Pharmacological Properties and Safe Use of 12 Medicinal Plant Species and Their Bioactive Compounds Affecting the Immune System

This paper presents raw plant materials and their characteristic compounds which may affect the immune system. Plant-derived agents in specific doses affect the body's non-specific, antigen-independent defense system. They have immunostimulatory effects on the entire immune regulatory system. They can enhance the immune response through various factors such as macrophages, leukocytes, and granulocytes, as well as through mediators released by the cellular immune system. This paper was inspired by the threats caused by the COVID-19 pandemic. The proper functioning of the immune system is important in limiting the effects of viral infection and restoring the normal functioning of the body. This paper also emphasizes the importance of the skillful use of plant immunostimulants by potential patients, but also by those who prescribe drugs. It is important not only to choose the right plant drug but above all to choose the correct dose and duration of treatment.

Type 1 diabetes and environment . . . and other stories

A linked ecological analysis of environmental and demographic variables identified several factors, including poor air quality, outdoor light at night, and higher population density that were negatively associated with the incidence of diabetes (Diabetologia doi:10.1007/s00125-020-05087-7). A case-control study using a database of people known to have autoimmune disease raises anxiety about central nervous system inflammatory events (JAMA Neurol doi:10.1001/jamaneurol.2020.1162). A history of exposure to TNF inhibitors carried a threefold increase in risk both of demyelinating diseases, such as multiple sclerosis and optic neuritis, and of non-demyelinating conditions, such as encephalitis, neurosarcoidosis, and vasculitis.

Effect of synbiotics on inflammatory markers and white blood cell count in COVID-19 patients: a randomized, double-blind, placebo-controlled clinical trial

PurposeToday, coronavirus disease-19 (COVID-19) treatment is an evolving process, and synbiotic administration has been suggested as a new therapeutic strategy. This study aims to investigate the effect of synbiotic supplementation in COVID-19 patients.Design/methodology/approachIn this placebo-controlled trial, 80 patients were randomized to receive oral synbiotic capsule (containing fructooligosaccharide and seven bacterial strains;Lactobacillus (L) casei, L. rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, L. acidophilus, Bifidobacterium longum, L. bulgaricus, each one 109 colony-forming units) or placebo for two months. Inflammatory markers (Interleukin-6 [IL-6], C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]) and white blood cell (WBC) count were evaluated at two timepoints (baseline, two months later). The measured variables were adjusted for confounders and analyzed by SPSS v21.0.FindingsAll 80 enrolled patients completed the study. The study adherence was good (approximately 70%). The mean changes for IL-6 were not significant (Δ = −0.6 ± 10.4 pg/mL vs Δ = +11.2 ± 50.3 pg/mL, p > 0.05). There were no significant improvements for CRP, ESR and WBC.Originality/valueAdministration of synbiotics for two months did not improve inflammatory markers in COVID-19 patients.

Selected Phytochemicals to Combat Lungs Injury: Natural Care.

The human has two lungs responsible for respiration and drug metabolism. Severe lung infection caused by bacteria, mycobacteria, viruses, fungi, and parasites may lead to lungs injury. Smoking and tobacco consumption may also produce lungs injury. Inflammatory and pain mediators are secreted by alveolar macrophages. The inflammatory mediators, such as cytokines, interleukin (IL)-1, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α, neutrophils, and fibroblasts are accumulated in the alveoli sac, which becomes infected. It may lead to hypoxia followed by severe pulmonary congestion and the death of the patient. There is an urgent need for the treatment of artificial respiration and ventilation. However, the situation may be the worst for patients suffering from lung cancer, pulmonary tuberculosis, and acute pneumonia caused by acute respiratory distress syndrome (ARDS). Re-urgency has been happening in the case of coronavirus disease of 2019 (COVID-19) patients. Therefore, it is needed to protect the lungs with the intake of natural phytomedicines. In the present review, several selected phyto components having the potential role in lung injury therapy have been discussed. Regular intake of natural vegetables and fruits bearing these constituents may save the lungs even in the dangerous attack of SARS-CoV-2 in lung cancer, pulmonary TB, and pneumatic patients.

