An evaluation of matrix metalloproteinase-9 (Mmp-9) and tissue inhibitor metalloprotein-ase-1 (Timp-1) Serum levels and the Mmp-9/Timp-1 Ratio in Covid-19 patients

Background: The progression of COVID-19 has different clinical presentations, which raises a number of immunological questions. Objective(s): This study aimed to investigate MMP-9 and TIMP-1 levels in patients diagnosed with COVID-19 and whether the MMP-9/TIMP-1 ratio is associated with lung involvement in COVID-19. Method(s): This study was conducted with 192 patients and 45 healthy controls. ELISA was used to measure the MMP-9 and TIMP-1. Result(s): The MMP-9 and TIMP-1 levels of the patients were found to be higher than those of the controls. MMP-9 and TIMP-1 were detected more in patients with lung involvement on chest CT scans than in those with no lung involvement on chest CT scans. A comparison of lung involvement levels revealed no difference was found between the groups. The MMP-9/TIMP-1 ratio was 5.8 in the group with lung involvement on chest CT scans and 6.1 in the group without lung involvement on chest CT scans. No difference was found between the two groups. A comparison with respect to lung involvement levels showed that the MMP-9/TIMP-1 ratio difference was found between the groups. Conclusion(s): Diagnostic and treatment methods targeting MMP-9 activity or neutrophil activation may be important in predict-ing lung involvement in COVID-19 and directing clinical outcomes.Copyright © 2023 Demir NA et al. Licensee African Health Sciences.

Proteolytic Biosensors with Functional Nanomaterials: Current Approaches and Future Challenges.

Proteolytic enzymes are one of the important biomarkers that enable the early diagnosis of several diseases, such as cancers. A specific proteolytic enzyme selectively degrades a certain sequence of a polypeptide. Therefore, a particular proteolytic enzyme can be selectively quantified by changing detectable signals causing degradation of the peptide chain. In addition, by combining polypeptides with various functional nanomaterials, proteolytic enzymes can be measured more sensitively and rapidly. In this paper, proteolytic enzymes that can be measured using a polypeptide degradation method are reviewed and recently studied functional nanomaterials-based proteolytic biosensors are discussed. We anticipate that the proteolytic nanobiosensors addressed in this review will provide valuable information on physiological changes from a cellular level for individual and early diagnosis.

Ultradiluted SARS-CoV-2 Spike Protein mitigates hyperinflammation in lung via ferritin and MMP-9 regulation in BALB/c mice.

AIM: This study investigated the prophylactic and therapeutic role of ultradiluted preparation of the Delta variant of SARS-CoV-2 recombinant spike (S) protein during S antigen-induced inflammatory process of disease progression along with the probable mechanism of action. MAIN METHODS: Ultradiluted S protein (UDSP) was prepared and administered orally to adult BALB/c mice before and after administration of S antigen intranasally. After an observation period of 72 h, animals were sacrificed and expression level of ferritin was assayed through ELISA. The genetic expressions of cytokines, IL-6, IL-10, IL-1ß, TNFα, IL-17, MMP-9, TIMP-1, ferritin light and heavy chains, and mitochondrial ferritin from lung tissues were investigated through RT-PCR. Formalin-fixed lung tissue sections were stained with hematoxylin and eosin to observe the degree of pathological changes. The activity of MMP-9 in lung tissues was investigated through gelatin zymography and immunofluorescence of MMP-9 in lung tissue sections was performed to revalidate the finding from gelatin zymography. Systems biology approach was used to elucidate a probable pathway where UDSP attenuated the inflammation through the regulation of pro- and anti-inflammatory cytokines. KEY FINDINGS: UDSP attenuated the S antigen-induced hyperinflammation in the lung by regulating pro- and anti-inflammatory cytokines, calming cytokine storm, reducing ferritin level both in transcriptional and translational levels, and restoring critical ratio of MMP-9: TIMP-1. SIGNIFICANCE: Our findings suggest a probable pathway by which UDSP might have attenuated inflammation through the regulation of cytokines, receptors, and other molecules. This proclaims UDSP as a promising antiviral agent in the treatment of COVID-19-induced immunopathogenesis.

COVID-19 Affects Serum Brain-Derived Neurotrophic Factor and Neurofilament Light Chain in Aged Men: Implications for Morbidity and Mortality.

