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PURPOSE: To evaluate the diagnostic value of ultrasound elastography (USE) for characterizing hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: The protocol was pre-registered a priori at ( https://osf.io/namvk/ ). Using PubMed, Web of Science, Embase, and Cochrane Library, we found studies up to April 20, 2024 by searching HCC, ICC, and USE as keywords. Parameters of USE were directly compared between HCC and ICC patients using random-effects bivariate model on STATA 17.0, MedCalc 20.0, and Psychometrica. Trim & fill method and sensitivity analysis were also performed. RESULTS: Eighteen studies were included with 1057 patients, consisting of 863 HCC lesions, 188 ICC lesions, and 6 mixed lesions. The pooled Emean values of HCC and ICC were 28.3 (CI = 19.8 to 36.8) and 44.0 (CI = 20.9 to 67.2). HCC tumors were 34.3% softer than ICC while peritumoral tissue in HCC lesions was 75% stiffer than ICC lesions based on Emean. The strain value index (tumoral-to-peritumoral ratio) in HCC patients was 49.4% less than that of ICC patients. USE demonstrated a pool sensitivity of 87% (CI = 73-95%), specificity of 82% (CI = 65-92%), positive likelihood ratio of 4.8 (CI = 2.2 to 10.3), negative likelihood ratio of 0.16 (CI = 0.07 to 0.37), and diagnostic odds ratio of 31 (CI = 7 to 127) in differentiation of ICC from HCC. CONCLUSION: By evaluating tumoral and pre-tumoral stiffness, along with strain value index, USE may provide a valuable quantitative diagnostic tool for accurately differentiating HCC and ICC.
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PURPOSE: Primary hepatocellular carcinoma (HCC) represents a substantial global health challenge. Early diagnosis of HCC is crucial for improved patient outcomes. The aim of this study was to assess qualitative and quantitative diagnostic performance of PET/CT using 11C-acetate and [18F]-fluorodeoxyglucose (FDG) in detection of primary HCC and to determine if 11C-acetate added to [18F]-FDG alleviates the low sensitivity rate mentioned in guidelines. METHODS: Protocol was pre-registered at https://osf.io/2vcb9 . We searched PubMed, Web of Science, Embase, and the Cochrane Library for included studies. Quality Assessment of Diagnostic Accuracy Studies 2 was used to assess the risk of bias. Possible sources of statistical heterogeneity were explored. Additionally, mentioned three PET/CT tests were evaluated for their diagnostic performance in differentiating HCC from its differential diagnoses. Grades of Recommendation, Assessment, Development, and Evaluation was used to assess quality of generated evidence. RESULTS: Twenty-four studies were analyzed. Qualitative dual-tracer PET/CT demonstrated 92.0% per-lesion sensitivity, and a significantly higher direct sensitivity difference of 30% to conventional CT, 44.7% to [18F]-FDG, and 12.0% to 11C-acetate. Regarding differentiation rate, [18F]-FDG was superior to 11C-acetate in poorly differentiated lesions while 11C-acetate was superior in well-differentiated lesions. Regarding size, dual tracer combination solved the high missing rate of HCC lesions in 1-2 cm and 2-5 cm groups but could not help in size < 1 cm. CONCLUSION: Dual-tracer PET/CT utilizing 11C-acetate and [18F]-FDG represents a sensitive method for detecting primary HCC. By concurrently quantifying or qualifying the uptake of 11C-acetate and [18F]-FDG, this multimodal approach enables precise localization of intrahepatic lesions.
