Future challenges and their impact on respiratory health and lung cancer

Air pollution, climate and population health are closely related in terms of their impacts on respiratory health and lung cancer. Air pollutants contribute to the exacerbation of chronic respiratory problems such as COPD and asthma. Air pollutants are also toxic and carcinogenic, initiating and promoting lung cancer development. Climate change in relation to environmental pollution affects the geographical distribution of food supply and diseases such as pneumonia in adults and children. The threat of air pollution, and hence global warming and climate changes, and their effects on population and respiratory health, is an imminent threat to the world and deserves immediate and sustainable combating strategies and efforts. The goals are to increase public awareness and engagement in action, with alignment of international collaboration and policy, and with steering towards further research. Now is the prime time for international collaborative efforts on planning and actions to fight air pollution and climate change before it is too late.Copyright © ERS 2021.

Helicobacter Pylori and Sars-Cov-2: A Dangerous Pathogenetic Correlation?

Background and aim: The correlation between Covid-19 and nonrespiratory bacteria is mostly unexplored. The following considerations led us to investigate a possible correlation between Hp and SARS-CoV2: both are microbial agents with a very large-scale epidemiology;both can cause GI symptoms;both can persist in the GI tract for long time [Fei Xiao, 2022];patients with pre-existing HP gastric colonization, once infected by SARS-CoV-2, complain more frequently and with greater severity of GI symptoms such as abdominal pain and diarrhea [Balamtekin, 2019];SARS-CoV-2 binds ACE-2 receptors to enter cells, which are widely expressed in the GI tract. In addition, Hp is known to increase the expression of ACE-2 receptors. This study aims to investigate, by C13 Urea BT, the prevalence of Hp infection and the DOB (delta over baseline), in pre-pandemic period (pPP), from Sept. 2017 to Dec. 2019, and during Covid-19 pandemic period (PP), from Jan. 2020 to Apr. 2022, to evaluate whether SARS-CoV-2 and Hp infection association is only due to chance or whether represents a pathogenetic correlation. Material(s) and Method(s): This is a retrospective preliminary study on 1532 randomized patients: 825 and 707 referring respectively to pPP and PP. Result(s): 316 patients underwent C13 Urea BT for the diagnosis of Hp infection: 36 out of 179 (20.11%), and 74 out of 137 (54.01%), respectively in pPP and in PP, tested positive for Hp. The DOB of patients tested during the PP was 40.4+/-17.5, significantly higher when compared to the mean value found in pPP: 17.4+/-16.5 (p=0.0001). [Figure presented] Conclusion(s): Neglecting the search for Hp, also due to difficulties encountered in this period to access BT, represents a risk condition for gastric diseases, especially considering the remarkable elevation of the prevalence and the DOB caused, somehow, by the SARS-CoV-2 virus. Particularly, the higher the DOB, the higher the bacterial load, but, more significantly, the greater the ability of the bacterial strains to produce urease: the strains with the greatest urease-activity are cagA+ strains (those capable of producing the oncogenic protein involved in the process of carcinogenesis) [Moreno-Ochoa, 2020]. Thus, it can be assumed that the higher the DOB, the greater the risk of developing serious gastric problems in the absence of treatment. So, in conclusion, Sars-Cov-2 and HP infection may influence each other. GI morphological and functional alterations due to Sars-Cov-2 infection, which can promote HP colonization and replication, need further investigation.Copyright © 2023. Editrice Gastroenterologica Italiana S.r.l.

