Disrupted gut microecology after high-dose 131I therapy and radioprotective effects of arachidonic acid supplementation.

BACKGROUND: Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose 131I therapy, the alterations and regulatory mechanisms dependent on intestinal microecology remain poorly understood. We aimed to identify the characteristics of the gut microbiota and metabolites in DTC patients suffering from high-dose 131I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment. METHODS: A total of 102 patients with DTC were recruited, with fecal samples collected before and after 131I therapy for microbiome and untargeted and targeted metabolomic analyses. Mice were exposed to total body irradiation with ARA replenishment and antibiotic pretreatment and were subjected to metagenomic, metabolomic, and proteomic analyses. RESULTS: 131I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after 131I treatment, and metabolites with decreased levels and pathways related to ARA and linoleic acid were observed. In an irradiation mouse model, ARA supplementation not only improved quality of life and recovered hematopoietic and gastrointestinal systems but also ameliorated oxidative stress and inflammation and preserved enteric microecology composition. Additionally, antibiotic intervention eliminated the radioprotective effects of ARA. Proteomic analysis and ursolic acid pretreatment showed that ARA therapy greatly influenced intestinal lipid metabolism in mice subjected to irradiation by upregulating the expression of hydroxy-3-methylglutaryl-coenzyme A synthase 1. CONCLUSION: These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects.

Artificial intelligence for disease diagnostics still has a long way to go.

Artificial intelligence (AI) can sometimes resolve difficulties that other advanced technologies and humans cannot. In medical diagnostics, AI has the advantage of processing figure recognition, especially for images with similar characteristics that are difficult to distinguish with the naked eye. However, the mechanisms of this advanced technique should be well-addressed to elucidate clinical issues. In this letter, regarding an original study presented by Takayama et al, we suggest that the authors should effectively illustrate the mechanism and detailed procedure that artificial intelligence techniques processing the acquired images, including the recognition of non-obvious difference between the normal parts and pathological ones, which were impossible to be distinguished by naked eyes, such as the basic constitutional elements of pixels and grayscale, special molecules or even some metal ions which involved into the diseases occurrence.

PQS and pyochelin in Pseudomonas aeruginosa share inner membrane transporters to mediate iron uptake.

Bacteria absorb different forms of iron through various channels to meet their needs. Our previous studies have shown that TseF, a type VI secretion system effector for Fe uptake, facilitates the delivery of outer membrane vesicle-associated Pseudomonas quinolone signal (PQS)-Fe3+ to bacterial cells by a process involving the Fe(III) pyochelin receptor FptA and the porin OprF. However, the form in which the PQS-Fe3+ complex enters the periplasm and how it is moved into the cytoplasm remain unclear. Here, we first demonstrate that the PQS-Fe3+ complex enters the cell directly through FptA or OprF. Next, we show that inner membrane transporters such as FptX, PchHI, and FepBCDG are not only necessary for Pseudomonas aeruginosa to absorb PQS-Fe3+ and pyochelin (PCH)-Fe3+ but are also necessary for the virulence of P. aeruginosa toward Galleria mellonella larvae. Furthermore, we suggest that the function of PQS-Fe3+ (but not PQS)-mediated quorum-sensing regulation is dependent on FptX, PchHI, and FepBCDG. Additionally, the findings indicate that unlike FptX, neither FepBCDG nor PchHI play roles in the autoregulatory loop involving PchR, but further deletion of fepBCDG and pchHI can reverse the inactive PchR phenotype caused by fptX deletion and reactivate the expression of the PCH pathway genes under iron-limited conditions. Finally, this work identifies the interaction between FptX, PchHI, and FepBCDG, indicating that a larger complex could be formed to mediate the uptake of PQS-Fe3+ and PCH-Fe3+. These results pave the way for a better understanding of the PQS and PCH iron absorption pathways and provide future directions for research on tackling P. aeruginosa infections.IMPORTANCEPseudomonas aeruginosa has evolved a number of strategies to acquire the iron it needs from its host, with the most common being the synthesis, secretion, and uptake of siderophores such as pyoverdine, pyochelin, and the quorum-sensing signaling molecule Pseudomonas quinolone signal (PQS). However, despite intensive studies of the siderophore uptake pathways of P. aeruginosa, our understanding of how siderophores transport iron across the inner membrane into the cytoplasm is still incomplete. Herein, we reveal that PQS and pyochelin in P. aeruginosa share inner membrane transporters such as FptX, PchHI, and FepBCDG to mediate iron uptake. Meanwhile, PQS and pyochelin-mediated signaling operate to a large extent via these inner membrane transporters. Our study revealed the existence of shared uptake pathways between PQS and pyochelin, which could lead us to reexamine the role of these two molecules in the iron uptake and virulence of P. aeruginosa.