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The aim of this study was to quantify the diagnostic value of dual-tracer PET/computed tomography (CT) with 11 C-acetate and fluorodeoxyglucose (FDG) in per-lesion and per-patient and its effect on clinical decision-making for choosing the most appropriate management. The study protocol is registered a priori at https://osf.io/rvm75/ . PubMed, Web of Science, Embase , and Cochrane Library were searched for relevant studies until 1 June 2023. Studies regarding the review question were included. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to assess bias risk. Per-lesion and per-patient diagnostic performance were calculated for: (1) 11 C-acetate alone; (2) FDG alone; and (3) dual tracer of 11 C-acetate and FDG. A direct comparison of these three combinations was made. The possible sources of statistical heterogeneity were also examined. We also calculated the percentage change in clinical decision-making when dual-tracer PET/CT was added to conventional imaging routinely used for metastatic evaluation (CT/MRI). Grading of Recommendations, Assessment, Development, and Evaluations tool was used to evaluate the certainty of evidence. Eight studies including 521 patients and 672 metastatic lesions were included. Dual-tracer PET/CT had a per-lesion sensitivity of 96.3% [95% confidence interval (CI), 91.8-98.4%] and per-patient sensitivity of 95.5% (95% CI, 89.1-98.2%) which were highly superior to either of tracers alone. Per-patient specificity was 98.5% (84.1-99.9%) which was similar to either of tracers alone. Overall, 9.3% (95% CI, 4.7-13.9%) of the patients had their management beneficially altered by adding dual-tracer PET/CT to their conventional CT/MRI results. Dual-tracer PET/CT substantially outperforms single-tracer methods in detecting extrahepatic hepatocellular carcinoma metastases, evidencing its reliability and significant role in refining clinical management strategies based on robust diagnostic performance.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Metástase Neoplásica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias , Fluordesoxiglucose F18RESUMO
BACKGROUND: Distal necrosis and inflammation are two of the most common health consequences of random-pattern skin flaps survival (SFS). Anti-inflammatory effects of spermidine have been identified in various studies. On the other hand, considering the involvement of the nitric oxide molecule in the spermidine mode of action and also its role in skin tissue function, we analyzed the possible effects of spermidine on the SFS and also, potential involvement of nitrergic pathway and inflammatory cytokine in these phenomena. METHODS: Each rat was pretreated with either a vehicle (control) or various doses of spermidine (0.5, 1, 3, 5, 10 and 30 mg/kg) and then was executed a random-pattern skin flap paradigm. Also, spermidine at the dose of 5 mg/kg was selected and one group rats received spermidine 20 min prior to surgery and one additional dose 1 day after operation. Then, 7 days after operations, interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon-gamma (IFN-γ), and nitrite levels were inquired in the tissue samples by ELIZA kit. Vascular endothelial growth factor expression was assessed by DAPI staining and fluorescent microscopes. The concentrations of three polyamines, including spermidine, spermine, and cadaverine, were analyzed using HPLC. RESULTS: Pretreatment with spermidine 5 mg/kg improved SFS considerably in microscopic skin H&E staining analysis and decreased the percentage of necrotic area. Moreover, spermidine exerted promising anti-inflammatory effects via the modulation of nitric oxide and reducing inflammatory cytokines. CONCLUSIONS: Spermidine could improve skin flaps survival, probably through the nitrergic system and inflammation pathways. This preclinical study provides level III evidence for the potential therapeutic effects of spermidine on SFS in rats, based on the analysis of animal models. Further studies are needed to confirm these findings in clinical settings. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Introduction Cirrhotic cardiomyopathy (CCM) is recognized by impaired cardiac responsiveness to stress, prolonged QT interval, and systolic and diastolic dysfunctions. Connexins are a family of transmembrane proteins that play a key role in cardiac physiology. Connexin 43 (Cx43) inhibition showed cardio-protective effects. Peptide drug Cx43 inhibitor, Gap 26, could inhibit gap junction 43. This study was designed to evaluate the effects of a connexin mimetic peptide, Gap 26, in the CCM model in rats. Methods The cirrhosis was induced through carbon tetrachloride (CCl4). On day 56, electrocardiography (ECG) was recorded, spleen weight was measured, and tissue and serum samples were collected. Further, Cx43 mRNA expression in heart tissue was checked. Results The chronotropic responses decreased in the CCl4/saline and increased in the CCl4/Gap. The spleen weight, QTc interval, and brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), aspartate aminotransferase (AST), alanine transaminase (ALT), and malondialdehyde (MDA) levels elevated in the CCl4/saline, and the spleen weight, QTc interval, and MDA and ALT levels were reduced by Gap 26 treatment. The level of nuclear factor (erythroid-derived 2) factor 2 (Nrf2) decreased in the CCl4/saline. The Cx43 expression was downregulated in the CCl4/saline and upregulated with the Gap 26 treatment. Conclusion Gap 26 not only alleviated the chronotropic hyporesponsiveness and the severity of liver damage and upregulated the atrial Cx43 expression, but it also had an antioxidant effect on the heart.
