Emodin attenuates cardiomyocyte pyroptosis in doxorubicin-induced cardiotoxicity by directly binding to GSDMD.

BACKGROUND: Doxorubicin (Dox), which is an anticancer drug, has significant cardiac toxicity and side effects. Pyroptosis occurs during Dox-induced cardiotoxicity (DIC), and drug inhibition of this process is one therapeutic approach for treating DIC. Previous studies have indicated that emodin can reduce pyroptosis. However, the role of emodin in DIC and its molecular targets remain unknown. HYPOTHESIS/PURPOSE: We aimed to clarify the protective role of emodin in mitigating DIC, as well as the mechanisms underlying this effect. METHODS: The model of DIC was established via the intraperitoneal administration of Dox at a dosage of 5 mg/kg per week for a span of 4 weeks. Emodin at two different doses (10 and 20 mg/kg) or a vehicle was intragastrically administered to the mice once per day throughout the Dox treatment period. Cardiac function, myocardial injury markers, pathological morphology of the heart, level of pyroptosis and mitochondrial function were assessed. Protein microarray, biolayer interferometry and pull-down assays were used to confirm the target of emodin. Moreover, GSDMD-overexpressing plasmids were transfected into GSDMD-/- mice and HL-1 cells to further verify whether emodin suppressed GSDMD activation. RESULTS: Emodin therapy markedly enhanced cardiac function and reduced cardiomyocyte pyroptosis in mice induced by Dox. Mechanistically, emodin binds to GSDMD and inhibits the activation of GSDMD by targeting the Trp415 and Leu290 residues. Moreover, emodin was able to mitigate Dox-induced cardiac dysfunction and myocardial injury in GSDMD-/- mice overexpressing GSDMD, as shown by increased EF and FS, decreased serum levels of CK-MB, LDH and IL-1ß and mitigated cell death and cell morphological disorder. Additionally, emodin treatment significantly reduced GSDMD-N expression and plasma membrane disruption in HL-1 cells overexpressing GSDMD induced by Dox. In addition, emodin reduced mitochondrial damage by alleviating Dox-induced GSDMD perforation in the mitochondrial membrane. CONCLUSION: Emodin has the potential to attenuate DIC by directly binding to GSDMD to inhibit pyroptosis. Emodin may become a promising drug for prevention and treatment of DIC.

Biomedical Analytics of Four Chinese Medicinals in Treatment of Insomnia Based on Network Pharmacology.

Aim: Our aim is to recommend the appropriate Chinese medicinals in clinical treatment of insomnia, which are suanzaorén (Semen Ziziphi Spinosae), chuanxiong (Rhizoma Chuanxiong), fúlíng (Poria), and báisháo (Radix Paeoniae Alba). Method: Based on network pharmacology, the active molecules and mechanism of these four Chinese medicinals treating insomnia were sought and analyzed. The components of the four Chinese medicinals with potential activity were collected and screened. Moreover, the recollected human disease-related targets were correlated through Cytoscape 3.8.2, and the network diagram of drug component disease targets was drawn. Based on the human protein-protein interaction database, the above network diagram was imported to establish the protein-protein interaction (PPI) and composite target pathway (C-T-P) networks. After selecting important information, the pathway analysis was carried out to show the biological process, core target, and core pathway of insomnia treatment. Result: In this study, 44 active components and 81 drug-disease common targets were obtained; 307 key targets were found in the PPI network; a core cluster composed of 14 nodes and 50 functional associations was found. Conclusion: In summary, the four Chinese medicinals' effective components and main mechanism of in the treatment of insomnia may be related to their participation in the regulation of endocrine. Compared with the existing network pharmacological analysis results of SuanZaoRénTang (Sour Jujube Decoction), which is commonly used in insomnia, they have similar effects on the immune system and HPA axis, while the focus of the four Chinese medicinals is mainly on endocrine regulation, and SuanZaoRénTang (Sour Jujube Decoction) is mainly on anti-inflammatory effect.

Contrasting effects of carbon source recalcitrance on soil phosphorus availability and communities of phosphorus solubilizing microorganisms.

Carbon (C) additions to soil interact through chemical and microbiological processes to cause changes in soil phosphorus (P) availability. However, the response of soil P transformations and relevant microbial communities to C additions having different degrees of recalcitrance remains uncertain. We studied the effects of glucose, hemicellulose and lignin addition on soil P availability, P transformation processes and relevant microbial activity and communities in a P-deficient flooded soil. Lignin significantly increased soil available P concentrations, which was attributed to chemical release of inorganic P and increased alkaline phosphatase activity. Glucose and hemicellulose additions stimulated microbial metabolism of C thereby enhancing microbial demand for P, with increased soil P availability especially in the early incubation period. Glucose or hemicellulose addition changed soil microbial diversity and community composition, leading to enhanced growth and interactions of P solubilizing microorganisms such as Desulfitobacterium, Bacillus and Desulfosporosinus. Our results infer the importance of pH alteration and competitive sorption between PO4 and functional groups of recalcitrant C (e.g., lignin) with Fe/Al (hydr) oxides in regulating soil P availability. Further, the microbial response to labile C additions led to increased P availability in the P-deficient soil. This study provides important mechanistic information to guide microbially-regulated soil P management in agricultural ecosystems.

The add-on effect of Chinese herbal medicine on COVID-19: A systematic review and meta-analysis.

