The preventive effect and mechanism of Dayuanyin in hypoxic pulmonary hypertension through NF-kappaB signaling pathway.

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg.kg-1), and positive control sildenafil group (100 mg.kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% +/- 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF- kappaB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF- kappaB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-kappaB and signal transducer and activator of transcription 3 (STAT3) by DYY.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

Clinical observation of Suhexiang Pills in treatment of patients infected with SARS-CoV-2

Objective To explore the clinical effect and safety of Suhexiang Pills () in the treatment of patients infected with SARS-CoV-2. Methods A total of 192 patients infected with SARS-CoV-2 admitted to 17 hospitals including Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University from December 2022 to January 2023 were randomly divided into control group and treatment group, with 89 patients in the treatment group and 103 in the control group. The patients in control group received basic treatment according to the Diagnosis and Treatment Protocol for COVID-19 (Trial Version 10). The patients in treatment group were oral administered with Suhexiang Pills on the basis of the control group, one pill each time, twice day. The patients in two groups were treated for 5 d. The clinical efficacy of the two groups after treatment was compared. The differences in scores of headache, chest pain, limb pain and inflammatory indexes before and after treatment were compared. Results After treatment, the total clinical effective rate of the treatment group was 95.51%, which was significantly higher than that of the control group (81.55%, P < 0.05). After treatment, headache, chest pain and limb pain scores were significantly decreased in both groups (P < 0.05), the headache score of the treatment group was significantly lower than that of the control group from the first day of treatment (P < 0.05), the chest pain score of the treatment group was significantly lower than that of the control group on the fifth day of treatment (P < 0.05), the limb pain score of the treatment group was significantly lower than that of the control group from the third day of treatment (P < 0.05). After treatment, the levels of C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6) in the two groups were decreased significantly (P < 0.05) and the levels of CRP and IL-6 in the treatment group were significantly lower than those of the control group (P < 0.05). There was no significant difference in the incidence of adverse events between the two groups. Conclusion Suhexiang Pills have a certain effect on headache, chest pain and limb pain, inhibiting the inflammatory response in patients infected with SARS-CoV-2, with good safety.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

Nitric-oxide enriched plasma-activated water inactivates 229E coronavirus and alters antiviral response genes in human lung host cells

The ongoing pandemic caused by the novel coronavirus, SARS-CoV-2, is influencing global health. Moreover, there is a major threat of future coronaviruses affecting the entire world in a similar, or even more dreadful, manner. Therefore, effective and biocompatible therapeutic options against coronaviruses are urgently needed. To address this challenge, medical specialists require a well-informed and safe approach to treating human coronaviruses (HCoVs). Herein, an environmental friendly approach for viral inactivation, based on plasma technology, was considered. A microwave plasma system was employed for the generation of the high amount of gaseous nitric oxide to prepare nitric oxide enriched plasma-activated water (NO-PAW), the effects of which on coronaviruses, have not been reported to date. To determine these effects, alpha-HCoV-229E was used in an experimental model. We found that NO-PAW treatment effectively inhibited coronavirus infection in host lung cells, visualized by evaluating the cytopathic effect and expression level of spike proteins. Interestingly, NO-PAW showed minimal toxicity towards lung host cells, suggesting its potential for therapeutic application. Moreover, this new approach resulted in viral inactivation and greatly improved the gene levels involved in host antiviral responses. Together, our findings provide evidence of an initiation point for further progress toward the clinical development of antiviral treatments, including such coronaviruses. © 2022 The Authors

EZH2 Expression and Response to Neoadjuvant Endocrine Therapy in Estrogen Receptor Positive Invasive Breast Cancer