Transcriptome analysis of long non-coding RNA and mRNA Profiles in VSV-infected BHK-21 Cells.

BACKGROUND: Vesicular stomatitis virus (VSV) is a typical non-segmented negative-sense RNA virus of the genus Vesiculovirus in the family Rhabdoviridae. VSV can infect a wide range of animals, including humans, with oral blister epithelial lesions. VSV is an excellent model virus with a wide range of applications as a molecular tool, a vaccine vector, and an oncolytic vector. To further understand the interaction between VSV and host cells and to provide a theoretical basis for the application prospects of VSV, we analyzed the expression of host differentially expressed genes (DEGs) during VSV infection using RNA-Seq. RESULTS: Our analyses found a total of 1015 differentially expressed mRNAs and 161 differentially expressed LncRNAs in BHK-21 cells infected with VSV for 24 h compared with controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment showed that the differentially expressed lncRNAs and their target genes were mainly concentrated in pathways related to apoptosis, cancer, disease, and immune system activation, including the TNF, P53, MAPK, and NF-kappaB signaling pathways. The differentially expressed lncRNA can modulate immune processes by regulating genes involved in these signaling transmissions. Ten randomly selected DEGs, namely, Il12rb2, F2, Masp2, Mcl1, FGF18, Ripk1, Fas, BMF, POLK, and JAG1, were validated using RT-qPCR. As predicted through RNA-Seq analysis, these DEGs underwent either up- or downregulation, suggesting that they may play key regulatory roles in the pathways mentioned previously. CONCLUSIONS: Our study showed that VSV infection alters the host metabolic network and activates immune-related pathways, such as MAPK and TNF. The above findings provide unique insights for further study of the mechanism of VSV-host interactions and, more importantly, provide a theoretical basis for VSV as an excellent vaccine carrier.

TRIM54 alleviates inflammation and apoptosis by stabilizing YOD1 in rat tendon-derived stem cells.

Tendinopathy is a disorder of musculoskeletal system that primarily affects athletes and the elderly. Current treatment options are generally comprised of various exercise and loading programs, therapeutic modalities, and surgical interventions and are limited to pain management. This study is to understand the role of TRIM54 (tripartite motif containing 54) in tendonitis through in vitro modeling with tendon-derived stem cells (TDSCs) and in vivo using rat tendon injury model. Initially, we observed that TRIM54 overexpression in TDSCs model increased stemness and decreased apoptosis. Additionally, it rescued cells from tumor necrosis factor α-induced inflammation, migration, and tenogenic differentiation. Further, through immunoprecipitation studies, we identified that TRIM54 regulates inflammation in TDSCs by binding to and ubiquitinating YOD1. Further, overexpression of TRIM54 improved the histopathological score of tendon injury as well as the failure load, stiffness, and young modulus in vivo. These results indicated that TRIM54 played a critical role in reducing the effects of tendon injury. Consequently, these results shed light on potential therapeutic alternatives for treating tendinopathy.

Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma.

Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial function in PTC. We find that fasting impairs glycolysis and reduces mitochondrial dysfunction in vitro and in vivo and also fasting in vitro and fasting mimicking diets (FMD) in vivo significantly increase the expression of lncRNA-protein kinase C theta antisense RNA 1 (PRKCQ-AS1), during the inhibition of TPC cell glycolysis and mitochondrial function. Moreover, lncRNA PRKCQ-AS1 was significantly lower in PTC tissues and cells. In addition, PRKCQ-AS1 overexpression increased PTC cell glycolysis and mitochondrial function; PRKCQ-AS1 knockdown has the opposite effect. On further mechanistic analysis, we identified that PRKCQ-AS1 physically interacts with IGF2BPs and enhances protein arginine methyltransferases 7 (PRMT7) mRNA, which is the key player in regulating glycolysis and mitochondrial function in PTC. Hence, PRKCQ-AS1 inhibits tumor growth while regulating glycolysis and mitochondrial functions via IGF2BPs/PRMT7 signaling. These results indicate that lncRNA PRKCQ-AS1 is a key downstream target of fasting and is involved in PTC metabolic reprogramming. Further, the PRKCQ-AS1/IGF2BPs/PRMT7 axis is an ideal therapeutic target for PTC diagnosis and treatment.

