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.

Study on potential common action and mechanism of Reduning Injection against SARS, MERS and COVID-19 based on network pharmacology and molecular docking technology.

Objective To explore the potential common mechanism and active ingredients of Reduning Injection against SARS, MERS and COVID-19 through network pharmacology and molecular docking technology. Methods The TCMSP database was used to retrieve the chemical components and targets of Artemisiae Annuae Herba, Lonicerae Japonicae Flos and Gardeniae Fructus in Reduning Injection. The gene corresponding to the target was searched by UniProt database, and Cytoscape 3.8.2 was used to build a medicinal material-compound-target (gene) network. Three coronavirus-related targets were collected in the Gene Cards database with the key words of "SARS""MERS" and "COVID-19", and common target of three coronavirus infection diseases were screened out through Venny 2.1.0 database. The common targets of SARS, MERS and COVID-19 were intersected with the targets of Reduning Injection, and the common targets were selected as research targets. Protein-protein interaction (PPI) network map were constructed by Cytoscape3.8.2 software after importing the common targets into the STRING database to obtain data. R language was used to carry out GO biological function enrichment analysis and KEGG signaling pathway enrichment analysis, histograms and bubble charts were drew, and component-target-pathway network diagrams was constructed. The key compounds in the component-target-pathway network were selected for molecular docking with important target proteins, novel coronavirus (SARS-CoV-2) 3CL hydrolase, and angiotensin-converting enzyme II (ACE2). Results 31 active compounds and 207 corresponding targets were obtained from Reduning Injection. 2 453 SARS-related targets, 805 MERS-related targets, 2 571 COVID-19-related targets, and 786 targets for the three diseases. 11 common targets with Reduning Injection: HSPA5, CRP, MAPK1, HMOX1, TGFB1, HSP90AA1, TP53, DPP4, CXCL10, PLAT, PRKACA. GO function enrichment analysis revealed 995 biological processes (BP), 71 molecular functions (MF), and 31 cellular components (CC). KEGG pathway enrichment analysis screened 99 signal pathways (P < 0.05), mainly related to prostate cancer, fluid shear stress and atherosclerosis, hepatocellular carcinoma, proteoglycans in cancer, lipid and atherosclerosis, human T-cell leukemia virus 1 infection, MAPK signaling pathway, etc. The molecular docking results showed that the three core active flavonoids of quercetin, luteolin, and kaempferol in Reduning Injection had good affinity with key targets MAPK1, PRKACA, and HSP90AA1, and the combination of the three active compounds with SARS-CoV-2 3CL hydrolase and ACE2 was less than the recommended chemical drugs. Conclusion Reduning Injection has potential common effects on the three diseases of SARS, MERS and COVID-19. This effect may be related to those active compounds such as quercetin, luteolin, and kaempferol acting on targets such as MAPK1, PRKACA, HSP90AA1 to regulate multiple signal pathways and exert anti-virus, suppression of inflammatory storm, and regulation of immune function.Copyright © 2022 Drug Evaluation Research. All rights reserved.

Drug discovery for coronavirus disease 2019 based on text mining and biomedical databases.

Objective Based on text mining technology and biomedical database, data mining and analysis of coronavirus disease 2019 (COVID-19) were carried out, and COVID-19 and its main symptoms related to fever, cough and respiratory disorders were explored. Methods The common targets of COVID-19 and its main symptoms cough, fever and respiratory disorder were obtained by GenCLiP 3 website, Gene ontology in metascape database (GO) and pathway enrichment analysis, then STRING database and Cytoscape software were used to construct the protein interaction network of common targets, the core genes were screened and obtained. DGIdb database and Symmap database were used to predict the therapeutic drugs of traditional Chinese and Western medicine for the core genes. Results A total of 28 gene targets of COVID-19 and its main symptoms were obtained, including 16 core genes such as IL2, IL1B and CCL2. Through the screening of DGIdb database, 28 chemicals interacting with 16 key targets were obtained, including thalidomide, leflunomide and cyclosporine et al. And 70 kinds of Chinese meteria medica including Polygonum cuspidatum, Astragalus membranaceus and aloe. Conclusion The pathological mechanism of COVID-19 and its main symptoms may be related to 28 common genes such as CD4, KNG1 and VEGFA, which may participate in the pathological process of COVID-19 by mediating TNF, IL-17 and other signal pathways. Potentially effective drugs may play a role in the treatment of COVID-19 through action related target pathway.Copyright © 2022 Tianjin Press of Chinese Herbal Medicines. All Rights Reserved.