BACKGROUND AND METHODS: Severe COVID-19 is known to induce neurological damage (NeuroCOVID), mostly in aged individuals, by affecting brain-derived neurotrophic factor (BDNF), matrix metalloproteinases (MMP) 2 and 9 and the neurofilament light chain (NFL) pathways. Thus, the aim of this pilot study was to investigate BDNF, MMP-2, MMP-9, and NFL in the serum of aged men affected by COVID-19 at the beginning of the hospitalization period and characterized by different outcomes, i.e., attending a hospital ward or an intensive care unit (ICU) or with a fatal outcome. As a control group, we used a novelty of the study, unexposed age-matched men. We also correlated these findings with the routine blood parameters of the recruited individuals. RESULTS: We found in COVID-19 individuals with severe or lethal outcomes disrupted serum BDNF, NFL, and MMP-2 presence and gross changes in ALT, GGT, LDH, IL-6, ferritin, and CRP. We also confirmed and extended previous data, using ROC analyses, showing that the ratio MMPs (2 and 9) versus BDNF and NFL might be a useful tool to predict a fatal COVID-19 outcome. CONCLUSIONS: Serum BDNF and NFL and/or their ratios with MMP-2 and MMP-9 could represent early predictors of NeuroCOVID in aged men.

Investigation of the relationship between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 with SARS CoV-2 infections

SARS-CoV-2 stands for severe acute respiratory syndrome coronavirus 2. Matrix metalloproteinases-9 (MMP-9) performs a crucial physiological role. In addition to its roleICLEin the molecular basis of lung fibrosis, this enzyme may also play a part in the "cytokine storm," which may represent one of the potential scenarios during coronavirus infection. Tissue inhibitors of metalloproteinase (TIMPs) are well-known for their ability to regulate MMP activity during remodeling of the extracellular matrix. As cytokines, they are also thought of as signaling molecules that impact on a wide range of biological processes. This study aimed to investigate the link between each of MMP-9 and TIMP-1, and COVID19 disease. A total of 58 COVID-19 patients and 30 apparently healthy adults enrolled in this study. The ORF1ab, E and N genes of SARS-CoV-2 were detected using multiplex real-time PCR, while the ELISA technique was used to estimate the level of serum MMP-9, TIMP-1, and C-reactive protein (CRP). The study results demonstrated higher concentrations of MMP-9 in COVID-19 patients (2810 ± 1160 pg/ml) compared to controls (2110 ± 850 pg/ml), with non-significant differences (p=0.002). Unlike, TIMP-1, showed considerably higher levels in the patient's group (541.53 ± 201.42 pg/ml) than in controls (276.33 ± 67.26 pg/ml) with high significant differences (p ≤ 0.001). Considering this study, TIMP-1 in COVID patients most likely play an important role in inflammatory response. Its clinical utility as a biomarker may be insufficient, but it provides a useful data in the diagnosis of COVID‐19. © 2023, Bangladesh Society for Microbiology, Immunology and Advanced Biotechnology. All rights reserved.

Pathway and Network Analyses Identify Growth Factor Signaling and MMP9 as Potential Mediators of Mitochondrial Dysfunction in Severe COVID-19.

Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease progression at the cellular level. Our current study aimed to understand how cellular metabolism contributes to COVID-19 outcomes. Metacore pathway enrichment analyses on differentially expressed genes (encoded by both mitochondrial and nuclear deoxyribonucleic acid (DNA)) involved in cellular metabolism, regulation of mitochondrial respiration and organization, and apoptosis, was performed on RNA sequencing (RNASeq) data from blood samples collected from healthy controls and patients with mild/moderate or severe COVID-19. Genes from the enriched pathways were analyzed by network analysis to uncover interactions among them and up- or downstream genes within each pathway. Compared to the mild/moderate COVID-19, the upregulation of a myriad of growth factor and cell cycle signaling pathways, with concomitant downregulation of interferon signaling pathways, were observed in the severe group. Matrix metallopeptidase 9 (MMP9) was found in five of the top 10 upregulated pathways, indicating its potential as therapeutic target against COVID-19. In summary, our data demonstrates aberrant activation of endocrine signaling in severe COVID-19, and its implication in immune and metabolic dysfunction.

