Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
1.
Gene ; 921: 148524, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38735598

RESUMO

Polycystic ovary syndrome (PCOS) is a prevalent endocrinologic and gynecologic disorder that affects women of reproductive age; besides, insulin resistance (IR) occurs in 50-70 % of PCOS cases. Metformin (Met) is commonly prescribed for IR management; however, it does not affect IR with some gastrointestinal symptoms. Spirulina platensis (SP) is a blue-green alga that may increase insulin sensitivity. Therefore, our study aims to evaluate SP as an alternative treatment to Met for improving glucose homeostasis by assessing the expression of 11 crucial genes involved in the insulin signaling pathway. After induction of the PCOS model using dehydroepiandrosterone (DHEA) (60 mg/kg bwt) for 30 consecutive days, rats were allocated into six groups. Relative liver weight, glutamic pyruvic transaminase (GPT) serum levels, glutamic-oxaloacetic transaminase (GOT), and insulin were determined. Furthermore, the gene expression of Ins1, Irs1, Pik3ca, Prkcz, Foxo1, Srebf1, Ppargc1a, Pklr, Gk, G6pc, and Pepck in the rat's liver tissue was determined using qRT-PCR. Treatment of the PCOS control group with Met or SP revealed a decrease in all these parameters compared with the PCOS model. Additionally, we found a statistically significant difference in the expression of both the Gk and Prkcz genes. To summarize our study results, SP or Met supplementation to PCOS rats had almost the same effect on assessed relative liver weight, GOT, GPT, and insulin levels compared with PCOS control rats. If further studies confirm and detect more impact of SP on IR in PCOS, SP could be used instead of Met since the latter causes many side effects.


Assuntos
Modelos Animais de Doenças , Resistência à Insulina , Insulina , Metformina , Síndrome do Ovário Policístico , Transdução de Sinais , Spirulina , Animais , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Feminino , Metformina/farmacologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Insulina/sangue , Fígado/metabolismo , Fígado/efeitos dos fármacos , Ratos Wistar , Hipoglicemiantes/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos
2.
Am J Hum Genet ; 111(3): 584-593, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38417439

RESUMO

Variants of uncertain significance (VUSs) in BRCA2 are a common result of hereditary cancer genetic testing. While more than 4,000 unique VUSs, comprised of missense or intronic variants, have been identified in BRCA2, the few missense variants now classified clinically as pathogenic or likely pathogenic are predominantly located in the region encoding the C-terminal DNA binding domain (DBD). We report on functional evaluation of the influence of 462 BRCA2 missense variants affecting the DBD on DNA repair activity of BRCA2 using a homology-directed DNA double-strand break repair assay. Of these, 137 were functionally abnormal, 313 were functionally normal, and 12 demonstrated intermediate function. Comparisons with other functional studies of BRCA2 missense variants yielded strong correlations. Sequence-based in silico prediction models had high sensitivity, but limited specificity, relative to the homology-directed repair assay. Combining the functional results with clinical and genetic data in an American College of Medical Genetics (ACMG)/Association for Molecular Pathology (AMP)-like variant classification framework from a clinical testing laboratory, after excluding known splicing variants and functionally intermediate variants, classified 431 of 442 (97.5%) missense variants (129 as pathogenic/likely pathogenic and 302 as benign/likely benign). Functionally abnormal variants classified as pathogenic by ACMG/AMP rules were associated with a slightly lower risk of breast cancer (odds ratio [OR] 5.15, 95% confidence interval [CI] 3.43-7.83) than BRCA2 DBD protein truncating variants (OR 8.56, 95% CI 6.03-12.36). Overall, functional studies of BRCA2 variants using validated assays substantially improved the variant classification yield from ACMG/AMP models and are expected to improve clinical management of many individuals found to harbor germline BRCA2 missense VUS.


