Adhesion G protein-coupled receptors (aGPCRs) play an important role in neurodevelopment, immune defence and cancer; however, their role throughout viral infections is mostly unexplored. We have been searching for specific aGPCRs involved in SARS-CoV-2 infection of mammalian cells. In the present study, we infected human epithelial cell lines derived from lung adenocarcinoma (Calu-3) and colorectal carcinoma (Caco-2) with SARS-CoV-2 in order to analyse changes in the level of mRNA encoding individual aGPCRs at 6 and 12 h post infection. Based on significantly altered mRNA levels, we identified four aGPCR candidates-ADGRB3/BAI3, ADGRD1/GPR133, ADGRG7/GPR128 and ADGRV1/GPR98. Of these receptors, ADGRD1/GPR133 and ADGRG7/GPR128 showed the largest increase in mRNA levels in SARS-CoV-2-infected Calu-3 cells, whereas no increase was observed with heat-inactivated SARS-CoV-2 and virus-cleared conditioned media. Next, using specific siRNA, we downregulated the aGPCR candidates and analysed SARS-CoV-2 entry, replication and infectivity in both cell lines. We observed a significant decrease in the amount of SARS-CoV-2 newly released into the culture media by cells with downregulated ADGRD1/GPR133 and ADGRG7/GPR128. In addition, using a plaque assay, we observed a reduction in SARS-CoV-2 infectivity in Calu-3 cells. In summary, our data suggest that selected aGPCRs might play a role during SARS-CoV-2 infection of mammalian cells.

• Klíčová slova
• ADGRD1, ADGRG7, Caco-2, Calu-3, GPR128, GPR133, SARS-CoV-2, adhesion GPCR, mRNA expression,
• MeSH
• adenokarcinom plic * genetika   virologie   patologie   metabolismus   MeSH
• Caco-2 buňky MeSH
• COVID-19 * genetika   virologie   metabolismus   MeSH
• lidé MeSH
• messenger RNA * genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory plic genetika   virologie   patologie   metabolismus   MeSH
• receptory spřažené s G-proteiny * metabolismus   genetika   MeSH
• SARS-CoV-2 * genetika   fyziologie   metabolismus   MeSH
• upregulace * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• messenger RNA * MeSH
• receptory spřažené s G-proteiny * MeSH

Nanomedicine for treating post-viral infectious disease syndrome is at an emerging stage. Despite promising results from preclinical studies on conventional antioxidants, their clinical translation as a therapy for treating post-COVID conditions remains challenging. The limitations are due to their low bioavailability, instability, limited transport to the target tissues, and short half-life, requiring frequent and high doses. Activating the immune system during coronavirus (SARS-CoV-2) infection can lead to increased production of reactive oxygen species (ROS), depleted antioxidant reserve, and finally, oxidative stress and neuroinflammation. To tackle this problem, we developed an antioxidant nanotherapy based on lipid (vesicular and cubosomal types) nanoparticles (LNPs) co-encapsulating ginkgolide B and quercetin. The antioxidant-loaded nanocarriers were prepared by a self-assembly method via hydration of a lyophilized mixed thin lipid film. We evaluated the LNPs in a new in vitro model for studying neuronal dysfunction caused by oxidative stress in coronavirus infection. We examined the key downstream signaling pathways that are triggered in response to potassium persulfate (KPS) causing oxidative stress-mediated neurotoxicity. Treatment of neuronally-derived cells (SH-SY5Y) with KPS (50 mM) for 30 min markedly increased mitochondrial dysfunction while depleting the levels of both glutathione peroxidase (GSH-Px) and tyrosine hydroxylase (TH). This led to the sequential activation of apoptotic and necrotic cell death processes, which corroborates with the crucial implication of the two proteins (GSH-Px and TH) in the long-COVID syndrome. Nanomedicine-mediated treatment with ginkgolide B-loaded cubosomes and vesicular LNPs showed minimal cytotoxicity and completely attenuated the KPS-induced cell death process, decreasing apoptosis from 32.6% (KPS) to 19.0% (MO-GB), 12.8% (MO-GB-Quer), 14.8% (DMPC-PEG-GB), and 23.6% (DMPC-PEG-GB-Quer) via free radical scavenging and replenished GSH-Px levels. These findings indicated that GB-LNPs-based nanomedicines may protect against KPS-induced apoptosis by regulating intracellular redox homeostasis.