Continuous Glucose Monitoring in Hypoxic Environments Based on Water Splitting-Assisted Electrocatalysis

Conventional enzyme-based continuous glucose sensors in interstitial fluid usually rely on dissolved oxygen as the electron-transfer mediator to bring electrons from oxidase to electrode while generating hydrogen peroxide. This may lead to several problems. First, the sensor may provide biased detection results owing to fluctuation of oxygen in interstitial fluid. Second, the polymer coatings that regulate the glucose/oxygen ratio can affect the dynamic response of the sensor. Third, the glucose oxidation reaction continuously produces corrosive hydrogen peroxide, which may compromise the long-term stability of the sensor. Here, we introduce an oxygen-independent nonenzymatic glucose sensor based on water splitting-assisted electrocatalysis for continuous glucose monitoring. For the water splitting reaction (i.e., hydrogen evolution reaction), a negative pretreatment potential is applied to produce a localized alkaline condition at the surface of the working electrode for subsequent nonenzymatic electrocatalytic oxidation of glucose. The reaction process does not require the participation of oxygen;therefore, the problems caused by oxygen can be avoided. The nonenzymatic sensor exhibits acceptable sensitivity, reliability, and biocompatibility for continuous glucose monitoring in hypoxic environments, as shown by the in vitro and in vivo measurements. Therefore, we believe that it is a promising technique for continuous glucose monitoring, especially for clinically hypoxic patients.

Discovering a Dihydrofluorescein Analogue as a Promising Fluorescence Substrate to HRP

Horseradish peroxidase (HRP) combined with its fluorescence substrates is attracting increasing attention for biochemical analysis. Amplex red is the most widely used fluorescence substrate to HRP;however, it suffers from some drawbacks, such as nonspecific responsiveness toward carboxylesterases. Discovering a new small molecular fluorescence substrate with improved sensitivity and selectivity for HRP is thus desired. Herein, three dihydrofluorescein derivatives (DCFHs) are presented to serve as HRP substrates through fluorescence turn-on methods. The most promising one, 2,7-dichloro-9-(2-(hydroxymethyl)phenyl)-9H-xanthene-3,6-diol (DCFH-1), exhibited excellent sensitivity in the detection of HRP. Moreover, DCFH-1 does not respond to carboxylesterase, thus holding advantages over Amplex red. In the further study, the detection reagent in the commercial ELISA kits was replaced with DCFH-1 to establish a new fluorescence ELISA, which works very well in the quantification of inflammatory cytokine biomarkers from in vitro models.

Lichen planus after COVID-19 infection and vaccination.

Lichen planus (LP) is an inflammatory disorder believed to result from CD8 + cytotoxic T-cell (CTL)-mediated autoimmune reactions against basal keratinocytes. We present a review of LP following COVID-19 infection and vaccination. Literature searches were conducted on PubMed and Google Scholar from 2019 to 7/2022. 36 articles were selected based on subject relevance, and references within articles were also screened. 39 cases of post-vaccination LP and 6 cases of post-infection LP were found among case reports and case series. 152 cases of post-vaccination LP and 12 cases of post-infection LP were found in retrospective and prospective studies. LP is a rare complication of COVID-19 infection and vaccination that may be mediated by overstimulation of T-cell responses and proinflammatory cytokine production. However, it does not represent a limitation against COVID-19 vaccination, and the benefits of vaccination considerably outweigh the risks.

T4 Novel lung organoid model reveals crucial role of lung resident mesenchymal stromal cells in COPD pathogenesis

T4 Figure 1Cellular condensation of primary distal lung cells;epithelial, endothelial, and mesenchymal stromal cells in Matrigel results in a large multicellular structure that matures over a period of 21 d to resemble the normal human alveoli. A Whole organoid imaging reveleas protruding bulbous structures projecting away from the main organoid body, are composed of SPC+ epithelial cells and are connected by a basic network of CD31+endothelial cells. Scale bar: 250 μm. Blue: DAPI, Green: SPC, Magenta: CD31. B Alveolar-like spheres are composed of SPC+ (green) and AQP5+ (red)cells. Scale bar: 100 μm. Blue: DAPI, Green: SPC, Red: AQP5. C Organoids formed with the seeding of MSCs isolated from healthy lungs (top) and MSCs isolated from lungs of COPD (bottom). Replacement of healthy MSCs with COPD MSCs results in loss of organoid symmetry and reduced size. Scale bar 1000 μm D HGF secretion levels are significantly lower in the organoids formed with COPD MSCs compared to organoids with healthy MSCs (P<0.05, Kurskal-Wallis)[Figure omitted. See PDF]ConclusionCondensation of primary pulmonary cells provides a physiologically relevant distal lung organoid model that features endothelial cell presence. COPD lung MSCs are not able to support growth of endothelial cells and induce irregular spatial organisation of alveolar epithelial cells.FundingMRC UK MR/S009426/1 to Dr. Anna KrasnodembskayaPlease refer to page A208 for declarations of interest related to this .

