Development of a multi-recombinase polymerase amplification assay for rapid identification of COVID-19, influenza A and B.

The coronavirus disease 2019 (COVID-19) pandemic caused extensive loss of life worldwide. Further, the COVID-19 and influenza mix-infection had caused great distress to the diagnosis of the disease. To control illness progression and limit viral spread within the population, a real-time reverse-transcription PCR (RT-PCR) assay for early diagnosis of COVID-19 was developed, but detection was time-consuming (4-6 h). To improve the diagnosis of COVID-19 and influenza, we herein developed a recombinase polymerase amplification (RPA) method for simple and rapid amplification of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 and Influenza A (H1N1, H3N2) and B (influenza B). Genes encoding the matrix protein (M) for H1N1, and the hemagglutinin (HA) for H3N2, and the polymerase A (PA) for Influenza B, and the nucleocapsid protein (N), the RNA-dependent-RNA polymerase (RdRP) in the open reading frame 1ab (ORF1ab) region, and the envelope protein (E) for SARS-CoV-2 were selected, and specific primers were designed. We validated our method using SARS-CoV-2, H1N1, H3N2 and influenza B plasmid standards and RNA samples extracted from COVID-19 and Influenza A/B (RT-PCR-verified) positive patients. The method could detect SARS-CoV-2 plasmid standard DNA quantitatively between 102 and 105 copies/ml with a log linearity of 0.99 in 22 min. And this method also be very effective in simultaneous detection of H1N1, H3N2 and influenza B. Clinical validation of 100 cases revealed a sensitivity of 100% for differentiating COVID-19 patients from healthy controls when the specificity was set at 90%. These results demonstrate that this nucleic acid testing method is advantageous compared with traditional PCR and other isothermal nucleic acid amplification methods in terms of time and portability. This method could potentially be used for detection of SARS-CoV-2, H1N1, H3N2 and influenza B, and adapted for point-of-care (POC) detection of a broad range of infectious pathogens in resource-limited settings.

Carbonyl-Containing Thermally Activated Delayed Fluorescence Emitters for Narrow-Band Electroluminescence.

Carbonyl-containing derivatives show enduring vitality in the field of thermally activated delayed fluorescence (TADF) materials; they can realize high device efficiency by using both singlet and triplet excitons for electroluminescence. Recently, a system based on fused ketone/amine exhibited huge potential for constructing multi-resonance TADF (MR-TADF) emitters, which exhibit higher narrow-band emission than conventional TADF emitters with twisted donor-acceptor (D-A) structure. Herein, we summarize current research progress in both traditional and MR-type ketone derivatives with TADF characteristics for introducing the molecular design strategy of maintaining high device efficiency while keeping narrow-band emission profile. We hope this review can inspire the emergence of more high-performance narrow-band materials.

Cellular Senescence: Ageing and Androgenetic Alopecia.

Androgenetic alopecia (AGA) is the most common type of hair loss and features progressive miniaturization of hair follicles. Generally, the occurrence of AGA has long been thought to be driven by genetic and androgen predisposition. However, increasingly, data proposed ageing and AGA are intimately linked. Elevated senescent cell burden and androgen and oxidative stress-induced senescence mechanisms in ageing may be initial targets to improve AGA. This review summarizes the biological links between ageing and AGA, with special focus on cellular senescence. In addition, we discuss the potential therapeutic strategies for improving cellular senescence in AGA, such as inhibiting dermal papilla cells and hair follicle stem cells senescence driven by androgen and reactive oxygen species, removing senescent cell, and reducing senescence-associated secretory phenotype (SASP).

Introducing Spiro-locks into the Nitrogen/Carbonyl System towards Efficient Narrowband Deep-blue Multi-resonance TADF Emitters.

