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1.
BMC Med Educ ; 24(1): 71, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233910

RESUMO

BACKGROUND: Leadership in health system is a universal challenge. The Young Innovative Leadership Program (YILP) designed for undergraduate and postgraduate medical sciences students, implemented at the Isfahan University of Medical Sciences, aimed to cultivate leadership capacities through a 16-week training program. This program comprises ten modules covering innovation, change leadership, and management skills, with mentor-facilitated group discussions. This study aimed to provide a qualitative report of the experiences of participants in the YILP. METHODS: A qualitative study was conducted in 2022, three months after the end of the training program, to investigate the participants' perspectives. Data was extracted through in-depth, semi-structured interviews with 14 participants. RESULTS: In this study 14 undergraduate and postgraduate medical sciences students who had participated in the YILP the previous year were included. Four main categories emerged from the interviews: "emergence of new horizons", "values as beacon", "an expanded toolbox", and "program's structure: a learning atmosphere". CONCLUSIONS: The results of our study indicated that medical science students would benefit from leadership development programs. In this regard, the framework utilized to implement YILP could serve as a role model.


Assuntos
Currículo , Liderança , Humanos , Pesquisa Qualitativa , Aprendizagem
2.
Cancer Cell Int ; 23(1): 312, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057843

RESUMO

The metastasis of melanoma cells to regional lymph nodes and distant sites is an important contributor to cancer-related morbidity and mortality among patients with melanoma. This intricate process entails dynamic interactions involving tumor cells, cellular constituents, and non-cellular elements within the microenvironment. Moreover, both microenvironmental and systemic factors regulate the metastatic progression. Central to immunosurveillance for tumor cells are natural killer (NK) cells, prominent effectors of the innate immune system with potent antitumor and antimetastatic capabilities. Recognizing their pivotal role, contemporary immunotherapeutic strategies are actively integrating NK cells to combat metastatic tumors. Thus, a meticulous exploration of the interplay between metastatic melanoma and NK cells along the metastatic cascade is important. Given the critical involvement of NK cells within the melanoma tumor microenvironment, this comprehensive review illuminates the intricate relationship between components of the melanoma tumor microenvironment and NK cells, delineating their multifaceted roles. By shedding light on these critical aspects, this review advocates for a deeper understanding of NK cell dynamics within the melanoma context, driving forward transformative strategies to combat this cancer.

3.
Environ Res ; 237(Pt 2): 116980, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37648188

RESUMO

Melanoma, an aggressive malignant tumor originating from melanocytes in humans, is on the rise globally, with limited non-surgical treatment options available. Recent advances in understanding the molecular and cellular mechanisms underlying immune escape, tumorigenesis, drug resistance, and cancer metastasis have paved the way for innovative therapeutic strategies. Combination therapy targeting multiple pathways simultaneously has been shown to be promising in treating melanoma, eliciting favorable responses in most melanoma patients. CAR T-cells, engineered to overcome the limitations of human leukocyte antigen (HLA)-dependent tumor cell detection associated with T-cell receptors, offer an alternative approach. By genetically modifying apheresis-collected allogeneic or autologous T-cells to express chimeric antigen receptors, CAR T-cells can appreciate antigens on cell surfaces independently of major histocompatibility complex (MHC), providing a significant cancer cell detection advantage. However, identifying the most effective target antigen is the initial step, as it helps mitigate the risk of toxicity due to "on-target, off-tumor" and establishes a targeted therapeutic strategy. Furthermore, evaluating signaling pathways and critical molecules involved in melanoma pathogenesis remains insufficient. This study emphasizes the novel approaches of CAR T-cell immunoediting and presents new insights into the molecular signaling pathways associated with melanoma.

