ABSTRACT
The corona virus disease 2019(COVID-19)in 2019 has shown a global pandemic status in a short time since its outbreak, and many variants of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)were highly infectious and pathogenic. SARS-CoV-2 may infect tissue cells through the mediation of angiotensin-converting enzyme-2(ACE2)and transmembrane serine protease 2(TMPRSS2), leading to different diseases. Clinically, respiratory, cardiovascular, and gastrointestinal systems diseases are relatively common; many patients also seek medical attention based on eye symptoms as their main complaint. Compared with severe systemic diseases, eye-related symptoms are easily overlooked. This article reviews the pathogenesis and cases of various eye diseases related to SARS-CoV-2, aiming to enhance clinicians' attention to SARS-CoV-2-related eye diseases, avoid delaying the disease and causing irreversible loss of vision, and provide new ideas for the prevention and treatment of eye diseases.
ABSTRACT
In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC50 values of 3.77 μmol·L-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.
ABSTRACT
The COVID-19 pandemic brought on by the SARS-COV-2 is a novel healthcare problem. A cytokine storm caused by the hyper-inflammation present in this pandemic leads to serious consequences such micro thrombosis. There have been reports of some male genital organs being impacted by very severe illness instances, leading to erectile dysfunction (ED). Given the high rate of COVID-19 transmission, ED could also be a serious outcome for a sizable portion of the population. It is still little understood and is crucial given that the virus has been discovered in pensile tissue. In this account, we sought to compile potential explanations for the ED development driven by COVID-19. The psychological toll of COVID-19 and endothelial dysfunction, which are among the routes of ED, are now better understood according to recent research.
ABSTRACT
Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.
ABSTRACT
Resumen El COVID-19 es una patología producida por el SARS-CoV-2, virus de carácter zoonótico capaz de producir patologías multiorgánicas. La sintomatología que produce es variada. Ante la infección algunos pacientes presentan condiciones de gravedad. Los estudios han demostrado que el rol genético tiene gran afluencia sobre la respuesta ante la infección. El objetivo de investigación es detallar los genes que están implicados en la gravedad de la infección por SARS-CoV- 2. Metodología . Se realizó una revisión sistemática, con base a la búsqueda y análisis de artículos originales en bases de datos de alto impacto como PudMed, Google Académico, Scopus, Taylor & Francis, ProQuest SciencieDirect; se utilizaron operadores booleanos, criterios de inclusión y exclusión con el objetivo de obtener información precisa. Los genes de inmunidad como el HLA, ACE2 y TMPRSS2 están directamente involucrados con la gravedad de la infección por SARS-CoV- 2. Los polimorfismos de los genes del polyQ del receptor de andrógenos, factor ABO coadyuvan a un deterioro del estado patológico como consecuencia de la COVID-19. Conclusión. Los estudios demostraron que existen genes involucrados en la gravedad ante la infección de SARS -CoV-2, pues mencionan que los polimorfismos de los genes; HLA, del polyQ del receptor de andrógenos y factor ABO producen susceptibilidad ante el COVID-19. Así mismo los genes ACE2 y TMPRSS2 intervienen en el ingreso y expansión del virus. En las diversas razas existen variantes de los genes CCL2 y MBL lo que indica que algunas poblaciones son más susceptibles que otras.
Abstract COVID-19 is a pathology caused by SARS-CoV-2, a zoonotic virus capable of producing multi-organ pathologies. The symptomatology it produces is varied. Some patients present severe conditions after infection. Studies have shown that the genetic role has a great influence on the response to infection. Methodology . A systematic review was carried out, based on the search and analysis of original articles in high impact databases such as PudMed, Google Scholar, Scopus, Taylor & Francis, ProQuest SciencieDirect; Boolean operators, inclusion and exclusion criteria were used in order to obtain accurate information. Immunity genes such as HLA, ACE2 and TMPRSS2 are directly involved with the severity of SARS-CoV- 2 infection. Polymorphisms of androgen receptor polyQ genes, ABO factor contribute to a deterioration of the pathological state as a consequence of COVID-19. Conclusion . The studies demonstrated that there are genes involved in the severity of SARS-CoV-2 infection, since they mention that polymorphisms of the HLA, androgen receptor polyQ and ABO factor genes produce susceptibility to COVID-19. Likewise, ACE2 and TMPRSS2 genes intervene in the entry and expansion of the virus. In the different breeds there are variants of the CCL2 and MBL genes, which indicates that some populations are more susceptible than others.