The current availability of multi-resonance thermally activated delayed fluorescence (MR-TADF) materials with excellent color purity and high device efficiency in the deep-blue region is appealing. To address this issue in the emerged nitrogen/carbonyl MR-TADF system, we propose a spiro-lock strategy. By incorporating spiro functionalization into a concise molecular skeleton, a series of emitters (SFQ, SOQ, SSQ, and SSeQ) can enhance molecular rigidity, blue-shift the emission peak, narrow the emission band, increase the photoluminescence quantum yield by over 92 %, and suppress intermolecular interactions in the film state. The referent CZQ without spiro structure has a more planar skeleton, and its bluer emission in the solution state redshifts over 40 nm with serious spectrum broadening and a low PLQY in the film state. As a result, SSQ achieves an external quantum efficiency of 25.5 % with a peak at 456 nm and a small full width at half maximum of 31 nm in a simple unsensitized device, significantly outperforming CZQ. This work discloses the importance of spiro-junction in modulating deep-blue MR-TADF emitters.

Omentin1 ameliorates myocardial ischemia-induced heart failure via SIRT3/FOXO3a-dependent mitochondrial dynamical homeostasis and mitophagy.

BACKGROUND: Adipose tissue-derived adipokines are involved in various crosstalk between adipose tissue and other organs. Omentin1, a novel adipokine, exerts vital roles in the maintenance of body metabolism, insulin resistance and the like. However, the protective effect of omentin1 in myocardial ischemia (MI)-induced heart failure (HF) and its specific mechanism remains unclear and to be elucidated. METHODS: The model of MI-induced HF mice and oxygen glucose deprivation (OGD)-injured cardiomyocytes were performed. Mice with overexpression of omentin1 were constructed by a fat-specific adeno-associated virus (AAV) vector system. RESULTS: We demonstrated that circulating omentin1 level diminished in HF patients compared with healthy subjects. Furthermore, the fat-specific overexpression of omentin1 ameliorated cardiac function, cardiac hypertrophy, infarct size and cardiac pathological features, and also enhanced SIRT3/FOXO3a signaling in HF mice. Additionally, administration with AAV-omentin1 increased mitochondrial fusion and decreased mitochondrial fission in HF mice, as evidenced by up-regulated expression of Mfn2 and OPA1, and downregulation of p-Drp1(Ser616). Then, it also promoted PINK1/Parkin-dependent mitophagy. Simultaneously, treatment with recombinant omentin1 strengthened OGD-injured cardiomyocyte viability, restrained LDH release, and enhanced the mitochondrial accumulation of SIRT3 and nucleus transduction of FOXO3a. Besides, omentin1 also ameliorated unbalanced mitochondrial fusion-fission dynamics and activated mitophagy, thereby, improving the damaged mitochondria morphology and controlling mitochondrial quality in OGD-injured cardiomyocytes. Interestingly, SIRT3 played an important role in the improvement effects of omentin1 on mitochondrial function, unbalanced mitochondrial fusion-fission dynamics and mitophagy. CONCLUSION: Omentin1 improves MI-induced HF and myocardial injury by maintaining mitochondrial dynamical homeostasis and activating mitophagy via upregulation of SIRT3/FOXO3a signaling. This study provides evidence for further application of omentin1 in cardiovascular diseases from the perspective of crosstalk between heart and adipose tissue.

Aminoacylase-1 plays a key role in myocardial fibrosis and the therapeutic effects of 20(S)-ginsenoside Rg3 in mouse heart failure.

We previously found that the levels of metabolite N-acetylglutamine were significantly increased in urine samples of patients with heart failure (HF) and in coronary artery ligation (CAL)-induced HF mice, whereas the expression of its specific metabolic-degrading enzyme aminoacylase-1 (ACY1) was markedly decreased. In the current study, we investigated the role of ACY1 in the pathogenesis of HF and the therapeutic effects of 20(S)-ginsenoside Rg3 in HF experimental models in vivo and in vitro. HF was induced in mice by CAL. The mice were administered Rg3 (7.5, 15, 30 mg · kg-1· d-1, i.g.), or positive drug metoprolol (Met, 5.14 mg · kg-1· d-1, i.g.), or ACY1 inhibitor mono-tert-butyl malonate (MTBM, 5 mg · kg-1 · d-1, i.p.) for 14 days. We showed that administration of MTBM significantly exacerbated CAL-induced myocardial injury, aggravated cardiac dysfunction, and pathological damages, and promoted myocardial fibrosis in CAL mice. In Ang II-induced mouse cardiac fibroblasts (MCFs) model, overexpression of ACY1 suppressed the expression of COL3A1 and COL1A via inhibiting TGF-ß1/Smad3 pathway, whereas ACY1-siRNA promoted the cardiac fibrosis responses. We showed that a high dose of Rg3 (30 mg · kg-1· d-1) significantly decreased the content of N-acetylglutamine, increased the expression of ACY1, and inhibited TGF-ß1/Smad3 pathway in CAL mice; Rg3 (25 µM) exerted similar effects in Ang II-treated MCFs. Meanwhile, Rg3 treatment ameliorated cardiac function and pathological features, and it also attenuated myocardial fibrosis in vivo and in vitro. In Ang II-treated MCFs, the effects of Rg3 on collagen deposition and TGF-ß1/Smad3 pathway were slightly enhanced by overexpression of ACY1, whereas ACY1 siRNA partially weakened the beneficial effects of Rg3, suggesting that Rg3 might suppress myocardial fibrosis through ACY1. Our study demonstrates that N-acetylglutamine may be a potential biomarker of HF and its specific metabolic-degrading enzyme ACY1 could be a potential therapeutic target for the prevention and treatment of myocardial fibrosis during the development of HF. Rg3 attenuates myocardial fibrosis to ameliorate HF through increasing ACY1 expression and inhibiting TGF-ß1/Smad3 pathway, which provides some references for further development of anti-fibrotic drugs for HF.

The viral distribution and pathological characteristics of BALB/c mice infected with highly pathogenic Influenza H7N9 virus.

BACKGROUND: The highly pathogenic Influenza H7N9 virus is believed to cause multiple organ infections. However, there have been few systematic animal experiments demonstrating the virus distribution after H7N9 virus infection. The present study was carried out to investigate the viral distribution and pathological changes in the main organs of mice after experimental infection with highly pathogenic H7N9 virus. METHODS: Infection of mice with A/Guangdong/GZ8H002/2017(H7N9) virus was achieved via nasal inoculation. Mice were killed at 2, 3, and 7 days post infection. The other mice were used to observe their illness status and weight changes. Reverse transcription polymerase chain reaction and viral isolation were used to analyse the characteristics of viral invasion. The pathological changes of the main organs were observed using haematoxylin and eosin staining and immunohistochemistry. RESULTS: The weight of H7N9 virus-infected mice increased slightly in the first two days. However, the weight of the mice decreased sharply in the following days, by up to 20%. All the mice had died by the 8th day post infection and showed multiple organ injury. The emergence of viremia in mice was synchronous with lung infection. On the third day post infection, except in the brain, the virus could be isolated from all organs (lung, heart, kidney, liver, and spleen). On the seventh day post infection, the virus could be detected in all six organs. Brain infection was detected in all mice, and the viral titre in the heart, kidney, and spleen infection was high. CONCLUSION: Acute diffuse lung injury was the initial pathogenesis in highly pathogenic H7N9 virus infection. In addition to lung infection and viremia, the highly pathogenic H7N9 virus could cause multiple organ infection and injury.

Absent atherosclerotic risk factors are associated with carotid stiffening quantified with ultrafast ultrasound imaging.

OBJECTIVES: To evaluate carotid stiffening in participants without conventional cardiovascular risk factors (CVRFs) by using ultrafast pulse wave velocity (ufPWV). METHODS: The present study enrolled 517 participants without conventional CVRFs (CVRF-Free total population). Subjects in this population were defined as current non-smokers with untreated blood pressure < 140/90 mmHg, fasting blood glucose (FBG) < 7.0 mmol/L, total cholesterol (TC) < 6.2 mmol/L, low-density lipoprotein cholesterol < 4.1 mmol/L, and high-density lipoprotein cholesterol ≥ 1.0 mmol/L. Participants in the subgroup with optimal CVRFs (CVRF-Optimal subgroup; n = 188) were defined as having blood pressure < 120/80 mmHg, TC < 5.2 mmol/L, and FBG < 5.6 mmol/L. Clinical interviews, physical examinations, serum draw, carotid intima-media thickness (cIMT), and ufPWV were evaluated. Adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression models were used. RESULTS: Carotid stiffening was present in 46.2-54.5% of CVRF-Free subjects. Age, male sex, and body mass index (BMI) were independently associated with carotid stiffening in both the CVRF-Free total population and CVRF-Optimal subgroup (OR for age = 1.10-1.11, OR for male sex = 2.65-7.19, OR for BMI = 1.34-1.62; p < 0.05). Carotid stiffening was associated with TC only in the CVRF-Free total population (OR for TC = 1.84; p = 0.034). CONCLUSIONS: Many CVRF-Free individuals have carotid stiffening. ufPWV for atherosclerotic stiffening aids the assessment of early atherogenesis and may further clarify the true status of healthy adults without CVRFs. KEY POINTS: • CVRF-Optimal individuals have a lower carotid stiffness than CVRF-Free populations. • ufPWV is a quantitative predictor for the early assessment of AS. • Absent major CVRFs cannot be considered low risk for carotid stiffening and atherosclerosis.

Novel in vivo and in vitro mechanisms of positive inotropic effect of atractylodin.

This study was to investigate the inotropic effect of atractylodin and its underlying mechanism. The cardiac pressure-volume loop (P-V loop), Langendroff-perfused isolated rat heart, patch-clamp, Ca2+ transient and western blot techniques were used. The results demonstrated that atractylodin (3 mg/kg, ip) remarkably increased the left ventricular stroke work, cardiac output, stroke volume, heart rate, ejection fraction, end-systolic pressure, peak rates of rise and fall of left ventricular pressures (+dP/dtmax , -dP/dtmax ), the slopes of end-systolic pressure-volume relationship (also named as end-systolic elastance, Ees) and reducing end-systolic volume and end-diastolic volume in the in vivo rat study. Also, atractylodin (3 mg/kg, ip) significantly decreased diastolic blood pressure and the arterial elastance (Ea) without significant systolic blood pressure change. In addition, atractylodin (0.1, 1, 10 µmol/L) also increased the isolated rat heart left ventricular developed pressure which is the difference between the systolic and diastolic pressure in non-pacing and pacing modes. Furthermore, JMV-2959 (1 µmol/L), a ghrelin receptor unbiased antagonist, blocked the increased left ventricular developed pressure of atractylodin in isolated rat hearts. Finally, atractylodin (5 µmol/L) increased the amplitude of Ca2+ transient by enhancing SERCA2a activity, the sarcoplasmic reticulum Ca2+ content and the phosphorylation of phospholamban at 16-serine. These results demonstrated that atractylodin had a positive inotropic effect by enhancing SERCA2a activity which might be mediated by acting ghrelin receptor in myocardium. In conclusion, atractylodin which had the positive inotropic effect and decreased diastolic blood pressure might serve as an agent for the treatment of heart failure in clinical settings.

[Investigation, analysis and identification of disease of Gastrodia elata f. glauca].

Fungal disease is an important factor restricting the healthy development of Gastrodia elata industry. The control of fungal disease in G. elata is an important issue in production. This paper makes a detailed investigation on the current situation of G. elata disease in China through statistics on the failure rate, rotten pit rate and occurrence rate of G. elata disease in the main producing areas of China. It was found that G. elata disease was mainly infected from the top bud and junction, causing the occurrence rate of disease was 6%-17%, and the yield decreased by 10%-30%. The 23 dominant fungi were isolated from 18 typical G. elata disease samples. Through identification of colony morphology, mycelium morphology, spore morphology and genetic characteristics, they were finally identified as 13 species, belonging to 7 families and 7 genera. Trichoderma harzianum, Ilyonectria sp. and Ilyonectria destructans are the most frequently separated. Their isolation frequency were 22.22%,16.67%,16.67% respectively. Ilyonectria sp. and I. destructans were the first time isolated from G. elata disease samples. They may be the main pathogens causing soil-borne diseases of G. elata. T. harzianum has certain potential as Gastrodia biocontrol bacteria. This study can provide a theoretical basis for the research and development of control technology of Gastrodia fungi disease.

Carotid stiffness and atherosclerotic risk: non-invasive quantification with ultrafast ultrasound pulse wave velocity.

