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BACKGROUND: In recent years, various coronaviruses have caused severe respiratory illnesses worldwide. For example the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections of COVID-19 outbreak in 2019 in Wuhan, China. Genome-wide association studies (GWAS) have significantly expanded our comprehension of how specific genetic variations are linked to diseases. Research has demonstrated the existence of genetic factors influencing susceptibility to coronaviruses. The objective of this study was to examine the association of certain loci with the COVID-19 in Saudi population. METHODS: In the present study we have examined the link between the COVID-19 disease and certain genetic variants in hospitalized COVID-19 patients (n = 16) in Tabuk and Bisha, Kingdom Saudi Arabia. We used the genome Analysis Toolkit (GATK) and Comprehensive variant annotation was performed different databases and tools such as Search Tool for the Retrieval of Interacting Genes (STRING), PanelApp and PolyPhen-2. RESULTS: The study showed that the genetic variants associated with genes such as Homeostatic Iron Regulator (HFE) (found in 7 patients, representing 44%), complement factor H (CFH) (6 patients, 38%), cadherin 23 (CDH23) (4 patients, 25%), cytotoxic T-lymphocyte associated protein 4 (CTLA-4) (3 patients, 19%), Transforming Growth Factor Beta 1 (TGFB1) (3 patients, 19%), CREB-binding protein (CREBBP) (2 patients, 13%), E1A Binding Protein P300 (EP300) (2 patients, 13%), hemoglobin subunit beta (HBB) (2 patients, 13%), interferon regulatory factor 7 (IRF7) (2 patients, 13%), and unc-119 lipid binding chaperone (UNC119) (2 patients, 13%) might be associated with susceptibility to coronavirus. We also identified mutations in the COVID-19 patient that are pathogenic or likely pathogenic. CONCLUSION: A recurrent pathogenic mutation, HFE p.His63Asp (H63D), was identified in 7 patients, suggesting its potential contribution to disease severity. Additionally, a likely pathogenic variant, HBB p.Glu7Val (E7V), was present in 2 patients, highlighting its potential role in disease susceptibility. Our results shed light on the key genetic mechanisms of COVID-19 pathogenesis and help to identify and stratify the individuals or populations that are at risk to corona virus infection. The identification of susceptible individuals or populations assist in prevention and/or in treatment programs.
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COVID-19 , Sequenciamento do Exoma , Proteína da Hemocromatose , SARS-CoV-2 , Humanos , COVID-19/genética , COVID-19/virologia , COVID-19/mortalidade , SARS-CoV-2/genética , Masculino , Pessoa de Meia-Idade , Feminino , Arábia Saudita/epidemiologia , Proteína da Hemocromatose/genética , Adulto , Predisposição Genética para Doença , Idoso , Mutação , Estudo de Associação Genômica AmplaRESUMO
Dorstenia psilurus is a widely used plant spice in traditional African medicine to treat pain-related conditions. However, the anti-inflammatory mechanisms underlying this activity and the main active ingredients of D. psilurus have not yet been fully characterized. This study aimed to isolate and identify the main active anti-inflammatory constituents of the D. psilurus extract and to investigate the underlying anti-inflammatory mechanisms in murine macrophages. Chromatographic techniques and spectroscopic data were used for compound isolation and structure elucidation. The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and 15-lipoxygenase activity, respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit, and Th1/Th2 cytokine measurement was performed using a flow cytometer. The results indicated that the extract and fractions of D. psilurus inhibit NO production and proliferation of RAW 264.7 macrophage cells. Bioguided fractionation led to the identification of psoralen, a furocoumarin, as the main bioactive anti-inflammatory compound. Psoralen inhibited NO production and 15-lipoxygenase activity and reduced pro-inflammatory Th1 cytokines (IFN-γ, TNF-α, and IL-2) while increasing the secretion of anti-inflammatory cytokines (IL-4, IL-6, and IL-10) in activated RAW 264.7 macrophage cells. The encouraging results obtained in this study suggest that psoralen-based multiple modulation strategies could be a useful approach to address the treatment of inflammatory diseases.