Resumo COVID-19 é uma patologia causada pelo SARS-CoV-2, um vírus zoonótico capaz de produzir patologias multiorganismos. Os sintomas que ela produz são variados. Alguns pacientes se apresentam com condições severas após a infecção. Estudos demonstraram que o papel da genética desempenha um papel importante na resposta à infecção. O objetivo desta pesquisa é detalhar os genes que estão envolvidos na gravidade da infecção pelo SARS-CoV- 2. Metodologia. Foi realizada uma revisão sistemática, baseada na busca e análise de artigos originais em bancos de dados de alto impacto como PudMed, Google Scholar, Scopus, Taylor & Francis, ProQuest SciencieDirect; operadores booleanos, critérios de inclusão e exclusão foram utilizados para obter informações precisas. Resultados. Os genes de imunidade como HLA, ACE2 e TMPRSS2 estão diretamente envolvidos na gravidade da infecção pelo SARS-CoV- 2. Os polimorfismos dos genes receptores de androgênio polyQ, fator ABO contribuem para uma deterioração do estado patológico como conseqüência da COVID-19. Conclusão. Os estudos demonstraram que existem genes envolvidos na gravidade da infecção pelo SRA-CoV-2, pois mencionam que os polimorfismos dos genes HLA, androgênio receptor policarbonato e fator ABO produzem suscetibilidade à COVID-19. Os genes ACE2 e TMPRSS2 também estão envolvidos na entrada e propagação do vírus. Existem variantes dos genes CCL2 e MBL nas diferentes raças, indicando que algumas populações são mais suscetíveis do que outras.
ABSTRACT
Introducción: La COVID-19 es un importante problema de salud definido como pandemia. Estudios en felinos y murinos describieron cuadros de conjuntivitis, uveítis anterior, retinitis y neuritis óptica. En humanos lo más frecuente es la conjuntivitis viral aguda, sin embargo, su estudio continúa en evolución. Se investiga la infección por coronavirus adquirida mediante la transmisión ocular, pero su mecanismo no se ha esclarecido totalmente. Objetivos: Describir las principales manifestaciones oftalmológicas, así como el papel del dinamismo de la superficie ocular y la presencia de receptores moleculares en la transmisión del SARS-CoV-2 por esta vía. Métodos: Se realizó una revisión de la literatura en idioma español e inglés, en los repositorios PubMed, Ebsco, Scielo y Google Académico desde el 1ro de enero hasta el 31 de julio de 2020. Además, se consultaron sitios web de organismos y asociaciones oftalmológicas. Conclusiones: La conjuntivitis viral es la principal presentación oftalmológica del coronavirus 2019. Aunque existe un bajo riesgo de infestación a través de lágrimas, su mecanismo de transmisión por esta vía se ha descrito. Incluso en ausencia de conjuntivitis, el SARS-CoV-2 puede existir o replicarse en la conjuntiva, por tanto, la protección ocular es aconsejable(AU)
Introduction: COVID-19 is an important global health problem which has been declared pandemic by the World Health Organization. Studies on felines and murines have described cases of conjunctivitis, anterior uveitis, retinitis and optic neuritis. The most common condition in humans is acute viral conjunctivitis; however, its study is still in progress. Research is conducted about coronavirus infection acquired by ocular transmission, the mechanism of which has not been totally clarified. Objectives: Describe the main ophthalmic manifestations, as well as the role played by ocular surface dynamics and the presence of molecular receptors in SARS-CoV-2 transmission by this route. Methods: A literature review was conducted of papers published in Spanish or English in the repositories PubMed, Ebsco, Scielo and Google Scholar from 1 January to 31 July 2020. Websites of ophthalmological agencies and associations were also consulted. Conclusions: Viral conjunctivitis is the main ophthalmic presentation of coronavirus 2019. Although the risk of contagion through tears is low, the transmission mechanism by this route has not been described. Even in the absence of conjunctivitis, SARS-CoV-2 may exist or replicate in the conjunctiva. Ocular protection is therefore advisable(AU)
Subject(s)
Humans , Uveitis, Anterior , Conjunctivitis, Viral , Coronavirus Infections , COVID-19/complicationsABSTRACT
Abstract Some studies have discovered a connection between prostate cancer and COVID-19. In this study, we evaluated the link between prostate cancer and COVID-19, contributing to elucidate the connection between TMPRSS2 and ACE2. We discovered 209 number of variants in TMPRSS2 gene, and 110 variants represent EA populations and 99 of them represent AA populations. Moreover, we found 23 suspected missense and 3 unknown variants. Then, linked genes to TMPRSS2 and ACE2 were found in our study. We investigated the expression level of TMPRSS2 and the results showed that it was very high in the prostate, colon, lung, kidney, and saliva-secreting gland. Also, the important role of the AR gene was revealed in addition to other oncogenes and tumor suppressor genes for prostate cancer by KEGG Pathway analysis. In conclusion, these results can highlight several molecular mechanisms of SARS-CoV-2, and also TMPRSS2, ACE2, and AR connection explains the high expression level of AR gene found in the male lung.