HOXD9/miR-451a/PSMB8 axis is implicated in the regulation of cell proliferation and metastasis via PI3K/AKT signaling pathway in human anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is a deadly disease with a poor prognosis. Thus, there is a pressing need to determine the mechanism of ATC progression. The homeobox D9 (HOXD9) transcription factor has been associated with numerous malignancies but its role in ATC is unclear. In the present study, the carcinogenic potential of HOXD9 in ATC was investigated. We assessed the differential expression of HOXD9 on cell proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) in ATC and explored the interactions between HOXD9, microRNA-451a (miR-451a), and proteasome 20S subunit beta 8 (PSMB8). In addition, subcutaneous tumorigenesis and lung metastasis in mouse models were established to investigate the role of HOXD9 in ATC progression and metastasis in vivo. HOXD9 expression was enhanced in ATC tissues and cells. Knockdown of HOXD9 inhibited cell proliferation, migration, invasion, and EMT but increased apoptosis in ATC cells. The UCSC Genome Browser and JASPAR database identified HOXD9 as an upstream regulator of miR-451a. The direct binding of miR-451a to the untranslated region (3'-UTR) of PSMB8 was established using a luciferase experiment. Blocking or activation of PI3K by LY294002 or 740Y-P could attenuate the effect of HOXD9 interference or overexpression on ATC progression. The PI3K/AKT signaling pathway was involved in HOXD9-stimulated ATC cell proliferation and EMT. Consistent with in vitro findings, the downregulation of HOXD9 in ATC cells impeded tumor growth and lung metastasis in vivo. Our research suggests that through PI3K/AKT signaling, the HOXD9/miR-451a/PSMB8 axis may have significance in the control of cell proliferation and metastasis in ATC. Thus, HOXD9 could serve as a potential target for the diagnosis of ATC.

The epidemiological characteristics and infection risk factors for extrapulmonary tuberculosis in patients hospitalized with pulmonary tuberculosis infection in China from 2017 to 2021.

BACKGROUND: Pulmonary tuberculosis (PTB) complicated with extrapulmonary tuberculosis (EPTB) infection can aggravate the disease, but there have been few reports. METHODS: Retrospective analysis was used to collect the clinical data of PTB patients with pathogen positive in a teaching hospital from 2017 to 2021. We describe the incidence, the invasive site of EPTB patients, and analyze the infection risk factors for PTB with EPTB by univariate and multivariate logistic regression models. We also compared the complications, disease burden with chi-square test and rank-sum test. RESULTS: A total of 1806 PTB were included, of which 263 (14.6%) were complicated with EPTB. The common invasive sites for EPTB were neck lymph nodes (16.49%), intestines (16.13%), and meninges (10.75%). Age ≤ 40 (OR = 1.735; 95%CI [1.267-2.376]; P = 0.001), malnutrition (OR = 2.029; 95%CI [1.097-3.753]; P = 0.022), anemia (OR = 1.739; 95%CI[1.127-2.683]; P = 0.012), and osteoporosis (OR = 4.147; 95%CI [1.577-10.905]; P = 0.004) were all independent risk factors for PTB infection with EPTB. The incidence of extrathoracic hydrothorax, intestinal bacterial infection, urinary tract bacterial infection, and abdominal bacterial infection were higher in patients with PTB with EPTB. PTB with EPTB patients also had longer median hospitalization durations (19 vs. 14 days), during which time they incurred higher total costs, laboratory test costs, imaging examination costs, and drug use costs. CONCLUSION: This study found important risk factors for PTB complicated with EPTB, such as age ≤ 40, malnutrition, anemia, and osteoporosis. PTB with EPTB patients have more extrapulmonary complications and higher hospitalization disease burden.

18F-Fluorodeoxyglucose PET/CT and MRI Imaging Characteristics of Monomorphic Epitheliotropic Intestinal T-cell Lymphoma: A case report.

Background Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare, rapidly progressive, primary intestinal T-cell lymphoma. The most common site of occurrence is on the small intestine. The prognosis of MEITL is extremely poor due to delayed diagnosis and lack of targeted therapy. Case Summary A case of MEITL involving the entire small bowel, part of the colon, rectum, mesenteric lymph nodes, and liver is herein reported. We are presenting the 18F-FDG PET/CT features of MEITL, which showed all involved lesions with increased FDG activity. The MRI and pathological characteristics of MEITL were also described. Furthermore, some malignant diseases and benign diseases should be considered in the differential diagnosis. Conclusion Based on the lesions with a high accumulation of FDG, our case shows the involved extent of MEITL, which is helpful for biopsy and treatment option decisions. We expect more could know about this disease and make an early diagnosis to improve the outcomes of MEITL.

Future therapeutic implications of new molecular mechanism of colorectal cancer.

High incidence (10.2%) and mortality (9.2%) rates led to the ranking of colorectal cancer (CRC) as the second most malignant tumor spectrum worldwide in 2020. Treatment strategies are becoming highly dependent on the molecular characteristics of CRC. The classical theories accept two models depicting the origin of CRC: The progression of adenoma to cancer and transformation from serrated polyps to cancer. However, the molecular mechanism of CRC development is very complex. For instance, CRCs originating from laterally spreading tumors (LST) do not adhere to any of these models and exhibit extremely serious progression and poor outcomes. In this article, we present another possible pathway involved in CRC development, particularly from LST, with important molecular characteristics, which would facilitate the design of a novel strategy for targeted therapy.

Cellular Innate Biological Nano Confinements Control Cancer Metastasis Through Materials Seizing and Signaling Regulating.

Cancer is a debilitating disease, causing millions of deaths annually throughout the world. Due to their adaptive ability to meet nutritional demands, cancer cells often utilize more energy than normal cells. In order to develop new strategies to treat cancer, it is necessary to understand the underlying mechanisms of energy metabolism, which is yet largely unknown. Recent studies have shown that cellular innate nanodomains are involved in cellular energy metabolism and anabolism and GPCRs signaling regulation, which have a direct effect on cell fate and functions. Therefore, harnessing cellular innate nanodomains may evoke significant therapeutic impact and shift the research focus from exogenous nanomaterials to cellular innate nanodomains, which will have great potential to develop a new treatment modality for cancer. Keeping these points in view, we briefly discuss the impact of cellular innate nanodomains and their potential for advancing cancer therapeutics, and propose the concept of innate biological nano confinements, which include any innate structural and functional nano domains both in extracellular and intracellular with spatial heterogeneity.

Pseudomonas aeruginosa H3-T6SS Combats H2O2 Stress by Diminishing the Amount of Intracellular Unincorporated Iron in a Dps-Dependent Manner and Inhibiting the Synthesis of PQS.

The type VI secretion system (T6SS), a protein translocation nanomachine, is widely distributed in Gram-negative bacteria and delivers effectors directly into target cells or the extracellular environment to help the bacteria gain a competitive fitness advantage and promote bacterial survival in harmful environments. In this study, we demonstrated that the synthesis of the Pseudomonas quinolone signal (PQS) in Pseudomonas aeruginosa PAO1 was inhibited by the H3-T6SS gene cluster under iron-rich conditions, and that this inhibition was relieved under iron starvation conditions. Conversely, PQS differentially regulated the expression of the H3-T6SS structural genes and the effector protein gene tseF. The expression of tseF was inhibited by PQS, while the expressions of the H3-T6SS structural genes were positively regulated by PQS. Further studies showed that the H3-T6SS was involved in the resistance of P. aeruginosa to oxidative stress caused by hydrogen peroxide (H2O2). Interestingly, H3-T6SS expression was neither induced by H2O2 stress nor regulated by OxyR (a global anti-oxidative transcriptional regulator) but was positively regulated by RpoS (a major transcription regulator of the stress response). In addition, we found that the clpV3 (a structural gene of H3-T6SS) mutation resulted in upregulation of two proteins related to PQS synthesis and many proteins related to oxidative stress resistance, while the expression of some iron storage proteins, especially Dps, were significantly downregulated. Furthermore, the clpV3 mutation led to an increase in the intracellular free Fe2+ content of P. aeruginosa. Further studies showed that both the PQS deficient mutation and overexpression of dps effectively restored the H2O2 sensitive phenotype of the H3-T6SS mutant. Finally, we proposed the following model of H3-T6SS-mediated resistance to H2O2 stress in P. aeruginosa. H3-T6SS not only reduces the intracellular free Fe2+ level by upregulating the expression of ferritin Dps, but also inhibits the synthesis of PQS to mediate the resistance of P. aeruginosa to H2O2 stress. This study highlights the important role of H3-T6SS in the ability of P. aeruginosa to combat H2O2 stress and provides a perspective for understanding the stress response mechanism of bacteria.