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Citocinas , Ficusina , Lipopolissacarídeos , Macrófagos , Raízes de Plantas , Animais , Camundongos , Células RAW 264.7 , Citocinas/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Raízes de Plantas/química , Lipopolissacarídeos/farmacologia , Ficusina/farmacologia , Ficusina/química , Células Th1/efeitos dos fármacos , Células Th1/metabolismo , Células Th2/metabolismo , Células Th2/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Óxido Nítrico/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/químicaRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in developing nations. The high prevalence of obesity and related diabetes cases are attributed to rapid economic progress, physical inactivity, the consumption of high-calorie foods, and changing lifestyles. OBJECTIVES: We investigated the roles of pro-inflammatory chemokines CCL1, 2, 4, and 5 in T2DM with varying levels of obesity in the Asir region of Saudi Arabia. MATERIALS AND METHODS: In total, 170 confirmed T2DM subjects and a normal control group were enrolled. Demographic data, serum levels of CCL-1, 2, 4, and 5, and biochemical indices were assessed in the subjects and control groups by standard procedures. RESULTS: T2DM subjects were divided into four groups: A (normal body weight), B (overweight), C (obese), and D (highly obese). We observed that male and female control subjects had similar mean serum concentrations of pro-inflammatory chemokines CCL-1, 2, 4, and 5. T2DM subjects in all the four groups showed significantly higher levels of all the four chemokines compared to the controls, regardless of gender. In T2DM subjects with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL-1, 2, and 4 in T2DM subjects with increasing BMI. Serum CCL5 levels increased significantly in all T2DM subject groups. The increase in CCL5 was more predominant in normal-weight people, compared to overweight and obese T2DM subjects. CONCLUSIONS: Male and female control subjects had similar serum levels of pro-inflammatory chemokines CCL-1, 2, 4, and 5. The progressive rise in blood concentrations of three pro-inflammatory chemokines CCL-1, 2, and 4 in T2DM subjects with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM subject groups. The selective and more pronounced increase in CCL5 in the T2DM group with normal BMI, compared to subjects with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 underexpression in overweight and obese T2DM subjects is due to some unexplained counterbalancing processes.
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Sorafenib is a multikinase inhibitor employed for managing hepatocellular carcinoma (HCC). The emergence of sorafenib resistance presents an obstacle to its therapeutic efficacy. One notable approach to overcoming sorafenib resistance is the exploration of combination therapies. The role of hedgehog signaling in sorafenib resistance has been also examined in HCC. R51211, known as itraconazole, has been safely employed in clinical practice. Through in vitro and in vivo investigations, we assessed the potential of R51211 to enhance the therapeutic efficacy of sorafenib by inhibiting the hedgehog signaling. The zero-interaction potency synergy model demonstrated a synergistic interaction between R51211 and sorafenib, a phenomenon reversed by the action of a smoothened receptor agonist. This dual therapy exhibited an increased capacity to induce apoptosis, as evidenced by alterations in the Bax/BCL-2 ratio and caspase-3, along with a propensity to promote autophagy, as indicated by changes in BECN1, p62, and the LC3I/LC3II ratio. Furthermore, the combination therapy resulted in significant reductions in biomarkers associated with liver preneoplastic alterations, improved liver microstructure, and mitigated changes in liver function enzymes. The substantial decrease in hedgehog components (Shh, SMO, GLI1, and GLI2) following R51211 treatment appears to be a key factor contributing to the increased efficacy of sorafenib. In conclusion, our study highlights the potential of R51211 as an adjunct to sorafenib, introducing a new dimension to this combination therapy through the modulation of the hedgehog signaling pathway. Further investigations are essential to validate the therapeutic efficacy of this combined approach in inhibiting the development of liver cancer.
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Carcinoma Hepatocelular , Proteínas Hedgehog , Itraconazol , Neoplasias Hepáticas , Transdução de Sinais , Sorafenibe , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Proteínas Hedgehog/metabolismo , Humanos , Animais , Transdução de Sinais/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Camundongos , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Apoptose/efeitos dos fármacos , Masculino , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sinergismo Farmacológico , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Autofagia/efeitos dos fármacosRESUMO
Introduction: There is a growing interest in studying natural products for the identification of novel lead compounds for drug development for treating inflammatory diseases. Although some studies have focused anti-inflammatory activity of benzophenones and xanthones, exploring additional targets such as enzymes and cytokines, involved in their inflammatory response could provide more comprehensive understanding of the compounds' anti-inflammatory effects. In this study, four xanthones ananixanthone (1), smeathxanthone A (2), smeathxanthone B (3), and 1,3,5,8-tetrahydroxy-2-(3-methybut-2-enyl)-4-(3,7-dimethyloct-2,6-dienyl) xanthone (4); and three benzophenones guttiferone O (5), guttiferone M (6), and aristophenone A (7) from Garcinia smeathmannii (Planch. & Triana) Oliv. were investigated for their effect on nitric oxide production, cyclooxygenase, lipoxygenase inhibition, and Th1/Th2 cytokines production in activated RAW 264.7 macrophages. Methods: The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and the 15-lipoxygenase activity respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit and measurement of Th1/Th2 cytokines was performed using a flow cytometer. Results: All the tested compounds exhibited a dose-dependent inhibition of NO production with varying degrees of inhibitory effects on 15-LOX activity. Compound (6), displays the best inhibitory effect on COX-1/COX-2 activity. A general trend of the tested compounds on cytokines profiles revealed that compound (5) showed a pronounced enhancement of anti-inflammatory cytokines (IL-4 and IL-10). Conclusion: This observation supports future exploration of ananixanthone (1), guttiferone O (5), and guttiferone (6) as potential candidates for the development of anti-inflammatory drugs.