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INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung condition that produces symptoms including coughing which may cause by excessive accumulation of scar tissue inflammatory and oxidative stress exacerbation. Sumatriptan, utilized for migraine treatment as a selective 5-HT1B/1D receptor agonist, has demonstrated significant anti-inflammatory and antioxidant properties in multiple preclinical investigations. Operating primarily on serotonin receptors, sumatriptan leverages the diverse physiological functions of serotonin, playing a pivotal role in regulating both inflammation and oxidative stress which is particularly relevant in the context of IPF. MATERIALS & METHODS: Thirty-five male Wistar rats were divided to five group, including: Sham (without IPF induction), control (BLM 5â¯mg/kg, intraperitoneally), and three fibrosis group with sumatriptan (0.5, 1, and 3â¯mg/kg, i.p. for 2 weeks) administration. IPF was induced by injection of BLM (single dose, 5â¯mg/kg intratracheally). Lung tissues were separated for measurement of myeloperoxidase (MPO) as an oxidative stress hallmark, and tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-ß), and transforming growth factor-ß (TGF-ß) as inflammatory markers as well as alpha smooth muscle actin (α-SMA). Also, for histological investigations, tissue damages were assessed by Hematoxylin-eosin (H&E) and Masson's trichrome staining method. RESULTS: BLM-induced fibrosis could increase α-SMA, MPO, TNF-α, IL-1ß, and TGF-ß, while treatment with sumatriptan has reversed the α-SMA, MPO, and IL-1ß levels. Moreover, the results of H&E and Masson's trichrome staining indicated that sumatriptan (1 and 3â¯mg/kg) reduced tissue damages, alveolar wall thickness, collagen accumulation, and pulmonary fibrosis induced by BLM. CONCLUSION: According to the data achieved from this study, Sumatriptan appears to have therapeutic benefits in IPF, possibly via reducing α-SMA as well as inflammation and the toxicity caused by oxidative stress.
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Actinas , Bleomicina , Inflamação , Estresse Oxidativo , Fibrose Pulmonar , Ratos Wistar , Sumatriptana , Animais , Bleomicina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Masculino , Sumatriptana/farmacologia , Ratos , Actinas/metabolismo , Inflamação/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/induzido quimicamente , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismoRESUMO
Purpose: We aimed to investigate empty sella syndrome in somatotrophic pituitary adenoma for possible etiology, complications, and treatment options. Method: Among over 2,000 skull base masses that have been managed in our center since 2013, we searched for growth hormone-producing adenomas. Clinical, surgical, and imaging data were retrospectively collected from hospital records to check for sella that lacked pituitary tissue on routine imaging. Result: In 220 somatotrophic adenomas, 23 patients had an empty sella with surgical and follow-up data. The mean age of the sample was 46 years with the same male-to-female ratio. Five cases had partial empty sella and the rest were complete empty sellas. The most common simultaneous hormonal disturbance was high prolactin levels. Six had adenoma invasion into the clivus or sphenoid sinus and 10 had cavernous sinus intrusion. Peri-operative low-flow and high-flow cerebrospinal fluid (CSF) leaks were encountered in one and two patients, respectively, which were successfully sealed by abdominal fat. The majority of cases required growth hormone replacement therapy while it was controlled without any replacement therapy in nine patients. No pituitary hormonal disturbance occurred after transsphenoidal surgery except for hypothyroidism in one patient. Conclusion: An empty sella filled with fluid can be detected frequently in pituitary adenomas, especially in the setting of acromegaly. The pituitary gland may be pushed to the roof of the sella and might be visible as a narrow rim on imaging or may be detected in unusual places out of the sella. The pathophysiology behind such finding originates from soft and hard tissue changes and CSF pressure alternations during abundant growth hormone production.
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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a pulmonary fibrotic disease characterized by a poor prognosis, which its pathogenesis involves the accumulation of abnormal fibrous tissue, inflammation, and oxidative stress. Ivermectin, a positive allosteric modulator of GABAA receptor, exerts anti-inflammatory and antioxidant properties in preclinical studies. The present study investigates the potential protective effects of ivermectin treatment in rats against bleomycin-induced IPF. MATERIALS AND METHODS: The present study involved 42 male Wistar rats, which were divided into five groups: control (without induction of IPF), bleomycin (IPF-induced by bleomycin 2.5 mg/kg, by intratracheal administration), and three fibrosis groups receiving ivermectin (0.5, 1, and 3 mg/kg). lung tissues were harvested for measurement of oxidative stress [via myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione (GSH)] and inflammatory markers (tumor necrosis factor-α [TNF-α], interleukin-1ß [IL-1ß], and transforming growth factor-ß [TGF-ß]). Histological assessments of tissue damage were performed using hematoxylin-eosin (H&E) and Masson's trichrome staining methods. RESULTS: The induction of fibrosis via bleomycin was found to increase levels of MPO as well as TNF-α, IL-1ß, and TGF-ß while decrease SOD activity and GSH level. Treatment with ivermectin at a dosage of 3 mg/kg was able to reverse the effects of bleomycin-induced fibrosis on these markers. In addition, results from H&E and Masson's trichrome staining showed that ivermectin treatment at this same dose reduced tissue damage and pulmonary fibrosis. CONCLUSION: The data obtained from this study indicate that ivermectin may have therapeutic benefits for IPF, likely due to its ability to reduce inflammation and mitigate oxidative stress-induced toxicity.
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Fibrose Pulmonar , Ratos , Masculino , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/prevenção & controle , Bleomicina/efeitos adversos , Ivermectina/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismo , Ratos Wistar , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Pulmão/metabolismo , Estresse Oxidativo , Fator de Crescimento Transformador beta , Glutationa/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Background and Aim: This study aims to demonstrate the hemostatic effect of the hydroalcoholic extract of Achillea millefolium L. in localized bleeding and to assess the safety of its topical application on rat liver. Materials and Methods: The aerial parts of A. millefolium were macerated in methanol for two days. Twelve female Wistar rats, weighing 120-220 g, underwent anesthesia and laparotomy. The liver was exposed, and two incisions were made to induce bleeding. One incision was treated with a sponge soaked in A. millefolium extract, while the other served as a control. The animals were divided into two groups: in one, A. millefolium (150 mg/kg) was applied to the first incision, and in the other, to the second incision. Liver biopsies were collected after 4, 6, and 8 weeks. Results: Application of A. millefolium to liver incisions, whether first or second, significantly reduced bleeding time (by 36.1% and 31.9%, respectively). Histopathological analysis showed no signs of toxicity or hepatic damage after 4, 6, and 8 weeks in the female rats. Conclusion: The study confirms the hemostatic effect of the hydroalcoholic extract of A. millefolium in localized bleeding and establishes its safety for topical use.
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BACKGROUND: Hematologic malignancies have a great essential role in cancer global burden. Leukemia which two major subtypes based on the onset, is one of the common subtypes of this malignancy. METHOD: For the GBD 2019 study, cancer registry data and vital registration system were used to estimate leukemia mortality. The Meta-Regression-Bayesian Regularized Trimmed (MR-BRT), Cause of Death Ensemble model (CODEm) and Spatiotemporal Gaussian Process Regression (ST-GPR) were used to model our data and estimate each quantity of interest. Mortality to incidence ratios (MIR) were used to generate incidence and survival from mortality rate. Prevalence and survival were used to generate years lived with disability (YLDs). Age-specific mortality and life expectancy at the same age were used to estimate years of life lost (YLLs). The sum of YLLs and YLDs generates DALYs. RESULTS: The total national incidence of leukemia increased from 6092 (UI 95%: 3803-8507) in 1990 to 6767 (4646-7890) new cases in 2019. However, leukemia age-standardized incidence ratio(ASIR) decreased from 11.6 (8-14.8) to 8.9 (6.2-10.3) new cases per 100,000 in this exact period. At the national level, deaths from leukemia increased 1.5-fold between 1990 and 2019, from 3287 (2284-4201) to 4424 (3137-5030), whereas the age-standardized death rate(ASDR) decreased from 8.3 (6.1-9.8) in 1990 to 6 (4.3-6.8) per 100,000 in 2019. In the study period, total leukemia DALYs decreased 12.2% and reached 162850 (110681-188806), in 2019. The age-standardized DALYs decreased 36.7% from 324.3 (224.8-413.4) in 1990 to 205.3 (140.3-237.8) in 2019. ASDR, DALYs, YLLs, and YLDs rate to high BMI was increasing while smoking and occupational exposure to benzene and formaldehyde were decreasing in the study period. CONCLUSION: This study provided a better understanding of leukemia burden and to reduce controversies of leukemia across Iran. The leukemia status alteration of the country, is trackable.
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Leucemia , Neoplasias , Humanos , Carga Global da Doença , Anos de Vida Ajustados por Qualidade de Vida , Teorema de Bayes , Expectativa de Vida , Fatores de Risco , Neoplasias/epidemiologia , Leucemia/epidemiologia , Saúde GlobalRESUMO
Cushing's syndrome is a condition leading to overproducing of cortisol by the adrenal glands. If the pituitary gland overproduces cortisol, it is called Cushing's disease. Cushing's syndrome and even Cushing's disease during and after pregnancy are rare events. There is not enough literature and guidance for managing and treating these patients. The diagnosis of Cushing's syndrome in pregnancy is often delayed because the symptoms overlap. We presented a thin 31-year-old woman, admitted 2 months after a normal-term delivery, with an atypical presentation of Cushing's disease, unusual clinical features, and a challenging clinical course. She had no clinical discriminatory features of Cushing's syndrome. Given that the patient only presented with psychosis and proximal myopathy and had an uncomplicated pregnancy, our case was considered unusual. The patients also had hyperpigmentation and severe muscle weakness which are among the less common presentations of Cushing's syndrome. Our findings suggest that an early diagnosis of Cushing's disease is important in pregnancy period for its prevalent fetal and maternal complications, and it should be treated early to optimize fetal and maternal outcomes as there is an increasing trend toward live births in treated participants.
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Síndrome de Cushing , Hipersecreção Hipofisária de ACTH , Transtornos Psicóticos , Adulto , Feminino , Humanos , Síndrome de Cushing/complicações , Síndrome de Cushing/diagnóstico , Hidrocortisona , Debilidade Muscular , Hipersecreção Hipofisária de ACTH/complicações , Período Pós-Parto , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/etiologiaRESUMO
Diffuse gliomas exhibit different molecular and genetic profiles with a wide range of heterogeneity and prognosis. Recently, molecular parameters including ATRX, P53, and IDH mutation status or absence or presence of 1p/19q co-deletion have become a crucial part of the diagnosis of diffuse glioma. In the present study, we tried to analyze the routine practice of the above-mentioned molecular markers focusing on the IHC method in cases of adult diffuse gliomas to evaluate their utility in the integrated diagnosis of adult diffuse gliomas. In total, 134 cases of adult diffuse glioma were evaluated. Using the IHC method, 33,12, and 12 cases of IDH mutant Astrocytoma grade 2, 3, 4, and 45 cases of gliobalstoma, IDH wild type, were molecularly diagnosed. By adding the FISH study for 1p/19q co-deletion, 9 and 8 cases of oligodendroglioma grade 2 and 3 also were included. Two IDH mutant cases were negative for IDH1 in IHC but revealed a positive mutation in further molecular testing. Finally, we were not able to incorporate a complete integrated diagnosis in 16/134(11.94%) of cases. The main molecularly unclassified group was histologically high-grade diffuse glial tumors in patients less than 55 years old and negative IDH1 immunostaining. P53 was positive in 23/33 grade 2, 4/12 grade 3, and 7/12 grade 4 astrocytomas, respectively. Four out of 45 glioblastomas showed positive immunostain, and all oligodendrogliomas were negative. In conclusion, a panel of IHC markers for IDH1 R132H, P53, and ATRX significantly improves the molecular classification of adult diffuse gliomas in daily practice and can be used as a tool to select limited cases for co-deletion testing in the low resources area.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Oligodendroglioma , Humanos , Proteína Supressora de Tumor p53/genética , Imuno-Histoquímica , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proteína Nuclear Ligada ao X/genética , Glioma/diagnóstico , Glioma/genética , Glioma/patologia , Glioblastoma/patologia , Oligodendroglioma/diagnóstico , Oligodendroglioma/genética , Oligodendroglioma/patologia , Mutação , Aberrações Cromossômicas , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismoRESUMO
Cancer is one of the important health problems in Iran, which is considered as the third cause of death. Endocrine cancers are rare but mostly curable. Thyroid cancer, the most common endocrine tumors, includes about one percent of malignant cancer. In this study, we examined the 15-year national trend of endocrine cancer incidence in Iranian men and women. The data in each province were evaluated based on age, gender, and cancer type according to International Classification of Disease Codes version 10 (ICD-10) from 2005 to 2020 in Iran. All data were obtained from the reports of the Statistics Center of Iran (SCI), 6 phases of the step-by-step approach to monitoring the risk factors of chronic diseases over 18 years old (STEPs), and 3 periods of the CASPIAN study (survey of non-communicable diseases in childhood and adolescence). Statistical analyzes and graph generation were done using R statistical software. Poisson regression with mixed effects was used for data modeling and incidence rate estimation. The incidence of thyroid gland malignancy is higher in women than in men. On the other hand, the incidence of adrenal gland cancer is slightly higher in men than in women. The same pattern is observed for other endocrine neoplasms and related structures. The incidence rate of these types of cancers has generally increased from 2005 to 2020 in Iran. This increase is more in women than in men. In addition, in the middle of the country, there is a strong region in terms of the occurrence of these types of cancers. The incidence rate in these provinces is relatively higher for both sexes and all studied periods. We conducted a study to observe the changing trends for various types of endocrine cancers over 15 years in men and women. Considering the increasing trend of thyroid cancers in Iran, therefore, creating essential policies for the management of these types of cancers for prevention, rapid diagnosis, and, timely treatment is particularly important.
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Neoplasias das Glândulas Suprarrenais , Neoplasias das Glândulas Endócrinas , Neoplasias , Neoplasias da Glândula Tireoide , Masculino , Adolescente , Humanos , Feminino , Incidência , Irã (Geográfico)/epidemiologia , Neoplasias/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Sistema de RegistrosRESUMO
Single-cell sequencing has become one of the most used techniques across the wide field of biology. It has enabled researchers to investigate the whole transcriptome at the cellular level across tissues, which unlocks numerous potentials for basic and applied studies in future diagnosis and therapy. Here, we review the impact of single-cell RNA sequencing, as the prominent single-cell technique, in pancreatic biology and cancer. We discuss the most recent findings about pancreatic physiology and pathophysiology owing to this technological advancement in the past few years. Using single-cell RNA sequencing, researchers have been able to discover cellular heterogeneity across healthy cell types, as well as cancer tissues of the pancreas. We will discuss the new immunological targets and new molecular mechanisms of progression in the microenvironment of pancreatic cancer studied using single-cell RNA sequencing. The scope is not limited to cancer tissues, and we cover novel developmental, evolutionary, physiological, and heterogenic insights that have also been achieved recently for pancreatic tissues. We cover all biological insights derived from the single-cell RNA sequencing data, discuss the corresponding pros and cons, and finally, conclude how future research can move better by utilizing single-cell analysis for pancreatic biology.
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Neuropathic pain is one of the most critical types of chronic pain despite the increasing advances in medical science. Spermidine (SPD) is a natural polyamine that has wide roles in several cellular processes inducing autophagy and reducing oxidative stress. This study aimed to investigate the effects of SPD on oxidative stress markers and pain threshold in the neuropathic rat model of chronic constriction injury (CCI) model. Eighteen adult male rats were divided into three groups: sham, CCI and CCI+SPD. After induction of neuropathy via CCI model in the CCI and CCI+SPD groups, SPD (1 mg/kg/day, orally) was administered to the CCI+SPD group for 3 weeks. The behavioral tests (von Frey, hot plate) were done four times during the experiment. At the end of the study, electrophysiological tests, the H & E staining, and oxidative stress assay of the prefrontal cortex (PFC), spinal cord, and sciatic nerve were performed. The threshold of pain in hot plate and von Frey tests was significantly lower in the CCI group than in the sham group, which was reversed by SPD treatment in the CCI+ SPD group. In addition, nerve conduction was considerably lower in the CCI group than in the sham and CCI+SPD groups (P < 0.01, P < 0.05, respectively). The CCI group showed neuronal degeneration and fibrosis in the different tissues in the H & E assay; elevated tissues level of nitrite, decreased levels of superoxide dismutase (SOD), glutathione (GPx), and catalase were also observed. However, SPD treatment modulated the pathological changes and oxidative stress biomarkers. In conclusion, SPD showed beneficial effects in decreasing neuropathic pains. SPD treatment reduced oxidative stress and improved histopathological changes and behavioral tests in the CCI-induced neuropathic pain in in vivo model.