4.
Environ Res ; 238(Pt 1): 117083, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37690629

RESUMO

Liquid biopsy includes the isolating and analysis of non-solid biological samples enables us to find new ways for molecular profiling, prognostic assessment, and better therapeutic decision-making in cancer patients. Despite the conventional theory of tumor development, a non-vertical transmission of DNA has been reported among cancer cells and between cancer and normal cells. The phenomenon referred to as horizontal gene transfer (HGT) has the ability to amplify the advancement of tumors by disseminating genes that encode molecules conferring benefits to the survival or metastasis of cancer cells. Currently, common liquid biopsy approaches include the analysis of extracellular vesicles (EVs) and tumor-free DNA (tfDNA) derived from primary tumors and their metastatic sites, which are well-known HGT mediators in cancer cells. Current technological and molecular advances expedited the high-throughput and high-sensitive HGT materials analyses by using new technologies, such as microfluidics in liquid biopsies. This review delves into the convergence of microfluidic-based technologies and the investigation of Horizontal Gene Transfer (HGT) materials in cancer liquid biopsy. The integration of microfluidics offers unprecedented advantages such as high sensitivity, rapid analysis, and the ability to analyze rare cell populations. These attributes are instrumental in detecting and characterizing CTCs, circulating nucleic acids, and EVs, which are carriers of genetic cargo that could potentially undergo HGT. The phenomenon of HGT in cancer has raised intriguing questions about its role in driving genomic diversity and acquired drug resistance. By leveraging microfluidic platforms, researchers have been able to capture and analyze individual cells or genetic material with enhanced precision, shedding light on the potential transfer of genetic material between cancer cells and surrounding stromal cells. Furthermore, the application of microfluidics in single-cell sequencing has enabled the elucidation of the genetic changes associated with HGT events, providing insights into the evolution of tumor genomes. This review also discusses the challenges and opportunities in studying HGT materials using microfluidic-based technologies. In conclusion, microfluidic-based technologies have significantly advanced the field of cancer liquid biopsy, enabling the sensitive and accurate detection of HGT materials. As the understanding of HGT's role in tumor evolution and therapy resistance continues to evolve, the synergistic integration of microfluidics and HGT research promises to provide valuable insights into cancer biology, with potential implications for precision oncology and therapeutic strategies.


Assuntos
Microfluídica , Neoplasias , Humanos , Transferência Genética Horizontal , Medicina de Precisão , Biópsia Líquida , DNA
5.
Immunopharmacol Immunotoxicol ; 45(2): 240-252, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36073178

RESUMO

CONTEXT: Opioids are available for the management of severe and chronic pain. However, long-term use of high-dose opioids could lead to physiologic tolerance, hyperalgesia, gastrointestinal immobility, addiction, respiratory depression, tumor progression, and inhibition of the immune system. It seems some of these adverse effects of opioids might be induced by TLR-4 signaling. OBJECTIVE: The review aims to investigate the potential interplay between opioids and TLR-4 in CNS, gastrointestinal, cancer, and immune system. METHODS: The search of PubMed, Embase, Scopus, web of sciences, and Google scholar was performed for all relevant studies published. From a total of 513 papers obtained at the initial database search, publications including in silico, in vitro, and in vivo studies were selected for the review. RESULTS: A comprehensive review of studies indicated that using opioids for the reduction of pain might induce adverse effects such as analgesic tolerance, hyperalgesia, cancer progression, and suppression of the immune system. Some studies have indicated these effects may be due to a change in the level of expression and signaling pathway of TLR-4. The generalizability of the results was limited due to the inconsistency of findings. CONCLUSIONS: More studies are needed to clarify TLR-4-mediated opioid effects on the biology or stages of the disease as well as the role of different types of opioids, appropriate dosage, and exposure in various contexts. Designing the drug candidate and doing many formulation studies for different diseases and various stages of disease could be associated with effective treatment and pain management.


Assuntos
Analgésicos Opioides , Neoplasias , Humanos , Analgésicos Opioides/efeitos adversos , Receptor 4 Toll-Like , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Dor/tratamento farmacológico , Neoplasias/tratamento farmacológico
6.
Stem Cells ; 39(12): 1625-1649, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33786925

RESUMO

Organoids are powerful systems to facilitate the study of individuals' disorders and personalized treatments. This emerging technology has improved the chance of translatability of drugs for preclinical therapies and mimicking of the complexity of organs, proposing numerous approaches for human disease modeling, tissue engineering, drug development, diagnosis, and regenerative medicine. In this review, we outline the history of organoid technology and summarize its faithful applications, and then we discuss the challenges and limitations encountered by three-dimensional organoids. Finally, we propose that human organoids offer a basic mechanistic infrastructure for "human modeling" systems to prescribe personalized medicines.