• Klíčová slova
• ginkgolide B, glutathione peroxidase, long COVID syndrome, nanomedicine, oxidative stress, quercetin,
• MeSH
• antioxidancia * farmakologie   MeSH
• COVID-19 metabolismus   MeSH
• farmakoterapie COVID-19 * MeSH
• ginkgolidy * farmakologie   MeSH
• glutathionperoxidasa * metabolismus   MeSH
• laktony farmakologie   MeSH
• lidé MeSH
• nanočástice * MeSH
• nanomedicína * metody   MeSH
• neurony účinky léků   virologie   MeSH
• oxidační stres * účinky léků   MeSH
• quercetin farmakologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• SARS-CoV-2 účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ginkgolide B MeSH Prohlížeč

Coronavirus disease 2019 (COVID-19), the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which counts more than 650 million cases and more than 6.6 million of deaths worldwide, affects the respiratory system with typical symptoms such as fever, cough, sore throat, acute respiratory distress syndrome (ARDS), and fatigue. Other nonpulmonary manifestations are related with abnormal inflammatory response, the "cytokine storm", that could lead to a multiorgan disease and to death. Evolution of effective vaccines against SARS-CoV-2 provided multiple options to prevent the infection, but the treatment of the severe forms remains difficult to manage. The cytokine storm is usually counteracted with standard medical care and anti-inflammatory drugs, but researchers moved forward their studies on new strategies based on cell therapy approaches. The perinatal tissues, such as placental membranes, amniotic fluid, and umbilical cord derivatives, are enriched in mesenchymal stromal cells (MSCs) that exert a well-known anti-inflammatory role, immune response modulation, and tissue repair. In this review, we focused on umbilical-cord-derived MSCs (UC-MSCs) used in in vitro and in vivo studies in order to evaluate the weakening of the severe symptoms, and on recent clinical trials from different databases, supporting the favorable potential of UC-MSCs as therapeutic strategy.

• Klíčová slova
• COVID-19, SARS-CoV-2, Wharton’s jelly, cell-based therapy, cell-free therapy, clinical trials, cytokine storm, extracellular vesicles, inflammatory diseases, mesenchymal stromal cells, umbilical-cord-derived mesenchymal stromal cells,
• MeSH
• COVID-19 * metabolismus   MeSH
• cytokiny metabolismus   MeSH
• lidé MeSH
• mezenchymální kmenové buňky * metabolismus   MeSH
• pandemie MeSH
• placenta metabolismus   MeSH
• pupečník MeSH
• SARS-CoV-2 metabolismus   MeSH
• těhotenství MeSH
• vakcíny proti COVID-19 MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH
• vakcíny proti COVID-19 MeSH

OBJECTIVE: A summary of new knowledge on embryo implantation in dependence on quality of the endometrium. METHODS: Literature review from August 2022 of the relevant publications in Web of Science, Scopus and PubMed/Medline databases, focused on “endometrial receptivity”, “polycystic ovary syndrome”, “endometriosis”, “SARS-CoV-2”. RESULTS: The receptive state of the endometrium is a result of physiological remodeling and immune system activity modulated by the microbio-me. This balance can be disturbed by myomas, polyps, sactosalpings, adenomyosis, endometriosis, polycystic ovary syndrome, infections. The effect of SARS-CoV-2 infection is being discussed. For a successful implantation, timing of transfer is crucial. The ultrasound examination is used conventionally. In specific cases, hysteroscopy and endometrium bio-psy are recommended. Histological and immunohistochemical evaluation is performed together with examination of microbio-me or transcriptome. To support the implantation, gestagenes are used, or metformin in the patients with polycystic ovary syndrome. In cases of a repeated implantation failure, the intrauterine infusion of mononuclear cells or platelet rich plasma is used, subcutaneous application of granulocyte colony stimulating growth factor, intravenous application of atosiban or intrauterine application of human chorionic gonadotropin. CONCLUSION: Recent research in the field of transcriptomics, proteomics and reproductive immunology uncovers the process of implantation more deeply and opens a new stage of the assisted reproduction.