Assuntos
Neoplasias da Mama , Predisposição Genética para Doença , Humanos , Feminino , Proteína BRCA2/genética , Testes Genéticos , Mutação de Sentido Incorreto/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Células Germinativas/patologia , DNA
3.
BMC Cardiovasc Disord ; 23(1): 392, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37559011

RESUMO

BACKGROUND: Minimally invasive approaches like mini-thoracotomy and mini-sternotomy for Aortic Valve Replacement (AVR) showed impressive outcomes. However, their advantages for obese patients are questionable. We aimed in this network meta-analysis to compare three surgical approaches: Full sternotomy (FS), Mini-sternotomy (MS), and Mini-thoracotomy (MT) for obese patients undergoing AVR. METHODS: We followed the PRISMA extension for this network meta-analysis. PubMed/Medline, Scopus, Web of Science, and Cochrane searched through March 2023 for relevant articles. The analysis was performed using R version 4.2.3. RESULTS: Out of 344, 8 articles met the criteria with 1392 patients. The main outcomes assessed were perioperative mortality, re-exploration, atrial fibrillation, renal failure, ICU stay, hospital stay, cross-clamp time, and bypass time. In favor of MS, the length of ICU stay and hospital stay was significantly lower than for FS [MD -0.84, 95%CI (-1.26; -0.43)], and [MD -2.56, 95%CI (-3.90; -1.22)], respectively. Regarding peri-operative mortality, FS showed a significantly higher risk compared to MS [RR 2.28, 95%CI (1.01;5.16)]. Also, patients who underwent minimally invasive approaches; MT and MS, required less need of re-exploration compared to FS [RR 0.10, 95%CI (0.02;0.45)], and [RR 0.33, 95%CI (0.14;0.79)], respectively. However, Intraoperative timings; including aortic cross-clamp, and cardiopulmonary bypass time, were significantly lower with FS than for MS [MD -9.16, 95%CI (-1.88; -16.45)], [MD -9.61, 95%CI (-18.64; -0.59)], respectively. CONCLUSION: Our network meta-analysis shows that minimally invasive approaches offer some advantages for obese patients undergoing AVR over full sternotomy. Suggesting that these approaches might be considered more beneficial alternatives for obese patients undergoing AVR.


Assuntos
Valva Aórtica , Implante de Prótese de Valva Cardíaca , Humanos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Metanálise em Rede , Implante de Prótese de Valva Cardíaca/efeitos adversos , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Esternotomia/efeitos adversos , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/cirurgia , Estudos Retrospectivos
4.
Indian Heart J ; 75(2): 98-107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36758831

RESUMO

INTRODUCTION: radiofrequency catheter ablation (RFA) is the first-line therapy for symptomatic Wolff Parkinson White (WPW) patients according to the American Heart Association. We conducted this study to assess the success rate, recurrence rate, and rate of complications associated with the utilization of radiofrequency catheter ablation for managing patients with WPW. METHOD: We searched PubMed, Cochrane library, Web of Science and Scopus databases using all identified keywords and index terms through 4 January 2022. We included all studies conducted on WPW patients who were treated with ablation. We conducted the analysis using Open Meta Analyst and MedCalc version 19.1. RESULTS: Among 2268 unique articles identified, only 11 articles met our inclusion criteria. The pooled effect estimates showed high success rate (94.1%[95%CI:92.3-95.9], p < 0.001)), low recurrence rate (6.2% [95%CI:4.5-7.8, p < 0.001]) and low rate of complications (1%[95%CI:0.4-1.5, p < 0.001]). CONCLUSION: RFA showed a high success rate, low recurrence rate and low rate of complications in WPW patients.


Assuntos
Ablação por Cateter , Síndrome de Wolff-Parkinson-White , Estados Unidos , Humanos , Síndrome de Wolff-Parkinson-White/diagnóstico , Síndrome de Wolff-Parkinson-White/cirurgia , Síndrome de Wolff-Parkinson-White/complicações , Ablação por Cateter/efeitos adversos , American Heart Association , Gerenciamento de Dados
5.
Surg Endosc ; 37(3): 2173-2181, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36326931