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BACKGROUND: Malnutrition among adolescents is a major public health issue. This problem is particularly pressing in Sudan, an African country where there is scarce published data on the nutritional status of adolescents. In this study, we aimed to assess the nutritional status of adolescents in eastern Sudan. METHODS: A community-based cross-sectional survey was carried out in Gadarif, eastern Sudan. A questionnaire was used to collect sociodemographic data, and the anthropometric measurements (weight and height) of adolescent participants were recorded. Height-for-age and body mass index-for-age Z-scores were calculated using the WHO anthropometric standards. Binary and multivariate multinomial regression analyses were performed. RESULTS: A total of 388 adolescents were included in this survey, 207 (53.4%) were female, and 181 (46.6%) were male. The median (interquartile) age was 13.9 (12.0-16.0) years. The results showed that a total of 29 (7.5%), 93 (24.0%), 33 (8.5%), and 16 (4.1%) adolescents were stunted, thin, overweight, and obese, respectively. None of the investigated factors (age, sex, parents' education levels, and occupation) were associated with stunting. In the multivariate multinomial analysis, the male sex was associated with thinness (OR = 2.41, 95.0% CI = 1.47-3.94). Moreover, adolescents whose mothers had an education lower than secondary level were at a lower risk of overweight/obesity (OR = 0. 0.35, 95.0% CI = 0. 0.35). CONCLUSIONS: While both undernutrition and overnutrition exist in eastern Sudan, undernutrition is more common. Male sex and mothers' education levels are associated with malnutrition.
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Estado Nutricional , Humanos , Sudão/epidemiologia , Feminino , Masculino , Adolescente , Estudos Transversais , Criança , Magreza/epidemiologia , Desnutrição/epidemiologia , Índice de Massa Corporal , Transtornos do Crescimento/epidemiologia , Sobrepeso/epidemiologiaRESUMO
Background: Headache disorder is the second-highest cause of disability worldwide; however, data are scarce on headache among adolescents, especially in Africa. There has yet to be published data on headache among adolescents in Sudan, the third-largest country in Africa. This study aimed to assess the prevalence of primary headache disorders and associated factors among adolescents (10-19 years) in eastern Sudan. Methods: A community-based cross-sectional study was conducted in the city of Gadarif in eastern Sudan. Questionnaires were used to gather the adolescents' sociodemographic characteristics. Headache diagnostic questions were based on the beta version of the International Classification of Headache Disorders-III (ICHD-3). Multivariate analysis was conducted to assess the associated factors for primary headache disorders, and the results were expressed as risk ratios (RRs) and 95.0% confidence interval (CI). Results: Of the 401 enrolled adolescents, 186 (46.4%) and 215 (53.6%) were male and female, respectively. The median (IQR) age was 14.0 (12.1-16.2) years. Eighty-one (20.2%) of the 401 adolescents reported experiencing primary headache disorders, including migraine with aura in 16 (4.0%), migraine without aura in 33 (8.2%), tension-type in 14 (3.5%), and undifferentiated headache in 18 (4.5%) adolescents. The prevalence of primary headache disorders was significantly higher in females than in males [55/215 (67.9%) vs. 26/186 (32.1%), p = 0.004]. In the multivariate analysis, increased age (RR = 1.09, 95.0 CI = 1.02-1.16) and being female (RR = 1.75, 95.0 CI = 1.14-2.67) were associated with increased RR of primary headache disorders. Parents' education level and occupation, smoking/snuff use, and body mass index were not associated with primary headache disorders. Conclusion: One-fifth of the adolescents in eastern Sudan reported experiencing primary headache disorders, which was more common in females and with increased age.