Analysis of Marine Microplastic Pollution of Disposable Masks under COVID-19 Epidemic-A DPSIR Framework.

Marine microplastic pollution (MMP) is becoming one of the most pressing environmental problems facing humanity today. The novel coronavirus epidemic has raised the issue of environmental contamination caused by large-scale improper disposal of medical waste such as disposable masks (DMs). To assess the impact of MMP caused by DMs and to seek solutions for the prevention and control of MMP, this study uses the Driving force-Pressure-State-Impact-Response (DPSIR) framework to establish a causal chain of MMP caused by DMs. The conclusion shows that the novel coronavirus epidemic has led to a surge in the use of DMs, which has brought pressure on resource constraints and environmental pollution at the same time. Improperly DMs enter the environment and eventually transform into MMP, which not only endangers the marine ecological system but also poses potential human health risks as well as economic and social hazards. In addition, further research on environmentally friendly masks (cloth masks and biodegradable masks) is essential to mitigate the environmental damage caused by the large-scale global use of DMs. This study provides a scientific and theoretical basis for the assessment of MMP from discarded DMs, and the findings of this study will provide a reference for the formulation of relevant policies.

MMP-9/BDNF ratio predicts more severe COVID-19 outcomes.

COVID-19 clinically manifests from asymptomatic to the critical range. Immune response provokes the pro-inflammatory interactions, which lead to the cytokines, reactive oxygen/nitrogen species, peptidases, and arachidonic acid metabolites enlargement and activation of coagulation components. Matrix metalloproteinases (MMPs) contribute to tissue destruction in the development of COVID-19. Due to the endothelial, systemic course of the disease, VEGF A participates actively in COVID-19 development, while neurotrophic and metabolic effects of BDNF recommends for the prediction of complications in COVID-19 patients. Searching for a marker that would improve and simplify the ranking in COVID-19, the study intended to evaluate the relationship of MMP-9 with VEGF A, BDNF, and MMP-8 with the COVID-19 severity. Upon admission to the hospital and before the therapy administration, 77 patients were classified into a mild, moderate, severe, or critical group. Due to the inflammatory stage in COVID-19, a comparison between groups showed related differences in leukocytes, neutrophils, lymphocytes, and platelets counts as anticipated. Only in seriously ill patients, there is a significant increase in the serum concentration of MMP-9, MMP-8, and VEGF A, while BDNF values did not show significant variations between groups. However, all those parameters positively correlated with each other. The ratio of MMP-9/BDNF markedly decreased in the severe and critically patients compared to the mild group. Testing the capability of this ratio to predict the COVID-19 stage by ROC curves, we found the MMP-9/BDNF could be a suitable marker for differentiating stages I/II (AUC 0.7597), stage I/III (AUC 0.9011), and stage I/IV (AUC 0.7727). Presented data describe for the first time the high-level systemic MMP-9/BDNF ratio in patients with COVID-19. This parameter could contribute to a more precise determination of the phase of the disease.

Anti-COVID-19 terpenoid from marine sources: A docking, admet and molecular dynamics study.

Traditional medicines contain natural products (NPs) as main ingredient which always give new direction and paths to develop new advanced medicines. In the COVID-19 pandemic, NPs can be used or can help to find new compound against it. The SARS coronavirus-2 main protease (SARS CoV-2 Mpro) enzyme, arbitrate viral replication and transcription, is target here. The study show that, from the electronic features and binding affinity of all the NPs with the enzyme, the compounds with higher hydrophobicity and lower flexibility can be more favorable inhibitor. More than fifty NPs were screened for the target and one terpenoid (T3) from marine sponge Cacospongia mycofijiensis shows excellent SARS CoV-2 Mpro inhibitory activity in comparison with known peptide based inhibitors. The molecular dynamics simulation studies of the terpenoids with the protein indicates that the complex is stable and hydrogen bonds are involved during the complexation. Considering binding affinity, bioavailability, pharmacokinetics and toxicity of the compounds, it is proposed that the NP T3 can act as a potential drug candidate against COVID-19 virus.

Hypothesized neuroprotective effect of minocycline against COVID-19-induced stroke and neurological dysfunction: possible role of matrix metalloprotease signaling pathway.