Silymarin: A Phytoconstituent with Significant Therapeutic Potential-A Narrative Review

Silymarin, is a phytoactive constituent isolated from the fruits and seeds of Silybum maria-num L Gaetn.), also called milk thistle belonging to the family of Asteracease. The phytoactive has been used to treat several physiological disorders. The objective of this manuscript was to review the therapeutic prospective of silymarin due to its ability to treat several physiological disorders. The da-tabases such as Pubmed, Elsevier, and Google Scholar were reviewed for the investigations or reviews published related to the title. The discussion is focused on the immunomodulatory, chemopreventive, and anti-inflammatory mechanisms of silymarin in various metabolic and dermatological disorders. In addition, the review discusses the different therapeutic potentials of silymarin such as the management of the liver disorder, skin carcinogenesis, cardiovascular disorders, diabetes mellitus, neurodegenera-tive disorders, and several dermatological disorders such as melasma, anti-aging, acne, rosacea, atopic dermatitis, and psoriasis. Silymarin is safe even with a dose higher than the therapeutic dose. Si-lymarin had good potential for the safe and effective treatment of numerous metabolic and dermatological disorders. © 2023 Bentham Science Publishers.

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.

The Impact of COVID-19 on Breast Cancer Recurrence: A Brief Review

COVID-19 has affected several aspects of health care systems worldwide. While our understanding of the impact of cancer and its treatment on COVID-19 mortality is improving, there is still little known regarding the possible mechanisms by which COVID-19 might affect cancer cells, especially breast cancer. Several factors activated during COVID-19 have been implicated in tumorigenesis and the development of metastasis. Inflammation, hypoxia, reduced levels of angiotensin-converting enzyme 2, and elevated levels of interleukin 6 and some other cytokines that are hallmarks of COVID-19 are capable of inducing tumor relapse and metastasis. Understanding the interaction between COVID-19 and breast cancer cells is essential for evaluating the potential long-term risks of COVID-19 in patients and for scheduling necessary preventive, screening, and therapeutic interventions.Copyright © 2022 Elsevier Masson SAS. All rights reserved.

14th German Endocrine Brain Immune Network, GEBIN

The proceedings contain 48 papers. The topics discussed include: mental and physical health in informal caregiving and associations with relationship quality between caregiver and care recipient - a pilot study;immune-mediated early endocrine response during tumorigenesis;characterization of circulating dendritic cells in major depressive disorder;immune age correlates with cardiorespiratory fitness, but not with general intelligence;investigation of the relationship between immune age and vaccination against SARS-CoV-2;the steroid hormone dehydroepiandrosterone (DHEA) counteracts the consequences of psychological trauma on immunocellular ageing and mitochondrial bioenergetics;prediction of antibody levels after COVD-19 vaccination: evidence for immune interoception;and temporal dynamics of cytokine changes in blood, cerebrospinal fluid and brain tissue of endotoxemic rats.

In vitro and in silico perspectives to explain anticancer activity of a novel syringic acid analog ((4-(1H-1, 3-benzodiazol-2-yl)-2, 6-dimethoxy phenol)) through apoptosis activation and NFkB inhibition in K562 leukemia cells.

Syringic acid (SA) is an active carcinogenesis inhibitor; however, the low bioavailability and unstable functional groups hinder its activity. Here, a chemically synthesized novel SA analog (SA10) is evaluated for its anticancer activity using in-vitro and in-silico studies. K562 cell line study revealed that SA10 had shown a higher rate of inhibition (IC50 = 50.40 µg/mL) than its parental compound, SA (IC50 = 96.92 µg/mL), at 50 µM concentration. The inhibition ratio was also been evaluated by checking the expression level of NFkB and Bcl-2 and showing that SA10 has two-fold increase in the inhibitory mechanism than SA. This result demonstrates that SA10 acts as an NFkB inhibitor and an apoptosis inducer. Further, molecular docking and simulation have been performed to get insights into the possible inhibitory mechanism of SA and SA10 on NFkB at the atomistic level. The molecular docking results exemplify that both SA and SA10 bind to the active site of NFkB, thereby interfering with the association between DNA and NFkB. SA10 exhibits a more robust binding affinity than SA and is firmly docked well into the interior of the NFkB, as confirmed by MM-PBSA calculations. In a nutshell, the Benzimidazole scaffold containing SA10 has shown more NFkB inhibitory activity in K562 cells than SA, which could be helpful as an ideal therapeutic NFkB inhibitor for treating cancers.