• Klíčová slova
• Endometriosis, SARS-CoV-2, adenomyosis, endometrial receptivity, implantation, polycystic ovaries, proteome, receptivity of endometrium, secretome,
• MeSH
• choriogonadotropin MeSH
• COVID-19 * metabolismus   MeSH
• endometrióza * MeSH
• endometrium fyziologie   MeSH
• implantace embrya fyziologie   MeSH
• lidé MeSH
• SARS-CoV-2 MeSH
• syndrom polycystických ovarií * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• choriogonadotropin MeSH

Despite the growing list of identified SARS-CoV-2 receptors, the human angiotensin-converting enzyme 2 (ACE2) is still viewed as the main cell entry receptor mediating SARS-CoV-2 internalization. It has been reported that wild-type mice, like other rodent species of the Muridae family, cannot be infected with SARS-CoV-2 due to differences in their ACE2 receptors. On the other hand, the consensus heparin-binding motif of SARS-CoV-2's spike protein, PRRAR, enables the attachment to rodent heparan sulfate proteoglycans (HSPGs), including syndecans, a transmembrane HSPG family with a well-established role in clathrin- and caveolin-independent endocytosis. As mammalian syndecans possess a relatively conserved structure, we analyzed the cellular uptake of inactivated SARS-CoV-2 particles in in vitro and in vivo mice models. Cellular studies revealed efficient uptake into murine cell lines with established syndecan-4 expression. After intravenous administration, inactivated SARS-CoV-2 was taken up by several organs in vivo and could also be detected in the brain. Internalized by various tissues, inactivated SARS-CoV-2 raised tissue TNF-α levels, especially in the heart, reflecting the onset of inflammation. Our studies on in vitro and in vivo mice models thus shed light on unknown details of SARS-CoV-2 internalization and help broaden the understanding of the molecular interactions of SARS-CoV-2.

• Klíčová slova
• SARS-CoV-2, cellular uptake, heparan sulfate proteoglycans, mouse, syndecans,
• MeSH
• angiotensin konvertující enzym 2 metabolismus   MeSH
• COVID-19 * metabolismus   virologie   MeSH
• heparansulfát proteoglykany metabolismus   MeSH
• internalizace viru * MeSH
• lidé MeSH
• myši MeSH
• SARS-CoV-2 * metabolismus   MeSH
• savci metabolismus   MeSH
• syndekany metabolismus   MeSH
• tkáňová distribuce * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• angiotensin konvertující enzym 2 MeSH
• heparansulfát proteoglykany MeSH
• syndekany MeSH

Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and is a promising drug target for novel antivirals against SARS-CoV-2. The marine natural product gallinamide A and several synthetic analogues were identified as potent inhibitors of cathepsin L with IC50 values in the picomolar range. Lead molecules possessed selectivity over other cathepsins and alternative host proteases involved in viral entry. Gallinamide A directly interacted with cathepsin L in cells and, together with two lead analogues, potently inhibited SARS-CoV-2 infection in vitro, with EC50 values in the nanomolar range. Reduced antiviral activity was observed in cells overexpressing transmembrane protease, serine 2 (TMPRSS2); however, a synergistic improvement in antiviral activity was achieved when combined with a TMPRSS2 inhibitor. These data highlight the potential of cathepsin L as a COVID-19 drug target as well as the likely need to inhibit multiple routes of viral entry to achieve efficacy.