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Most post-pancreaticoduodenectomy hemorrhages (PPH) are of arterial origin, and some studies have suggested that an interventional radiology approach is most effective in reducing mortality. Venous PPH is rare, and identifying its source can be challenging. We report a case of late venous PPH in the context of a pancreatic fistula following pancreaticoduodenectomy. During surgical exploration, the area of ââpotential bleeding was inaccessible due to major inflammatory adhesions aggravated by the presence of pancreatic fistula and the delay of relaparotomy. No intra-abdominal bleeding was detected on imaging studies or during abdominal exploration; only a massive bleeding through the drain orifice, which required packing, was observed. Percutaneous transhepatic portography was performed to localize and treat the origin of the bleeding. The hemorrhage was successfully treated by endovascular approach. We found no reports in the literature on the use of interventional radiology with venous stenting to treat venous PPH, except in cases of gastrointestinal variceal hemorrhage due to portal occlusion.
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Non-alcoholic steatohepatitis (NASH) is characterized by liver inflammation, fat accumulation, and collagen deposition. Due to the limited availability of effective treatments, there is a pressing need to develop innovative strategies. Given the complex nature of the disease, employing combination approaches is essential. Hedgehog signaling has been recognized as potentially promoting NASH, and cholesterol can influence this signaling by modifying the conformation of PTCH1 and SMO activity. HSP90 plays a role in the stability of SMO and GLI proteins. We revealed significant positive correlations between Hedgehog signaling proteins (Shh, SMO, GLI1, and GLI2) and both cholesterol and HSP90 levels. Herein, we investigated the novel combination of the cholesterol-lowering agent lovastatin and the HSP90 inhibitor PU-H71 in vitro and in vivo. The combination demonstrated a synergy score of 15.09 and an MSA score of 22.85, as estimated by the ZIP synergy model based on growth inhibition rates in HepG2 cells. In a NASH rat model induced by thioacetamide and a high-fat diet, this combination therapy extended survival, improved liver function and histology, and enhanced antioxidant defense. Additionally, the combination exhibited anti-inflammatory and anti-fibrotic potential by influencing the levels of TNF-α, TGF-ß, TIMP-1, and PDGF-BB. This effect was evident in the suppression of the Col1a1 gene expression and the levels of hydroxyproline and α-SMA. These favorable outcomes may be attributed to the combination's potential to inhibit key Hedgehog signaling molecules. In conclusion, exploring the applicability of this combination contributes to a more comprehensive understanding and improved management of NASH and other fibrotic disorders.
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Proteínas de Choque Térmico HSP90 , Proteínas Hedgehog , Inibidores de Hidroximetilglutaril-CoA Redutases , Hepatopatia Gordurosa não Alcoólica , Transdução de Sinais , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Masculino , Humanos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Células Hep G2 , Dieta Hiperlipídica/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Quimioterapia Combinada , Ratos , Ratos Sprague-Dawley , Colesterol/metabolismoRESUMO
BACKGROUND: Maternal diabetes mellitus (MDM) is associated with increased risks for adverse neonatal outcomes. However, the impact of MDM on neonatal outcomes in Bisha, a city in Saudi Arabia, is not well documented. This study aims to investigate the impact of MDM on neonatal outcomes in the Maternity and Children's Hospital (MCH), Bisha, Saudi Arabia. METHODS: A retrospective cohort study was conducted on 181 pregnant women with diabetes and their neonates who were diagnosed at the Maternity and Children's Hospital (MCH), Bisha, Saudi Arabia, between 5 October 2020 and 5 November 2022. The primary outcome was a composite of adverse neonatal outcomes, including stillbirth, neonatal death, macrosomia, preterm birth, respiratory distress syndrome, hypoglycemia, and congenital anomalies. Logistic regression analyses were used to adjust for potential confounders. RESULTS: The total sample size was 181. The average age of patients was 34 years (SD = 6.45). The majority of the patients were diagnosed with GDM, 147 (81.2%), and pre-GDM, 34 (18.8%). Neonates born to mothers with MDM had a higher risk of adverse neonatal outcomes compared to those born to mothers without MDM (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI]: 1.25-1.70). The risks of macrosomia (aOR = 1.74, 95% CI: 1.38-2.19), LBW (aOR = 1.32, 95% CI: 1.06-1.66), and RDS (aOR = 1.57, 95% CI: 1.28-1.93) were significantly higher among neonates born to mothers with MDM. The types of DM were statistically significant in terms of their correlation with the following neonatal outcomes: hypoglycemia (p-value = 0.017), macrosomia (p-value = 0.050), and neonatal death (p-value = 0.017). CONCLUSIONS: MDM is associated with an increased risk of adverse neonatal outcomes in Bisha. The early identification and management of MDM may improve neonatal outcomes and reduce the burden of neonatal morbidity and mortality in this population.