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Neuralgia , Espermidina , Ratos , Masculino , Animais , Espermidina/farmacologia , Constrição , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Limiar da Dor , Nervo Isquiático , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologiaRESUMO
BACKGROUND: The second leading mortality cause in the world is cancer, making it a critical issue that impacts human health. As a result, scientists are looking for novel biomarkers for cancer detection. The oral microbiome, made up of approximately 700 species-level taxa, is a significant source for discovering novel biomarkers. In this review, we aimed to prepare a summary of research that has investigated the association between the oral microbiome and gastrointestinal cancers. METHODS: We searched online scientific datasets including Web of Science, PubMed, Scopus, and Google Scholar. Eligibility criteria included human studies that reported abundances of the oral microbiome, or its diagnostic/prognostic performance in patients with gastrointestinal cancers. RESULTS: Some phyla of the oral microbiome have a relationship with cancers. Some particular phyla of the oral microbiome that may be related to gastrointestinal cancers consist of Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, and Fusobacteria. Changes in the abundances of Porphyromonas, Fusobacterium, Prevotella, and Veillonella are correlated with carcinogenesis, and may be used for distinguishing cancer patients from healthy subjects. Oral, colorectal, pancreatic, and esophageal cancers are the most important cancers related to the oral microbiome. CONCLUSION: The results of this study may help future research to select bacteria as an early diagnostic or prognostic biomarker of gastrointestinal cancer. Given the current state of our knowledge, additional research is required to comprehend the multiplex processes underlying the role of bacterial microbiota upon cancer progression and to characterize the complex microbiota-host interaction network.
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Neoplasias Esofágicas , Microbiota , Humanos , Disbiose/diagnóstico , Disbiose/microbiologia , Bactérias , BiomarcadoresRESUMO
BACKGROUND: One of the major complications associated with random-pattern skin flaps is distal necrosis. Cannabidiol (CBD) has recently gained much attention as a therapeutic anti-inflammatory agent. We aimed to evaluate the efficacy of CBD on the random-pattern skin flap survival (SFS) in rats and to explore the possible involvement of cannabinoid type-2 (CB2) receptors. METHODS: In this controlled experimental study, we randomly divided male Wistar rats into seven study groups (six rats each). We performed a random-pattern skin flap model in each rat following pretreatment with vehicle (control) or multiple doses of CBD (0.3, 1, 5, or 10 mg/kg). In a separate group, we injected SR144528 (2 mg/kg), a high affinity and selective CB2 inverse agonist, before the most effective dose of CBD (1 mg/kg). A sham nontreated and nonoperated group was also included. Seven days after surgeries, the percentage of necrotic area (PNA) was calculated. Histopathological microscopy, CB2 expression level, and interleukin (IL)-1ß and tumor necrosis factor (TNF)-α concentrations were also investigated in the flap tissue samples. RESULTS: A PNA of 72.7 ± 7.5 (95% confidence interval [CI]: 64.8-80.6) was captured in the control group. Following treatment with CBD 0.3, 1, 5, and 10 mg/kg, a dose-dependent effect was observed with PNAs of 51.0 ± 10.0 (95% CI: 40.5-61.5; p <0.05), 15.4 ± 5.8 (95% CI: 9.3-21.5; p <0.001), 37.1 ± 10.2 (95% CI: 26.3-47.8; p <0.001), and 46.4 ± 14.0 (95% CI: 31.7-61.1; p <0.001), respectively. Histopathologically, tissues enhanced significantly. Besides, CB2 expression surged remarkably, IL-1ß and TNF-α concentrations decreased considerably after treatment with CBD of 1 mg/kg compared with the control (p <0.05 and <0.001, respectively). Administering SR144528 reversed the favorable effects of CBD of 1 mg/kg, both macroscopically and microscopically. CONCLUSION: Pretreatment with CBD of 1 mg/kg improved SFS considerably in rats and exerted desirable anti-inflammatory effects which were possibly mediated by CB2 receptors.
