and autophagy in rats with ischemic cardiomyopathy. METHODS: Thirty-six male SD rats were divided into normal control group, ischemic cardiomyopathy group and astragalus injection group, 12 in each group. Electrocardiogram (ECG) and echocardiography were performed before operation in three groups. Rats in ischemic cardiomyopathy group and astragalus injection group underwent thoracotomy and ligation of coronary artery for 20 minutes, then thoracic cavity was closed after reperfusion. In the astragalus injection group,10 g/kg body weight of Astragalus injection was injected once a week, four times in total. Four weeks after operation, rats in three groups were executed by echocardiography and their hearts were collected for Hematoxylin-Eosin (HE) staining and Van Gieson (VG) staining to observe myocardial pathological changes. Calumenin, LC3-I, LC3-II expressions and LC3-I/LC3-II ratio were detected by Western blot. RESULTS: Compared with ischemic cardiomyopathy group, the echocardiography and myocardial pathology of rats in astragalus injection group changed obviously, and the expressions of calumenin, LC3-I, LC3-II and LC3-I/LC3-II ratio changed significantly (P＜0.01). CONCLUSION: Astragalus injection has apparent inhibitory effect on ventricular remodeling and autophagy of myocardial cells in rats with ischemic cardiomyopathy, which may be mediated by calumenin.

A photothermally-induced HClO-releasing nanoplatform for imaging-guided tumor ablation and bacterial prevention.

Photothermal therapy (PTT) is a cure that can inhibit tumor growth effectively and even remove tumor via photo-induced local hyperthermia. However, its shortcoming lies in the fact that excessive heat is most likely to lead to thermal injury at the epidermis of the tumor region and even the area of the surrounding tissue. As a consequence, the exposure of the thermally-induced wound would result in the increased risk of bacterial infection. To date, few PTT platforms have attached importance to the prevention of bacterial infection at the photothermally-induced wound. Herein, we reported a thermally-sensitive liposome nanosystem (Lipo-B-TCCA) containing aza-BODIPY and trichloroisocyanuric acid, which is conductive for the PTT of tumor and the prevention of bacteria. It is observed that the designed nanoplatform could exhibit remarkable stability, high photothermal conversion efficiency (31.4%), and efficient HClO-releasing ability in vitro and in vivo. Moreover, Lipo-B-TCCA is able to eliminate tumor efficiently via near infrared fluorescence and photothermal imaging guidance with low side effects. Most importantly, Lipo-B-TCCA could prevent the growth of S. aureus in the thermal wound during the process of PTT. The imaging-guided photothermally-induced HClO-releasing PTT nanoplatform for tumor ablation and bacterial prevention shows excellent performance and great potential for biomedical applications.