RESUMO

BACKGROUND: Gastro-cutaneous fistula is a rare complication after laparoscopic sleeve gastrectomy (LSG) with incidence of occurrence 1-2%. Most of gastro-cutaneous fistulae do not respond to conservative management and need intervention either surgically or endoscopically. METHODS: This prospective randomized clinical study included referred patients who had LSG performed at our department or other centers, and complicated with post-LSG leak or gastro-cutaneous fistula between December/2019 and March/2021. Included patients were ASA Physical status I-II. Primary and secondary outcomes were recurrence of the fistula and mortality in each group after the intervention during the 18 months follow-up period, respectively. RESULTS: Thirty patients were randomized into two groups: Surgery Group (SG, n = 15) and Endoscopy Group (EG, n = 15). Mean age of patients was 42.3 ± 8.7 and 42.6 ± 8.3 years-old in SG and EG, respectively. Females constituted 73.3% and 80% in SG and EG, respectively. Median time-to-gastric leak post LSG was six (range: 4-7) days in both groups. SG patients were surgically managed with primary repair of the gastric fistula and gastrojejunostomy in 13 patients or converting SG into Roux-en-Y gastric bypass in two patients, while EG patients were endoscopically managed with stitching, stenting, stenting and dilation, and clipping and dilation in 5, 4, 4 and 2 patients, respectively. Incidence of recurrent leak during 1st week was significantly higher in SG than EG (p < 0.001). No mortality reported in EG, while 2 patients died in SG (p = 0.48). CONCLUSION: Endoscopic intervention may offer a successful modality in managing post-LSG gastric leak and gastro-cutaneous fistula that do not respond to conservative measures in stable patients.


Assuntos
Fístula Cutânea , Derivação Gástrica , Fístula Gástrica , Laparoscopia , Obesidade Mórbida , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Fístula Gástrica/etiologia , Fístula Gástrica/cirurgia , Fístula Cutânea/etiologia , Fístula Cutânea/cirurgia , Estudos Prospectivos , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Laparoscopia/efeitos adversos , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos
6.
bioRxiv ; 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38168194

RESUMO

Germline BRCA2 loss-of function (LOF) variants identified by clinical genetic testing predispose to breast, ovarian, prostate and pancreatic cancer. However, variants of uncertain significance (VUS) (n>4000) limit the clinical use of testing results. Thus, there is an urgent need for functional characterization and clinical classification of all BRCA2 variants. Here we report on comprehensive saturation genome editing-based functional characterization of 97% of all possible single nucleotide variants (SNVs) in the BRCA2 DNA Binding Domain hotspot for pathogenic missense variants that is encoded by exons 15 to 26. The assay was based on deep sequence analysis of surviving endogenously targeted haploid cells. A total of 7013 SNVs were characterized as functionally abnormal (n=955), intermediate/uncertain, or functionally normal (n=5224) based on 95% agreement with ClinVar known pathogenic and benign standards. Results were validated relative to batches of nonsense and synonymous variants and variants evaluated using a homology directed repair (HDR) functional assay. Breast cancer case-control association studies showed that pooled SNVs encoding functionally abnormal missense variants were associated with increased risk of breast cancer (odds ratio (OR) 3.89, 95%CI: 2.77-5.51). In addition, 86% of tumors associated with abnormal missense SNVs displayed loss of heterozygosity (LOH), whereas 26% of tumors with normal variants had LOH. The functional data were added to other sources of information in a ClinGen/ACMG/AMP-like model and 700 functionally abnormal SNVs, including 220 missense SNVs, were classified as pathogenic or likely pathogenic, while 4862 functionally normal SNVs, including 3084 missense SNVs, were classified as benign or likely benign. These classified variants can now be used for risk assessment and clinical care of variant carriers and the remaining functional scores can be used directly for clinical classification and interpretation of many additional variants. Summary: Germline BRCA2 loss-of function (LOF) variants identified by clinical genetic testing predispose to several types of cancer. However, variants of uncertain significance (VUS) limit the clinical use of testing results. Thus, there is an urgent need for functional characterization and clinical classification of all BRCA2 variants to facilitate current and future clinical management of individuals with these variants. Here we show the results from a saturation genome editing (SGE) and functional analysis of all possible single nucleotide variants (SNVs) from exons 15 to 26 that encode the BRCA2 DNA Binding Domain hotspot for pathogenic missense variants. The assay was based on deep sequence analysis of surviving endogenously targeted human haploid HAP1 cells. The assay was calibrated relative to ClinVar known pathogenic and benign missense standards and 95% prevalence thresholds for functionally abnormal and normal variants were identified. Thresholds were validated based on nonsense and synonymous variants. SNVs encoding functionally abnormal missense variants were associated with increased risks of breast and ovarian cancer. The functional assay results were integrated into a ClinGen/ACMG/AMP-like model for clinical classification of the majority of BRCA2 SNVs as pathogenic/likely pathogenic or benign/likely benign. The classified variants can be used for improved clinical management of variant carriers.

