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Cancer chemoresistance is a problematic dilemma that significantly restrains numerous cancer management protocols. It can promote cancer recurrence, spreading of cancer, and finally, mortality. Accordingly, enhancing the responsiveness of cancer cells towards chemotherapies could be a vital approach to overcoming cancer chemoresistance. Tumour cells express a high level of sphingosine kinase-1 (SphK1), which acts as a protooncogenic factor and is responsible for the synthesis of sphingosine-1 phosphate (S1P). S1P is released through a Human ATP-binding cassette (ABC) transporter to interact with other phosphosphingolipids components in the interstitial fluid in the tumor microenvironment (TME), provoking communication, progression, invasion, and tumor metastasis. Also, S1P is associated with several impacts, including anti-apoptotic behavior, metastasis, mesenchymal transition (EMT), angiogenesis, and chemotherapy resistance. Recent reports addressed high levels of S1P in several carcinomas, including ovarian, prostate, colorectal, breast, and HCC. Therefore, targeting the S1P/SphK signaling pathway is an emerging therapeutic approach to efficiently attenuate chemoresistance. In this review, we comprehensively discussed S1P functions, metabolism, transport, and signaling. Also, through a bioinformatic framework, we pointed out the alterations of SphK1 gene expression within different cancers with their impact on patient survival, and we demonstrated the protein-protein network of SphK1, elaborating its sparse roles. Furthermore, we made emphasis on different machineries of cancer resistance and the tight link with S1P. We evaluated all publicly available SphK1 inhibitors and their inhibition activity using molecular docking and how SphK1 inhibitors reduce the production of S1P and might reduce chemoresistance, an approach that might be vital in the course of cancer treatment and prognosis.
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Recently, COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, caused > 6 million deaths. Symptoms included respiratory strain and complications, leading to severe pneumonia. SARS-CoV-2 attaches to the ACE-2 receptor of the host cell membrane to enter. Targeting the SARS-CoV-2 entry may effectively inhibit infection. Acid sphingomyelinase (ASMase) is a lysosomal protein that catalyzes the conversion of sphingolipid (sphingomyelin) to ceramide. Ceramide molecules aggregate/assemble on the plasma membrane to form "platforms" that facilitate the viral intake into the cell. Impairing the ASMase activity will eventually disrupt viral entry into the cell. In this review, we identified the metabolism of sphingolipids, sphingolipids' role in cell signal transduction cascades, and viral infection mechanisms. Also, we outlined ASMase structure and underlying mechanisms inhibiting viral entry 40 with the aid of inhibitors of acid sphingomyelinase (FIASMAs). In silico molecular docking analyses of FIASMAs with inhibitors revealed that dilazep (S = - 12.58 kcal/mol), emetine (S = - 11.65 kcal/mol), pimozide (S = - 11.29 kcal/mol), carvedilol (S = - 11.28 kcal/mol), mebeverine (S = - 11.14 kcal/mol), cepharanthine (S = - 11.06 kcal/mol), hydroxyzin (S = - 10.96 kcal/mol), astemizole (S = - 10.81 kcal/mol), sertindole (S = - 10.55 kcal/mol), and bepridil (S = - 10.47 kcal/mol) have higher inhibition activity than the candidate drug amiodarone (S = - 10.43 kcal/mol), making them better options for inhibition.
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COVID-19 , Humanos , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Esfingomielina Fosfodiesterasa/metabolismo , Ceramidas/metabolismo , EsfingolípidosRESUMEN
Oxidative stress is a sophisticated situation that orignates from the accumulation of reactive free radicals within cellular compartments. The antioxidant mechanism of the MnSOD enzyme facilitates the removal of these lethal oxygen species from cellular components. The main goal of this pertained work is to study the contribution of the SOD2 (rs4880; p.Val16Ala) variant to the development of bronchial asthma among children. The study's design was carried out based on a total of 254 participants including 127 asthmatic children (91 atopic and 36 non-atopic) along with 127 unrelated healthy controls. Allelic discrimination analysis was executed using the T-ARMS-PCR protocol. This potential variant conferred a significant association with decreased risk of bronchial asthmatic children under allelic (OR = 0.56, P-value = 0.002), recessive (OR = 0.32, P-value = 0.011), and dominant (OR = 0.51, P-value = 0.040) models. Additionally, atopic and non-atopic asthmatic children indicated a protection against bronchial asthma development under allelic, and dominant models (p-value < 0.05). Our findings suggested that the SOD2*rs4880 variant was correlated with decreased risk of childhood bronchial asthma.