ABSTRACT
Prostate cancer is the most common malignant tumor in men in Europe and the United States, but the mechanism of prostate cancer occurrence and development is not completely clear. In prostate cancer, the TMPRSS2-ERG fusion gene has a high incidence, which promotes ERG overexpression and causes changes in target genes and signaling pathways, such as androgen receptors, spotted zinc finger structural proteins, Notch pathways. In-depth understanding of the transcriptional regulation mechanism of TMPRSS2-ERG fusion gene products in prostate cancer cells can provide new targets for drug action in the treatment of prostate cancer.
ABSTRACT
Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG fusion) is a common genetic alteration in prostate cancer among Western populations and has been suggested as playing a role in tumorigenesis and progression of prostate cancer. However, the prevalence of TMPRSS2-ERG fusion differs among different ethnic groups, and contradictory results have been reported in Asian patients. We aim to evaluate the prevalence and significance of TMPRSS2-ERG fusion as a molecular subtyping and prognosis indicator of prostate cancer in Asians. We identified the fusion status in 669 samples from prostate biopsy and radical prostatectomy by fluorescence in situ hybridization and/or immunohistochemistry in China. We examined the association of TMPRSS2-ERG fusion with clinicopathological characteristics and biochemical recurrence by Chi-square test and Kaplan-Meier analysis. Finally, a systematic review was performed to investigate the positive rate of the fusion in Asian prostate cancer patients. McNemar's test was employed to compare the positive rates of TMPRSS2-ERG fusion detected using different methods. The positive rates of TMPRSS2-ERG fusion were 16% in our samples and 27% in Asian patients. In our samples, 9.4% and 19.3% of cases were recognized as fusion positive by fluorescence in situ hybridization and immunohistochemistry, respectively. No significant association between the fusion and clinical parameters was observed. TMPRSS2-ERG fusion is not a frequent genomic alteration among Asian prostate cancer patients and has limited significance in clinical practices in China. Besides ethnic difference, detection methods potentially influence the results showing a positive rate of TMPRSS2-ERG fusion.
ABSTRACT
Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG fusion) is a common genetic alteration in prostate cancer among Western populations and has been suggested as playing a role in tumorigenesis and progression of prostate cancer. However, the prevalence of TMPRSS2-ERG fusion differs among different ethnic groups, and contradictory results have been reported in Asian patients. We aim to evaluate the prevalence and significance of TMPRSS2-ERG fusion as a molecular subtyping and prognosis indicator of prostate cancer in Asians. We identified the fusion status in 669 samples from prostate biopsy and radical prostatectomy by fluorescence in situ hybridization and/or immunohistochemistry in China. We examined the association of TMPRSS2-ERG fusion with clinicopathological characteristics and biochemical recurrence by Chi-square test and Kaplan-Meier analysis. Finally, a systematic review was performed to investigate the positive rate of the fusion in Asian prostate cancer patients. McNemar's test was employed to compare the positive rates of TMPRSS2-ERG fusion detected using different methods. The positive rates of TMPRSS2-ERG fusion were 16% in our samples and 27% in Asian patients. In our samples, 9.4% and 19.3% of cases were recognized as fusion positive by fluorescence in situ hybridization and immunohistochemistry, respectively. No significant association between the fusion and clinical parameters was observed. TMPRSS2-ERG fusion is not a frequent genomic alteration among Asian prostate cancer patients and has limited significance in clinical practices in China. Besides ethnic difference, detection methods potentially influence the results showing a positive rate of TMPRSS2-ERG fusion.