• MeSH
• antivirové látky chemická syntéza   chemie   farmakologie   MeSH
• biologické přípravky chemická syntéza   chemie   farmakologie   MeSH
• buňky A549 MeSH
• Cercopithecus aethiops MeSH
• COVID-19 metabolismus   MeSH
• farmakoterapie COVID-19 * MeSH
• inhibitory cysteinových proteinas chemická syntéza   chemie   farmakologie   MeSH
• kathepsin L antagonisté a inhibitory   metabolismus   MeSH
• kationické antimikrobiální peptidy chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• molekulární konformace MeSH
• proteomika MeSH
• SARS-CoV-2 účinky léků   MeSH
• Vero buňky MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antivirové látky MeSH
• biologické přípravky MeSH
• CTSL protein, human MeSH Prohlížeč
• gallinamide A MeSH Prohlížeč
• inhibitory cysteinových proteinas MeSH
• kathepsin L MeSH
• kationické antimikrobiální peptidy MeSH

Mitochondrial DNA (mtDNA) heteroplasmy is the dynamically determined co-expression of wild type (WT) inherited polymorphisms and collective time-dependent somatic mutations within individual mtDNA genomes. The temporal expression and distribution of cell-specific and tissue-specific mtDNA heteroplasmy in healthy individuals may be functionally associated with intracellular mitochondrial signaling pathways and nuclear DNA gene expression. The maintenance of endogenously regulated tissue-specific copy numbers of heteroplasmic mtDNA may represent a sensitive biomarker of homeostasis of mitochondrial dynamics, metabolic integrity, and immune competence. Myeloid cells, monocytes, macrophages, and antigen-presenting dendritic cells undergo programmed changes in mitochondrial metabolism according to innate and adaptive immunological processes. In the central nervous system (CNS), the polarization of activated microglial cells is dependent on strategically programmed changes in mitochondrial function. Therefore, variations in heteroplasmic mtDNA copy numbers may have functional consequences in metabolically competent mitochondria in innate and adaptive immune processes involving the CNS. Recently, altered mitochondrial function has been demonstrated in the progression of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Accordingly, our review is organized to present convergent lines of empirical evidence that potentially link expression of mtDNA heteroplasmy by functionally interactive CNS cell types to the extent and severity of acute and chronic post-COVID-19 neurological disorders.

• Klíčová slova
• COVID-19, Central nervous system, Gut microbiome, Immune response, Mitochondrial DNA, SARS-CoV-2,
• MeSH
• COVID-19 komplikace   genetika   imunologie   metabolismus   MeSH
• heteroplazmie genetika   MeSH
• imunita MeSH
• lidé MeSH
• mitochondriální DNA genetika   MeSH
• mitochondrie metabolismus   MeSH
• nemoci nervového systému komplikace   genetika   imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mitochondriální DNA MeSH

In December of 2019, several cases of unknown atypical respiratory diseases emerged in Wuhan, Hubei Province in China. After preliminary research, it was stated that the disease is transmittable between humans and was named COVID-19. Over the course of next months, it spread all over the world by air and sea transport and caused a global pandemic which affects life of everyone now-a-days. A large number of countries, have since been forced to take precautions such as curfews, lockdowns, wearing facemasks etc. Even with vaccines being produced in mass numbers, lack of targeted therapy continues to be a major problem. According to studies so far it seems that elderly people are more vulnerable to severe symptoms while children tend to by asymptomatic or have milder form the disease. In our review, we focused on gathering data about the virus itself, its characteristics, paths of transmission, and its effect on hormone production and secretion. In such, there is insufficient information in the literature worldwide, especially the ones that focus on the effect of COVID-19 on individual organs systems within the human body. Hence, the present evidence-based study focused on the possible effects of COVID-19 on adrenal gland and gonads i.e. on the process of steroidogenesis and fertility.