Severe Acute Respiratory Syndrome Coronavirus-2 (COVID-19) is a respiratory disease that causes dysfunction in respiration. Since late 2019, this virus has infected and killed millions of people around the world and imposed many medical and therapeutic problems in the form of a pandemic. According to recent data, COVID-19 disease can increase the risk of stroke, which can be deadly or cause many neurological disorders after the disease. During the last two years, many efforts have been made to introduce new therapies for management of COVID-19-related complications, including stroke. To achieve this goal, several conventional drugs have been investigated for their possible therapeutic roles. Minocycline, a broad-spectrum, long-acting antibiotic with anti-inflammatory and antioxidant properties, is one such conventional drug that should be considered for treating COVID-19-related stroke, as indirect evidence indicates that it exerts neuroprotective effects, can modulate stroke occurrence, and can play an effective and strategic role in management of the molecular signals caused by stroke and its destructive consequences. The matrix metalloprotease (MMP) signaling pathway is one of the main signaling pathways involved in the occurrence and exacerbation of stroke; however, its role in COVID-19-induced stroke and the possible role of minocycline in the management of this signaling pathway in patients with COVID-19 is unclear and requires further investigation. Based on this concept, we hypothesize that minocycline might act via MMP signaling as a neuroprotective agent against COVID-19-induced neurological dysfunction, particularly stroke.

Cytokine Patterns in COVID-19 Patients: Which Cytokines Predict Mortality and Which Protect Against?

(1) Background/Aim: People infected with SARS-CoV-2 may develop COVID-19 in a wide range of clinical severity. Pulmonary fibrosis is characterized by several grades of chronic inflammation and collagen deposition in the interalveolar space. SARS-CoV-2 infection has been demonstrated to cause lung fibrosis without a currently elucidated mechanism. Some studies emphasize the role of proinflammatory cytokines. This research studies the correlation of the released cytokines with mortality or lung injury in COVID-19 patients. (2) Methods: Electronic medical record data from 40 patients diagnosed with COVID-19 in the COVID-19 Department, Galilee Medical Center, Nahariya, Israel, were collected. Epidemiological, clinical, laboratory, and imaging variables were analyzed. The cytokine levels were measured upon admission and discharge. A correlation between cytokine levels and severity and mortality or lung involvement was undertaken. (3) Results: IFN-gamma and IL-10 are the most powerful risk factors for mortality in the COVID-19 patient groups in a multivariate analysis. However, in a univariate analysis, TGF-ß, CXCL-10, IFN gamma, and IL-7 affected mortality in COVID-19 patients. MMP-7 was significantly correlated with a cytokine storm and a high 4-C (severity) score in COVID-19 patients. MMP-7, TGF-ß, IL-10, IL-7, TNF-α, and IL-6 were correlated with high lung involvement in COVID-19 patients. Serum concentrations of IGF-1 were significantly increased upon discharge, but MMP-7 was decreased. (4) Conclusions: Proinflammatory cytokines predict clinical severity, lung fibrosis, and mortality in COVID-19 patients. High concentrations of TGF-ß, CXCL-10, IL-10, IL-6, and TNF-α are correlated to severity and lung injury. However, certain cytokines have protective effects and higher levels of these cytokines increase survival levels and lower lung damage. High levels of INF-γ, IL-7, MMP-7, and IGF-1 have protection probabilities against lung injury and severity.

Association of Candida Species with Novel SARS-CoV-2 and Biomarkers for Fungal Premalignant Oral Lesions.

Oral fungal infections can be caused by certain species of fungi among which candida albicans is the most implicated. Oral candidiasis is correlated with multiple conditions, such as coronavirus disease-2019, oral leukoplakia and oral erythroplakia. Tenascin is a glycoprotein and is present at the site of tissue injury and chronic inflammation, and tends to be over-expressed in cases of malignancy. Matrix metalloproteinase-9 belongs to a family of zinc-dependent endopeptidases and is involved in the degradation of extracellular matrix, leading to tissue invasion and metastasis. The current narrative review was planned to shed light on the fungal co-infections of coronavirus disease-2019 and molecular mechanisms of matrix metalloproteinase-9 and tenascin involved in the pathogenesis of fungus-associated oral leukoplakia and oral erythroplakia.