Assuntos
Organoides , Medicina Regenerativa , Humanos , Modelos Biológicos , Medicina de Precisão/métodos , Engenharia Tecidual
7.
JAMA ; 328(16): 1604-1615, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36215063

RESUMO

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID). Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration. Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022. Exposures: Symptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age. Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months. Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.


Assuntos
COVID-19 , Transtornos Cognitivos , Fadiga , Insuficiência Respiratória , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Teorema de Bayes , COVID-19/complicações , COVID-19/epidemiologia , Fadiga/epidemiologia , Fadiga/etiologia , Dor/epidemiologia , Dor/etiologia , SARS-CoV-2 , Síndrome , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/etiologia , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Internacionalidade , Saúde Global/estatística & dados numéricos , Transtornos do Humor/epidemiologia , Transtornos do Humor/etiologia , Síndrome de COVID-19 Pós-Aguda
8.
Int J Mol Sci ; 23(14)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35886906

RESUMO

Recent genome-wide association studies uncovered part of blood pressure's heritability. However, there is still a vast gap between genetics and biology that needs to be bridged. Here, we followed up blood pressure genome-wide summary statistics of over 750,000 individuals, leveraging comprehensive epigenomic and transcriptomic data from blood with a follow-up in cardiovascular tissues to prioritise likely causal genes and underlying blood pressure mechanisms. We first prioritised genes based on coding consequences, multilayer molecular associations, blood pressure-associated expression levels, and coregulation evidence. Next, we followed up the prioritised genes in multilayer studies of genomics, epigenomics, and transcriptomics, functional enrichment, and their potential suitability as drug targets. Our analyses yielded 1880 likely causal genes for blood pressure, tens of which are targets of the available licensed drugs. We identified 34 novel genes for blood pressure, supported by more than one source of biological evidence. Twenty-eight (82%) of these new genes were successfully replicated by transcriptome-wide association analyses in a large independent cohort (n = ~220,000). We also found a substantial mediating role for epigenetic regulation of the prioritised genes. Our results provide new insights into genetic regulation of blood pressure in terms of likely causal genes and involved biological pathways offering opportunities for future translation into clinical practice.


Assuntos
Epigênese Genética , Estudo de Associação Genômica Ampla , Pressão Sanguínea/genética , Epigenômica/métodos , Genômica/métodos , Humanos , Transcriptoma
9.
Electrophoresis ; 42(20): 2018-2026, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34013529

RESUMO

Extracellular vesicles (EVs) are cell-derived nanoscale vesicles involved in intracellular communication and the transportation of biomarkers. EVs released by mesenchymal stem cells have been recently reported to play a role in cell-free therapy of many diseases. However, the demand for better research tools to replace the tedious conventional methods used to study EVs is getting stronger. EVs' manipulation using alternating current (AC) electrokinetic forces in a microfluidic device has appeared to be a reliable and sensitive diagnosis and trapping technique. Given that different AC electrokinetic forces may contribute to the overall motion of particles and fluids in a microfluidic device, EVs' electrokinetic trapping must be examined considering all dominant forces involved depending on the experimental conditions. In this paper, AC electrokinetic trapping of EVs using an interdigitated electrode arrays is investigated. A 2D numerical simulation incorporating the two significant AC electrokinetic phenomena (Dielectrophoresis and AC electroosmosis) has been performed. Theoretical predictions are then compared with experimental results and allow for a plausible explanation of observations inconsistent with DEP theory. It is demonstrated that the inconsistencies can be attributed to a significant extent to the contribution of the AC electroosmotic effect.