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Diabetes Gestacional , Resultado da Gravidez , Humanos , Gravidez , Feminino , Estudos Retrospectivos , Recém-Nascido , Adulto , Arábia Saudita/epidemiologia , Diabetes Gestacional/epidemiologia , Gravidez em Diabéticas , Macrossomia Fetal/epidemiologia , Nascimento Prematuro/epidemiologiaRESUMO
BACKGROUND: Distractor efficiency (DE) of multiple-choice questions (MCQs) responses is a component of the psychometric analysis used by the examiners to evaluate the distractors' credibility and functionality. This study was conducted to evaluate the impact of the DE on the difficulty and discrimination indices. METHODS: This cross-sectional study was conducted from April to June 2023. It utilizes the final exam of the Principles of Diseases Course with 45 s-year students. The exam consisted of 60 type A MCQs. Item analysis (IA) was generated to evaluate KR20, difficulty index (DIF), discrimination index (DIS), and distractor efficiency (DE). DIF was calculated as the percentage of examinees who scored the item correctly. DIS is an item's ability to discriminate between higher and lower 27% of examinees. For DE, any distractor selected by less than 5% is considered nonfunctional, and items were classified according to the non-functional distractors. The correlation and significance of variance between DIF, DI, and DE were evaluated. RESULTS: The total number of examinees was 45. The KR-20 of the exam was 0.91. The mean (M), and standard deviation (SD) of the DIF of the exam was 37.5(19.1), and the majority (69.5%) were of acceptable difficulty. The M (SD) of the DIS was 0.46 (0.22), which is excellent. Most items were excellent in discrimination (69.5%), only two were not discriminating (13.6%), and the rest were of acceptable power (16.9%). Items with excellent and good efficiency represent 37.3% each, while only 3.4% were of poor efficiency. The correlation between DE and DIF (p = 0.000, r= -0.548) indicates that items with efficient distractors (low number of NFD) are associated with those having a low difficulty index (difficult items) and vice versa. The correlation between DE and DIS is significantly negative (P = 0.0476, r=-0.259). In such a correlation, items with efficient distractors are associated with low-discriminating items. CONCLUSIONS: There is a significant moderate negative correlation between DE and DIF (P = 0.00, r = -0.548) and a significant weak negative correlation between DE and DIS (P = 0.0476, r = -0.259). DIF has a non-significant negative correlation with DIS (P = 0.7124, r = -0.0492). DE impacts both DIF and DIS. Items with efficient distractors (low number of NFD) are associated with those having a low difficulty index (difficult items) and discriminating items. Improving the quality of DE will decrease the number of NFDs and result in items with acceptable levels of difficulty index and discrimination power.
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Avaliação Educacional , Psicometria , Humanos , Estudos Transversais , Avaliação Educacional/métodos , Feminino , MasculinoRESUMO
Ulcerative colitis (UC) is an inflammatory condition that affects the colon's lining and increases the risk of colon cancer. Despite ongoing research, there is no identified cure for UC. The recognition of NLRP3 inflammasome activation in the pathogenesis of UC has gained widespread acceptance. Notably, the ketone body ß-hydroxybutyrate inhibits NLRP3 demonstrating its anti-inflammatory properties. Additionally, BD-AcAc 2 is ketone mono ester that increases ß-hydroxybutyrate blood levels. It has the potential to address the constraints associated with exogenous ß-hydroxybutyrate as a therapeutic agent, including issues related to stability and short duration of action. However, the effects of ß-hydroxybutyrate and BD-AcAc 2 on colitis have not been fully investigated. This study found that while both exogenous ß-hydroxybutyrate and BD-AcAc 2 produced the same levels of plasma ß-hydroxybutyrate, BD-AcAc 2 demonstrated superior effectiveness in mitigating dextran sodium sulfate-induced UC in rats. The mechanism of action involves modulating the NF-κB signaling, inhibiting the NLRP3 inflammasome, regulating antioxidant capacity, controlling tight junction protein expression and a potential to inhibit apoptosis and pyroptosis. Certainly, BD-AcAc 2's anti-inflammatory effects require more than just increasing plasma ß-hydroxybutyrate levels and other factors contribute to its efficacy. Local ketone concentrations in the gastrointestinal tract, as well as the combined effect of specific ketone bodies, are likely to have contributed to the stronger protective effect observed with ketone mono ester ingestion in our experiment. As a result, further investigations are necessary to fully understand the mechanisms of BD-AcAc 2 and optimize its use.