7.
Int J Gen Med ; 15: 6173-6187, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35864993

RESUMO

Purpose: To investigate the compositional and functional characteristics of T1DM-associated gut microbiota in two Egyptian cities and to study the geographical locality effects. Patients and Methods: This case-control study included 32 children with controlled T1DM and 16 controls, selected from two different regions of Egypt. The gut microbiota of both diabetic and control children was analyzed through 16S rRNA gene sequencing; this was done using the Illumina MiSeq platform. Results: Consistent findings among the diabetic children included significantly lower alpha diversity than the control children, as well as a lower mean Firmicutes/Bacteroidetes (F/B) ratio, and reduced proportions of Firmicutes and the genera Prevotella and Ruminococcus. In the diabetic children, there were also significantly enriched representations of Actinobacteria, Bacteroidetes, and Proteobacteria and the genera Lactobacilli, Bacteroides, and Faecalibacterium. When comparing the two diabetic groups, the Ismailia group (IsDM) was found to have a significantly higher F/B ratio and diversity indices, with resultant differences at the functional level. Conclusion: There are a number of consistent changes in the microbiota profile characterizing the diabetic groups irrespective of the geographical location including significantly lower alpha diversity, mean Firmicutes/ Bacteroidetes (F/B) ratio, and reduced proportions of Firmicutes and genera Prevotella and Ruminococcus. There are also significantly enriched representations of Actinobacteria, Bacteroidetes, and Proteobacteria and genera Lactobacilli, Bacteroides, and Faecalibacterium pointing to the greater driving power of the disease.

8.
World J Emerg Surg ; 17(1): 24, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35610657

RESUMO

BACKGROUND: Peptic ulcer perforation is a common life-threatening surgical emergency. Graham omental patch is performed for plugging of perforated peptic ulcer. Many endoscopic methods have been used to treat acute perforated peptic ulcer such as over the scope clips, standard endoscopic clips, endoscopic sewing and metallic stents. The main idea in endoscopic management of acute perforated peptic ulcer is early decontamination and decrease sepsis by interventional radiologic drainage. METHODS: This is a prospective randomized controlled clinical trial. This study included patients who were developed acute perforated peptic ulcer manifestations and were admitted to our hospital between December 2019 and August 2021. Sample size was 100 patients divided into 2 equal groups. Endoscopic group (EG): included 50 patients who were subjected to endoscopic management. Surgical group (SG): included 50 patients who were subjected to surgical management. RESULTS: One hundred patients were randomized into 2 groups: SG (50) and EG (50). Median age of patients was 36 (range 27:54) and 47 (range 41:50) years-old in SG and EG, respectively. Males constituted 72% and 66% in SG and EG, respectively. Median length of postoperative hospital stay was 1 (range: 1-2) days in EG, while in SG was 7 (range 6-8) days. Postoperative complications in SG patients were 58% in form of fever, pneumonia, leak, abdominal abscess, renal failure and incisional hernia (11%, 5%, 5%, 3%, 2% and 3%, respectively). Postoperative complications in EG patients were 24% in form of fever, pneumonia, leak, abdominal abscess, renal failure and incisional hernia (10%, 0%, 2%, 0%, 0% and 0%, respectively). CONCLUSION: Combined endoscopic and interventional radiological drainage can effectively manage acute perforated peptic ulcer without the need for general anesthesia, with short operative time, in high risk surgical patients with low incidence of morbidity & mortality.