Mesenchymal Stem/Stromal Cells: Late Breaking Abstract: FIRST EVIDENCE FOR THE TRANSLATIONAL POTENTIAL OF MESENCURE™, A PROFESSIONALIZED ALLOGENEIC MESENCHYMAL CELL THERAPY, FOR TREATING IMMUNOTHERAPY-RELATED CYTOKINE RELEASE SYNDROME

Background & Aim: Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) are related side effects of immunotherapies seen in up to 76% of patients treated with CAR-T and 48% of those treated with BiTEs. In up to 27% of the patients, these syndromes may lead to severe consequences. Current treatments for severe CRS are ineffective in >30% of the cases and can worsen ICANS prognosis, calling for novel treatments, especially in light of the expanding use of immunotherapies. Despite their obvious potential, mesenchymal cell (MSC) therapies were seldom investigated in this context. In the present study, Bonus BioGroup has set to assess the potential for treating CRS with MesenCure™, our allogeneic MSC platform, professionalized to enhance the cells’ potency and shown safe and effective in severe COVID patients. Methods, Results & Conclusion: A highly translational and validated CRS model was established in humanized NSG mice bearing human PBMCs, B-cell lymphoma, and CAR-T cells. CAR-T introduction significantly increased the serum levels of proinflammatory cytokines in model animals, indicative of CRS (Fig. 1A). Two IV MesenCure injections were well-tolerated in this model (Fig. 1B) and did not obstruct the CAR-Ts’ ability to inhibit tumor growth by 89% (Fig. 1C, p<0.0001). Remarkably, significant reductions in all proinflammatory cytokines tested (excluding IL-6) were measured in model animals treated with MesenCure, substantiating its potential to treat CRS (Fig. 1A). Interestingly, the magnitudes of these reductions resembled those observed in 50 severe COVID patients treated with MesenCure. MesenCure’s robust immunomodulatory capacity was further demonstrated in vitro by its ability to inhibit the proliferation of activated CD4 T cells with an IC50 of 6k MSC/200k PBMCs, twice more effectively than non-professionalized MSCs. Comparable results were also obtained with CD8 T cells. Similarly, MesenCure inhibited neutrophils’ ROS production by up to 80% within an hour following activation (IC50 19k MSC/200k neutrophils). These effects are likely mediated, in part, by IDO, whose RNA levels were found to be 6.8-fold higher in MesenCure cells than in non-professionalized MSCs (p<0.05), two hours after activation with IFNγ. Moreover, IDO inhibition by 1-MT (1 mM) reduced MesenCure’s (Figure Presented) Fig. 1 (A) The levels of serum proinflammatory cytokines measured in tumor-bearing NSG mice after CRS induction by injection of human PBMCs/CAR-Ts (or saline control) and MesenCure treatment (or saline control). Experimental groups’ designation: Control – not injected with PBMCs/CAR-Ts and not treated by MesenCure;CAR-T – CRS model animals, injected with PBMCs/CAR-Ts but not treated with MesenCure;MesenCure – treated with MesenCure but not injected with PBMCs/CARTs;and CAR-T + MesenCure – CRS model animals treated with MesenCure. (B) Relative change in body weight from the day of tumor induction (Day 0) and (C) IVIS analysis of tumor burden (dorsal aspect) in the above four experimental groups. Statistical significance indicators: ns – not significant, * p<0.05, *** p<0.001, **** p<0.0001. Statistical tests: Holm-Šídák’s multiple comparisons test (A) and two- sided t-test (C). ability to inhibit T cells’ proliferation by 73%. In conclusion, we provide the first evidence for the potential of MSCs and MesenCure, in particular, for treating immunotherapy-related CRS.

Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation Studies of the Molecular Targets and Mechanisms of ChuanKeZhi in the Treatment of COVID-19

Objectives: Coronavirus disease 2019 (COVID-19) has had a global impact and is spreading quickly. ChuanKeZhi injection (CKZI) is widely used in asthma patients. In this paper, we aimed to explore active compounds of CKZ and determine potential mechanisms against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through network pharmacology, molecular docking and dynamic simulation studies. Materials and Methods: We used the Systematic Pharmacology Database and Analysis Platform of Traditional Chinese Medicine (TCMSP) to screen active compounds and potential target proteins of CKZ. COVID-19 target genes were screened via the American National Center for Biotechnology Information (NCBI) gene database and human gene database (GeenCards). The protein interaction network was constructed by the Protein Interaction Network Database (Search Tool for the Retrieval of Interacting Genes/Proteins (STRING)) platform. GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by the Metascape database. The main active compounds of CKZ were docked with angiotensin-converting enzyme 2 (ACE2), spike protein S1, and SARS-CoV-2-3CL pro and also docked with hub targets. We performed molecular dynamics (MD) simulation studies for validation. Results: We finally obtained 207 CKZ potential targets and 4681 potential COVID-19 targets. Key targets included mainly AKT1, TNF, IL6, VEGFA, IL1B, TP53, JUN, CASP3, etc. There were 217 Gene Ontology (GO) items in the GO enrichment analysis (p < 0.05). The main KEGG pathways included the advanced glycation end products (AGE)- receptor for AGE (RAGE) signalling pathway in diabetic complications, rheumatoid arthritis, chemical carcinogenesis-receptor activation, alcoholic liver disease, etc. Molecular docking and dynamics simulation studies both exhibited great binding capacity. Conclusions: Network pharmacology, molecular docking and dynamics simulation studies were used to identify the potential and key targets, pharmacological functions, and therapeutic mechanisms of CKZI in the treatment of COVID-19. CKZI may be an effective and safe drug in COVID-19 treatment. However, further work is needed for validation.

Microarray-Based Transcriptome Analysis of Peripheral Blood Mononuclear Cells in Lung Cancer Patients

: Lung cancer is the most commonly occurring cancer in men worldwide. To search for new biological markers of this pathology, the transcriptome of the blood mononuclear cells from patients and healthy donors (residents of Kemerovo oblast, Russia) was studied using SurePrint G3 Human Gene Expression microarray technology. A total of 288 differentially expressed genes were identified, including 108 up-regulated genes and 180 down-regulated genes. Functional enrichment analysis using the WebGestalt resource and different databases (Gene Ontology, KEGG, and Reactome) indicated changes in the expression profiles of genes involved in the processes of immune response, protein synthesis, cell cycle control, and apoptosis. Analysis of protein–protein interactions using the STRING algorithm made it possible to identify functional clusters of gene products with different expression levels.

Production of meat products based on organic rabbit breeding resources with the inclusion of protein-carbohydrate composites of plant origin

The World Health Organization recommends limiting the consumption of processed and red meat products due to the increased risk of developing cancer of the gastrointestinal tract of people and a decrease in immunity with a new coronavirus infection. An alternative to red meat is rabbit meat, rich in polyunsaturated fatty acids, which prevent carcinogenesis, causing apoptosis, control the cell cycle and the production of eicosanoids. For the production of meat products, dietary supplements are traditionally used to improve the consistency and increase the yield of finished products, which in some cases do not meet safety requirements. In this context, the use of rationally selected biopolymer plant complexes in combination with a protein component of animal origin is promising and can be safely used in the production cycle of products of various compositions. To obtain meat products based on rabbit meat using biotechnological approaches, protein-carbohydrate complexes containing sprouted forms of legumes, jerusalem artichoke dietary fibers and composites of animal and vegetable origin have been developed. Protein-carbohydrate complexes contained 17.2 – 23.7% protein, 2.20 – 4.70% fat and 18.2 – 21.8% dietary fiber in their composition. And conducting a biological assessment on a test culture indicates that the developed protein-carbohydrate complexes are physiological for biotest, that is, they have the necessary level of safety, which allows them to be recommended for enriching meat-based food systems and expanding the range of products produced by meat processing enterprises.