• MeSH
• COVID-19 metabolismus   patofyziologie   virologie   MeSH
• fertilita * MeSH
• gonády metabolismus   patofyziologie   virologie   MeSH
• interakce hostitele a patogenu MeSH
• lidé MeSH
• nadledviny metabolismus   patofyziologie   virologie   MeSH
• SARS-CoV-2 patogenita   MeSH
• steroidy biosyntéza   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• steroidy MeSH

COVID-19 (Coronavirus Disease) is an infectious disease caused by the coronavirus SARS-CoV-2 (Severe acute respiratory syndrome Coronavirus 2), which belongs to the genus Betacoronavirus. It was first identified in patients with severe respiratory disease in December 2019 in Wuhan, China. It mainly affects the respiratory system, and in severe cases causes serious lung infection or pneumonia, which can lead to the death of the patient. Clinical studies show that SARS-CoV-2 infection in critical cases causes acute tissue damage due to a pathological immune response. The immune response to a new coronavirus is complex and involves many processes of specific and non-specific immunity. Analysis of available studies has shown various changes, especially in the area of specific cellular immunity, including lymphopenia, decreased T cells (CD3+, CD4+ and CD8+), changes in the T cell compartment associated with symptom progression, deterioration of the condition and development of lung damage. We provide a detailed review of the analyses of immune checkpoint molecules PD-1, TIM-3, LAG-3 CTLA-4, TIGIT, BTLA, CD223, IDO-1 and VISTA on exhausted T cells in patients with asymptomatic to symptomatic stages of COVID-19 infection. Furthermore, this review may help to better understand the pathological T cell immune response and improve the design of therapeutic strategies for patients with SARS-CoV-2 infection.

• MeSH
• COVID-19 imunologie   metabolismus   virologie   MeSH
• fenotyp MeSH
• interakce hostitele a patogenu MeSH
• lidé MeSH
• proteiny kontrolních bodů imunitní reakce metabolismus   MeSH
• SARS-CoV-2 imunologie   patogenita   MeSH
• signální transdukce MeSH
• T-lymfocyty imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• proteiny kontrolních bodů imunitní reakce MeSH

In this review, we discuss the role of pulmonary surfactant in the host defense against respiratory pathogens, including novel coronavirus SARS-CoV-2. In the lower respiratory system, the virus uses angiotensin-converting enzyme 2 (ACE2) receptor in conjunction with serine protease TMPRSS2, expressed by alveolar type II (ATII) cells as one of the SARS-CoV-2 target cells, to enter. ATII cells are the main source of surfactant. After their infection and the resulting damage, the consequences may be severe and may include injury to the alveolar-capillary barrier, lung edema, inflammation, ineffective gas exchange, impaired lung mechanics and reduced oxygenation, which resembles acute respiratory distress syndrome (ARDS) of other etiology. The aim of this review is to highlight the key role of ATII cells and reduced surfactant in the pathogenesis of the respiratory form of COVID-19 and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS patients.

• MeSH
• angiotensin konvertující enzym 2 metabolismus   MeSH
• COVID-19 imunologie   metabolismus   virologie   MeSH
• farmakoterapie COVID-19 MeSH
• interakce hostitele a patogenu MeSH
• internalizace viru MeSH
• lidé MeSH
• plíce účinky léků   imunologie   metabolismus   virologie   MeSH
• plicní surfaktanty terapeutické užití   MeSH
• pneumocyty účinky léků   imunologie   metabolismus   virologie   MeSH
• proteiny asociované s plicním surfaktantem metabolismus   MeSH
• SARS-CoV-2 imunologie   patogenita   MeSH
• serinové endopeptidasy metabolismus   MeSH
• virové receptory metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• ACE2 protein, human MeSH Prohlížeč
• angiotensin konvertující enzym 2 MeSH
• plicní surfaktanty MeSH
• proteiny asociované s plicním surfaktantem MeSH
• serinové endopeptidasy MeSH
• TMPRSS2 protein, human MeSH Prohlížeč
• virové receptory MeSH