Assuntos
Abscesso Abdominal , Hérnia Incisional , Laparoscopia , Úlcera Péptica Perfurada , Insuficiência Renal , Doença Aguda , Adulto , Humanos , Hérnia Incisional/cirurgia , Masculino , Úlcera Péptica Perfurada/cirurgia , Complicações Pós-Operatórias/cirurgia , Insuficiência Renal/cirurgia
9.
Iran J Pathol ; 16(2): 162-173, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936227

RESUMO

BACKGROUND & OBJECTIVE: Diagnosis and discrimination of lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC) is critical to select the appropriate treatment regimen as recently targeted therapies require accurate subtyping of nonsmall-cell lung carcinoma (NSCLCs). There are currently several biomarkers that could be used for differentiation between LUAD and LUSC, but they have less sensitivity, specificity, and clinical applicability. The aim of this study was to assess the diagnostic and prognostic values of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin tissue expression in the tissues retrieved from LUAD and LUSC patients using immunohistochemistry. METHODS: The current study was performed on the samples retrieved from sixty primary lung masses that were diagnosed as LUAD and LUSC. Immunohistochemistry was performed by using a panel of CLCA2, SPATS2, and ST6GALNAC1. We assessed the diagnostic roles of the studied markers in the discrimination between LUAD and LUSC and their prognostic values. RESULTS: SPATS2 and CLCA2 were expressed higher in LUSC than LUAD. ST6GALNAC1 and Adipophilin showed higher expression in LUAD than LUSC (P <0.001). The sensitivity and specificity of CLCA2, SPATS2, ST6GALNAC1 and Adipophilin in adequate subtyping and reaching the accurate diagnosis was 100%. We found only significant difference in survival rate between the patients with negative and positive CLCA2 expression (P=0.038 and P=0.019, respectively). CONCLUSION: The combination of biomarkers of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin may lead to an appropriate subtyping of lung cancer and reaching accurate diagnosis with the highest sensitivity and specificity.

10.
Egypt J Immunol ; 27(1): 97-107, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33180392

RESUMO

Lupus nephritis (LN) is a common major organ manifestation and main cause of morbidity and mortality of the disease. We aimed to determine the level of serum and urinary monocyte chemoattractant protein-1(sMCP-1 and uMCP-1) in systemic lupus erythematosus (SLE) patients with and without LN and analyze their association with different clinical and serologic parameters of disease activity. We enrolled 60 female patients with SLE (32 with LN and 28 without LN) and 20 controls.MCP-1 and anti-dsDNA were measured by ELISA. There was statistically significant increase in serum and urinary MCP-1 in all SLE patients (mean=711.59, 676.68 pg/ml respectively) as compared to the control group (mean= 635.70, 632.40 pg/ml respectively), P=0.034, 0.020 respectively. Among patients with LN there was statistically significant increase in sMCP-1 (mean=723.58) compared to the control group (P=0.038, and in uMCP-1 (mean=699.08) compared to patients without LN (mean=651.07) and control group (mean=632.40), P=0.007, 0.002 respectively. Urinary, but not serum MCP-1, positively correlated with 24 hour proteinuria, anti-dsDNA, renal SLEDAI ,biopsy activity index (r=0.362, P=0.004; r=0.303, P=0.019; r= 0.267, P=0.039; r=0.353, P=0.047 respectively) and negatively correlated with serum albumin (r=-0.329, P=0.010).There was statistically significant increase in uMCP-1 and anti-dsDNA in patients with poor response compared to patients with good response to immunosuppressant therapy (P= 0.025; P=0.034 respectively). In conclusion, uMCP-1 is associated with LN and disease activity and may be used as a useful tool for diagnosis and follow up.