Assuntos
Polpa Dentária , Técnicas Eletroquímicas , Vesículas Extracelulares , Modelos Químicos , Células-Tronco
10.
Tumour Biol ; 43(1): 141-157, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34420992

RESUMO

Cancers evolve as a result of the accelerated proliferation of cancer cells in a complicated, enriched, and active microenvironment. Tumor microenvironment (TME) components are the master regulators of any step of cancer development. The tumor microenvironment is composed of many cellular and noncellular components that contribute to the evolution of cancer cells. Cancer-associated fibroblasts (CAFs) are activated fibroblasts in the TME that implicate in tumor progression and metastasis dissemination through secretion of oncogenic factors which are carried to the secondary metastatic sites through exosomes. In this review, we aimed to assess the role of CAF-derived exosomes in TME construction and pre-metastatic niche formation in different cancers of the digestive system in order to better understand some important mechanisms of metastasis and provide possible targets for clinical intervention. This review article is divided into two thematic parts explaining the general mechanisms of pre-metastatic niche formation and metastasis and the role of CAF-derived exosomes in different digestive system cancers including colorectal, gastric, esophageal, pancreatic, and liver cancers.


Assuntos
Fibroblastos Associados a Câncer/patologia , Neoplasias do Sistema Digestório/patologia , Exossomos/patologia , Microambiente Tumoral , Animais , Neoplasias do Sistema Digestório/etiologia , Humanos , Metástase Neoplásica
11.
Cancer Cell Int ; 21(1): 62, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472628

RESUMO

Hypoxia is a common feature of solid tumors, and develops because of the rapid growth of the tumor that outstrips the oxygen supply, and impaired blood flow due to the formation of abnormal blood vessels supplying the tumor. It has been reported that tumor hypoxia can: activate angiogenesis, thereby enhancing invasiveness and risk of metastasis; increase survival of tumor, as well as suppress anti-tumor immunity and hamper the therapeutic response. Hypoxia mediates these effects by several potential mechanisms: altering gene expression, the activation of oncogenes, inactivation of suppressor genes, reducing genomic stability and clonal selection. We have reviewed the effects of hypoxia on tumor biology and the possible strategiesto manage the hypoxic tumor microenvironment (TME), highlighting the potential use of cancer stem cells in tumor treatment.

12.
Cancer Cell Int ; 21(1): 194, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823861

RESUMO

Colorectal cancer (CRC) is the third most common cause of cancer globally and the fourth attributable cause of mortality and morbidity due to cancer. An emerging factor contributing to CRC is the gut microbiota and the cellular changes associated with it. Further insights on this may help in the prevention, diagnosis and new therapeutic approaches to colorectal cancer. In most cases of CRC, genetic factors appear to contribute less to its aetiology than environmental and epigenetic factors; therefore, it may be important to investigate these environmental factors, their effects, and the mechanisms that may contribute to this cancer. The gut microbiota has recently been highlighted as a potential risk factor that may affect the structural components of the tumor microenvironment, as well as free radical and enzymatic metabolites directly, or indirectly. Many studies have reported changes in the gut microbiota of patients with colorectal cancer. What is controversial is whether the cancer is the cause or consequence of the change in the microbiota. There is strong evidence supporting both possibilities. The presence of Fusobacterium nucleatum in human colorectal specimens has been demonstrated by RNA-sequencing. F. nucleatum has been shown to express high levels of virulence factors such as FadA, Fap2 and MORN2 proteins. Our review of the published data suggest that F. nucleatum may be a prognostic biomarker of CRC risk, and hence raises the potential of antibiotic treatment of F. nucleatum for the prevention of CRC.