OBJECTIVES: To evaluate the value of ultrafast pulse wave velocity (ufPWV) for the quantitative assessment of carotid stiffness and its associated with atherosclerosis (AS) risk. METHODS: The present study included 233 patients with hyperlipoidaemia (AS risk group) and 114 healthy adults as the control group. The carotid (n = 694) intima-media thickness (cIMT), pulse wave velocity-beginning of systole (PWV-BS) and pulse wave velocity-end of systole (PWV-ES) were measured on sample images. Differences, distributive characteristics and correlation evaluation were assessed in patients (ages 18-29, 30-39, 40-49, 50-59, 60-69 and ≥70) and carotids (control group vs AS risk group). RESULTS: The cIMT, PWV-BS and PWV-ES increased with age; PWV-ES and cIMT showed an early significant increase in the 30-39 years group, whereas PWV-BS displayed a significant increase at 40-49 years compared with the 18- to 29-years group. Besides, PWV-ES correlated well with age compared with PWV-BS and cIMT. For carotid level, cIMT, PWV-BS and PWV-ES measurements were higher in the AS risk group compared with control. To compare the value of ufPWV and cIMT in early AS assessment, we subdivided groups into cIMT subgroups using a cut-off thickness of 0.050 cm. PWV-ES measurements were higher in the AS risk group compared with the control in the 0.040-0.050 cm (not thickened) and 0.051-0.060 cm (thickened) cIMT subgroups. CONCLUSIONS: Carotid ufPWV measurement at PWV-ES is a novel modality for the early diagnosis and quantitative assessment of arterial stiffness associated with atherosclerotic risk. KEY POINTS: • ufPWV technique is real-time and well repeatable for assessing carotid stiffness • ufPWV measurements increase and correlate well with age • PWV-ES is a quantitative predictor for the early assessment of AS.

Liguzinediol Enhances the Inotropic Effect of Rat Hearts via Inhibition of Protein Phosphatase (PP1 and PP2A) Activities.

It has been demonstrated that liguzinediol (2,5-dihydroxymethyl-3,6-dimethylpyrazine, LZDO), a derivative of ligustrazine from Ligusticum wallichii Franch, exerts positive inotropy in isolated rat heart mediated by the sarcoplasmic reticulum Ca-ATPase (SERCA2a). Here, we further explore the underlying mechanism of the positive inotropic effect of LZDO in rat hearts. In vivo and ex vivo rat heart experiments, biochemistry, and Western blot techniques were used to analyze the rat heart contractility, and SERCA2a activity, phospholamban (PLB) phosphorylation, and protein phosphatase (PP1 and PP2A) activities in rat left ventricular myocytes, respectively. LZDO (20 mg/kg) significantly increased the inotropy of rat heart in vivo. In isolated rat heart experiments, LZDO (100 µM) restored the decreased inotropy induced by caffeine (0.5 mM); however, calyculin A (4 nM), an inhibitor of PP1 and PP2A, eliminated the inotropic effect of LZDO (100 µM). Moreover, LZDO (1, 10, and 100 µM) significantly enhanced SERCA2a activity and increased the levels of phosphorylated PLB on both serine-16 (Ser-16) and threonine-17 (Thr-17). In addition, LZDO (100 µM) significantly inhibited the activities of PP1 and PP2A. The positive inotropic effects of LZDO on in vivo and ex vivo rat hearts seem to be mediated through inhibition of PP1/PP2A, which may suppress dephosphorylated PLB and enhance SERCA2a activity. LZDO may prove effective in treating heart failure in clinical settings based on its unique biological mechanism.

Unveiling the role of silicon in boosting electrochemical carbon dioxide reduction via carbon nanotubes@bismuth silicates.