Role of atrial natriuretic peptide receptor in inhibition of laterally spreading tumors via Wnt/ß-catenin signaling.

Colorectal cancer (CRC) is the third most prevalent malignancy worldwide. Laterally spreading tumors (LSTs), as special manifestations of digestive tract tumors, are often misdiagnosed or undiagnosed due to their unique morphological and pathological features. LST has no protruding lesions and progresses rapidly, and prognoses are consequently poor. LST progression to CRC is complicated. Clinical data indicate that the heart is rarely the site of primary tumorigenesis, and a class of atrial natriuretic peptides (ANPs) secreted by heart tissue play an important role in this phenomenon, which is closely related to the Wnt/ß-catenin signaling pathway. However, previous studies focused solely on correlations between the Wnt/ß-catenin signaling pathway, downstream gene expression and LST. Thus, correlational studies of ANP/ANP receptor, LST and CRC may be of great help in understanding the occurrence, development and treatment of LST, as well as in establishing specific and sensitive methods for detecting LST.

Impact of Liver Functions by Repurposed Drugs for COVID-19 Treatment.

Liver injury is an important complication that may arise in patients suffering from coronavirus disease 2019 (COVID-19) and is accompanied by a transient increase of transaminases and/or other liver enzymes. Liver function test (LFT) abnormalities generally disappear when the COVID-19 resolves or hepatotoxic drugs are discontinued. The LFT abnormalities are associated with drug-induced liver injury (DILI), due to the overuse of antimalarials, antivirals, and antimicrobials. Studies have reported varying levels of these liver injuries in COVID-19 patients; however, most involve elevated serum aminotransferases. Hepatic dysfunction is significantly high in patients with severe illness and has poor outcome. Normally, the liver is involved in the metabolism of many drugs, including nucleoside analogs and protease inhibitors, which are currently repurposed to treat COVID-19. In addition to the manifestation of COVID-19, drugs implemented in its treatment may aggravate liver injuries. Thus, DILI should be considered especially in those COVID-19 patients with underlying liver disease. It was unclear whether the elevated liver enzymes have originated from the underlying disease or DILI in this population. Furthermore, it is difficult to establish a direct relationship between a specific drug and liver injury. Another possible effect of liver damage may due to inflammatory cytokine storm in severe COVID-19. Liver injury can change metabolism, excretion, dosing, and expected concentrations of the drugs, which may make it difficult to achieve a therapeutic dose of the drug or increase the risk of adverse effects. These repurposed drugs have shown limited efficacy against the virus and the disease itself; however, they still pose risk of adverse effects. Careful and close monitoring of LFTs in COVID-19 patients can provide early diagnosis of liver injury, and the risk of DILI could be reduced. Also, drug interactions in liver-transplanted patients should always be kept in mind for certain immunosuppressive therapies and their known signs of DILI. Altogether, abnormal LFTs should not be regarded as a contraindication to use COVID-19 experimental therapies if needed under emergent status.

Molecular mechanisms and effects of urocortin II on rat adventitial fibroblast calcification induced by calcified medium.

The present study aimed to assess the role of urocortin II (UII) in the process of vascular calcification in vitro by using a calcification model, to detect the changes in the mRNA and protein levels of associated markers in rat adventitial fibroblasts (AFs) during their phenotypic transformation to osteoblast cellsto clarify the main signal transduction pathway of UII responsible for regulating vascular calcification and AF phenotypic transformation of osteoblast cells, and to prove that UII was an endogenous factor promoting vascular calcification, so as to provide an effective experimental basis for the clinical regulation of related diseases caused by vascular calcification. Finally, we successfully constructed the calcified cell model, found that UII was an endogenous substance regulating vascular calcification, regulated the vascular calcification by promoting apoptosis and inhibiting autophagy through up- and downregulated BAX and BCL-2/BECLIN 1 (BECN1) level, and the Wnt/ß-catenin signaling pathway was involved.

An Overview of Neurological and Psychiatric Complications During Post-COVID Period: A Narrative Review.

The coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a multi-organ and multi-system disease with high morbidity and mortality in severe cases due to respiratory failure and severe cardiovascular events. However, the various manifestations of neurological and psychiatric (N/P) systems of COVID-19 should not be neglected. Some clinical studies have reported a high risk of N/P disorders in COVID-19 and post-COVID-19 patients and that their outcomes were positively associated with the disease severity. These clinical manifestations could attribute to direct SARS-CoV-2 invasion into the central nervous system (CNS), which is often complicated by systemic hypoxia, the dysfunctional activity of the renin-angiotensin system and other relevant pathological changes. These changes may remain long term and may even lead to persistent post-COVID consequences on the CNS, such as memory, attention and focus issues, persistent headaches, lingering loss of smell and taste, enduring muscle aches and chronic fatigue. Mild confusion and coma are serious adverse outcomes of neuropathological manifestations in COVID-19 patients, which could be diversiform and vary at different stages of the clinical course. Although lab investigations and neuro-imaging findings may help quantify the disease's risk, progress and prognosis, large-scale and persistent multicenter clinical cohort studies are needed to evaluate the impact of COVID-19 on the N/P systems. However, we used "Boolean Operators" to search for relevant research articles, reviews and clinical trials from PubMed and the ClinicalTrials dataset for "COVID-19 sequelae of N/P systems during post-COVID periods" with the time frame from December 2019 to April 2022, only found 42 in 254,716 COVID-19-related articles and 2 of 7931 clinical trials involved N/P sequelae during post-COVID periods. Due to the increasing number of infected cases and the incessant mutation characteristics of this virus, diagnostic and therapeutic guidelines for N/P manifestations should be further refined.

Potential of sphingosine-1-phosphate in preventing SARS-CoV-2 infection by stabilizing and protecting endothelial cells: Narrative review.

ABSTRACT: Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, resulting in over 250 million infections and >5 million deaths. Most antiviral drugs and vaccines have shown limited efficacy against SARS-CoV-2. Clinical data revealed that except for the large number of self-healing mild cases, moderate and severe cases mostly survived after supportive treatment but not specific drug administration or vaccination. The endothelial system is the first physiological barrier, and its structural stability is of critical importance in conferring disease resistance. Membrane lipid components, particularly sphingosine-1-phosphate (S1P), play a central role in stabilizing the cell membrane.Here, we used "Boolean Operators" such as AND, OR, and NOT, to search for relevant research articles in PubMed, then reviewed the potential of S1P in inhibiting SARS-CoV-2 infection by stabilizing the endothelial system, this is the major aim of this review work.Reportedly, vasculitis and systemic inflammatory vascular diseases are caused by endothelial damage resulting from SARS-CoV-2 infection. S1P, S1P receptor (SIPR), and signaling were involved in the process of SARS-CoV-2 infection, and S1P potentially regulated the function of EC barrier, in turn, inhibited the SARS-CoV-2 to infect the endothelial cells, and ultimately has the promising therapeutic value to coronavirus disease 2019.Taken together, we conclude that maintaining or administering a high level of S1P will preserve the integrity of the EC structure and function, in turn, lowering the risk of SARS-CoV-2 infection and reducing complications and mortality.

Aldosterone is a possible new stimulating factor for promoting vascular calcification.

Background: Aldosterone is an important hormone in the renin-angiotensin-aldosterone system (RAAS), and playing a pivotal role in the development of hypertension, heart failure, and other cardiovascular diseases. Material and method: In this study, the role of the aldosterone in vascular calcification was underwent in rat model compared with other drugs. Vascular calcification, calcium concentration, activity of alkaline phosphatase (ALP), aldosterone, Urotensin II, mineralocorticoid receptor (MR) and Osteopontin (OPN) were detected or confirmed by the von Kossa staining, colorimetric assays, immunohistochemistry and radioimmunoassay, separately. Result: Results revealed that the aldosterone was significantly increased compared calcification + aldosterone group with calcification group, whereas it was notably decreased in calcification + Spironolactone group in the aortic wall. Compared with control group and aldosterone group, calcium content in vascular tissues was increased in calcification group and calcification + aldosterone group. As the immunoreactivity of the MR, OPN, Urotensin II, IL-6, monocyte chemoattractant protein-1, and deposition of collagen in calcification group and aldosterone group, they all were increased slightly, but were significantly increased in calcification + aldosterone group. Conclusion: It is implied that aldosterone may be involved in the development of vascular calcification, however, the mechanism needs to be further studied.