Matrix Metalloproteinases Expression Is Associated with SARS-CoV-2-Induced Lung Pathology and Extracellular-Matrix Remodeling in K18-hACE2 Mice.

The COVID-19 pandemic caused by the SARS-CoV-2 infection induced lung inflammation characterized by cytokine storm and fulminant immune response of both resident and migrated immune cells, accelerating alveolar damage. In this work we identified members of the matrix metalloprotease (MMPs) family associated with lung extra-cellular matrix (ECM) destruction using K18-hACE2-transgenic mice (K18-hACE2) infected intranasally with SARS-CoV-2. Five days post infection, the lungs exhibited overall alveolar damage of epithelial cells and massive leukocytes infiltration. A substantial pulmonary increase in MMP8, MMP9, and MMP14 in the lungs post SARS-CoV-2 infection was associated with degradation of ECM components including collagen, laminin, and proteoglycans. The process of tissue damage and ECM degradation during SARS-CoV-2 lung infection is suggested to be associated with activity of members of the MMPs family, which in turn may be used as a therapeutic intervention.

Health effects and known pathology associated with the use of E-cigarettes.

In recent years, new nicotine delivery methods have emerged, and many users are choosing electronic cigarettes (e-cigarettes) over traditional tobacco cigarettes. E-cigarette use is very popular among adolescents, with more than 3.5 million currently using these products in the US. Despite the increased prevalence of e-cigarette use, there is limited knowledge regarding the health impact of e-cigarettes on the general population. Based on published findings by others, E-cigarette is associated with lung injury outbreak, which increased health and safety concerns related to consuming this product. Different components of e-cigarettes, including food-safe liquid solvents and flavorings, can cause health issues related to pneumonia, pulmonary injury, and bronchiolitis. In addition, e-cigarettes contain alarmingly high levels of carcinogens and toxicants that may have long-lasting effects on other organ systems, including the development of neurological manifestations, lung cancer, cardiovascular disorders, and tooth decay. Despite the well- documented potential for harm, e-cigarettes do not appear to increase susceptibility to SARS-CoV- 2 infection. Furthermore, some studies have found that e-cigarette users experience improvements in lung health and minimal adverse effects. Therefore, more studies are needed to provide a definitive conclusion on the long-term safety of e-cigarettes. The purpose of this review is to inform the readers about the possible health-risks associated with the use of e-cigarettes, especially among the group of young and young-adults, from a molecular biology point of view.

Impact of High Serum Levels of MMP-7, MMP-9, TGF-ß and PDGF Macrophage Activation Markers on Severity of COVID-19 in Obese-Diabetic Patients.

OBJECTIVE: The aim of this study was to identify an association between the severity of COVID-19 in obese-diabetic patients and altered serum levels of MMP-7, MMP-9, TGF-ß, and PDGF macrophage activation markers. METHODOLOGY: The study included 70 COVID-19 patients, divided into two groups: Group 1 included: Obese COVID-19 patients with type 2 diabetes mellitus (T2D, n=22 patients) and group 2 included; non-obese, non-diabetic COVID-19 patients as an age- and sex-matched control group (n=48 patients). Serum levels of the tested biomarkers were measured by ELISA at admission and after one weak follow-up. RESULTS: There was a significant reduction in the serum levels of LBP in obese-diabetic COVID-19 patients versus the control group (8.34±3.94 vs 20.78±7.61) (p 0.0001). Significant elevation of MMP-7, MMP-9, PDGF and TGF-ß was detected in obese diabetic COVID-19 patients compared to the non-obese non-diabetic group: 1044.7±519.6 vs 405.6±164.1, 483.05±46.5 vs 173.31±76.26, 154.5±62.78 vs 39.77±21.52, and 603.05±258.82 vs 180.29±97.17, respectively. The serum levels of macrophage activation markers in obese-diabetic patients one week after admission revealed that patients with acute respiratory distress syndrome (ARDS) had significantly higher serum levels of MMP-7 and MMP-9 than non-ARDS patients (p 0.02 and p 0.01 respectively). CONCLUSION: Macrophages were mainly polarized towards the M2 phenotype in obese-diabetic COVID-19 patients with significant upregulation of the pro-fibrotic markers MMP-7, MMP-9, PDGF, and TGF-ß. Thus, high levels of MMP-7 and MMP-9 are associated with ARDS in severe COVID-19 disease among obese-diabetic patients.