Electrochemical CO2 reduction reaction (CO2RR) is one of the most attractive measures to achieve the carbon neutral goal by converting CO2 into high-value chemicals such as formate. Si in Bi silicates is promising to enhance CO2 adsorption and activation due to its strong oxygenophilicity. Whereas, its role in boosting CO2RR via the cheap Bi-based catalysts is still not clear. Herein, we design CNT@Bi silicates catalyst, demonstrating the highest FEHCOOH of 96.3 % at -0.9 V vs. reversible hydrogen electrode with good stability. Through X-ray photoelectron spectroscopy (XPS), in-situ Attenuated Total Reflectance-Fourier Transform Infrared (In-situ ATR-SEIRAS) experiments, and Density Functional Theory (DFT) calculations, the role of Si in Bi silicates was unveiled: tuning the electronic structure of Bi, weakening the Bi-O bond, and strengthening electron transfer from Bi to CO2, thereby promoting the generation of CO2*- and *OCHO intermediates. Additionally, carbon nanotubes (CNTs) promote not only the conductivity but also the generation of abundant oxygen vacancies in CNT@Bi silicates evidenced by the electron transfer from CNT to Bi silicates from XPS results. Further, the CNT@Bi silicates endows it with the highest electrochemical activation area. These findings suggest the effectiveness of Si in Bi silicates and structure tuning to design highly selective CO2RR catalyst for HCOOH production.

The adjuvant treatment role of ω-3 fatty acids by regulating gut microbiota positively in the acne vulgaris.

Objectives:We aimed to explore the potential role of omega-3 (ω-3) fatty acids on acne vulgaris by modulating gut microbiota.Materials and Methods:We randomly divided the untreated acne patients into two groups with or without ω-3 fatty acids intervention for 12 weeks. The Sprague Dawley (SD) rats with acne model were given isotretinoin, ω-3 fatty acids or their combination respectively. Then the colonic contents samples of the drug intervention SD rats were transferred to the pseudo sterile rats with acne model. The severity of the disease was assessed by the Global Acne Grading System (GAGS) score of the patients, and the swelling rate of auricle and the pathological section of the rat with acne model. The 16S rDNA gene sequencing was performed to detect the alteration of the gut microbiota.Results:ω-3 fatty acids could increase the diversity of the gut microbiota and regulate the flora structure positively both in the patients and rats, increase the abundance of butyric acid producing bacteria and GAGS score in the patients, and alleviate the inflammation and comedones of rats.Conclusion:Supplementation of ω-3 fatty acids could alleviate the inflammation of acne vulgaris by increasing the abundance of butyric acid producing bacteria.

Tryptophan, an important link in regulating the complex network of skin immunology response in atopic dermatitis.

Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease, of which the pathogenesis is a complex interplay between genetics and environment. Although the exact mechanisms of the disease pathogenesis remain unclear, the immune dysregulation primarily involving the Th2 inflammatory pathway and accompanied with an imbalance of multiple immune cells is considered as one of the critical etiologies of AD. Tryptophan metabolism has long been firmly established as a key regulator of immune cells and then affect the occurrence and development of many immune and inflammatory diseases. But the relationship between tryptophan metabolism and the pathogenesis of AD has not been profoundly discussed throughout the literatures. Therefore, this review is conducted to discuss the relationship between tryptophan metabolism and the complex network of skin inflammatory response in AD, which is important to elucidate its complex pathophysiological mechanisms, and then lead to the development of new therapeutic strategies and drugs for the treatment of this frequently relapsing disease.

Inhibition of OAT1/3 and CMPF uptake attenuates myocardial ischemia-induced chronic heart failure via decreasing fatty acid oxidation and the therapeutic effects of ruscogenin.

Chronic heart failure (CHF) as a long-term disease is highly prevalent in elder people worldwide. Early diagnosis and treatments are crucial for preventing the development of CHF. Herein, we aimed to identify novel diagnostic biomarker, therapeutic target and drug for CHF. Untargeted metabolomic analysis has been used to characterize the different metabolomic profile between CHF patients and healthy people. Meanwhile, the targeted metabolomic study demonstrated the elevation of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) in the serum of CHF patients and coronary artery ligation-induced CHF mice. Subsequently, we firstly observed that elevation of CMPF impaired cardiac function and aggravated myocardial injury by enhancing fatty acid oxidation (FAO). Interestingly, inhibition of responsible transporters organic anion transporter 1/3 (OAT1/3) has been found to decrease the CMPF level, and suppress FAO-related key protein expressions including peroxisome proliferator-activated receptor alpha, peroxisome proliferative activated receptor-α, carnitine palmitoyl transferase 1, and malonyl CoA decarboxylase in coronary artery ligation-induced CHF mice. Meanwhile, the inhibitor of OAT1/3 presented an excellent improvement in cardiac function and histological injury. Based on the above findings, molecular docking was adopted to screen the potential therapeutic drug targeting OAT1/3, and ruscogenin (RUS) exhibited a great binding affinity with OAT1 and OAT3. Next, it was verified that RUS could remarkedly decrease the expression of OAT1/3 and CMPF levels in heart tissue of CHF mice, as well as suppress the expression of FAO-related proteins. What's more, RUS can effectively improve cardiac function, myocardial fibrosis and morphological damage. Collectively, this study provided a potential metabolic marker CMPF and novel target OAT1/3 for CHF, which were demonstrated to be involved in FAO. And RUS was identified as a potential anti-FAO drug for CHF by regulating OAT1/3.