BACKGROUND: Chinese herbal medicine (CHM) is thought to be a potential intervention in the treatment of coronavirus disease (COVID-19). PURPOSE: This study aimed to investigate the efficacy and safety of CHM or CHM combination therapy for COVID-19. STUDY DESIGN: Systematic review and meta-analysis METHODS: We searched for relevant studies in the CNKI, CBM, Wanfang Data, PubMed, Cochrane Library, Embase, and other resources from their inception to April 15, 2020. Randomized controlled trials, cohort studies, and case-control studies on CHM or CHM combination therapy for COVID-19 were included. Meta-analysis was performed according to the Cochrane Handbook. RESULTS: Overall, 19 studies with 1474 patients were included. Meta-analysis showed that the overall clinical effectiveness (OR = 2.67, 95% CI 1.83-3.89, I2 = 0%), improvement in the CT scan (OR = 2.43, 95% CI 1.80-3.29, I2 = 0%), percentage of cases turning to severe/critical (OR = 0.40, 95% CI 0.24-0.67, I2 = 17.1%), reverse transcription-polymerase chain reaction (RT-PCR) negativity rate (OR = 2.55, 95% CI 1.06-6.17, I2 = 56.4%) and disappearance rate of symptoms (fever, cough, and fatigue) were superior by combined CHM treatment of COVID-19. However, there was no statistical difference between the two groups in terms of length of hospital stay (WMD = -0.46, 95% CI -3.87 - 2.95, I2 = 99.5%), and rate of adverse effects (OR = 1.21, 95% CI 0.48-3.07, I2 = 43.5%). The quality of evidence was very low to low. CONCLUSION: The combined treatment of COVID-19 with Chinese and Western medicine may be effective in controlling symptoms and reducing the rate of disease progression due to low quality evidence.

Spasmodic Dysphonia.

Spasmodic dysphonia (SD) is a rare focal laryngeal dystonia. It is characterized by task-specific voice dysfluency resulting from selective intrinsic laryngeal musculature hyperfunction. Symptoms may be attenuated by a sensory trick. Although SD can be seen at times in generalized dystonia syndromes, it is typically a sporadic phenomenon. Involvement of the laryngeal adductor muscles is more common than abductor muscles. The standard treatment of this disorder is with botulinum toxin injection, usually electromyography-guided, which must be repeated periodically as the toxin wears off. A number of non-reversible surgical procedures have also been described to mitigate the symptoms. Other treatment modalities are under investigation, including implantable electrical stimulation devices and deep brain stimulation.

Biodegradation of Petroleum Hydrocarbons by Bacillus subtilis BL-27, a Strain with Weak Hydrophobicity.

The biodegradation of petroleum hydrocarbons has many potential applications and has attracted much attention recently. The hydrocarbon-degrading bacterium BL-27 was isolated from petroleum-polluted soil and was compounded with surfactants to improve biodegradation. Its 16S rDNA and rpoD gene sequences indicated that it was a strain of Bacillus subtilis. Strain BL-27 had extensive adaptability and degradability within a broad range of temperatures (25-50 °C), pH (4.0-10.0) and salinity (0-50 g/L NaCl). Under optimal conditions (45 °C, pH 7.0, 1% NaCl), the strain was able to degrade 65% of crude oil (0.3%, w/v) within 5 days using GC-MS analysis. Notably, strain BL-27 had weak cell surface hydrophobicity. The adherence rate of BL-27 to n-hexadecane was 29.6% with sucrose as carbon source and slightly increased to 33.5% with diesel oil (0.3%, w/v) as the sole carbon source, indicating that the cell surface of BL-27 is relatively hydrophilic. The strain was tolerant to SDS, Tween 80, surfactin, and rhamnolipids at a concentration of 500 mg/L. The cell surface hydrophobicity reduced more with the addition of surfactants, while the chemical dispersants, SDS (50-100 mg/L) and Tween 80 (200-500 mg/L), significantly increased the strain's ability to biodegrade, reaching 75-80%. These results indicated that BL-27 has the potential to be used for the bioremediation of hydrocarbon pollutants and could have promising applications in the petrochemical industry.

Hydrogen Evolution Activity of Ruthenium Phosphides Encapsulated in Nitrogen- and Phosphorous-Codoped Hollow Carbon Nanospheres.

RuPx nanoparticles (NPs) encapsulated in uniform N,P-codoped hollow carbon nanospheres (RuPx @NPC) have been synthesized through a facile route in which aniline-pyrrole copolymer nanospheres are used to disperse Ru ions followed by a gas phosphorization process. The as-prepared RuPx @NPC exhibits a uniform core-shell hollow nanospherical structure with RuPx NPs as the core and N,P-codoped carbon (NPC) as the shell. This strategy integrates many advantages of hollow nanostructures, which provide a conductive substrate and the doping of a nonmetal element. At high temperatures, the obtained thin NPC shell can not only protect the highly active phase of RuPx NPs from aggregation and corrosion in the electrolyte but also allows variation in the electronic structures to improve the charge-transfer rate greatly by N,P codoping. The optimized RuPx @NPC sample at 900 °C exhibits a Pt-like performance for the hydrogen evolution reaction (HER) and long-term durability in acidic, alkaline, and neutral solutions. The reaction requires a small overpotential of only 51, 74, and 110 mV at 10 mA cm-2 in 0.5 m H2 SO4 , 1.0 m KOH, and 1.0 m phosphate-buffered saline, respectively. This work provides a new way to design unique phosphide-doped carbon heterostructures through an inorganic-organic hybrid method as excellent electrocatalysts for HER.