Assuntos
Quimiocina CCL2/sangue , Quimiocina CCL2/urina , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Humanos , Nefrite Lúpica/diagnóstico , Índice de Gravidade de Doença
11.
Heliyon ; 6(8): e04711, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32904114

RESUMO

This study sought to examine whether supplementation of Black Seed Oil (BSO) can improve pulmonary function tests (PFTs), inflammation, and oxidant-antioxidant markers in COPD patients. The study involved 100 patients of mild to moderate COPD divided randomly into 2 groups who were appointed to receive standard medication only (control group) or with additional Black Seed Oil (BSO group). They were assessed initially and after 3 months, 44 patients responded in control group and 47 patients in BSO group. BSO group evidenced a significant decreasing in oxidant and inflammatory markers; thiobarbituric acid reactive-substances (TBARS), protein carbonyl (PC) content, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), a significant increase in antioxidants; superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), vitamin C, and E, and a significant improvement in PFTs versus control group and baseline levels. Supplementation of Black Seed Oil may be an effective adjunct therapy to improve pulmonary functions, inflammation, and oxidant-antioxidant imbalance in COPD patients.

12.
Microorganisms ; 8(7)2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32640728

RESUMO

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder with complex immunopathogenesis. Dysbiosis has been linked to many autoimmune diseases, but its detailed role in autoimmune hepatitis (AIH) still needs rigorous evaluation, especially in Egypt. We aimed to identify the shift in the gut microbiota profile and resultant metabolic pathways in AIH Egyptian patients compared to healthy individuals. Stool samples were collected from 15 AIH-naive patients and from 10 healthy individuals. The V3-V4 hyper-variable regions in16S rRNA gene was amplified and sequenced using Illumina MiSeq platform. Significantly lower bacterial diversity in AIH patients was found compared to the controls. A phylum-level analysis showed the overrepresentation of Firmicutes, Bacteroides, and Proteobacteria. At the genus level, AIH-associated enrichment of Faecalibacterium, Blautia, Streptococcus, Haemophilus, Bacteroides, Veillonella, Eubacterium, Lachnospiraceae and Butyricicoccus was reported in contrast to Prevotella, Parabacteroides and Dilaster, which were significantly retracted in such patients. Overall, the predicted metabolic pathways associated with dysbiosis in AIH patients could orchestrate the potential pathogenic roles of gut microbiota in autoimmune disease, though not in a disease-specific manner, calling for future large-scale studies.

13.
Immunol Res ; 67(2-3): 157-165, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31028612

RESUMO

Toll-like receptors (TLRs) have a role in chronic inflammation. Still, little is known about the expression of TLRs in hepatocellular carcinoma (HCC). Herein, we tried to assess the prognostic value of TLR2 and TLR4 expression on circulating monocytes in HCC patients and correlate their levels with some clinical, laboratory data, and treatment outcomes. Forty patients with hepatic focal lesions diagnosed radiologically as HCC by triphasic multislice CT pelviabdominal and chest, and in some patients MRI diffusion and 38 age and sex matching healthy controls were enrolled in the study. Subjects were evaluated for liver functions, alpha-fetoprotein (AFP), imaging, response to different treatments, and overall survival. TLR2 and TLR4 expression by monocytes was detected by flow cytometry. The expression of both TLR2 and TLR4 on monocytes was significantly increased in HCC patients than the controls, in patients with more progressive HCC than those with lower progression and in patients with poor response to treatment than patients with better treatment response. Moreover, their levels showed positive correlations with ALT, AST, and AFP and inverse correlations with the overall survival of HCC patients. The results of the current study suggest that increased expression ofTLR2 and TLR4 on peripheral monocytes might reflect the development and progression of HCC and can be used to indicate poor prognosis. In addition, high expression of TLR2 correlated significantly with poor response to treatment, while high expression of both TLR2 and TLR4 were associated with poor survival. Our findings will help to design more studies on the role of TLRs in HCC pathogenesis and prognosis which may provide new therapeutic targets for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Monócitos/metabolismo , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Biomarcadores , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Estudos de Casos e Controles , Terapia Combinada , Gerenciamento Clínico , Egito , Feminino , Humanos , Imunofenotipagem , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Masculino , Prognóstico , Análise de Sobrevida , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Resultado do Tratamento
14.
Cell Physiol Biochem ; 52(3): 595-605, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30897324