Plantamajoside alleviates hypoxia-reoxygenation injury through integrin-linked kinase/c-Src/Akt and the mitochondrial apoptosis signaling pathways in H9c2 myocardial cells.

Myocardial ischemia-reperfusion injury(MIRI) is one of the common complications after myocardial infarction surgery, Oxidative stress is among the main mechanisms of myocardial ischemia-reperfusion injury. Plantamajoside (PMS), the main effective ingredient in the genus Plantain, has been reported to possess an antioxidation, anti-inflammatory and anti-apoptosis role. However, whether PMS can attenuate myocardial ischemia-reperfusion injury is not yet known. Herein, we explored the effects of PMS on hypoxia-reoxygenation (H/R) injury in H9c2 cardiomyocytes and the underling molecular mechanisms of the treatment. Network pharmacological analysis screened the top 31 key genes in the treatment of MIRI disease treated with PMS, and the result of molecular docking further illustrated the roles that the PMS play in the treatment of MIRI through its interference with integrin-linked kinase (ILK) target protein. PMS was not cytotoxic in the concentration range of 5-40 µM and increased cell survival after H/R injury in a concentration-dependent manner without affecting proliferation or growth. PMS significantly reduced the levels of lactate dehydrogenase, malonic dialdehyde, reactive oxygen species and cell apoptosis, and increased soperoxide dismutase activity compared with those of the H/R injury group. PMS promoted the protein and mRNA expression of ILK and Bcl-2, the protein expression of p-Akt, and reduced the protein and mRNA expression of Bax, Caspase-3, and Cytochrome c, the protein expression of p-c-Src. PMS has protective effects against H/R injury in H9c2 cells, and its protective mechanism may be related to reactive oxygen species clearance, activation of the ILK/c-Src/Akt pathway and inhibition of the mitochondrial apoptosis.

Effect of Proprietary Chinese Medicine on Coronary Microvascular Dysfunction in Patients with Microvascular Angina: A Systematic Review and Meta-Analysis.

Background: Microvascular angina (MVA) has received increasing attention and interest in recent years, but there are still some shortcomings in the diagnosis and treatments at current stage. In recent years, several studies have confirmed the efficacy of proprietary Chinese medicines (PCMs) in improving MVA symptoms; however, there is no systematic review and meta-analysis to comprehensively assess the efficacy of PCMs in this area. Objective: Investigating the clinical efficacy of proprietary Chinese medicines for treating MVA and coronary microvascular function. Methods: We looked up articles from January 1, 2012, to the present from eight databases. Then, we screened the literature and followed the 2019 version 2 of Cochrane risk of bias tool for systematic review. The Stata/SE 15.0 software was used for the meta-analysis. Results: There are 21 studies, including 1,641 patients who were included in this review. According to the results, the combination of PCMs and conventional MVA treatment was able to further enhance clinical efficacy [RR = 1.28, 95% CI (1.20, 1.36), p < 0.001], prolong the time of duration on the treadmill exercise testing (TET) [SMD = 1.49, 95% CI (0.63, 2.36), p = 0.001] and improve levels of NO [SMD = -1.77 95% CI (-2.11, -1.43), p < 0.001]. At the same time, PCMs could also decrease the microvascular resistance index (IMR) [SMD = -1.79, 95% CI (-2.58, -1.00), p < 0.001)], serum level of hs-CRP [SMD = -1.21, 95% CI (-1.84, -0.58), p < 0.001] and ET-1 [SMD = -1.77 95% CI (-2.11, -1.43), p < 0.001]. Regards to medication safety, a total of 27 adverse events occurred, including 10 cases in the intervention group and 17 cases in the control group. Conclusion: The study suggests that the combination of PCMs and conventional MVA treatment enhances clinical efficacy and could better improve coronary microvascular function. In the future, we expect more high-quality, randomized, double-blind clinical studies to validate the safety, and efficacy of PCMs to provide valuable evidence-based medicine (EBM) for the treatment of MVA with PCMs.