Neuroendocrine cancer of the prostate. Two case reports

Background: Neuroendocrine cancer of the prostate can present in diverse clinical pictures, potentially hampering the diagnosis and probably leading to underdiagnosis. Methods: Two cases are presented corresponding respectively to two forms of the disease: de novo neuroendocrine cancer and dedifferenciation of an adenocarcinoma of the prostate to neuroendocrine cancer under long term luteinising hormone releasing hormone (LHRH) agonist treatment. Results: Suspicion of neuroendocrine cancer may be raised in prostate cancer patients presenting either clinical or radiological metastatic progression without prostate specific antigen (PSA) rise, or relatively extended metastatic disease right at diagnosis associated to relatively low PSA, yet any non-pulmonary visceral metastases. Neuroendocrine cancer of the prostate can also turn out to be the origin of an adenocarcinoma of unknown primary. Conclusion: In case these considerations are respected the risk of missing the correct diagnosis of a neuroendocrine cancer of the prostate may be minimised.

Never Cared for What They Do: High Structural Stability of Guanine-Quadruplexes in the Presence of Strand-Break Damage

DNA integrity is an important factor that assures genome stability and, more generally, the viability of cells and organisms. In the presence of DNA damage, the normal cell cycle is perturbed when cells activate their repair processes. Although efficient, the repair system is not always able to ensure complete restoration of gene integrity. In these cases, mutations not only may occur, but the accumulation of lesions can either lead to carcinogenesis or reach a threshold that induces apoptosis and programmed cell death. Among the different types of DNA lesions, strand breaks produced by ionizing radiation are the most toxic due to the inherent difficultly of repair, which may lead to genomic instability. In this article we show, by using classical molecular simulation techniques, that compared to canonical double-helical B-DNA, guanine-quadruplex (G4) arrangements show remarkable structural stability, even in the presence of two strand breaks. Since G4-DNA is recognized for its regulatory roles in cell senescence and gene expression, including oncogenes, this stability may be related to an evolutionary cellular response aimed at minimizing the effects of ionizing radiation.

The Multifaceted Effects of Gut Microbiota on the Immune System of the Intestinal Mucosa

The gut microbiota has diverse microbial components, including bacteria, viruses, and fungi. The interaction between gut microbiome components and immune responses has been studied extensively over the last decade. Several studies have reported the potential role of the gut microbiome in maintaining gut homeostasis and the development of disease. The commensal microbiome can preserve the integrity of the mucosal barrier by acting on the host immune system. Contrastingly, dysbiosis-induced inflammation can lead to the initiation and progression of several diseases through inflammatory processes and oxidative stress. In this review, we describe the multifaceted effects of the gut microbiota on several diseases from the perspective of mucosal immunological responses.

The time-dependency of the cyclobutane pyrimidine dimer-evoked cellular damages using a CPD-specific photolyase-encoding mRNA-based model system

UVB damages DNA predominantly by the formation of cyclobutane pyrimidine dimers (CPDs) that are repaired by nucleotide excision repair system in humans. Organisms more primitive than placental mammals remove CPDs by photolyase in a process of photoreactivation that uses the energy of visible light. Our previously established model system based on transient transfection of human keratinocytes with in vitro transcribed CPD-photolyase mRNA containing 1-methylpseudouridine modifications (CPD-PL mRNA). The RNA composition is similar to that used in the BioNTech COVID-19 vaccine. Immediately, 6, 8, 12 and 24 hours after UVB irradiation, CPD-PL mRNA- transfected HaCaT and NHEK keratinocytes were either exposed to photoreactivating light or kept in the dark. Keratinocytes express functional photolyase upon transfection of CPD-PL mRNA. CPDs were effectively removed by photoreactivation immediately as well as 6 hour after transfection relieving the negative effects of UVB on cell viability and prevented the loss of cell proliferation and G2/M cell cycle block. Using our model system, it has been proved that CPDs are responsible for production of mitochondrial reactive oxygen species followed by the activation of several energy sensor enzymes, and compensatory metabolic changes in keratinocytes exposed to UVB. CPDs could be removed not only from nuclear genome but from mitochondrial genome as well and restored mitochondrial DNA copy number suggesting that damage to mitochondria can also be repaired by photolyase activation. UVB-induced mutagenesis was completely abrogated by photoreactivation emphasizing the key role of CPDs in mediating DNA damage and carcinogenesis. These results suggest that activation of a non-human photolyase encoded by nucleoside-modified mRNA is able to prevent UVB-induced cellular damage even hours after UVB exposure.