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The renin-angiotensin-aldosterone system has an indispensable function in the uteroplacental circulation, placental growth, and blood pressure optimization. The angiotensin I converting enzyme (ACE) gene is a critical integrator for electrolyte balance, and water retention, along with inhibiting preeclampsia. The main goal of this pertaining study is to assess the contribution of ACE*(Ins/Del) variant with the susceptibility for preeclampsia with focus on the severity of the disease among gestational hypertensive women. This retrospective study included 225 participants [125 PE gestational women, and 100 normotensive healthy controls] matching with age, and geographical region. PE women classified into 82 early-onset PE women, accompanied with 43 late-onset PE women. Additionally, PE women categorized into 59 mild PE women, together with 66 severe PE women. The genotyping and characterization of ACE*(Ins/Del) variant were applied using the PCR technique. Our findings indicated higher frequency of the ACE*(Del/Del) genotype and ACE*(D allele) with elevated risk of preeclampsia compared to normotensive controls under recessive (OR = 2.09, and p-value = 0.007), and allelic (OR = 1.75, and p-value = 0.012) models. In addition, testing logistic regression revealed that the levels of endothelin-1 and malondialdehyde exposed significant difference for the ACE*(Del/Del) genotype among early-onset and late-onset PE women (p-value = 0.024, and 0.23, respectively). Furthermore, carriers of the ACE*(Del/Del) genotype observed statistically significant with lower sodium concentrations among severe PE women (p-value = 0.034). The ACE*(Del/Del) genotype and ACE*(D allele) were associated with increased risk preeclampsia among gestational women. Furthermore, early-onset PE and late-onset PE were correlated with endothelin-1 and malondialdehyde concentrations among Egyptian women.
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BACKGROUND: The prevalence rate of breast carcinoma (BC) among multiple ethnic populations required more explanations to understand the pathogenesis mechanisms for the development of this type of cancer. The principal purpose of this work is to validate the correlation of the CCND1 (c.723G > A; rs9344) variant with an increased risk of breast carcinoma. METHODS: This retrospective case-controlled study was designed appertaining to 200 women including 100 BC patients and 100 unrelated cancer-free controls. The amplification of genomic DNA was genotyped utilizing the PCR-RFLP technique. RESULTS: The frequencies of the CCND1 (c.723G > A; rs9344) variant revealed a significant association with increased risk of breast carcinoma under different genetic models including allelic (OR = 2.84, P-value < 0.001), recessive (OR = 4.83, P-value < 0.001), and dominant (OR = 3.19, P-value < 0.001) models. CONCLUSIONS: Our findings concluded that the genetic biomarker of the CCND1 (c.723G > A; rs9344) variant is correlated with an elevated risk of breast carcinoma among Egyptian women.