13.
BMC Med Res Methodol ; 21(1): 146, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261439

RESUMO

BACKGROUND: Already at hospital admission, clinicians require simple tools to identify hospitalized COVID-19 patients at high risk of mortality. Such tools can significantly improve resource allocation and patient management within hospitals. From the statistical point of view, extended time-to-event models are required to account for competing risks (discharge from hospital) and censoring so that active cases can also contribute to the analysis. METHODS: We used the hospital-based open Khorshid COVID Cohort (KCC) study with 630 COVID-19 patients from Isfahan, Iran. Competing risk methods are used to develop a death risk chart based on the following variables, which can simply be measured at hospital admission: sex, age, hypertension, oxygen saturation, and Charlson Comorbidity Index. The area under the receiver operator curve was used to assess accuracy concerning discrimination between patients discharged alive and dead. RESULTS: Cause-specific hazard regression models show that these baseline variables are associated with both death, and discharge hazards. The risk chart reflects the combined results of the two cause-specific hazard regression models. The proposed risk assessment method had a very good accuracy (AUC = 0.872 [CI 95%: 0.835-0.910]). CONCLUSIONS: This study aims to improve and validate a personalized mortality risk calculator based on hospitalized COVID-19 patients. The risk assessment of patient mortality provides physicians with additional guidance for making tough decisions.


Assuntos
COVID-19 , Estudos de Coortes , Mortalidade Hospitalar , Hospitalização , Humanos , Irã (Geográfico) , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , SARS-CoV-2
14.
Br J Clin Pharmacol ; 86(9): 1875-1881, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32040868

RESUMO

AIMS: Breast cancer is the most frequently occurring cancer in women. Lumpectomy followed by radiotherapy is suggested to be as effective as a total mastectomy. Radiation-induced dermatitis often occurs as a result of breast radiotherapy. Recent studies suggest that doxepin has promising anti-inflammatory properties. This study was undertaken to evaluate the effects of doxepin therapy on radiation dermatitis. METHODS: A double-blind randomized clinical trial was launched from 2016 to 2017, with a total of 48 patients who had undergone breast-conserving surgery and received postoperative radiation therapy. Radiotherapy was applied 5 days per week for 5 weeks. Adverse dermatological effects were evaluated by a physician at the beginning of the fifth week of radiotherapy and the patients were then randomly assigned (1:1 ratio) to receive either doxepin (5%) or placebo cream for 7 days. RESULTS: There were no significant differences in the dermatitis grade between doxepin and placebo groups at baseline (P > .5). The occurrence of acute dermatitis (grade 2 or higher) was significantly lower with the use of doxepin than with placebo (P ≤ .0001, Zα = 1.96 at 95% confidence interval). CONCLUSION: Doxepin cream prevents dermatitis grade 2 or higher during post-operative breast irradiation. Doxepin cream is easy to use, affordable and prevents pain and irritation.


Assuntos
Neoplasias da Mama , Doxepina/farmacologia , Radiodermite , Neoplasias da Mama/radioterapia , Método Duplo-Cego , Feminino , Humanos , Mastectomia , Radiodermite/prevenção & controle , Método Simples-Cego
15.
Int J Vitam Nutr Res ; 90(3-4): 339-345, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32517587

RESUMO

Background: Genome Wide Association Studies (GWAS) have evaluated several genes related to vitamin D synthesis, metabolism and transport. They have proposed a genetic basis for low levels of vitamin D in the blood. The current study aims to investigate the relationship between certain vitamin D-associated gene variants and vitamin D deficiency in Iranian adolescents. Methods: In this case-control study, the genomic DNA was extracted by Real Time PCR High Resolution Melt (HRM). All measurements were carried out with triple repetition. The following factors were assessed: single nucleotide polymorphisms (SNPs) in Vitamin D binding protein (DBP, rs2282679), 7-Dehydrocholesterol reductase (DHCR7, rs12785878) and Cytochrome P450 2R1 (CYP2R1, rs10741657). Results: the genomic DNA of blood samples obtained from 481 adolescents. Participants with hypovitaminosis D were compared with a control group. The average vitamin D level of sufficient subjects (controls) was 44.88±14.01 ng/mL, while subjects who were insufficient (cases) had an average vitamin D level of 7.03±1.24 ng/mL. No statistically significant differences were found in the allelic and genotypic distributions between genders. The SNP frequency in CYP2R1 (rs10741657) and DBP (rs2282679) in the vitamin D deficient group was significantly higher than in the control group (p-values < 0.001 and 0.01 respectively). There were no statistically significant differences in the DHCR7 SNP (rs12785878) distributions between the Vitamin D deficient group and control group. Conclusion: The present study demonstrated evidence of the ability of the SNPs under investigation to predict circulating vitamin D concentration. Further study is needed to better understand if and how genetic factors contribute to vitamin D levels, and certain skeletal-associated disorders in adolescents.