RESUMO

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the fifth most common malignancy and most frequently develops in patients with cirrhosis. Surveillance strategies are recommended in high-risk groups because early detection of small lesions improves the likelihood of curative treatment. This study investigated the prospective clinical significance of serum levels of anti-Ku86 and plasma levels of lamin B1and vimentin as early markers of HCC. METHODS: We recruited 74 patients at Assiut University Hospital-37 with HCC and 37 with chronic liver disease (liver cirrhosis patients)-and 36 age- and sex-matched healthy controls. Lamin B1 and vimentin mRNA expression levels were evaluated by reverse transcription-PCR and serum levels of anti-Ku86 were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with liver disease patients and controls, HCC patients showed higher levels of lamin B1 mRNA (sensitivity, 96%; specificity, 65%), vimentin mRNA (sensitivity, 94%; specificity, 92%), and anti-Ku86 (sensitivity, 94%; specificity, 80%). LaminB1 levels were significantly higher in patients with a tumor size < 2 cm than in patients with tumors 2-5 cm and >5cm in size. Lamin B1 had significant positive correlations with alpha-fetoprotein (AFP) (P=0.034) and anti-Ku86 (P=0.002). Receiver operating characteristic curves for differentiating HCCfrom liver cirrhosis revealed a higher area under the curve(AUC).for vimentin than for AFP, lamin B1, and anti-Ku86 for the diagnosis of HCC (P<0.001). CONCLUSION: Circulating levels of anti-Ku86, lamin B1,and vimentin might be potential surrogate markers of HCC, either alone or in combination with AFP. However, independent and discriminative serological biomarkers with higher sensitivity and specificity are still needed for the early detection of HCC.


Assuntos
Anticorpos/sangue , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Hepatite C/diagnóstico , Lamina Tipo B/metabolismo , Neoplasias Hepáticas/diagnóstico , Vimentina/metabolismo , Adulto , Área Sob a Curva , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Hepatite C/complicações , Humanos , Autoantígeno Ku/imunologia , Lamina Tipo B/genética , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Vimentina/genética , alfa-Fetoproteínas/análise
15.
Egypt J Immunol ; 26(2): 55-63, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31926495

RESUMO

Chronic hepatitis C (CHC) infection is considered a high risk for development of end-stage liver diseases, particularly server hepatitis, decompensated liver cirrhosis, and hepatocellular carcinoma. Regulatory T cells (Treg) and T-helper 17 (TH17) associated cytokines presumed to play a pivotal role in the immune pathogenesis of HCV infection and stimulate autoimmune diseases. Herein, we tried to assess the association of Treg and TH 17 cytokines with HCV pathogenesis and liver pathology. Fifty CHC infected patients and twenty HCV free controls were included in this study, IL17, IL21, IL10, IL4, TGF- and IL35 serum levels were assessed in both groups using enzyme linked immunosorbent assay (ELISA). CHC infected patients had statistically significant higher values of all serum cytokine levels when compared to the control group (P < 0.0001) for each. Additionally, serum levels of IL17, IL10 and IL35 were positively correlated with viral load. Also, the serum level of IL17 IL21, IL10 and IL35 was positively correlated with ALT serum levels. Only IL21 and IL10 were positively correlated with AST levels. Serum IL17, IL10, TGF- and IL35 levels were significantly elevated in CHC patients with advanced fibrosis stages. We concluded that CHC infected patients displayed high serum levels of Treg and TH17 associated cytokines. Collectively, these results support the hypothesis that liver damage in CHC infection might be due to an immune-mediated destructive mechanism rather than to the direct cytopathic effect of the virus itself.