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Neoplasias de la Mama , Polimorfismo de Nucleótido Simple , Femenino , Humanos , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Estudios de Casos y Controles , Ciclina D1/genética , Predisposición Genética a la Enfermedad , Genotipo , Polimorfismo de Nucleótido Simple/genética , Estudios RetrospectivosRESUMEN
Endothelin-1 plays a crucial role in the pathophysiology of nephrotic syndrome (NS) in children. The primary purpose of this study is to evaluate the contribution of the EDN1 (3A/4A; rs1800997) variant to the risk of nephrotic syndrome. This study involves 200 participants (100 healthy controls, 50 steroid-sensitive nephrotic syndromes [SSNS] patients, and 50 steroid-resistant nephrotic syndromes [SRNS] patients]. Genomic DNA has been characterized using the PCR-RFLP technique. The predominant genotype that is common in this study population was the EDN1 3A/3A genotype (NS [75%] and healthy controls [88%]). The prevalence of EDN1 3A/4A genotype and EDN1 4A allele was significantly increased among NS patients compared with healthy subjects (p-value < 0.05). Furthermore, the frequency of the EDN1 (3A/4A; rs1800997) variant was statistically significant among SRNS patients (p-value < 0.05). The EDN1 3A/4A genotype and the EDN1 4A allele were identified as independent risk factors of the nephrotic syndrome among children.
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Regiones no Traducidas 5' , Endotelina-1/genética , Predisposición Genética a la Enfermedad , Síndrome Nefrótico/genética , Polimorfismo de Nucleótido Simple , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , MasculinoRESUMEN
OBJECTIVE: There are varying reports of the prevalence and effect of comorbid asthma in coronavirus disease-2019 (COVID-19) patients. We sought to conduct a meta-analysis comparing asthmatic and non-asthmatic patients to determine the clinical significance of preexisting asthma in COVID-19 patients. DATA SOURCES: Online databases PubMed, ScienceDirect, Web of Science, and Scopus, were searched up to July 15, 2020, for papers comparing asthma versus non-asthma COVID-19 patients. STUDY SELECTION: According to prespecified inclusion criteria, this analysis included eleven retrospective studies with 107,983 COVID-19 patients. Subgroup analysis was performed based on age groups. RESULTS: The mean age of the patients was 59.9 years (95%CI = 51.9-67.9). Across studies, the prevalence of asthma was 11.2% (95%CI: 9.1%-13.3%) among COVID-19 patients who attended the hospitals. Asthma patients were more likely to be younger (SMD = -0.36, 95%CI = -0.61 to -0.10, p = 0.005), and obese (OR = 1.98, 95%CI = 1.54-2.55, p < 0.001), there was no differential risk of hospitalization rate, ICU admission, or development of acute respiratory distress syndrome (ARDS) between asthmatic and non-asthmatic cohorts. However, asthmatic patients had increased risk of endotracheal intubation (RR = 1.27, 95%CI = 1.02-1.58, p = 0.030) especially patients aged <50 years (RR = 6.68, 95%CI = 1.76-11.13, p = 0.009). Despite this result, asthmatic patients had better recovery with a higher liability of being discharged and were less likely to die (RR = 0.80, 95%CI = 0.65-0.97, p = 0.026). CONCLUSION: To our knowledge, our meta-analysis is the largest to shed light on preexisting asthma as a predictor of intubation in COVID-19, especially in young and obese patients. Identifying high-risk groups is crucial for designing more effective intervention plans and optimization of efficient resource allocation.
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Asma , COVID-19 , Asma/epidemiología , COVID-19/epidemiología , COVID-19/terapia , Humanos , Persona de Mediana Edad , Obesidad/epidemiología , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: Studies have suggested that cesarean birth in pregnant women with COVID-19 may decrease maternal adverse events and perinatal transmission. This systematic review aimed to evaluate variations in clinical presentation, laboratory findings, and maternal/neonatal outcomes in COVID-19 patients who delivered vaginally versus via cesarean. METHODS: A comprehensive search following PRISMA guidelines was performed for studies published up to May 23, 2020, using PubMed, Web of Science, Scopus, Embase, Cochrane, Science Direct, and clinicaltrials.gov. Original retrospective and prospective studies, case reports, or case series with sufficient data for estimating the association of COVID-19 with different pregnancy outcomes with no language restriction and published in peer-reviewed journals were included. Pooled mean and arcsine transformation proportions were applied. Next, a two-arm meta-analysis was performed comparing the perinatal outcomes between the study groups. RESULTS: Forty-two studies with a total of 602 pregnant women with COVID-19 were included. The mean age was 31.8 years. Subgroup analysis showed that Americans had the lowest gestational age (mean = 32.7, 95%CI = 27.0-38.4, P < 0.001) and the highest incidence of maternal ICU admission (95%CI = 0.45%-2.20, P < 0.001) of all nationalities in the study. There was no significant difference in perinatal complications, premature rupture of membrane, placenta previa/accreta, or gestational hypertension/pre-eclampsia between women who delivered vaginally versus by cesarean. Importantly, there were also no significant differences in maternal or neonatal outcomes. CONCLUSION: Vaginal delivery was not associated with worse maternal or neonatal outcomes when compared with cesarean. The decision to pursue a cesarean birth should be based on standard indications, not COVID-19 status.
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COVID-19 , Nacimiento Prematuro , Adulto , Femenino , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Embarazo , Resultado del Embarazo/epidemiología , Mujeres Embarazadas , Nacimiento Prematuro/epidemiología , Estudios Prospectivos , Estudios Retrospectivos , SARS-CoV-2RESUMEN
OBJECTIVE: To quantify the time-varying reproductive rates for SARS-CoV-2 and its implication in Louisiana. SUMMARY OF BACKGROUND DATA: Basic reproductive number (R0) and effective reproductive number (Re or Rt) are 2 measures of the ability of an infectious agent to spread in the environment. They differ in that R0 assumes zero immunity in the population, while Re or Rt accounts for change over time. Reproductive number modeling is influenced by several factors, including serial interval, the time between the onset of symptoms in an infector, and a secondary case. Quantification of the ability of a pathogen to spread is essential in guiding policy. METHODS: Here, we construct epidemic curves and calculate daily Rt values for the state of Louisiana and each of its 9 regions. RESULTS: Our results demonstrated variation over both time and geography in calculated R0 and Rt values. Generally, as time has progressed, predicted R0 and Rt values have decreased. In Louisiana, mean Rt was calculated at 3.07 in March and 0.82 by May. A reproductive number less than one is important as it indicates infectious spread will decline with time. The most recent finding of mean Rt = 0.82 is important. It stands in stark contrast to the situation in April when New Orleans, Louisiana, had the highest per capita coronavirus mortality rate in the United States - twice that of New York City and 4 times the rate in Seattle. CONCLUSION: As locations around the world begin to lift restrictions, monitoring of infectious spread will be essential.
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COVID-19/epidemiología , Control de Enfermedades Transmisibles/métodos , Transmisión de Enfermedad Infecciosa/estadística & datos numéricos , Pandemias , SARS-CoV-2 , COVID-19/transmisión , Estudios de Seguimiento , Humanos , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
The DNA repair genes have a crucial function in the base excision repair (BER) mechanism among different cancerous disorders, particularly hepatocellular carcinoma (HCC). The foremost objective of this study is to explore the association of genetic variants of the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg with the susceptibility of HCC and to identify the computational bioinformatics frameworks of these missense variants. A total of 250 participants were enrolled in this study, including 150 HCC patients and 100 cancer-free controls. The genomic DNA was characterized and genotyped by applying the PCR-CTPP method. The frequency of the APEX1 (rs1130409*Glu) allele was statistically significant with increased risk of HCC (OR = 1.66, 95% CI = 1.12-2.45), while the XRCC1 (rs25487*Gln) allele conferred a protection against the progression of HCC (OR = 0.64, 95% CI = 0.42-0.96). Furthermore, HCC patients carrying the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg variants indicated no significant difference with the clinical, and laboratory parameters (p > .05). Our findings confirmed that the APEX1 p.Asp148Glu variant was associated with increased risk of HCC, while the XRCC1 p.Gln399Arg variant revealed protection against the development of HCC.
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Carcinoma Hepatocelular/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Predisposición Genética a la Enfermedad , Variación Genética , Genotipo , Neoplasias Hepáticas/genética , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genética , Alelos , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: As an immune modulator, vitamin D has been implicated in the coronavirus disease-2019 (COVID-19) outcome. We aim to systematically explore the association of vitamin D serum levels with COVID-19 severity and prognosis. METHODS: The standardized mean difference (SMD) or odds ratio and 95% confidence interval (CI) were applied to estimate pooled results from six studies. The prognostic performance of vitamin D serum levels for predicting adverse outcomes with detection of the best cutoff threshold was determined by receiver operating characteristic curve analysis. Decision tree analysis by combining vitamin D levels and clinical features was applied to predict severity in COVID-19 patients. RESULTS: Mean vitamin D serum level of 376 patients, was 21.9 nmol/L (95% CI = 15.36-28.45). Significant heterogeneity was found (I2 = 99.1%, p < .001). Patients with poor prognosis (N = 150) had significantly lower serum levels of vitamin D compared with those with good prognosis (N = 161), representing an adjusted standardized mean difference of -0.58 (95% Cl = -0.83 to -0.34, p < .001). CONCLUSION: Serum vitamin D levels could be implicated in the COVID-19 prognosis. Diagnosis of vitamin D deficiency could be a helpful adjunct in assessing patients' potential of developing severe COVID-19. Appropriate preventative and/or therapeutic intervention may improve COVID-19 outcomes.
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COVID-19/diagnóstico , SARS-CoV-2/patogenicidad , Deficiencia de Vitamina D/diagnóstico , Vitamina D/sangre , Factores de Edad , Biomarcadores/sangre , COVID-19/sangre , COVID-19/mortalidad , COVID-19/virología , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Curva ROC , SARS-CoV-2/metabolismo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/mortalidad , Deficiencia de Vitamina D/virologíaRESUMEN
A meta-analysis was performed to identify patients with coronavirus disease 2019 (COVID-19) presenting with gastrointestinal (GI) symptoms during the first and second pandemic waves and investigate their association with the disease outcomes. A systematic search in PubMed, Scopus, Web of Science, ScienceDirect, and EMBASE was performed up to July 25, 2020. The pooled prevalence of the GI presentations was estimated using the random-effects model. Pairwise comparison for the outcomes was performed according to the GI manifestations' presentation and the pandemic wave of infection. Data were reported as relative risk (RR), or odds ratio and 95% confidence interval. Of 125 articles with 25,252 patients, 20.3% presented with GI manifestations. Anorexia (19.9%), dysgeusia/ageusia (15.4%), diarrhea (13.2%), nausea (10.3%), and hematemesis (9.1%) were the most common. About 26.7% had confirmed positive fecal RNA, with persistent viral shedding for an average time of 19.2 days before being negative. Patients presenting with GI symptoms on admission showed a higher risk of complications, including acute respiratory distress syndrome (RR = 8.16), acute cardiac injury (RR = 5.36), and acute kidney injury (RR = 5.52), intensive care unit (ICU) admission (RR = 2.56), and mortality (RR = 2.01). Although not reach significant levels, subgroup-analysis revealed that affected cohorts in the first wave had a higher risk of being hospitalized, ventilated, ICU admitted, and expired. This meta-analysis suggests an association between GI symptoms in COVID-19 patients and unfavorable outcomes. The analysis also showed improved overall outcomes for COVID-19 patients during the second wave compared to the first wave of the outbreak.
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Tratamiento Farmacológico de COVID-19 , COVID-19/fisiopatología , Gastroenterología/métodos , Ageusia/epidemiología , Anorexia/epidemiología , Bases de Datos Factuales , Diarrea/epidemiología , Disgeusia/epidemiología , Heces/virología , Hematemesis/epidemiología , Hospitalización , Humanos , Náusea/epidemiología , Pandemias , Prevalencia , SARS-CoV-2 , Esparcimiento de VirusRESUMEN
Limited information has been offered regarding the association of mesothelin (MSLN) gene variants at the 3'-untranslated region with the risk of ovarian carcinoma. The primary objective of this work is to assess the impact of the MSLN (rs1057147 and rs57272256) variants on the progression of ovarian carcinoma among Egyptian women. The study was conceived based on 127 women diagnosed with ovarian carcinoma and 106 unrelated cancer-free controls. Genomic DNA of these MSLN variants was genotyped utilizing the PCR technique. The frequencies of the MSLN (rs1057147) variant revealed a significant association with increased risk of ovarian carcinoma under allelic and dominant models (P < .05). Nonetheless, ovarian cancer patients with the MSLN (rs57272256) variant did not attain considerable significance under all genetic models (P > .05). Together, our findings suggested that the MSLN (rs1057147) variant was associated with an increased risk of ovarian carcinoma, but not the MSLN (rs57272256) variant.