Assuntos
Colestanotriol 26-Mono-Oxigenase/genética , Sistema Enzimático do Citocromo P-450/genética , Família 2 do Citocromo P450/genética , Deficiência de Vitamina D , Proteína de Ligação a Vitamina D , Vitamina D/metabolismo , Adolescente , Estudos de Casos e Controles , Colestanotriol 26-Mono-Oxigenase/química , Colestanotriol 26-Mono-Oxigenase/metabolismo , Família 2 do Citocromo P450/química , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Irã (Geográfico) , Masculino , Polimorfismo de Nucleotídeo Único/genética , Proteína de Ligação a Vitamina D/genética
16.
J Pharm Pharm Sci ; 22(1): 418-423, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509504

RESUMO

BACKGROUND: Although previous studies demonstrated an anticancer effect for the ligands of peroxisome proliferator-activated receptor gamma (PPARγ) through activation of its anti-inflammatory responses, nevertheless the anti-tumor mechanism of PPARγ has not been intensively investigated. One of the molecules involved in cancer progression is toll-like receptor 4 (TLR4). METHODS: B16F10 melanoma cells were cultured with or without LPS for 24 hr. The cells were subcutaneously injected to two groups of C57BL/6 mice. After the development of palpable tumors each group of animals were divide to four sub-groups and received pioglitazone in different dose ranges (0,10,50,100 mg/kg/day) for 10 days. At the end of the study, the expression of Tlr4, Myd-88, Nf-kb1 genes was evaluated by qRT-PCR in different groups in mice tumor. The TLR-4 protein expression was evaluated by IHC. TNF-α level in mice tumor and serum were measured by ELISA kits. Tumor volume was measured with Vernier calipers. RESULTS: We observed that activation of PPARγ by its agonist, pioglitazone, reduces tumor volume, Tlr-4, Myd-88, Nf-kb1 mRNA expression, TLR4 protein expression and TNF-α production in melanoma tumor especially in groups that were injected with LPS -stimulated cells. Moreover, treatment of melanoma cells with pioglitazone showed that the inhibitory effects of pioglitazone on LPS-induced inflammatory responses were TLR4 dependent. CONCLUSIONS: The results indicate that pioglitazone, a PPARγ agonist, has a beneficial protective effect against melanoma via interfering with the TLR4-dependent signaling pathways.


Assuntos
Antineoplásicos/farmacologia , Melanoma/tratamento farmacológico , PPAR gama/agonistas , Pioglitazona/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Masculino , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Receptor 4 Toll-Like/metabolismo , Células Tumorais Cultivadas
17.
Twin Res Hum Genet ; 22(6): 579-582, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31955715

RESUMO

Twin studies are one of the main tools for studying the interaction between genes and the environment in the development of complex diseases such as cancers, cardiovascular diseases and diabetes. The Isfahan Twin Registry (ITR) was launched in Isfahan in 2017 as a pilot study to establish a nationwide twin registry in Iran and aims to obtain comprehensive information about complex diseases and their risk factors from twins and multiples living in Isfahan. ITR will continue to recruit twins and multiples until all twins residing in Isfahan are registered in the registry. Twins are identified from welfare agencies, public health homes, maternity hospitals, Persian Twins Association and the local media. Demographic information, twin similarities, lifestyle, family history of diseases and past medical history are collected using validated questionnaires. Anthropometric measurements and blood pressure are measured by health professionals. Hematology panel, fasting blood sugar, total cholesterol, low-density lipoprotein, high-density lipoprotein, aspartate aminotransferase, alanine aminotransferase and quantitative C-reactive protein are measured by an automated analyzer. Extra samples are obtained for future studies. For twins aged under 6 years, parents complete the questionnaires for their children and a brief questionnaire for themselves. Currently, 998 persons (395 pairs and 67 multiples) are registered in the ITR and have provided their data. Results of preliminary data analysis are discussed in this article. We plan to carry out longitudinal assessments. ITR can play an important role in future epigenetic, biomarkers and omics studies using the biobank materials.