Assuntos
Citocinas/imunologia , Hepatite C Crônica/imunologia , Cirrose Hepática/virologia , Linfócitos T Reguladores/imunologia , Estudos de Casos e Controles , Humanos , Cirrose Hepática/imunologia , Células Th17
16.
Surgery ; 162(1): 18-36, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28249738

RESUMO

BACKGROUND: We performed this systematic review and meta-analysis to compare the outcomes of Lichenstein hernia repair using either self-gripping mesh or techniques of sutured mesh fixation. METHODS: We searched PubMed, Cochrane CENTRAL, Scopus, Embase, and Web of Science for all clinical trials and observational studies that compared self-gripping mesh versus sutured mesh fixation in Lichtenstein hernia repair. Combined outcomes were pooled as odds ratios or mean differences in a fixed-effect model, using Comprehensive Meta-Analysis software for Windows. RESULTS: Twelve randomized, controlled trials and 5 cohort studies (n = 3,722 patients) were included in the final analysis. The two groups, using self-gripping mesh or sutured mesh fixation, did not differ significantly in terms of recurrence rate (odds ratio = 0.66, 95% confidence interval 0.18-2.44; P = .54) or postoperative chronic groin pain (odds ratio = 0.75, 95% confidence interval 0.54-1.05; P = .09). The operative time was less in the self-gripping mesh group (mean difference = -7.85, 95% confidence interval -9.94 to -5.76; P < .0001). For safety analysis, there were comparable risks between self-gripping mesh and sutured mesh fixation groups in terms of postoperative infection (odds ratio = 0.81, 95% confidence interval 0.53-1.23; P = .32), postoperative hematoma (odds ratio = 0.97, 95% confidence interval 0.7-1.36; P = .9), and urinary retention (odds ratio = 0.66, 95% confidence interval 0.18-2.44; P = .54). CONCLUSION: Data from our analysis did not favor either of the two fixation techniques over the other in terms of recurrence or postoperative chronic groin pain. Decreased operative time in the self-gripping mesh group cannot justify a recommendation for its routine use. Longer follow-up studies are needed to compare the risk of long-term recurrence for both meshes.


Assuntos
Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Telas Cirúrgicas , Técnicas de Sutura , Humanos
17.
Turk J Gastroenterol ; 27(4): 367-74, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27458853

RESUMO

BACKGROUND/AIMS: Cirrhotic cardiomyopathy (CCM) is defined as an abnormal heart structure and function in cirrhotic patients. CCM includes systolic and diastolic dysfunction, electrophysiological abnormalities, and structural changes, both microscopic and macroscopic. Currently, there is no one diagnostic test that can identify patients with CCM. Evaluation of the validity of galactin-3 and brain natriuretic peptide (BNP) as biomarkers in the early detection of CCM in comparison to conventional echocardiography. MATERIALS AND METHODS: A case control study was carried out in the Departments of internal medicine and tropical Medicine, Assuit University, Egypt. Seventy-one subjects were divided into the following three groups: 26 cirrhotic patients without ascites, 25 cirrhotic patients with ascites, and 20 healthy controls. All groups underwent clinical examination, and laboratory investigation including BNP, galactin-3, and echocardiography. RESULTS: There was a significant difference between the three groups (p < 0.001) with regard to corrected QT (cQT), BNP and galactin-3. Left ventricular diastolic dysfunction with different grades was the most recorded cardiac abnormality in the patient group I and II (88.5% and 96%; respectively) with significantly increased frequency and severity in ascetic patients and with the advancement of liver cirrhosis. BNP and galactin-3 were sensitive and specific biomarkers for the detection of diastolic dysfunction in cirrhotic patients (77.6%, 95.5%, 89.9% and 86.4%; respectively). CONCLUSION: Diastolic dysfunction is a common cardiac abnormality in cirrhotic patients that worsens with the advancement of cirrhosis. BNP and galactin-3 had higher sensitivity and specificity in the early detection of CCM compared with those of conventional echocardiography.


Assuntos
Cardiomiopatias/diagnóstico , Ecocardiografia/métodos , Galectina 3/sangue , Cirrose Hepática/complicações , Peptídeo Natriurético Encefálico/sangue , Adulto , Biomarcadores/sangue , Cardiomiopatias/etiologia , Estudos de Casos e Controles , Diagnóstico Precoce , Egito , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA