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.

Comparison of Comorbidities between Adults and Children with Glycogen Storage Disease Type Ia (GSDIA)

Objectives: Glycogen Storage Disease Type Ia (GSDIa) is a rare inherited disorder resulting in acute hypoglycemia due to impaired release of glucose from glycogen. Despite dietary management practices to prevent hypoglycemia in patients with GSDIa, complications still occur in children and throughout adulthood. This retrospective cohort study compared the prevalence of complications in adults and children with GSDIa. Method(s): Using ICD-10 diagnosis codes, the IQVIA Pharmetrics Plus database was searched for patients with >=2 GSDI claims (E74.01) from January 2016 through February 2020, with >=12 months continuous enrollment beginning prior to March 2019 (for one year of follow-up before COVID-19), and no inflammatory bowel disease diagnoses (indicative of GSDIb). Complication prevalence in adults and children with GSDIa was summarized descriptively. Result(s): In total, 557 patients with GSDIa were identified (adults, 67%;male, 63%), including 372 adults (median age, 41 years) and 185 children (median age, 7 years). Complications occurring only in adults were atherosclerotic heart disease (8.6%), pulmonary hypertension (3.0%), primary liver cancer (1.9%), dialysis (0.8%), and focal segmental glomerulosclerosis (0.3%). Other complications with the greatest prevalence in adults/children included gout (11.8%/0.5%), insomnia (10.0%/1.1%), osteoarthritis (22.0%/2.7%), severe chronic kidney disease (4.3%/0.5%), malignant neoplasm (10.8%/1.6%), hypertension (49.7%/8.7%), acute kidney failure (15.3%/2.7%), pancreatitis (3.0%/0.5%), gallstones (7.8%/1.6%), benign neoplasm (37.4%/8.1%), hepatocellular adenoma (7.0%/1.6%), neoplasm (41.1%/9.7%), and hyperlipidemia (45.2%/10.8%). Complications with the greatest prevalence in children/adults included poor growth (22.2%/1.9%), gastrostomy (29.7%/3.2%), kidney hypertrophy (2.7%/0.8%), seizure (1.6%/0.5%), hypoglycemia (27.0%/11.3%), hepatomegaly (28.7%/15.9%), kidney transplant (1.6%/1.1%), diarrhea (26.5%/18.6%), nausea and/or vomiting (43.8%/35.8%), acidosis (20.0%/17.2%), and anemia due to enzyme disorders (43.8%/40.6%). Conclusion(s): GSDIa is associated with numerous, potentially serious complications. Compared with children, adults with GSDIa had a greater prevalence of chronic complications, potentially indicating the progressive nature of disease. Children with GSDIa had more acute complications related to suboptimal metabolic control.Copyright © 2023

Research progress on the regulation of endothelial cells by natural products of traditional Chinese medicine in the prevention and treatment of atherosclerosis

[] Atherosclerosis (As) is the pathological basis of coronary heart disease, and vascular endothelial injury is the initiating factor of coronary atherosclerosis. Vascular endothelial cells are a single layer of cells located in the inner layer of blood vessels and regulates exchanges between the blood stream and the surrounding tissues, and their integrity is very important. Many active monomers and the derivatives in natural products of traditional Chinese medicine modulate the function of endothelial cells by intervening oxidative stress, regulating the release of vasoactive substances, reducing inflammation, and equilibrating coagulation and anticoagulant system. They have the advantages of multi-pathway, multi-link and multi-target regulation in protecting from endothelial injury and attenuating atherogenesis. They have also been used to protect against corona virus disease 2019 (COVID-19) induced endothelial injury and atheroslerosis. This article reviews the research progress of the above issues in this field. © 2023, Editorial Office of Chinese Journal of Arteriosclerosis. All rights reserved.

Exploration of potential mechanism of SARS-CoV-2 induced immune inflammatory response leading to progression of atherosclerosis and prediction of traditional Chinese medicine for preventing and treating based on bioinformatics.

Objective To explore the core targets and important pathways of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induced atherosclerosis (AS) progression from the perspective of immune inflammation, so as to predict the potential prevention and treatment of traditional Chinese medicine (TCM). Methods Microarray data were obtained from the Gene Expression Omnibus (GEO) database for coronavirus disease 2019 (COVID-19) patients and AS patients, and the "limmar" and "Venn" packages were used to screen out the common differentially expressed genes (DEGs) genes in both diseases. The gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses were performed on the common DEGs to annotate their functions and important pathways. The two gene sets were scored for immune cells and immune function to assess the level of immune cell infiltration. The protein-protein interaction (PPI) network was constructed by STRING database, and the CytoHubba plug-in of Cytoscape was used to identify the hub genes. Two external validation datasets were introduced to validate the hub genes and obtain the core genes. Immuno-infiltration analysis and gene set enrichment analysis (GSEA) were performed on the core genes respectively. Finally the potential TCM regulating the core genes were predicted by Coremine Medical database. Results A total of 7898 genes related to COVID-19, 471 genes related to AS progression;And 51 common DEGs, including 32 highly expressed genes and 19 low expressed genes were obtained. GO and KEGG analysis showed that common DEGs, which were mainly localized in cypermethrin-encapsulated vesicles, platelet alpha particles, phagocytic vesicle membranes and vesicles, were involved in many biological processes such as myeloid differentiation factor 88 (MyD88)-dependent Toll-like receptor signaling pathway transduction, interleukin-8 (IL-8) production and positive regulation, IL-6 production and positive regulation to play a role in regulating nicotinamide adenine dinucleotide phosphate oxidase activity, Toll-like receptor binding and lipopeptide and glycosaminoglycan binding through many biological pathways, including Toll-like receptor signaling pathways, neutrophil extracellular trap formation, complement and coagulation cascade reactions. The results of immune infiltration analysis demonstrated the state of immune microenvironment of COVID-19 and AS. A total of 5 hub genes were obtained after screening, among which Toll-like receptor 2 (TLR2), cluster of differentiation 163 (CD163) and complement C1q subcomponent subunit B (C1QB) genes passed external validation as core genes. The core genes showed strong correlation with immune process and inflammatory response in both immune infiltration analysis and GSEA enrichment analysis. A total of 35 TCMs, including Chuanxiong (Chuanxiong Rhizoma), Taoren (Persicae Semen), Danggui (Angelicae Sinensis Radix), Huangqin (Scutellariae Radix), Pugongying (Taraxaci Herba), Taizishen (Pseudostellariae Radix), Huangjing (Polygonati Rhizoma), could be used as potential therapeutic agents. Conclusion TLR2, CD163 and C1QB were the core molecules of SARS-CoV-2-mediated immune inflammatory response promoting AS progression, and targeting predicted herbs were potential drugs to slow down AS progression in COVID-19 patients.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

Platelet-monocyte aggregates: molecular mediators of thromboinflammation.

Platelets, key facilitators of primary hemostasis and thrombosis, have emerged as crucial cellular mediators of innate immunity and inflammation. Exemplified by their ability to alter the phenotype and function of monocytes, activated platelets bind to circulating monocytes to form monocyte-platelet aggregates (MPA). The platelet-monocyte axis has emerged as a key mechanism connecting thrombosis and inflammation. MPA are elevated across the spectrum of inflammatory and autoimmune disorders, including cardiovascular disease, systemic lupus erythematosus (SLE), and COVID-19, and are positively associated with disease severity. These clinical disorders are all characterized by an increased risk of thromboembolic complications. Intriguingly, monocytes in contact with platelets become proinflammatory and procoagulant, highlighting that this interaction is a central element of thromboinflammation.

Benefits and Harms of COVID-19 Vaccines in Cardiovascular Disease: A Comprehensive Review.

Patients with a history of cardiovascular disease (CVD) who contract coronavirus disease 2019 (COVID-19) tend to have a worse prognosis and more severe cardiovascular side effects. COVID-19 vaccines, which are intended to prevent COVID-19, may also potentially reduce the severity and complications (including cardiovascular sequelae) of COVID-19, especially in patients with a history of CVD. However, there have also been reports of cardiovascular side effects from COVID-19 vaccines of various brands and types. The purpose of this study is to review the benefits and harms of COVID-19 vaccines in relation to CVD. In this thorough review of the most current evidence on the benefits and harms of COVID-19 vaccines, we present information about the characteristics of cardiovascular complications. Most of the evidence focuses on myocarditis or pericarditis, which are most strongly associated with mRNA vaccines and predominantly occur in young males within days of receiving the second dose. Meanwhile, post-vaccination myocardial infarction is more common in older males, and the first dose of adenoviral vector vaccines appears to play a greater role in this complication. This information may guide us in formulating alternative options and implementing targeted surveillance. Gaining more knowledge about the potential benefits and harms of COVID-19 vaccines will improve our ability to make informed decisions and judgments about the balance of these factors.

Candidate SNP Markers Significantly Altering the Affinity of TATA-Binding Protein for the Promoters of Human Hub Genes for Atherogenesis, Atherosclerosis and Atheroprotection.

Atherosclerosis is a systemic disease in which focal lesions in arteries promote the build-up of lipoproteins and cholesterol they are transporting. The development of atheroma (atherogenesis) narrows blood vessels, reduces the blood supply and leads to cardiovascular diseases. According to the World Health Organization (WHO), cardiovascular diseases are the leading cause of death, which has been especially boosted since the COVID-19 pandemic. There is a variety of contributors to atherosclerosis, including lifestyle factors and genetic predisposition. Antioxidant diets and recreational exercises act as atheroprotectors and can retard atherogenesis. The search for molecular markers of atherogenesis and atheroprotection for predictive, preventive and personalized medicine appears to be the most promising direction for the study of atherosclerosis. In this work, we have analyzed 1068 human genes associated with atherogenesis, atherosclerosis and atheroprotection. The hub genes regulating these processes have been found to be the most ancient. In silico analysis of all 5112 SNPs in their promoters has revealed 330 candidate SNP markers, which statistically significantly change the affinity of the TATA-binding protein (TBP) for these promoters. These molecular markers have made us confident that natural selection acts against underexpression of the hub genes for atherogenesis, atherosclerosis and atheroprotection. At the same time, upregulation of the one for atheroprotection promotes human health.

Obstructive sleep apnea and subsequent risk of hospitalization with pneumonia, respiratory infection, and total infection: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to microaspiration, systemic inflammation and suboptimal immune function. RESEARCH QUESTION: Is OSA prospectively associated with risk of hospitalization with pneumonia, respiratory and total infections? STUDY DESIGN: Prospective cohort. METHODS: Participants of the Atherosclerosis Risk in Communities (ARIC) study (N=1,586) underwent polysomnography in 1996-1998 and were followed through 2018 for infection-related hospitalizations. The apnea-hypopnea index (AHI; events/hour) was used to categorize participants as having severe OSA (≥30), moderate OSA (15-29), mild OSA (5-14), or a normal breathing pattern (<5). Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CI). RESULTS: ARIC participants were on average 62.7 (SD=5.5) years old, and 52.8% were female. Severe OSA was present in 6.0%, moderate OSA in 12.7%, mild OSA in 30.0% and normal breathing in 51.3%. A total of 253 hospitalizations with pneumonia occurred over a median 20.4 (max 22.9) years follow-up. Participants with severe OSA were at 1.87 times (95% CI: 1.19-2.95) higher risk of hospitalization with pneumonia compared to those with a normal breathing pattern after adjustment for demographics and lifestyle behaviors. Results were attenuated modestly after adjustment for body mass index [1.62 (0.99-2.63)], and prevalent asthma and COPD [1.62 (0.99-2.63)]. A similar pattern existed for hospitalization with respiratory infection and composite infection [demographic and behavior-adjusted HRs: 1.47 (0.96-2.25) and 1.48 (1.07-2.04), respectively]. INTERPRETATION: Severe OSA was associated with increased risk of hospitalizations with pneumonia in this community-based cohort. OSA patients may benefit from more aggressive efforts to prevent pneumonia and other infectious conditions.

Diagnosis of familial hypercholesterolemia: a work in progress

Purpose: An ICD-10 code for Familial Hyperchole sterolemia (FH), E78.01, became effective October 2016 following a proposal in 2013 to the ICD-10 Coordination and Maintenance Committee by the Family Heart Foundation. The code differentiated FH from other forms of elevated cholesterol, signaling the need for differential diagnosis of a condition in which management in the first two decades of life can substantially reduce the burden of aggressive atherosclerosis. This study aims to characterize the % of FH patients diagnosed with E78.01 in an expansive, real-world US dataset. Method(s): The Family Heart DatabaseTM includes diagnostic/ procedural/prescription data from claims and/or laboratory data for >300 million individuals from the US who were screened or treated for any form of cardiovascular risk. This analysis dataset includes 197 million people, including 22 million children, with diagnostic data from October 2016 through June 2020. The number of total (diagnosed + undiagnosed) FH patients within the dataset was estimated assuming an occurrence of 1:250 individuals. Patients with FH (E78.01) were counted if the diagnostic code was applied for a single in-patient claim or at least twice, >7 days apart, for an out-patient claim. Result(s): The number of patients diagnosed with FH using E78.01 has increased substantially since 2016. During 2017 and 2018, use of the code was brisk and likely included previously and newly diagnosed individuals. Diagnosis was reduced dramatically with the onset of the COVID-19 pandemic corresponding with the marked reduction of in-person clinic visits and near halting of preventive care. By June 2020, 246,689 patients were diagnosed with FH representing 31.3% of the estimated total (diagnosed + undiagnosed) FH population of 787,886 within the dataset. Compared with all individuals in the analysis dataset, those diagnosed with FH were substantially more likely to have atherosclerotic cardiovascular disease (40% versus 8%). Conclusion(s): Prior to 2016, an estimated <1% of patients with FH in the US were diagnosed, but without an ICD code it was impossible to track. The number of patients diagnosed with FH (E78.01) has increased substantially since 2016. Within this large, real-world dataset of Americans, 31.3% of the estimated FH population had been diagnosed as of June 2020. However, despite clear screening guidelines, effective therapies, and classification of FH as a public health threat by the World Health Organization, most of the FH population remains undiagnosed, leaving these genetically vulnerable individuals at high risk for premature cardiovascular disease.

Improving Access to Extracranial-Intracranial Bypass Surgery in Border Hispanic Communities Utilizing Collaborative Approach Between Plastics and Neurological Surgery

INTRODUCTION: Hispanic patients such as those with Moyamoya disease are less likely to receive surgical revascularization therapy due to inequities in access (1). Our institution is a located in the Southern Texas- Mexico border region serving a largely Hispanic population. We previously referred patients for EC-IC bypass to other quaternary-care centers in Texas. While referrals were already challenging due to distance, mixed immigration status, and poor socioeconomic background of many patients;COVID-19 further exacerbated this problem with restriction of elective surgical volume. METHOD(S): A consecutive series of EC-IC bypasses performed by authors (SKD and MDLG) were retrospectively reviewed. Baseline clinical, perioperative radiographic, and post-operative outcomes were studied. All patients were offered option of a referral to a quaternary-care centers and also given local option for performing bypass surgery. Further, patients met preoperatively with both the plastic and neurological surgeon. Ultimately, decision was made by patient. RESULT(S): A total of 6 craniotomies for EC-IC bypass were performed during the study period. The diagnoses included Moyamoya in 5 cases and symptomatic intracranial atherosclerosis in one. All patients were Hispanic, female, and nonsmokers with mean age of 35.6 years. Mean preoperative HBa1c was 7.9, preoperative LDL was 82, and mean preoperative hemoglobin was 11.3. Direct bypass was performed in 40% of cases. Mean OR time was 3 hours and 7 minutes. CONCLUSION(S): We have found collaboration between plastic and neurological surgery for surgical revascularization is feasible and improved access to care for Hispanic Moyamoya disease patients residing in a border community.