ADAM17/MMP inhibition prevents neutrophilia and lung injury in a mouse model of COVID-19.

Severe coronavirus disease 2019 (COVID-19) is characterized by lung injury, cytokine storm, and increased neutrophil-to-lymphocyte ratio (NLR). Current therapies focus on reducing viral replication and inflammatory responses, but no specific treatment exists to prevent the development of severe COVID-19 in infected individuals. Angiotensin-converting enzyme-2 (ACE2) is the receptor for SARS-CoV-2, the virus causing COVID-19, but it is also critical for maintaining the correct functionality of lung epithelium and endothelium. Coronaviruses induce activation of a disintegrin and metalloprotease 17 (ADAM17) and shedding of ACE2 from the cell surface resulting in exacerbated inflammatory responses. Thus, we hypothesized that ADAM17 inhibition ameliorates COVID-19-related lung inflammation. We employed a preclinical mouse model using intratracheal instillation of a combination of polyinosinic:polycytidylic acid (poly(I:C)) and the receptor-binding domain of the SARS-CoV-2 spike protein (RBD-S) to mimic lung damage associated with COVID-19. Histologic analysis of inflamed mice confirmed the expected signs of lung injury including edema, fibrosis, vascular congestion, and leukocyte infiltration. Moreover, inflamed mice also showed an increased NLR as observed in critically ill COVID-19 patients. Administration of the ADAM17/MMP inhibitors apratastat and TMI-1 significantly improved lung histology and prevented leukocyte infiltration. Reduced leukocyte recruitment could be explained by reduced production of proinflammatory cytokines and lower levels of the endothelial adhesion molecules ICAM-1 and VCAM-1. Additionally, the NLR was significantly reduced by ADAM17/MMP inhibition. Thus, we propose inhibition of ADAM17/MMP as a novel promising treatment strategy in SARS-CoV-2-infected individuals to prevent the progression toward severe COVID-19.

Porcine Epidemic Diarrhea Virus Infection Disrupts the Nasal Endothelial Barrier To Favor Viral Dissemination.

Crossing the endothelium from the entry site and spreading in the bloodstream are crucial but obscure steps in the pathogenesis of many emerging viruses. Previous studies confirmed that porcine epidemic diarrhea virus (PEDV) caused intestinal infection by intranasal inoculation. However, the role of the nasal endothelial barrier in PEDV translocation remains unclear. Here, we demonstrated that PEDV infection causes nasal endothelial dysfunction to favor viral dissemination. Intranasal inoculation with PEDV compromised the integrity of endothelial cells (ECs) in nasal microvessels. The matrix metalloproteinase 7 (MMP-7) released from the PEDV-infected nasal epithelial cells (NECs) contributed to the destruction of endothelial integrity by degrading the tight junctions, rather than direct PEDV infection. Moreover, the proinflammatory cytokines released from PEDV-infected NECs activated ECs to upregulate ICAM-1 expression, which favored peripheral blood mononuclear cells (PBMCs) migration. PEDV could further exploit migrated cells to favor viral dissemination. Together, our results reveal the mechanism by which PEDV manipulates the endothelial dysfunction to favor viral dissemination and provide novel insights into how coronavirus interacts with the endothelium. IMPORTANCE The endothelial barrier is the last but vital defense against systemic viral transmission. Porcine epidemic diarrhea virus (PEDV) can cause severe atrophic enteritis and acute viremia. However, the mechanisms by which the virus crosses the endothelial barrier and causes viremia are poorly understood. In this study, we revealed the mechanisms of endothelial dysfunction in PEDV infection. The viral infection activates NECs and causes the upregulation of MMP-7 and proinflammatory cytokines. Using NECs, ECs, and PBMCs as in vitro models, we determined that the released MMP-7 contributed to the destruction of endothelial barrier, and the released proinflammatory cytokines activated ECs to facilitate PBMCs migration. Moreover, the virus further exploited the migrated cells to promote viral dissemination. Thus, our results provide new insights into the mechanisms underlying endothelial dysfunction induced by coronavirus infection.