Managing severe warm autoimmune haemolytic anaemia after the SARS-Cov- 2 vaccine with emergency splenectomy and eculizumab

Autoimmune haemolytic anaemia (AIHA) is rare but described after the SARS-CoV- 2 Pfizer-BioNTech vaccine. We present a case of severe refractory warm AIHA after this vaccine, managed with emergency splenectomy and complement inhibition with eculizumab. A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and AIHA (aged 6 years) presented to his district general hospital with jaundice, dark urine, fatigue and chest discomfort 48 h after the first dose of SARS-CoV- 2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed haemoglobin (Hb) of 70 g/L and bilirubin of 98 mumol/L, which was treated as AIHA. The patient initially responded to prednisolone (1 mg/kg, 60 mg) but subsequently deteriorated and failed to respond to second-line rituximab (375 mg/m2) and two units of packed red blood cells (PRBC). By day 29 the patient had developed life-threatening anaemia culminating in a Hb of 35 g/L (after transfusion), lactate dehydrogenase (LD) of 1293 units/L and bilirubin of 228 mumol/L. This necessitated an immediate transfer to our tertiary centre for specialist support. Further investigations revealed a haptoglobin <0.1 g/L and direct antiglobulin test (DAT) strongly positive for IgG (4+) and negative for C3d. The peripheral blood film showed severe anaemia, nucleated red cells, anisocytosis and spherocytes with no autoagglutination, schistocytes or platelet clumps. Thrombocytopaenia (platelets 49 +/- 109/L) was present. Differentials were ruled out, such as paroxysmal nocturnal haemoglobinuria and heparin-induced thrombocytopaenia. HIV and hepatitis serology were negative, as were adenovirus, cytomegalovirus and Epstein-Barr virus PCR assays. A CT showed splenomegaly of 15.5 cm. Urinalysis found urobilinogen and bilirubin at high concentrations and negative urinary haemosiderin. Together, the investigations were consistent with warm AIHA. On day 29, four units of PRBC were transfused alongside 100 mg methylprednisolone and 1 g/kg IVIG. On day 30 the patient deteriorated despite the escalated treatment: Hb had only increased to 54 g/L, bilirubin was 200 mumol/L and LD was rising. Considering this life-threatening fulminant haemolysis, an emergency splenectomy was performed. This slowed haemolysis but did not completely ameliorate it: by day 33 the patient had received 15 units of PRBC. Thus, eculizumab, a terminal complement pathway inhibitor, was trialled to arrest intravascular haemolysis, alongside rituximab, repeat IVIG 1 g/kg, prednisolone 40 mg and tacrolimus 2 mg. This showed a favourable response, requiring less frequent transfusions and settling haemolysis. This case highlights the rare complication of warm AIHA with the SARS-CoV- 2 Pfizer-BioNTech vaccine, the use of emergency splenectomy for disease control, and the potential of eculizumab for refractory cases.

COVID-19 Impact on Host at Pathophysiological and Cellular Level

The COVID-19 pandemic has put millions of lives at risk. SARS-CoV-2, the causative agent of COVID-19, primarily targets the respiratory system. The subsequent immune reactions may cause severe inflammation. The severe infection, disease progression, and dysregulated immune response can affect various sites of the body. Moreover, angiotensin-converting enzyme-2, the cellular receptor for viral entry, is expressed by different organs of the body. This hints at the possibility of virus infection and manifestations at miscellaneous sites. Indeed, COVID-19 patients with comorbidities like cardiovascular diseases, hypertension, diabetes, chronic kidney diseases, obesity, and immunosuppressive conditions have shown either increased disease severity, delayed viral clearance, or higher mortality. COVID-19 treatment with steroids and associated comorbidities like diabetes have also been shown to make people susceptible to lethal secondary infections like mucormycosis. Therefore, COVID-19 patients should be vigilantly monitored for symptoms and underlying conditions. In this regard, we comprehensively explained the aspects of COVID-19-associated comorbidities. As dysregulated inflammation is a key factor in worsening the disease conditions, we have also summarized the important molecular pathways associated with SARS-CoV-2 associated inflammation. This could further help researchers find targets for reducing COVID-19 inflammation and achieve better outcomes in comorbidity associated patients. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals

Background/Objectives: Emerging evidence suggests that complement system infection-dependent hyperactivation may worsen COVID-19 outcome. We investigated the role of predicted high impact variants -referred as Qualifying Variants (QVs) -of complement system genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease. Method(s): Exploiting Whole-Exome Sequencing (WES) data and 56 complement system genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (age >= 60 y.o.) and 56,885 European individuals from the gnomAD database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized COVID-19 patients. Result(s): We found an enrichment of QVs in three genes (MASP1, COLEC10 and COLEC11), which belong to the lectin pathway, in the asymptomatic cohort. Moreover, individuals with QVs showed lower serum levels of Masp1 and of prothrombin activity compared to controls while no differences were observed for CH50 and AH50 levels that measure the activity of classical and alternative complement pathways, respectively. Finally, integrative analyses of genome-wide association study and expression quantitative loci traits data showed a correlation between polymorphisms associated with asymptomatic COVID-19 and decreased expression of MASP1, COLEC11 and COLEC10 genes in lung tissue. Conclusion(s): This study suggests that rare genetic variants can protect from severe COVID-19 by mitigating the activation of lectin pathway and prothrombin activity.

HSPA5 Promotes Attachment and Internalization of Porcine Epidemic Diarrhea Virus through Interaction with the Spike Protein and the Endo-/Lysosomal Pathway.

Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the global pig industry. The swine enteric coronavirus spike (S) protein recognizes various cell surface molecules to regulate viral infection. In this study, we identified 211 host membrane proteins related to the S1 protein by pulldown combined with liquid-chromatography tandem mass spectrometry (LC-MS/MS) analysis. Among these, heat shock protein family A member 5 (HSPA5) was identified through screening as having a specific interaction with the PEDV S protein, and positive regulation of PEDV infection was validated by knockdown and overexpression tests. Further studies verified the role of HSPA5 in viral attachment and internalization. In addition, we found that HSPA5 interacts with S proteins through its nucleotide-binding structural domain (NBD) and that polyclonal antibodies can block viral infection. In detail, HSPA5 was found to be involved in viral trafficking via the endo-/lysosomal pathway. Inhibition of HSPA5 activity during internalization would reduce the subcellular colocalization of PEDV with lysosomes in the endo-/lysosomal pathway. Together, these findings show that HSPA5 is a novel PEDV potential target for the creation of therapeutic drugs. IMPORTANCE PEDV infection causes severe piglet mortality and threatens the global pig industry. However, the complex invasion mechanism of PEDV makes its prevention and control difficult. Here, we determined that HSPA5 is a novel target for PEDV which interacts with its S protein and is involved in viral attachment and internalization, influencing its transport via the endo-/lysosomal pathway. Our work extends knowledge about the relationship between the PEDV S and host proteins and provides a new therapeutic target against PEDV infection.

Efficient degradation of benzalkonium chloride by FeMn-CA300 catalyst activated persulfate process: Surface hydroxyl potentiation mechanism and degradation pathway.

The consumption of disinfectants increased dramatically with the outbreak of the COVID-19 epidemic. Benzalkonium chloride (DDBAC), a cationic surfactant disinfectant for import and export cargoes, is used for effective degradation method. For DDBAC effective degradation, polyhedral Fe-Mn bimetallic catalyst of Prussian blue analogue (FeMn-CA300) was novelty developed for rapid peroxymonosulfate (PMS) activation. Results showed that the Fe/Mn redox and surface hydroxyl groups in the catalyst played an important role in the DDBAC-enhanced degradation. The removal effectiveness of 10 mg L-1 DDBAC was up to 99.4% in 80 min under the initial pH = 7, catalyst dosage of 0.4 g L-1, and PMS concentration of 15 mmol L-1. In addition, FeMn-CA300 had a wide pH applicability range. The results indicated that hydroxyls, sulfate radicals, and singlet oxygen could effectively improve the degradation efficiency, where sulfate radicals played a crucial role. Finally, the corresponding degradation path of DDBAC was further provided according to GC-MS results. The results of this study provide new insights into the degradation of DDBAC, thereby highlighting the great potential of FeMnca300/PMS to control refractory organic compounds in the aqueous phase.