Abstracts From the American Heart Association's Epidemiology and Prevention/Lifestyle and Cardiometabolic Health 2022 Scientific Sessions

The proceedings contain 385 papers. The topics discussed include: racial and ethnic differences in the population burden of dementia attributable to modifiable risk factors in the United States;higher visit-to-visit variability in fasting glucose and HbA1c is associated with decline in global cognitive performance: the Multi-Ethnic Study of Atherosclerosis (MESA);prevalence of stroke symptoms among Hispanic/Latino adults in the Hispanic community health study/study of Latinos (HCHS/SOL);educational attainment and dementia risk: mediation by vascular risk factors at mid-life in the atherosclerosis risk in communities (ARIC) study;a healthy plant-based diet was associated with slower cognitive decline in African Americans: a biracial community-based cohort of older adults;outcome preferences related to cardiovascular preventive therapies in older adults: an online survey;subclinical myocardial injury, coagulopathy, and inflammation in Covid-19: a meta-analysis;COVID-19 and type II NSTEMI: a comprehensive overview;association of antecedent statin use with outcomes of people with Covid-19 admitted at northwestern medicine health system;and social determinants of health and ambulatory outcomes among Covid-19 positive patients: differences by race/ethnicity.

Pharmacogenetics-guided dalcetrapib therapy after an acute coronary syndrome: the dal-GenE trial.

AIMS: In a retrospective analysis of dal-Outcomes, the effect of dalcetrapib on cardiovascular events was influenced by an adenylate cyclase type 9 (ADCY9) gene polymorphism. The dal-GenE study was conducted to test this pharmacogenetic hypothesis. METHODS AND RESULTS: dal-GenE was a double-blind trial in patients with an acute coronary syndrome within 1-3 months and the AA genotype at variant rs1967309 in the ADCY9 gene. A total of 6147 patients were randomly assigned to receive dalcetrapib 600 mg or placebo daily. The primary endpoint was the time from randomization to first occurrence of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 39.9 months, the primary endpoint occurred in 292 (9.5%) of 3071 patients in the dalcetrapib group and 327 (10.6%) of 3076 patients in the placebo group [hazard ratio 0.88; 95% confidence interval (CI) 0.75-1.03; P = 0.12]. The hazard ratios for the components of the primary endpoint were 0.79 (95% CI 0.65-0.96) for myocardial infarction, 0.92 (95% CI 0.64-1.33) for stroke, 1.21 (95% CI 0.91-1.60) for death from cardiovascular causes, and 2.33 (95% CI 0.60-9.02) for resuscitated cardiac arrest. In a pre-specified on-treatment sensitivity analysis, the primary endpoint event rate was 7.8% (236/3015) in the dalcetrapib group and 9.3% (282/3031) in the placebo group (hazard ratio 0.83; 95% CI 0.70-0.98). CONCLUSION: Dalcetrapib did not significantly reduce the risk of occurrence of the primary endpoint of ischaemic cardiovascular events at end of study. A new trial would be needed to test the pharmacogenetic hypothesis that dalcetrapib improves the prognosis of patients with the AA genotype. CLINICAL TRIAL REGISTRATION: Trial registration dal-GenE ClinicalTrials.gov Identifier: NCT02525939.

Clinical case analysis of novel coronavirus pneumonia complicated with pulmonary hypertension.

Objective: To report the clinical features of pulmonary hypertension diagnosed by echocardiography in 5 patients with novel coronavirus pneumonia (COVID-19) in order to understand the special clinical manifestations of COVID-19 and explore the possible mechanism. Method(s): The echocardiographic data and clinical characteristics of COVID-19 patients complicated with pulmonary hypertension diagnosed by echocardiography in Beijing Ditan Hospital, Capital Medical University were analyzed descriptively from February 5 to March 31, 2020. Result(s): A total of 15 patients with severe and critical COVID-19 patients underwent echocardiography. Of them, 7 patients were diagnosed with pulmonary hypertension, 5 of which were confirmed as complications of COVID-19. Among the 5 patients, 4 were female and 1 was male, aged 62-78 years;4 were with hypertension, 3 were with diabetes, and 1 was with coronary atherosclerotic heart disease. All 5 critically ill patients with COVID-19 were given ventilator-assisted breathing, 2 of which were given extracorporeal membrane oxygenation at the same time. According to echocardiography, the systolic pressure of pulmonary artery in 5 patients was 43-65 mmHg, with an average of 54 mmHg. The severity of pulmonary hypertension was graded as mild in 1 patient and moderate in 4 patients. During the follow-up, pulmonary artery systolic pressure gradually decreased to normal in 4 patients, and then ventilator and ECMO were withdrawn;1 patient died due to respiratory failure and persistent pulmonary hypertension. Conclusion(s): Patients with COVID-19 may be complicated by pulmonary hypertension, which is often found in the critical patients. Echocardiography is an important imagingdiagnostic method for pulmonary hypertension in patients with COVID-19.Copyright © 2020 by the Chinese Medical Association.