Background: Neoadjuvant endocrine therapy (NET) is used to treat estrogen receptor (ER) positive invasive breast cancer (IBC). Tumors with Ki67 >10% after 2-4 weeks of NET are considered resistant to endocrine therapy (ET). Although high baseline Ki67 >30% is associated with higher level of ET resistance, many of these patients will still respond to NET. During the COVID- 19 pandemic NET is increasingly being used to defer surgery, hence better and more easily accessible biomarkers are needed to predict likelihood of response to NET. EZH2 is a oncoprotein which can be easily evaluated by immunohistochemistry and overexpression of EZH2 in ER+ IBC has been linked to resistance to ET. We examined the potential utility of EZH2 to predict response to NET . Design: We identified 34 pts with ER+ IBC of ductal or lobular type who received NET. Ki67 IHC was evaluated on pretherapy biopsies and post-therapy resections and scored according to guidelines of the International Ki67 Working Group with a global weighted score. We quantified EZH2 nuclear expression in pretherapy biopsies using a score which multiplied intensity (0=negative,1=weak,2=moderate,3=strong) by % of cells staining at each intensity X100 . Ki67 post therapy <=10% was considered endocrine responsive. Pretherapy Ki67 was dichotomized into >30% and <=30%. Results: The pt age range was 48 to 85 yrs (mean 64 yrs and median 65 yrs). All IBCs had ER expression levels >=80% and aromatase inhibitor was the most frequent NET (76%). Duration of NET ranged from 2-24 months (median 6 months and mean 6.5 months). Twenty pts had a pretherapy Ki67 < or =30 % and 14 had a pretherapy Ki67 >30%. Amongst the 20 pts with pretherapy Ki67<=30%, 11 were endocrine responsive and had a mean pretherapy EZH2 of 88 and median of 85 ( range 2-150) whereas 9 were resistant with a median pretherapy EZH2 of 108 and a median of 104 ( range 42-130). There was no significant difference in mean EZH2 score between groups ( t test p=.0.3971). Amongst the 14 pts with pretherapy Ki67>30% 5 were endocrine responsive and had a mean pretherapy EZH2 of 91 and median EZH2 of 93 (range 45-130) whereas 9 were resistant and had a mean pretherapy EZH2 of 186 and median of 178 ( range 120-240) There was a significant difference in mean EZH2 score between groups ( t test p=.0006). There was a significant association between pretherapy EZH2 score >130 and resistance to NET in pts with Ki67>30% pretherapy (p=.0030). Conclusions: In our pilot study EZH2 protein expression levels were significantly associated with response to NET in pts with high risk (Ki67>30%) ER+ IBC ;high EZH2 expression (>130) in IDC in pretherapy core biopsies was associated with resistance to NET in these pts. During the Covid-19 Pandemic , or in other situations where surgery might be deferred, our results suggest that EZH2 might be useful to predict tumor response to NET in high risk (Ki67>30%) ER+ IBC. (Table Presented).

Eicosapentaenoic acid favorably modulates protein expression in pulmonary endothelial inflammation

INTRODUCTION: SARS-CoV-2 and other viruses can cause endothelial cell (EC) dysfunction in multiple vascular beds, including pulmonary tissue. Infected patients may then develop acute respiratory distress syndrome (ARDS) and cardiovascular (CV) complications. The omega-3 fatty acid eicosapentaenoic acid (EPA) and its bioactive metabolites favorably modulate inflammation and EC function. These benefits of EPA may contribute to reduced CV events as reported in outcome trials (REDUCE-IT). Currently, EPA is being tested in patients with or at risk for COVID-19. This study tested the effects of either EPA pre- or post-treatment on global protein expression in human pulmonary ECs under conditions of inflammation using the cytokine IL-6 to simulate conditions of advanced viral infections. METHODS: Human lung microvascular endothelial cells (HMVEC-L) were pre-treated with either EPA (40 μM) or IL-6 (12 ng/mL) for 2 hr and then treated with IL-6 or EPA, respectively, for 24 hr in media with 2% FBS. Proteomic analysis was performed using LC/MS to assess relative protein expression levels. Only significant (p< 0.05) changes in protein expression between treatment groups >1-fold were analyzed. Expression of soluble intercellular adhesion molecule-1 (sICAM-1) was separately measured with immunochemistry. RESULTS: HMVEC-L pre- and post-treated with EPA during challenge with IL-6 showed significant changes in 100 (49/51 up/down) and 441 (229/212 up/down) proteins, respectively, compared with IL-6 treatment alone. Among the 31 proteins that were significantly modulated by both EPA pre- and post-treatment, thioredoxin reductase 1 increased relative to IL-6 alone, while matrix metalloproteinase 1 and fibronectin both decreased. Other proteins, such as hypoxia up-regulated protein 1, were differentially modulated by EPA relative to IL-6 (increased in pre-treatment, decreased in post-treatment). Finally, EPA significantly reduced sICAM- 1expression by 41% and 12% compared with IL-6 alone in the pre- and post-treatment models, respectively. CONCLUSIONS: These findings indicate that EPA favorably modulates the expression of multiple inflammatory and cytoprotective proteins during inflammation. These studies support a broad anti-inflammatory effect of EPA on pulmonary ECs that may have therapeutic implications for patients at risk for ARDS due to infectious agents including SARS-CoV-2 or other viruses.