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Canabidiol , Ratos , Masculino , Animais , Canabidiol/farmacologia , Receptores de Canabinoides , Ratos Wistar , Agonismo Inverso de DrogasRESUMO
Objectives: Multiple endocrine neoplasia type 1 (MEN-1) is a rare inherited autosomal dominant disease which manifests itself with at least one clinical scenario before 45 years of age. The value of somatostatin analogue therapy is unknown in the treatment of non-functioning pancreatic tumours and a few studies have been published in this field. Case presentation: We report a young patient with MEN-1 with multiple gastric and pancreatic neuroendocrine tumors that was treated with the monthly injection of Sandostatin LAR before and After Distal Pancreatectomy and partial gastrectomy. Conclusions: Now she is well after four years of treatment with Sandostatin LAR.
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Background: Thyroid cancer is the leading cause of mortality and morbidity among cancers of the endocrine system. We aimed to describe the trends of thyroid cancer burden in North Africa and Middle East for 1990-2019. Methods: Data on burden of thyroid cancer in North Africa and Middle East from 1990 to 2019 were obtained from the Global Burden of Disease (GBD) Study 2019. Decomposition analysis was used to estimate the effects of population growth, aging, and change in incident numbers on overall change of thyroid cancer incidence. Also, we used the comparative risk assessment framework of GBD to determine the burden of thyroid cancer attributable to a high body mass index (BMI). Results: In 2019, the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of thyroid cancer were 3.5 (2.9-4) and 0.5 (0.5-0.7) per 100,000, respectively. The highest age-standardized incidence, deaths, and disability-adjusted life year (DALY) rate were in Lebanon, Afghanistan, and United Arab Emirates, respectively. The ASIR of thyroid cancer in region was about 2.5 times higher among women, which had a positive association with increasing age. In 2019, the age-standardized deaths attributable to a high BMI was 16.7% of all deaths due to thyroid cancer. In 1990-2019, the overall change in thyroid cancer incident cases was a 396% increase which was mostly driven by the increase in disease-specific incidence rate (256.8%). Conclusions: Women, the elderly above about 60 years old, and countries with a higher sociodemographic index showed higher incidence rates of thyroid cancer. Regarding our findings, it is recommended to establish preventive plans by modification in life style like weight reduction programs.
RESUMO
AIMS: Liver cirrhosis defines by regenerative nodules and fibrotic septa, causing a complication called cirrhotic cardiomyopathy (CCM) with chronotropic hypo-responsiveness. In addition to lowering cholesterol levels, statins yield antioxidant and anti-inflammatory effects. In liver diseases animal models, statins have been shown to decrease hepatic inflammation, fibrogenesis, and portal pressure (PP). Therefore, we evaluated the atorvastatin effect on the heart in cirrhotic rats. MATERIALS AND METHODS: Bile duct ligation (BDL) or sham operation performed on male Wistar rats and grouped as cirrhotic; BDL/Saline, BDL/Ator-7d(days) (Atorvastatin 15 mg/kg/day), and BDL/Ator-14d groups, or control; Sham/Saline, Sham/Ator-7d, and Sham/Ator-14d groups. Corrected QT interval (QTc interval), chronotropic responses, serum brain natriuretic peptides (BNP), heart tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), and malondialdehyde (MDA) levels were studied along with atrial Ras homolog family member A (RhoA) and endothelial nitric oxide synthase (eNOS) gene expression. KEY FINDINGS: The chronotropic responses decreased in BDL/Saline and increased in BDL/Ator-7d group. The QTc interval, BNP, TNF-α, and MDA levels increased in BDL/Saline and decreased in BDL/Ator-14d group. The Nrf2 level did not change in BDL/Saline and increased in BDL/Ator-14d group. The liver inflammation and fibrosis increased in BDL/Saline and did not affect BDL/Ator-7d and BDL/Ator-14d groups. The RhoA expression was down-regulated in BDL/Saline, BDL/Ator-7d, and BDL/Ator-14d groups. The eNOS expression did not change in BDL/Saline and down-regulated in BDL/Ator-14d group. SIGNIFICANCE: Atorvastatin alleviates the chronotropic hypo-responsiveness and down-regulates the atrial RhoA and eNOS gene expression along with anti-inflammatory, antioxidant, and anti-stress effects in CCM.