Experience with tumour necrosis factor-alpha inhibitors for the treatment of cardiac sarcoidosis in a UK medical centre

P217 Table 1Case series outcomes table Case no. IFX dose& regime Follow-up duration (months) Change in prednisolone dose Change in FDG-PET uptake Change in LV systolic function Change in arrythmia burden Adverse events Composite Endpoint Dose pre-IFX(mg) Dose post-IFX(mg) Pre-IFX Post-IFX LVEF pre-IFX (%) LVEF post-IFX(%) Pre-IFX Post-IFX Infections Heart failure VT/VF (requiring device) All-cause mortality Aborted SCD (device) Cardiac Transplant Case 1 IFX 3 mg/kg every 8 weeks (break after 10th dose due to covid pandemic;restarted 3 months later) 29 20 15 Active CS(SUVmax 11.1) Improvement(SUVmax3.5) 58 59 N/A N/A 0 0 0 0 0 0 Case 2 IFX 3 mg/kg every 8 weeks. Stopped after 15.6 months due to resolution 15.6 10 10 Active CS(SUVmax 10.2) Improvement(SUVmax 2.65) 55 62 VA 0 1 (chest infection) 0 0 0 0 0 Case 2Relapse (7 months after stopping IFX) due to VT and FDG uptake IFX 3 mg/kg every 8 weeks 12 10 10 Active CS(SUVmax 3.3) Improvement(no uptake) N/A 50 VA 0 0 Mild LVSD 0 0 0 0 Case 3 IFX 3 mg/kg0 weeks and 4 weeks;missed 8 weeks’ appointment due to COVID-19 10 20 20 Active CS(SUVmax 11.3) N/A 55 N/A 0 N/A 1 (Covid-19) 0 0 0 0 0 Case 4 IFX 3 mg/kg at 0, 2 and 8 weeks afterwards 16 20 10 Active CS(SUVmax 13) Improved(SUVmax 3.4) 45 66 VA N/A 0 0 0 1 (PFO and shunt/complications) 0 0 Case 5 IFX 3 mg/kg 0, 2, 6 and every 8 weeks 8.5 30 15 Active CS(SUVmax 11.3) Improved(no uptake) 46 51 VA 0 0 0 0 0 0 0 Totals 6 IFX 3 mg/kg Mean=15.2 Mean=18.3 Mean=13.3 All had active CS 5 improved;1 data not available Mean=51.8 Mean=57.6 4 had VAs;1 data not available None had VA;3 had data not available 2 1 0 1 0 0 CS = cardiac sarcoidosis;FDG-PET =fluorodeoxyglucose positron emission tomography;IFX = Infliximab;LV = left ventricular;LVEF = left ventricular ejection fraction;LVSD = left ventricular systolic dysfunction;N/A = data not available;PFO= patent foramen ovale;

Therapeutic Effect of Gegentang Granules on Mouse Model with hCoV-229E Pneumonia and Hanshi Yidu Xifei Syndrome

Objective：To determine the therapeutic effect of Gegentang granules on a disease-syndrome mouse model combining human coronavirus 229E（hCoV-229E）pneumonia with Hanshi Yidu Xifei syndrome in vivo. Method： Mice were randomly divided into normal group，infection group，cold-dampness group，model group，chloroquine phosphate group（0.18 g·kg-1），interferon-α2b（IFN-α2b）group（1.83×106 U·kg-1）， Gegentang granules high-dose and low-dose groups（6.6，3.3 g·kg-1）with 10 mice in each group. Cold-dampness environment and hCoV-229E infection were used for modeling，and the general status and lung index of mice in each group were observed. The viral load in lung tissue was detected by real-time fluorescent quantitative polymerase chain reaction（Real-time PCR），the pathological changes in lung tissue were evaluated by hematoxylin-eosin（HE）staining，the levels of serum gastrointestinal hormones and inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assay（ELISA），and the percentage of peripheral blood lymphocytes was detected by flow cytometry. Result：Comparing with model group，Gegentang granules could significantly alleviate the physical signs of Hanshi Yidu Xifei syndrome，including listlessness，weakness of limbs，sticky stool，etc. Comparing with model group，Gegentang granules high-dose group significantly reduced lung index，histopathological score of interstitial lung and bronchus，and the level of serum motilin（P< 0.05，P<0.01），two doses of Gegentang granules could significantly increase the level of serum gastrin（P< 0.05，P<0.01），the percentage of CD4+ ，CD8+ T lymphocytes in peripheral blood（P<0.05，P<0.01），and the level of tumor necrosis factor-α（TNF-α）in lung tissue was significantly decreased（P<0.01），and the level of interleukin-6（IL-6）showed decreasing tendency. Conclusion： Gegentang granules has therapeutic effect on model mice. It can improve the appearance and behavior characterization，regulate the level of gastrointestinal hormones，decrease lung index and histopathological score，and possibly play an immunomodulatory role by inhibiting the expression of inflammatory cytokines in lung tissue and restoring the percentage of peripheral blood lymphocytes. © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Structural characterization and anti-inflammatory activity of fucoidan isolated from Ecklonia maxima stipe

Enzyme-assisted hydrolysis is frequendy used as a cost-effective and efficient method to obtain functional ingredients from bioresources. This study involved die enzyme-assisted hydrolyzation and purification of fucoidan from Ecklonia maxima stipe and die investigation of its anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Fucoidans of Viscozyme-assisted hydrolysate from E. maxima (EMSFs) harvested in Jeju, Korea. Structural and chemical characterizations were performed using fourier transform infrared spectroscopy, scanning electron microscope, and monosaccharide analysis. Among fucoidans, EMSF6 was rich in fucose and sulfate and had a similar structural character to commercial fucoidan. EMSF6 showed a strong inhibitory effect on nitric oxide generation in LPS-induced RAW 264.7 cells and significantly decreased die production of LPS-induced pro-inflammatory cytokines, including interleukin-6, interleukin-1 p, and tumor necrosis factor a. The anti-inflammatory potential of EMSF6 was mediated through the down-regulation of inducible nitric oxide synthase and cyclooxygenase-2 expression. Thus, fucoidans from&temppound;. maxima stipe are promising candidates for functional food products.

A systematic review and meta-analysis on blood levels of cytokines/chemokines in COVID-19 cases

We assessed the blood levels of the most important factors such as cytokines/chemokines in Coronavirus disease-2019 (COVID-19). PubMed/Medline and Scopus as two important databases were searched up to March 26, 2020. To analyze the data, we used Review Manager 5.3 software. Out of forty-two records retrieved from two databases, 10 studies were involved in the analysis. Thirty-three cytokines/chemokines were checked. The levels of 27 cytokines/chemokines in COVID-19 patients were higher than the healthy controls, and among 20 cytokines/chemokines;the levels of 10 cytokines/chemokines in severe COVID-19 patients were higher than non-severe COVID-19 patients. Also, out of three cytokines, one had a higher level in the intensive care unit (ICU) patients compared to the non-ICU patients. The findings showed the cytokine storm syndrome in COVID-19 patients, especially in patients with severe disease.

Impact of Dialysis Clinical Operating Conditions on Human Serum Protein-Mediated Inflammatory Biomarkers Released in Patients Using Polyarylethersulfone Membranes

Hemodialysis (HD) is a life-sustaining treatment of crucial importance in managing end-stage renal disease (ESRD). However, this membrane-based therapy is associated with acute side-effects due to bioincompatibility issues and limitations on the removal of uremic toxins. The present study assessed the influence of hydrodynamic conditions applied during HD treatment on protein-mediated inflammatory and thrombotic responses. The membrane modules considered are commonly used in Canadian hospitals and are comprised of a polymer blend of polyarylether sulfone-polyvinylpyrrolidone (PAES). The membranes morphology and hydrophilicity were assessed using SEM, AFM, BET, and zeta potential. An in vitro study evaluated the adsorptive behavior of fibrinogen (FB) to the membrane under different flow conditions. Lower rates of 200 mL/min promoted slower and significant FB adsorption, leading to more severe inflammatory and thrombotic responses. Hydrodynamic conditions also affected the concentration of all inflammatory biomarkers. Lower flow rates triggered more complement activation as well as coagulation, clotting, and inflammatory responses compared to higher flow rates. At the end of the dialysis session, patients treated with a Qb of 200 mL/min presented a significant increase in the concentration of C5a (232%), properdin (114%), serpin (545%), IL-1α (50%), IL-6 (450%), and vWF (212%). IL-1β and TNF-α concentrations declined by 12.5 and 35.5%, respectively. Male patients experienced more severe inflammatory responses than female patients at the operating conditions considered. Comparing the pre- and post-dialysis levels of female and male patients, female patients experienced significantly higher levels of IL-6 and properdin, while male patients presented higher levels of C5a, IL-1α, and IL-6. The results of this study will help clinical doctors evaluate the impact of HD operating conditions on blood activations before prescribing treatment and inform expectations for outcomes in female and male patients.