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Regiones no Traducidas 3' , Proteínas Ligadas a GPI/genética , Neoplasias Ováricas/genética , Polimorfismo Genético , Estudios de Casos y Controles , Egipto , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Mesotelina , Persona de Mediana Edad , Análisis Multivariante , Análisis de Componente PrincipalRESUMEN
AIM OF THE STUDY: The impact of annual flu vaccination on the patients' clinical course with COVID-19 and the outcome were tested. METHODS: A total of 149 patients with COVID-19-positive admitted from March 20 to May 10, 2020, were retrospectively enrolled. RESULTS: Ninety-eight (65.8%) patients received at least a single annual flu shot in the last year, and fifty-one (34.2%) were never vaccinated. On presentation, vaccinated patients were more likely to present with gastrointestinal symptoms (P < .05). There were no significant differences between study groups in laboratory findings or clinical outcomes. In multivariate analysis, receiving the annual shot did not influence risk of intensive care unit admission (OR = 1.17, 95%CI = 0.50-2.72, P = .72), intubation (OR = 1.40, 95%CI = 0.60-3.23, P = .43), complications (OR = 1.08, 95%CI = 0.52-2.26, P = .83) or mortality (OR = 1.29, 95%CI = 0.31-5.29, P = .73). CONCLUSION: Although the benefits of the influenza vaccine for preventing disease and reducing morbidity in influenza patients are well established, no differences in outcomes for hospitalised patients with COVID-19 who received their annual influenza vaccination versus the non-vaccinated cohort were evident. There is a need for future meta-analyses, including randomised controlled studies in which the number of cases is increased to validate these findings.
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COVID-19 , Vacunas contra la Influenza , Gripe Humana , Humanos , Gripe Humana/prevención & control , Estudios Retrospectivos , SARS-CoV-2 , VacunaciónRESUMEN
Several reports examined the association of the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant with the elevated risk of multiple cancerous diseases involving breast carcinoma, but with inconclusive findings. The primary purpose of this study is to test the association of this essential variant with the risk of breast carcinoma among Egyptian females. This case-control study was conducted based on 200 participants involving 100 women diagnosed with breast carcinoma and 100 unrelated cancer-free controls from the same district. The genomic DNA for all participants was genotyped utilizing T-ARMS-PCR procedure. The frequencies of the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant indicated a statistically significant with the elevated risk of breast carcinoma under various genetic models, including allelic (OR = 2.48, P-value < 0.001) and dominant (OR = 2.36, P-value = 0.003) models. In conclusion, the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant was considered as an independent risk factor for breast carcinoma among Egyptian women.
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Neoplasias de la Mama , Predisposición Genética a la Enfermedad , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Estudios de Casos y Controles , Egipto/epidemiología , Femenino , Genotipo , Gutatión-S-Transferasa pi/genética , Humanos , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
BACKGROUND: Coronavirus disease-2019 (COVID-19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID-19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by receiver operating characteristic curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in patients with COVID-19. RESULTS: A meta-analysis of 17 794 patients showed patients with high cardiac troponin I (OR = 5.22, 95% CI = 3.73-7.31, P < .001) and aspartate aminotransferase (AST) levels (OR = 3.64, 95% CI = 2.84-4.66, P < .001) were more likely to develop adverse outcomes. High troponin I more than 13.75 ng/L combined with either advanced age more than 60 years or elevated AST level more than 27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID-19 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches.