64th Annual Meeting of the Pathology Section of the German Veterinary Medical Association

These proceedings contain 25 papers from the 64th Annual Meeting of the Pathology Section of the German Veterinary Medical Association. Topics include tumour infiltrating lymphocytes in mammary carcinomas in domestic rabbits;what decides good or bad? - global gene expression analysis of the adenoma of the hepatoid perianal glands and adenocarcinoma the canine apocrine anal sac glands;the canine cutaneous histiocytoma - boring or perspective in immuno-oncology?;impact of antibiotic pretreatment on ventilator-induced lung injury: contradiction between histology and transcriptome analysis?;characterization of murine satellite glial cells of the dorsal root ganglia - a unique cell population with potential regenerative capacities;impact of antibiotic pretreatment on ventilator-induced lung injury: contradiction between histology and transcriptome analysis?;primary diffuse leptomeningeals oligodendrogliomatosis in a cat;pathomorphological studies of fibroadnexal dysplasia in dogs;pyogranulomatous inflammation in multiple Organs of a dog with evidence of Corynebacterium tuberculostearicum;ovary tumors in cats - overview of the examination material from 2009-2020 and case report of a recurrent dysgerminoma;atherosclerosis in the dog;spinal neuroenteric cyst in one Saint Bernard;MENX - an endogenous model for pseudohypoxic pheochromocytomas;molecular Level Evolution II: similarities of CLCA2 in sauropsids and mammals;in vivo detection of double-stranded Ribonucleic acid (RNA) as an early detection marker unclear viral infections using the example of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) in experimental infected hamsters;the role of different mast cell subtypes in the context of intestinal carcinogenesis - a species-comparative approach;an underestimated treasure in paraffin - establishment of a global transcriptome analysis canine tumors from FFPE material based on QuantSeq 3' technology;well researched? - an approximation of the role of CLCA1 in joints through usage molecular databases;integration of digitized historical and cytopathology into an open source DICOM database and viewer system;3R 3D: skin model for the study of viral infections;CARD9 signaling promotes hippocampal neurogenesis and cytokine balance in a mouse model of virus-induced encephalitis;neuropathological changes after intranasal infection with Rift Valley fever virus - a murine model for human encephalitis;a T-cell a day keeps Theiler away - the influence non-reactive T-cells on the course of a Theiler virus infection in mice with C57BL/6 background;digitization in pathology - new opportunities and their obstacles;and specific features of satellite glial cells of dog and pig.

Cell-cell communication analysis for single-cell RNA sequencing and its applications in carcinogenesis and COVID-19

Cell-cell communication is the basis of physiological processes and cell signals. The disease occurs when the cells do not adequately communicate and the messages are blocked. With ligand-receptor interaction databases and single-cell RNA sequencing (scRNA-seq) databases, we can detect intercellular signaling and reconstruct the cell-cell communications among different cell types. This review summarized the computational approaches for analyzing the cell-cell communication based on scRNA-seq data and discussed its applications in carcinogenesis and COVID-19. We believe that this review will accelerate the scRNA-seq data deciphering and facilitate the cell-cell communication studies for complex physiological processes, such as carcinogenesis and SARS-CoV-2 infection.