Seven days in medicine: 6-12 July 2022

NHS organisations will have to comply with the Climate Change Act 2008, which set targets to reduce greenhouse gas emissions, and the Environment Act 2021, which outlined targets for improving the natural environment, including air quality. Since the US Supreme Court’s overturning of Roe v Wade, 15 states have banned abortion or have severely limited the circumstances under which it is permitted. Emergency care Recovery plan is inadequate on all levels, says RCEM The government’s 10 point action plan to mitigate pressures and improve performance in urgent and emergency care services is “inadequate” on every metric, concluded a “report card” assessment by the Royal College of Emergency Medicine.

Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders

It has been found that soluble epoxide hydrolase (sEH;encoded by the EPHX2 gene) in the metabolism of polyunsaturated fatty acids (PUFAs) plays a key role in inflammation, which, in turn, plays a part in the pathogenesis of neuropsychiatric disorders. Meanwhile, epoxy fatty acids such as epoxyeicosatrienoic acids (EETs), epoxyeicosatetraenoic acids (EEQs), and epoxyeicosapentaenoic acids (EDPs) have been found to exert neuroprotective effects in animal models of neuropsychiatric disorders through potent anti-inflammatory actions. Soluble expoxide hydrolase, an enzyme present in all living organisms, metabolizes epoxy fatty acids into the corresponding dihydroxy fatty acids, which are less active than the precursors. In this regard, preclinical findings using sEH inhibitors or Ephx2 knock-out (KO) mice have indicated that the inhibition or deficiency of sEH can have beneficial effects in several models of neuropsychiatric disorders. Thus, this review discusses the current findings of the role of sEH in neuropsychiatric disorders, including depression, autism spectrum disorder (ASD), schizophrenia, Parkinson’s disease (PD), and stroke, as well as the potential mechanisms underlying the therapeutic effects of sEH inhibitors.

Current update on theranostic roles of cyclophilin A in kidney diseases

Cyclophilin A (CyPA) or peptidylprolyl isomerase A (PPIA), an immunophilin with peptidyl-prolyl cis/trans isomerase (PPIase) activity, is an abundant cellular protein widely expressed across various cell types and tissues, including the kidney. Expression of CyPA in the kidney is relatively higher in proximal tubular epithelial cells than others along the nephron. Alterations in expression and secretion of CyPA play important roles in physiological processes and pathophysiology of several diseases affecting the kidney. Herein, we provide a brief overview of CyPA structural biology and present the current update on its theranostic roles in various kidney diseases, including diabetic nephropathy, acute kidney injury, chronic kidney disease, renal fibrosis, and nephrotoxicity associated with organ transplantation. Notably, the diagnostic/prognostic role for urinary CyPA in several of these kidney diseases is promising. Finally, future perspectives on the CyPA research, especially targeting CyPA for therapeutics, are discussed. A comprehensive understanding of the theranostic roles of CyPA in kidney diseases is expected to provide novel insights into the design of new therapeutic interventions and prevention strategies.

Association of tumor necrosis factor alpha ‐308 single nucleotide polymorphism with SARS CoV‐2 infection in an Iraqi Kurdish population

Uncovering risk factors playing roles in the severity of Coronavirus disease 2019 (Covid‐19) are important for understanding pathoimmunology of the disease caused by severe acute respiratory syndrome Coronavirus 2 (SARS CoV‐2). Genetic variations in innate immune genes have been found to be associated with Covid‐19 infections. A single‐nucleotide polymorphism (SNP) in a promoter region of tumor necrosis factor alpha (TNF‐α) gene, TNF‐α −308G>A, increases expression of TNF‐α protein against infectious diseases leading to immune dysregulations and organ damage. This study aims to discover associations between TNF‐α −308G>A SNP and Covid‐19 infection. Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) was used for genotyping a general Kurdish population and Covid‐19 patients. The homozygous mutant (AA) genotype was found to be rare in the current studied population. Interestingly, the heterozygous (GA) genotype was significantly (p value = 0.0342) higher in the Covid‐19 patients than the general population. This suggests that TNF‐α −308G>A SNP might be associated with Covid‐19 infections. Further studies with larger sample sizes focusing on different ethnic populations are recommended.