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COVID-19/complicaciones , COVID-19/mortalidad , Enfermedades Cardiovasculares/virología , Lesiones Cardíacas/virología , Miocardio/patología , Biomarcadores/análisis , COVID-19/fisiopatología , Enfermedades Cardiovasculares/fisiopatología , Comorbilidad , Árboles de Decisión , Humanos , Pronóstico , Análisis de Regresión , Índice de Severidad de la EnfermedadRESUMEN
Numerous eligible articles investigated the potential impact of the promoter region of UCP2 (rs659366) variant and the susceptibility for obesity with questionable outcomes. Our team designed this case-control combined with meta-analysis survey to illustrate the contribution of this variant with obesity. This case-control survey was formulated based on 110 obese Egyptian patients and 122 non-obese controls. Genomic DNA was amplified for ascertaining of UCP2 (G-866A; rs659366) variant exploiting the PCR-RFLP technique. A literature search was completed to investigate the involvement of this variant with obesity from various genetic databases. In this case-control study, the distribution of UCP2 (rs659366) variant showed a significant association with obesity among Egyptian subjects under allelic and dominant models (P value = 0.0006 and < 0.001, respectively). Overall, twenty-five comparisons for this variant (8652 obese patients and 10,075 non-obese controls) were recruited in this meta-analysis survey. A noteworthy association of UCP2 (rs659366) variant with obesity was identified among Asians and Africans but not Caucasians under allelic, dominant as well as heterozygote models. Nevertheless, this meta-analysis could not accomplish a noticeable association with overall subjects under different genetic models. This case-controlled study revealed a robust association for UCP2 (rs659366) variant with obesity susceptibility in Egyptian subjects; however, this meta-analysis survey failed to achieve an association for this variant with obesity in overall subjects except among Asians and Africans.
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Obesidad/genética , Proteína Desacopladora 2/genética , Estudios de Casos y Controles , Egipto , Femenino , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Regiones Promotoras GenéticasRESUMEN
Interleukin-17 (IL-17) is a critical cytokine involved in inflammation-associated cancers. Single nucleotide polymorphisms (SNPs) might promote carcinogenesis. In this current meta-analysis, we investigated the association of IL-17A and IL-17F gene polymorphisms with gastric cancer (GC) risk. Eligible genetic association studies were retrieved from PubMed, Web of Science and Scopus database sources. Two reviewers independently assessed methodological quality and extracted data from eligible articles. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Quantitative data synthesis was conducted using comprehensive meta-analysis v2. Subgroup analysis and heterogeneity analysis were performed. Begg's funnel plot and Egger's regression tests were used to judge publication bias. In silico data analysis was executed to analyze the functional and structural impact of the SNPs. A total of 21 case-control studies for rs2275913 c.-197G > A (7660 patients and 9409 controls), 9 studies for rs3748067 c.*1249C > T (3378 patients and 4120 controls), and 14 studies for rs763780 c.482A > G (4481 patients and 5354 controls) were included. The pooled estimate revealed an association between IL-17A rs2275913 polymorphism and the risk of GC under all genetic models (A vs. G, OR 1.187, 95% CI 1.086-1.297, P < 0.001; GA vs. GG, OR 1.108, 95% CI 1.008-1.218, P = 0.033; AA vs. GG, OR 1.484, 95% CI 1.236-1.781, P < 0.001), while no evidence of association was found with IL-17A rs3748067 or IL-17F rs763780 polymorphisms. Our results showed that IL-17A promoter rs2275913 variant might represent a potential risk factor for gastric cancer susceptibility.