Persistence to long-term PCSK9 inhibitors treatment and its effectiveness in familial hypercholesterolemia: Data from the SAFEHEART study

Background: Most patients with heterozygous familial hypercholesterolemia (FH) do not achieve current LDL-C goals proposed by European guidelines with conventional lipid-lowering therapy (LLT). Chronic use of PCSK9 inhibitors (PCSK9i) have shown to reduce LDL-C levels up to 61% on top of statins. Persistence to chronic LLT is important to reduce the burden of atherosclerotic cardiovascular disease (ASCVD). Purpose(s): To analyze persistence and effectiveness of PCSK9i in clinical practice setting in FH patients from the SAFEHEART register with longterm follow-up. Method(s): SAFEHEART is an open, long-term prospective study of a cohort of subjects with molecular diagnosis of FH. Follow-up is carried out every year through a standardized phone-call to collect clinical conditions, persistence to medications, lipid profile, and cardiovascular events. This study analyses subjects >=18 years of age on stable LLT who have received PCSK9i. Result(s): 696 individuals (46% females), median age 56.4 years (IQR 49- 66) started with PCSK9i (49% alirocumab and 51% evolocumab). Out of them 38% had history of ASCVD, and 89% were on maximum LLT. Median LDL-C at the moment of starting PCSK9i was 145 mg/dL (IQR, 123- 177), representing a poor 2016 & 2019 ESC/EAS guidelines achievement (3% and 0.1% respectively). After a median follow-up of 3.7 years (IQR, 2.3-4.8), 669 patients (96%) remained on PCSK9i treatment during entire follow-up. Only 27 patients (4%) discontinued, 5 temporarily (0.7%) and 22 permanently (3.2%). Most common reasons for PCSK9i treatment interruption were medical decision (n=6), adverse event (AE) (n=5), patient decision not related with AE (n=5) and comorbidity (n=5). Median time to permanent discontinuation was 15 months (IQR, 4-33). Median LDL-C levels observed and % of LDL-C reduction obtained after 1 year of treatment and in the last follow-up visit were: 63 mg/dL (IQR, 43- 88), 61 mg/dL (IQR, 44-82), 57.6% (IQR, 39.5-69) and 58% (IQR, 44-68), respectively. 2016 ESC/EAS guidelines LDL-C goals was achieved by 70% of patients at year 1 and 77% in the last follow-up visit after the introduction of PCSK9i (p<0.001). 2019 ESC/EAS goals were achieved by 44.5% and 48% (p=0.1). Conclusion(s): Long-term persistence to PCSK9i treatment in FH patients is very high (96%) and reasons for discontinuation are diverse. This study shows that COVID-19 pandemic did not affected persistence to treatment. Effectiveness in LDL-C reduction and LDL-C goal achievement improved significantly with introduction of PCSK9i in clinical practice setting.

A Review on Therapeutic Potential of Indian Herbal Plants to Counter Viral Infection and Disease Pathogenesis