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Ácido 3-Hidroxibutírico , Colite Ulcerativa , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Ácido 3-Hidroxibutírico/farmacologia , Ratos , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos Sprague-Dawley , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Sulfato de Dextrana/toxicidade , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , NF-kappa B/metabolismo , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos , Cetonas/farmacologiaRESUMO
Epigenetic processes, including non-coding RNA, histone modifications, and DNA methylation, play a vital role in connecting the environment to the development of a disorder, especially when there is a favorable genetic background. Ankylosing Spondylitis (AS) is a chronic type of spinal arthritis that highlights the significance of epigenetics in diseases related to autoimmunity and inflammation. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in both normal and aberrant pathological and physiological gene expression. This study focuses on the pathophysiological pathways to clarify the role of miRNAs in AS. We have conducted a thorough investigation of the involvement of miRNAs in several processes, including inflammation, the production of new bone, T-cell activity, and the regulation of pathways such as BMP, Wnt, and TGFß signaling. Undoubtedly, miRNAs play a crucial role in enhancing our comprehension of the pathophysiology of AS, and their promise as a therapeutic strategy is quickly expanding.
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Biomarcadores , Epigênese Genética , MicroRNAs , Espondilite Anquilosante , Espondilite Anquilosante/genética , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/imunologia , Humanos , MicroRNAs/genética , Regulação da Expressão Gênica , Animais , Transdução de SinaisRESUMO
Wilms' tumors (WTs) are the most common type of kidney tumor in children, and a negative outlook is generally associated with widespread anaplastic. MicroRNAs (miRNAs) are crucial in the development of WT by regulating the expression of specific genes. There is an increasing amount of research that connects the dysregulation of miRNAs to the development of various renal illnesses. The conditions encompassed are renal fibrosis, renal cancers, and chronic and polycystic kidney disease. Dysregulation of several important miRNAs, either oncogenic or tumor-suppressing, has been found in WT. The present state of knowledge on the involvement of dysregulated miRNAs in the progression of WT is summarized in this review.
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Neoplasias Renais , MicroRNAs , Tumor de Wilms , Criança , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Tumor de Wilms/patologia , Neoplasias Renais/patologia , Rim/patologia , Transdução de Sinais/genéticaRESUMO
Plasma gelsolin (pGSN) correlates with clinical improvement in septic patients. We aimed to investigate pGSN levels as a diagnostic and prognostic marker of neonatal late-onset-sepsis (LOS). A case-control study was done on 184 neonates (92 with LOS and 92 controls). All participants were subjected to detailed history taking, full clinical evaluation, sepsis workup, and pGSN enzyme-linked immunosorbent-assay measurement. We detected significantly lower pGSN level among cases compared to controls (90.63â ±â 20.64 vs 451.83â ±â 209.59). It was significantly related to the severity of sepsis and mortality, with significantly lower values among cases with septic shock and multiorgan failure and non-survivors. Follow-up pGSN significantly increased after sepsis improvement in survivors compared to admission values. pGSN might be a reliable diagnostic and prognostic marker for LOS.
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Sepse Neonatal , Sepse , Recém-Nascido , Humanos , Sepse Neonatal/diagnóstico , Gelsolina , Estudos de Casos e Controles , Sepse/diagnóstico , HospitalizaçãoRESUMO
Intussusception in adults is less frequent than in children, and it is less commonly seen in the colon than in the intestines. This may be explained by the fixation of the colon to the retroperitoneum. We herein describe a case of sigmoid colon intussusception caused by a sigmoid colon adenocarcinoma. An 81-year-old man presented with abdominal pain and signs and symptoms of gastrointestinal obstruction. CT revealed a "target sign" with a mass in the sigmoid colon. We diagnosed the patient with colonic obstruction secondary to intussusception of the sigmoid colon and performed an emergency transverse colostomy. On the first postoperative day, the patient had a parastomal evisceration. Oncologic resection of the sigmoid colon without reduction of the intussusception was performed. The tumor was pathologically diagnosed as well-differentiated adenocarcinoma and classified as pT3N0. The patient was discharged on the ninth postoperative day with an uneventful postoperative course. The surveillance was validated for this patient.
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[This corrects the article DOI: 10.3389/fphar.2023.1239025.].
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Background: Bronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma. Methods: This study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs. Results: The current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma.
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INTRODUCTION: Parents' ability to engage and raise their children in a safe and appropriate manner is largely influenced by their knowledge of child development and childrearing. This study aimed to evaluate the parenting and developmental milestone (MS) knowledge of Western region Saudi parents and identify the related elements that influence their knowledge. METHODS: This crosssectional study was conducted for a period of six months. Ethical approval was duly sanctioned by the Institutional Review Board (IRB), and prior to participation, written informed consent was diligently procured from all the individuals involved in the study. In adherence to the paramount principles of privacy, rigorous measures were employed to deidentify the personal data of the participants, thereby safeguarding their confidentiality and anonymity. All research procedures were meticulously executed in strict compliance with the pertinent guidelines and regulatory standards governing research ethics. The study cohort consisted of Saudi parents from the Western Province of Saudi Arabia who had children aged up to six years and expressed a genuine willingness to participate in the research. This commitment was reaffirmed through their informed consent. Notably, the inclusion criteria for parental involvement did not impose any restrictions based on age or ethnic origin, ensuring a diverse and inclusive representation of this crucial demographic group. RESULTS: For assessing parental awareness and knowledge about children's developmental MSs, we examined a diverse sample of 873 participants, predominantly comprising females (77.00%). The age distribution revealed that a substantial portion of the respondents were below 30 (37.00%). Most respondents (62.40%) sought information from medical physicians and pediatricians. Gender had a significant effect, with males showing a lower awareness level compared to females (Beta = -0.582, 95% confidence interval (CI) [-0.890, -0.274], p-value < 0.001). Marital status demonstrated significance, where divorced individuals showed a lower awareness level than widowed participants (Beta = -1.641, 95% CI [-2.993, -0.288], p-value = 0.017). At the same time, no significant differences were found for singles or married individuals. CONCLUSION: Saudi parents lacked understanding of other parenting skills, such as a baby's personality and temperament, but they were well educated about some areas of childrearing, primarily physical safety precautions. It is advised that nurses and doctors give parenting advice to families at every step of their children's growth to educate and support them.
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Accumulating evidence suggests that dysregulation of FOXO3a plays a significant role in the progression of various malignancies, including hepatocellular carcinoma (HCC). FOXO3a inactivation, driven by oncogenic stimuli, can lead to abnormal cell growth, suppression of apoptosis, and resistance to anticancer drugs. Therefore, FOXO3a emerges as a potential molecular target for the development of innovative treatments in the era of oncology. Linagliptin (LNGTN), a DPP-4 inhibitor known for its safe profile, has exhibited noteworthy anti-inflammatory and anti-oxidative properties in previous in vivo studies. Several potential molecular mechanisms have been proposed to explain these effects. However, the capacity of LNGTN to activate FOXO3a through AMPK activation has not been investigated. In our investigation, we examined the potential repurposing of LNGTN as a hepatoprotective agent against diethylnitrosamine (DENA) intoxication. Additionally, we assessed LNGTN's impact on apoptosis and autophagy. Following a 10-week administration of DENA, the liver underwent damage marked by inflammation and early neoplastic alterations. Our study presents the first experimental evidence demonstrating that LNGTN can reinstate the aberrantly regulated FOXO3a activity by elevating the nuclear fraction of FOXO3a in comparison to the cytosolic fraction, subsequent to AMPK activation. Moreover, noteworthy inactivation of NFκB induced by LNGTN was observed. These effects culminated in the initiation of apoptosis, the activation of autophagy, and the manifestation of anti-inflammatory, antiproliferative, and antiangiogenic outcomes. These effects were concomitant with improved liver function and microstructure. In conclusion, our findings open new avenues for the development of novel therapeutic strategies targeting the AMPK/FOXO3a signaling pathway in the management of chronic liver damage.