Porcine Deltacoronavirus Infection Disrupts the Intestinal Mucosal Barrier and Inhibits Intestinal Stem Cell Differentiation to Goblet Cells via the Notch Signaling Pathway.

Goblet cells and their secreted mucus are important elements of the intestinal mucosal barrier, which allows host cells to resist invasion by intestinal pathogens. Porcine deltacoronavirus (PDCoV) is an emerging swine enteric virus that causes severe diarrhea in pigs and causes large economic losses to pork producers worldwide. To date, the molecular mechanisms by which PDCoV regulates the function and differentiation of goblet cells and disrupts the intestinal mucosal barrier remain to be determined. Here, we report that in newborn piglets, PDCoV infection disrupts the intestinal barrier: specifically, there is intestinal villus atrophy, crypt depth increases, and tight junctions are disrupted. There is also a significant reduction in the number of goblet cells and the expression of MUC-2. In vitro, using intestinal monolayer organoids, we found that PDCoV infection activates the Notch signaling pathway, resulting in upregulated expression of HES-1 and downregulated expression of ATOH-1 and thereby inhibiting the differentiation of intestinal stem cells into goblet cells. Our study shows that PDCoV infection activates the Notch signaling pathway to inhibit the differentiation of goblet cells and their mucus secretion, resulting in disruption of the intestinal mucosal barrier. IMPORTANCE The intestinal mucosal barrier, mainly secreted by the intestinal goblet cells, is a crucial first line of defense against pathogenic microorganisms. PDCoV regulates the function and differentiation of goblet cells, thereby disrupting the mucosal barrier; however, the mechanism by which PDCoV disrupts the barrier is not known. Here, we report that in vivo, PDCoV infection decreases villus length, increases crypt depth, and disrupts tight junctions. Moreover, PDCoV activates the Notch signaling pathway, inhibiting goblet cell differentiation and mucus secretion in vivo and in vitro. Thus, our results provide a novel insight into the mechanism underlying intestinal mucosal barrier dysfunction caused by coronavirus infection.

The coronavirus recombination pathway.

Recombination is thought to be a mechanism that facilitates cross-species transmission in coronaviruses, thus acting as a driver of coronavirus spillover and emergence. Despite its significance, the mechanism of recombination is poorly understood, limiting our potential to estimate the risk of novel recombinant coronaviruses emerging in the future. As a tool for understanding recombination, here, we outline a framework of the recombination pathway for coronaviruses. We review existing literature on coronavirus recombination, including comparisons of naturally observed recombinant genomes as well as in vitro experiments, and place the findings into the recombination pathway framework. We highlight gaps in our understanding of coronavirus recombination illustrated by the framework and outline how further experimental research is critical for disentangling the molecular mechanism of recombination from external environmental pressures. Finally, we describe how an increased understanding of the mechanism of recombination can inform pandemic predictive intelligence, with a retrospective emphasis on SARS-CoV-2.

Multi-omic and comparative analyses revealed monocyte-derived alpha-defensin-1 correlated with COVID-19 severity and inhibited SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological pathogen of coronavirus disease 2019 (COVID-19), a highly contagious disease, spreading quickly and threatening global public health. The symptoms of COVID-19 vary from mild reactions to severe respiratory distress or even fatal outcomes probably due to the different status of host immunity against the virus. Here in the study, we unveiled plasma proteomic signatures and transcriptional patterns of peripheral blood mononuclear cells (PBMCs) using blood samples of 10 COVID-19 patients with different severity. Through systemic analysis, α-defensin-1 (DEFA1) was identified to be elevated in both plasma and PBMCs, and correlated with disease severity and stages. In vitro study demonstrated that DEFA1 was secreted from immunocytes and suppressed SARS-CoV-2 infection of both original and mutated strains with dose dependency. By using sequencing data, we discovered that DEFA1 was activated in monocytes through NF-κB signaling pathway after infection, and secreted into circulation to perturb SARS-CoV-2 infection by interfering protein kinase C expression. It worked mainly during virus replication instead of entry in host cells. Together, the anti-SARS-CoV-2 mechanism of DEFA1 has unveiled a corner of how innate immunity is against SARS-CoV-2 and explored its clinical potential in disease prognosis and therapeutic intervention.

Integrative multi-omics approach for identifying molecular signatures and pathways and deriving and validating molecular scores for COVID-19 severity and status.