Herbal plant extracts or purified phytocomponents have been extensively used to treat several diseases since ancient times. The Indian Ayurvedic system and Chinese traditional medicines have documented the medicinal properties of important herbs. In Ayurveda, the polyherbal formulation is known to exhibit better therapeutic efficacy compared to a single herb. This review focuses on six key ayurvedic herbal plants namely, Tinospora cordifolia, Withania somnifera, Glycyrrhiza glabra/Licorice, Zingiber officinale, Emblica officinalis and Ocimum sanctum. These plants possess specific phytocomponents that aid them in fighting infections and keeping body healthy and stress-free. Plants were selected due to their reported antimicrobial and anti-inflammatory effects in several diseases and effectiveness in controlling viral pathogenesis. An ad-vanced literature search was carried out using Pubmed and google scholar. Result(s): These medicinal plants are known to exhibit several protective features against various diseases or infections. Here we have particularly emphasized on antioxidant, anti-inflammatory, anti-microbial and immunomodulatory properties which are common in these six plants. Recent literature analysis has revealed Ashwagandha to be protective for Covid-19 too. The formulation from such herbs can exhibit synergism and hence better effectiveness against infection and related dis-eases. The importance of these medicinal herbs becomes highly prominent as it maintains the har-monious balance by way of boosting the immunity in a human body. Further, greater mechanistic analyses are required to prove their efficacy in fighting infectious diseases like Covid-19. It opens the arena for in-depth research of identifying and isolating the active components from these herbs and evaluating their potency to inhibit viral infections as polyherbal formulations.Copyright © 2023 Bentham Science Publishers.

Trained innate immunity and diseases: Bane with the boon

Emerging research shows that innate immunity can also keep the memory of prior experiences, challenging the long-held notion that immunological memory is only the domain of the adaptive immune cells. However, the absence of immunological memory in innate immune responses has recently been brought into question. Now it is known that after a few transient activations, innate immune cells may acquire immunological memory phenotype, resulting in a stronger response to a subsequent secondary challenge. When exposed to particular microbial and/or inflammatory stimuli, trained innate immunity is characterized by the enhanced non-specific response, which is regulated by substantial metabolic alterations and epigenetic reprogramming. Trained immunity is acquired by two main reprogramming, namely, epigenetic reprogramming and metabolic adaptation/reprogramming. Epigenetic reprogramming causes changes in gene expression and cell physiology, resulting in internal cell signaling and/or accelerated and amplified cytokine release. Metabolic changes due to trained immunity induce accelerated glycolysis and glutaminolysis. As a result, trained immunity can have unfavorable outcomes, such as hyper inflammation and the development of cardiovascular diseases, autoinflammatory diseases, and neuroinflammation. In this review, the current scenario in the area of trained innate immunity, its mechanisms, and its involvement in immunological disorders are briefly outlined.Copyright © 2022

Hematopoietic bone marrow renin-angiotensin system in health and disease

A locally active renin–angiotensin system (RAS) present in the bone marrow, which controls the growth, production, proliferation, and differentiation of hematopoietic cells. Local bone marrow RAS has also a role in neoplastic hematopoiesis such as genesis of leukemia and other malignancies. The local RAS in bone marrow plays important roles in atherosclerosis. The "bone marrow response-to-lipid” hypothesis integrates the knowledge that proatherogenic features of hematopoietic and nonhematopoietic progenitors are determined by the local actions of modified LDL on the expression of local RAS genes. There is a relationship between the autonomic nervous system and bone marrow cells. This association between bone marrow stromal cells, hematopoietic stem cell, and nerve terminals has been described as the "neuroreticular complex.” A characteristic feature of early hypertension is endothelial dysfunction. Bone marrow–related endothelial progenitor cells contribute in the healing of injured endothelium. Relationship between autonomous nervous system and bone marrow vasculature could be an important mechanism of the pathophysiology of hypertension. Local bone marrow RAS has important role in COVID-19 syndrome. ACE2 receptor is presented on the surface of hematopoietic stem/progenitor cells within the context of local bone marrow RAS that characterizes a target for the SARS-CoV-2 attack on bone marrow hematopoiesis. Bone marrow and lung tissue are in a harmony in hematopoiesis under the control of tissue RAS. RAS genes are critical at the initiation of the infections initiated by coronavirus family members and can have an important association with the exchange of immune genes in due clinical course following the infection. The aim of this chapter is to focus on the impacts of the local bone marrow RAS on definitive and neoplastic hematopoiesis, as well as its interrelationships among atherosclerosis, hypertension, and COVID-19 syndrome. © 2023 Elsevier Inc. All rights reserved.