Subject(s)
Aged , Humans , Male , Middle Aged , China , Oncogene Fusion/genetics , Oncogene Proteins, Fusion/genetics , Prostatic Neoplasms/genetics , Serine Endopeptidases/genetics , Transcriptional Regulator ERG/geneticsABSTRACT
@#Introduction: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer. Methods: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade. Results: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01). Conclusion: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity. @*@#
ABSTRACT
Purpose To study the expression of TMPRSS2, ERG and ETV1 in prostatic cancer and their clinical pathologic signifi-cance. Methods Tissue microarray and immunohistochemistry (MaxVision) were used to detect TMPRSS2, ERG and ETV1 expres-sion in 70 prostatic cancer tissues, 10 prostatic intraepithelial neoplasia tissues and 18 benign prostate tissues. Results There was no statistical significance on positive rate of the expression of TMPRSS2 among prostatic cancer tissues, prostatic intraepithelial neoplasia tissues and benign prostate tissues (P>0. 05). The positive rate (81. 4%) of ERG in prostatic cancer tissues was significantly higher than that in prostatic intraepithelial neoplasia tissues ( 30. 0%) and benign prostate tissues ( 0. 0 ) ( P 0. 05). The expression of TMPRSS2, ERG and ETV1 was positively correlated to Gleason score and clinical stage (P0. 05). Conclusion ERG and ETV1 are expected to become therapeutic targets for prostate cancer. Detecting TMPRSS2, ERG and ETV1 at the same time is helpful to diagnosis and differential diagnosis of prostatic cancer, which might be new molecule markers of prostate cancer.
ABSTRACT
Objective To explore the prevalence of ETS gene fusion in prostate cancer and its correlation with patient's clinicopathologic index.Methods Ninety-one samples from prostate needle biopsy cases with median age 75 (55-90) years and 18 samples from radical prostatectomy cases with median age 72 (63-81) years were collected from Oct.2010 to Feb.2012.TMPRSS2-ERG,TMPRSS2-ETV1 and TMPRSS2-ETV4 fusions were tested by multi-probe fluorescence in situ hybridization (FISH) assay.Fusion positive and negative cases were compared with age,TNM stage,Gleason score (median Gleason score 7 (6-9)),and PSA value (median PSA 33.4 μg/L,mcan PSA 118.8 μg/L).In needle biopsy cases,there were early stage 32 (34％),locally advanced prostate cancer 36 (40％),metastasis 23 (26％) ; in radical prostatectomy cases,there were 9 cases in T2 stage,8 cases in T3 stage,1 cases in T4a stage,respectively.Results TMPRSS2-ERG fusions were present in 14.3％ (13/91,95％ confidence interval,0.071-0.215)biopsy specimens and in 11.1％ (2/18,95％ confidence interval,0-0.256) radical prostatectomy specimens.No TMPRSS2-ETV1 or TMPRSS2-ETV4 fusions were found in any cases.Altogether,13 (86.7％)cases possessed deletion pattern.And 7 (46.6％) hold insertion pattern.5 cases had both deletion and insertion pattern.38.5％ (5/13) deletion pattern had distant metastasis.Except one metastatic case harbored both deletion and insertion pattern,there was no insertion pattern accompanied with metastasis.There were no differences between fusion positive and negative cases in the distribution of age (P =1.000),PSA (P =1.138),primary Gleason score (P=2.186),Gleason score (P=2.107),TNM stage (P=2.052) and Risk Degree (P=2.597).Conclusions The TMPRSS2-ERG fusion positive cases harbor more deletion pattern than insertion pattern.There are no differences between fusion positive and negative cases in the distribution of age,PSA,Gleason score,TNM stage and Risk Degree.
ABSTRACT
PURPOSE: The aim of this study was to evaluate TMPRSS2:ERG fusion rates in tissue, urine, blood, and pubic hair samples in a cohort of patients with localized prostate cancer and to correlate these findings with various clinicopathological parameters. MATERIALS AND METHODS: A cohort of 40 patients undergoing radical prostatectomy for localized prostate cancer (RRP group) and 10 control patients undergoing prostate biopsy were enrolled between 2006 and 2008. Urine, pubic hair, and peripheral blood samples were obtained following prostatic massage before the needle biopsy or radical prostatectomy. Quantitative polymerase chain reaction analysis was performed on all collected samples. RESULTS: The patients' mean age was 62.4 (+/-5.5) years. We observed higher expressions of TMPRSS2:ERG fusion in tissue, urine, and blood samples from the RRP group than in samples from the control group. Overall, the fusion was present in urine samples of 23 RRP patients (57.5%). To predict high-stage cancer (>T3a), the Gleason score was the only significant factor in the logistic regression analysis (score, 10.579; p=0.001). Quantitative evaluation of the gene fusion in tissue (Pearson r=0.36, p=0.011) and urine (Pearson r=0.34, p=0.014) samples had a significant positive correlation with the preoperative prostate-specific antigen level. CONCLUSIONS: Urine sediments collected after prostatic massage appear to be a feasible noninvasive method of detecting TMPRSS2:ERG fusion. The Gleason score is the only significant factor to predict high-stage cancer (>T3a). No correlation between TMPRSS2:ERG gene fusion status and tumor stage, Gleason grade, prostate-specific antigen level, or surgical margin status was observed.