BACKGROUND: There is still more to learn about the pathobiology of COVID-19. A multi-omic approach offers a holistic view to better understand the mechanisms of COVID-19. We used state-of-the-art statistical learning methods to integrate genomics, metabolomics, proteomics, and lipidomics data obtained from 123 patients experiencing COVID-19 or COVID-19-like symptoms for the purpose of identifying molecular signatures and corresponding pathways associated with the disease. RESULTS: We constructed and validated molecular scores and evaluated their utility beyond clinical factors known to impact disease status and severity. We identified inflammation- and immune response-related pathways, and other pathways, providing insights into possible consequences of the disease. CONCLUSIONS: The molecular scores we derived were strongly associated with disease status and severity and can be used to identify individuals at a higher risk for developing severe disease. These findings have the potential to provide further, and needed, insights into why certain individuals develop worse outcomes.

COVID-19: A Possible Contribution of the MAPK Pathway.

BACKGROUND: COVID-19 is characterized by an uncontrolled inflammatory response with high pro-inflammatory cytokine production through the activation of intracellular pathways, such as mitogen-activated protein kinase (MAPK). Viruses are able to exploit the MAPK pathway to their advantage; this pathway relevance to severe COVID-19 is poorly described. The aim of this study was to quantify biomarkers involved in the MAPK pathway and to clarify its possible role in affecting some COVID-19-related clinical features. METHODS: H-RAS, C-RAF, MAPK1, MAPK2, and ERK were quantified through ELISA, and genetic polymorphisms were evaluated through real-time PCR. RESULTS: We prospectively recruited 201 individuals (158 positive and 43 negative for SARS-CoV-2): 35 were male, and their median age was 65 years. MAPK-related biomarker levels were increased in SARS-CoV-2-positive participants (n = 89) compared to negative ones (n = 29). Dyspnea was reported by 48%; this symptom was associated with PBMC C-RAF levels in positive participants (p = 0.022) and type of ventilation (p = 0.031). The highest degree of ventilation was used by 8% for invasive ventilation and 41% for continuous positive airway pressure (CPAP). CONCLUSIONS: This is the first study that showed a possible contribution of MAPK-related biomarkers in affecting COVID-19 clinical features, and this may be relevant for identifying COVID-19 positive participants at risk of serious complications.

A comprehensive review of stroke-related signaling pathways and treatment in western medicine and traditional Chinese medicine.

This review provides insight into the complex network of signaling pathways and mechanisms involved in stroke pathophysiology. It summarizes the historical progress of stroke-related signaling pathways, identifying potential interactions between them and emphasizing that stroke is a complex network disease. Of particular interest are the Hippo signaling pathway and ferroptosis signaling pathway, which remain understudied areas of research, and are therefore a focus of the review. The involvement of multiple signaling pathways, including Sonic Hedgehog (SHH), nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE), hypoxia-inducible factor-1α (HIF-1α), PI3K/AKT, JAK/STAT, and AMPK in pathophysiological mechanisms such as oxidative stress and apoptosis, highlights the complexity of stroke. The review also delves into the details of traditional Chinese medicine (TCM) therapies such as Rehmanniae and Astragalus, providing an analysis of the recent status of western medicine in the treatment of stroke and the advantages and disadvantages of TCM and western medicine in stroke treatment. The review proposes that since stroke is a network disease, TCM has the potential and advantages of a multi-target and multi-pathway mechanism of action in the treatment of stroke. Therefore, it is suggested that future research should explore more treasures of TCM and develop new therapies from the perspective of stroke as a network disease.

Mechanistic investigation of direct photodegradation of chloroquine phosphate under simulated sunlight.

Chloroquine phosphate (CQ) is an antiviral drug for Coronavirus Disease 2019 and an old drug for treatment of malaria, which has been detected in natural waters. Despite its prevalence, the environmental fate of CQ remains unclear. In this study, the direct photodegradation of CQ under simulated sunlight was investigated. The effect of various parameters such as pH, initial concentration and environmental matrix were examined. The photodegradation quantum yield of CQ (4.5 × 10-5-0.025) increased with the increasing pH value in the range of 6.0-10.0. The electron spin resonance (ESR) spectrometry and quenching experiments verified that the direct photodegradation of CQ was primarily associated with excited triplet states of CQ (3CQ*). The common ions had negligible effect and humic substances exhibited a negative effect on CQ photodegradation. The photoproducts were identified using high-resolution mass spectrometry and the photodegradation pathway of CQ was proposed. The direct photodegradation of CQ involved the cleavage of the C-Cl bond and substitution of the hydroxyl group, followed by further oxidation to yield carboxylic products. The photodegradation processes were further confirmed by the density functional theory (DFT) computation for the energy barrier of CQ dichlorination. The findings contribute to the assessment of the ecological risk associated with the overuse of Coronavirus drugs during global public health emergencies.