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Interleucina-17/genética , Neoplasias Gástricas/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Interleucina-17/metabolismo , Masculino , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
BACKGROUND: The relationship between GEMIN4 genetic variants and cancer, especially bladder carcinoma (BLCA), has been explored without conclusive results. This study aims to elucidate the link between GEMIN4 polymorphisms and BLCA susceptibility through genetic analyses, bioinformatics, and molecular dynamics (MD) simulations. METHODS: A cohort of 249 participants (121 BLCA patients and 128 unrelated controls) was enrolled. PCR was employed for allelic discrimination of GEMIN4 variants, followed by subgroup stratification, haplotype analyses, structural prediction using the AlphaFold2 prediction tool, subsequent MD simulations, structural analysis, and residue interaction mapping using Desmond, UCSF ChimeraX, and Cytoscape softwares. RESULTS: The rs.2740348*G variant demonstrated a protective role against BLCA in allelic (OR = 0.55, p = 0.002) and recessive (OR = 0.54, p = 0.017) models, whereas the rs.7813*T variant increased BLCA risk under the recessive model (OR = 1.90, p = 0.019). Haplotype analysis revealed a significant association between GEMIN4 haplotype (rs.2740348*C/rs.7813*T) with increased BLCA risk (OR = 2.01, p = 0.004). Univariate analysis revealed associations of the variants with albumin levels and absolute neutrophil count in BLCA patients. Pathogenicity evaluation categorized p.Gln450Glu as neutral and p.Arg1033Cys as deleterious. MD simulations revealed structural alterations and conformational shifts in the GEMIN4 protein induced by the Glu450 and Cys1033 mutations. CONCLUSIONS: The study highlights the dual role of GEMIN4 variants in BLCA susceptibility, with rs.2740348 conferring protection and rs.7813 increasing risk. The Glu450 residue positively impacted protein stability, while Cys1033 had a detrimental effect on protein function. These findings underscore the significance of GEMIN4 variants in BLCA susceptibility and pave the way for future diagnostic and therapeutic initiatives.
Asunto(s)
Carcinoma , Neoplasias de la Vejiga Urinaria , Humanos , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Biología Computacional , Alelos , Antígenos de Histocompatibilidad Menor , Ribonucleoproteínas Nucleares PequeñasRESUMEN
BACKGROUND: The human cytochrome P450 (CYP) superfamily encompasses different categories of isoenzymes that contribute to multiple metabolic processes involving drug detoxification, cellular signaling, and the proliferation of malignant tissues. Using genetic technology, customized bioinformatic analysis, and meta-analysis design, the main goal of this study was to identify the association between the CYP1A2*rs762551 variant and the susceptibility to breast carcinoma (BRCA). METHODS: The case-control study was conducted based on 104 BRCA women and 102 healthy controls. Using the TaqMan allelic discrimination assay, the CYP1A2 (rs762551; c.-9-154â¯C>A) variant was genotyped. Bioinformatic frameworks and logistic regression analysis were used to assess the involvement of this genetic variant in BRCA development. A meta-analysis design was accomplished based on our case-control study and other previously published records. Publication bias, heterogeneity between studies, and trial sequential analysis (TSA) were analyzed. RESULTS: The CYP1A2*rs762551 variant conferred protection against BRCA development under allelic (OR = 0.48, p-value < 0.001), dominant (OR = 0.34, p-value < 0.001), and recessive (OR = 0.44, p-value = 0.011) models. However, this intronic variant was correlated with a decreased risk of BRCA among late-onset menopause women compared to other cases. Bioinformatic analysis confirmed that this genetic variant has a functional impact on the progression of tumorgenesis. Moreover, this meta-analysis design included 12922 BRCA women and 15603 healthy controls. Our findings disclosed the contribution of the CYP1A2*rs762551 variant with protection against cancer development among Caucasian females under allelic (OR = 0.75, p-value = 0.025), and dominant (OR = 0.58, p-value = 0.015) models. CONCLUSIONS: This case-control study confirmed the contribution of the CYP1A2*rs762551 variant with decreased risk of BRCA development among Egyptian subjects. Moreover, BRCA women with late-onset menopause conferred protection against cancer progression compared to other subjects. Our findings identified that this meta-analysis design achieved protection against BRCA development among Caucasian women compared to other ethnicities.