Research on the mechanism of berberine in the treatment of COVID-19 pneumonia pulmonary fibrosis using network pharmacology and molecular docking.

Purpose Pulmonary fibrosis caused by COVID-19 pneumonia is a serious complication of COVID-19 infection, there is a lack of effective treatment methods clinically. This article explored the mechanism of action of berberine in the treatment of COVID-19 (Corona Virus Disease 2019, COVID-19) pneumonia pulmonary fibrosis with the help of the network pharmacology and molecular docking. Methods We predicted the role of berberine protein targets with the Pharmmapper database and the 3D structure of berberine in the Pubchem database. And GeneCards database was used in order to search disease target genes and screen common target genes. Then we used STRING web to construct PPI interaction network of common target protein. The common target genes were analyzed by GO and KEGG by DAVID database. The disease-core target gene-drug network was established and molecular docking was used for prediction. We also analyzed the binding free energy and simulates molecular dynamics of complexes. Results Berberine had 250 gene targets, COVID-19 pneumonia pulmonary fibrosis had 191 gene targets, the intersection of which was 23 in common gene targets. Molecular docking showed that berberine was associated with CCl2, IL-6, STAT3 and TNF-α. GO and KEGG analysis reveals that berberine mainly plays a vital role by the signaling pathways of influenza, inflammation and immune response. Conclusion Berberine acts on TNF-α, STAT3, IL-6, CCL2 and other targets to inhibit inflammation and the activation of fibrocytes to achieve the purpose of treating COVID-19 pneumonia pulmonary fibrosis.

The endothelial glycocalyx in critical illness: A pediatric perspective.

The vascular endothelium is the interface between circulating blood and end organs and thus has a critical role in preserving organ function. The endothelium is lined by a glycan-rich glycocalyx that uniquely contributes to endothelial function through its regulation of leukocyte and platelet interactions with the vessel wall, vascular permeability, coagulation, and vasoreactivity. Degradation of the endothelial glycocalyx can thus promote vascular dysfunction, inflammation propagation, and organ injury. The endothelial glycocalyx and its role in vascular pathophysiology has gained increasing attention over the last decade. While studies characterizing vascular glycocalyx injury and its downstream consequences in a host of adult human diseases and in animal models has burgeoned, studies evaluating glycocalyx damage in pediatric diseases are relatively few. As children have unique physiology that differs from adults, significant knowledge gaps remain in our understanding of the causes and effects of endothelial glycocalyx disintegrity in pediatric critical illness. In this narrative literature overview, we offer a unique perspective on the role of the endothelial glycocalyx in pediatric critical illness, drawing from adult and preclinical data in addition to pediatric clinical experience to elucidate how marked derangement of the endothelial surface layer may contribute to aberrant vascular biology in children. By calling attention to this nascent field, we hope to increase research efforts to address important knowledge gaps in pediatric vascular biology that may inform the development of novel therapeutic strategies.

Metalloproteinases 1 and 3 as Potential Biomarkers in Breast Cancer Development.

Breast cancer continues to be one of the main causes of morbidity and mortality globally and was the leading cause of cancer death in women in Spain in 2020. Early diagnosis is one of the most effective methods to lower the incidence and mortality rates of breast cancer. The human metalloproteinases (MMP) mainly function as proteolytic enzymes degrading the extracellular matrix and plays important roles in most steps of breast tumorigenesis. This retrospective cohort study shows the immunohistochemical expression levels of MMP-1, MMP-2, MMP-3, and MMP-9 in 154 women with breast cancer and 42 women without tumor disease. The samples of breast tissue are assessed using several tissue matrices (TMA). The percentages of staining (≤50%->50%) and intensity levels of staining (weak, moderate, or intense) are considered. The immunohistochemical expression of the MMP-1-intensity (p = 0.043) and MMP-3 percentage (p = 0.018) and intensity, (p = 0.025) present statistically significant associations with the variable group (control-case); therefore, expression in the tumor tissue samples of these MMPs may be related to the development of breast cancer. The relationships between these MMPs and some clinicopathological factors in breast cancer are also evaluated but no correlation is found. These results suggest the use of MMP-1 and MMP-3 as potential biomarkers of breast cancer diagnosis.