An International Student, a Researcher, or a Work-Ready Graduate? Exploring the Self-formation of International Students in Coursework Master's Programmes

Providing research pathways for coursework master's programme (CMP) students is a feature in the Australian higher education system. While a burgeoning number of international students in Australian CMPs participate in research units, it is constraining to rigidly categorise international students as belonging to either research or coursework streams. Acknowledging that, this chapter explores the detailed experiences of international students who have recently completed the research pathway in their CMP. Combining the concepts of self-formation and positioning theory, it investigates international students' interactions with social actors, negotiations with the self and external rules, such as social codes and educational structures. Through collaborative autoethnography, this chapter identifies four stages of self-formation, namely pre-positioning, positioning, performing, and transformation, and highlights the influences of COVID-19 on these four stages. This chapter suggests that collective efforts on an institutional level are required to improve the wellbeing of international students in four main areas, namely developing agency, resolving career anxiety, addressing financial difficulties, and handling mental issues. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Study on active compounds from Maxingganshi decoction for treatment of novel coronavirus pneumonia (COVID-19) based on network pharmacology and molecular docking method

Aim To explore the active compound of Maxingganshi decoction in treatment of novel coronavirus pneumonia(COVID-19). Methods With the help of TCMSP database, the chemical components and action targets of ephedra, almond, licorice, and gypsum in Maxingganshi decoction were searched, and then a C-T network, protein interaction analysis, GO functional enrichment analysis, and KEGG pathway enrichment were constructed. Analysis was performed to predict its mechanism of action. Results A total of 120 compounds in Maxingganshi decoction corresponded to 222 targets. PTGS2, ESR1, PPARG, AR, NOS2, NCOA2 acted on PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, T cell receptor signaling pathways, etc. The results of molecular docking showed that the affinity of quercetin, kaempferol, glabridin and other core compounds was similar to recommended drugs in treatment of COVID-19. Conclusions The active compounds of Maxingganshi decoction can target multiple pathways to achieve the therapeutic effect of COVID-19.Copyright © 2020 Publication Centre of Anhui Medical University. All rights reserved.

Evaluation of the Genes and Molecular Pathways Involved in Skin Lesions in Patients with COVID-19: Systems Biology and Bioinformatics Analysis Approach

Background: Coronavirus disease 2019 (COVID-19) was first identified in 2019 in Wuhan, China. Initially, although the number of COVID-19-infected individuals was very low, the infected cases increased as the virus spread worldwide. Skin manifestation is one of the symptoms observed in COVID-19 patients. Objectives: This study investigated the critical genes and molecular pathways involved in skin manifestations in COVID-19 patients through a biological system approach. Methods: In this study, the microarray dataset was downloaded from the Gene Expression Omnibus (GEO) database and analyzed for identifying differentially expressed genes (DEGs). The enrichment analysis of DEGs was evaluated using the DAVID database. Afterward, protein-protein interaction (PPI) networks were constructed via the STRING database and visualized using Cytoscape software. The hub genes were recognized using the cytoHubba. The interaction of the microRNA (miRNA)-hub genes, transcription factor (TF)-hub genes, and drug-hub genes was also evaluated in this study. Results: After analysis, some genes with the highest degree of connectivity, which were involved in the pathogenesis of HELLP syndrome were identified, and they were known as hub genes. These genes are as follows: IFN-gamma CXCL1, CCL2, CCL3, TLR2, IL-1B, CXCL6, IL-6, CCL4, and CXCL2. has-mir-34a-5p, has-mir-20a-5p, and has-mir-27a-3p as miRNA, as well as RELA as TF had the most interaction with the hub genes. Conclusion: Finally, IL-6 and CXCL10 that were compared to the other hub genes had the highest interaction with other genes;therefore, their role in Shamgir's pathogenesis is significant. Targeting the cited genes would be a strategy to prevent symptom manifestation and better patient management.

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.