Activation of NRF2 blocks HIV replication and apoptosis in macrophages.

Abnormal oxidative stress caused by human immunodeficiency virus (HIV) infection affects viral replication and causes non-acquired immune deficiency syndrome-related complications in infected individuals. The transcription factor NFE2-related factor 2 (NRF2), a key regulator of oxidative stress, responds to abnormal oxidative stress by regulating the expression of NRF2-dependent cytoprotective genes. The present study aimed to determine whether inhibition of oxidative stress could control HIV replication and improve cell survival. In this study, the NRF2 activator, methyl bardoxolone, was used to treat cells for HIV infection. The effects on HIV replication and apoptosis pathways were confirmed by NRF2 activation or knockdown. The results showed that NRF2 activation could block HIV replication in macrophages before the integration phase and inhibited the expression of apoptotic pathways in virus-exposed macrophages. The study presents an unconventional anti-viral strategy of activation antioxidant response for HIV infection blocking.

Ginsenoside Rd promotes omentin secretion in adipose through TBK1-AMPK to improve mitochondrial biogenesis via WNT5A/Ca2+ pathways in heart failure.

Ginsenoside Rd is an active ingredient in Panax ginseng CA Mey and can be absorbed into the adipose tissue. Adipokines play an important role in the treatment of cardiovascular diseases. However, the potential benefit of Rd on heart failure (HF) and the underlying mechanism associated with the crosstalk between adipocytes and cardiomyocytes remains to be illustrated. Here, the results identified that Rd improved cardiac function and inhibited cardiac pathological changes in transverse aortic constriction (TAC), coronary ligation (CAL) and isoproterenol (ISO)-induced HF mice. And Rd promoted the release of omentin from the adipose tissue and up-regulated omentin expression in lipopolysaccharide (LPS)-induced 3T3-L1 adipocytes. Further, Rd could increase TBK1 and AMPK phosphorylation in adipocytes. And also, the TBK1-AMPK signaling pathway regulated the expression of omentin in LPS-induced adipocytes. Moreover, the omentin mRNA expression was significantly decreased by TBK1 knockdown in LPS-induced 3T3-L1 adipocytes. Additionally, molecular docking and SPR analysis confirmed that Rd had a certain binding ability with TBK1, and co-treatment with TBK1 inhibitors or TBK1 knockdown partially abolished the effect of Rd on increasing the omentin expression and the ratio of p-AMPK to AMPK in adipocytes. Moreover, we found that circulating omentin level diminished in the HF patients compared with healthy subjects. Meanwhile, the adipose tissue-specific overexpression of omentin improved cardiac function, reduced myocardial infarct size and ameliorated cardiac pathological features in CAL-induced HF mice. Consistently, exogenous omentin reduced mtROS levels and restored ΔψM to improve oxygen and glucose deprivation (OGD)-induced cardiomyocytes injury. Further, omentin inhibited the WNT5A/Ca2+ signaling pathway and promoted mitochondrial biogenesis function to ameliorate myocardial ischemia injury. However, WNT5A knockdown inhibited the impairment of mitochondrial biogenesis and partially counteracted the cardioprotective effect of omentin in vitro. Therefore, this study indicated that Rd promoted omentin secretion from adipocytes through the TBK1-AMPK pathway to improve mitochondrial biogenesis function via WNT5A/Ca2+ signaling pathway to ameliorate myocardial ischemia injury, which provided a new therapeutic mechanism and potential drugs for the treatment of HF.