Assuntos
Biomarcadores/análise , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/genética , Epigênese Genética , Sistema de Registros/estatística & dados numéricos , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adolescente , Adulto , Criança , Pré-Escolar , Doenças em Gêmeos/fisiopatologia , Projetos de Pesquisa Epidemiológica , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Irã (Geográfico)/epidemiologia , Estilo de Vida , Masculino , Projetos Piloto , Prognóstico , Adulto Jovem
18.
J Acoust Soc Am ; 145(6): 3311, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31255151

RESUMO

A method is presented for measurements of secondary acoustic radiation forces acting on solid particles in a plain ultrasonic standing wave. The method allows for measurements of acoustic interaction forces between particles located in arbitrary positions such as in between a pressure node and a pressure antinode. By utilizing a model that considers both density- and compressibility-dependent effects, the observed particle-particle interaction dynamics can be well understood. Two differently sized polystyrene micro-particles (4.8 and 25 µm, respectively) were used in order to achieve pronounced interaction effects. The particulate was subjected to a 2-MHz ultrasonic standing wave in a microfluidic channel, such as commonly used for acoustophoresis. Observation of deflections in the particle pathways shows that the particle interaction force is not negligible under this circumstance and has to be considered in accurate particle manipulation applications. The effect is primarily pronounced when the distance between two particles is small, the sizes of the particles are different, and the acoustic properties of the particles are different relative to the media. As predicted by theory, the authors also observe that the interaction forces are affected by the angle between the inter-particle centerline and the axis of the standing wave propagation direction.

19.
Environ Res ; 146: 154-60, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26761592

RESUMO

BACKGROUND: This study aims to investigate the association of exposure to ambient air pollution during pregnancy with cord blood concentrations of surrogate markers of endothelial dysfunction. METHODS: This population-based cohort was conducted from March 2014 to March 2015 among 250 mother-neonate pairs in urban areas of Isfahan, the second large and air-polluted city in Iran. We analyzed the association between the ambient carbon monoxide (CO), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), particular matter 10 (PM10), and air quality index (AQI) with cord blood levels of endothelin-1, vascular adhesion molecule (VCAM), and intercellular adhesion molecule (ICAM). Multiple regression analysis was conducted after adjustment for potential confounding factors and covariates. The regression coefficient (beta), standard error of the estimate (SE), and 95% confidence intervals for each regression coefficient (95% CI) are reported. RESULTS: Data of 233 mother-neonate pairs were complete, and included in the analysis. Multiple regression analyses showed that AQI, CO and O3 had significant correlation with cord blood ICAM-1 [Beta (SE), 95%CI: 2.93 (0.72), 1.33,5.54; 2.28(1.44), 1.56,5.12; and 2.02(0.01), 1.03,2.04, respectively] as well as with VCAM-1 [2.78(0.91), 1.69,4.57; 2.47(1.47), 1.43,5.37; and 2.01(0.01),1.07,2.04, respectively]. AQI, PM10, and SO2 were significantly associated with Endothelin-1 concentrations [Beta (SE), 95%CI: 10.16(5.08),7.61,14.28; 9.70(3.46), 2.88,16.52; and 1.07(0.02), 1.03,2.11, respectively]. CONCLUSIONS: The significant associations of air pollutants with markers of endothelial dysfunction during fetal period may provide another evidence on the adverse health effects of air pollutants on early stages of atherosclerosis from fetal period. Our findings underscore the importance of considering environmental factors in primordial prevention of chronic diseases.


Assuntos
Poluentes Atmosféricos/sangue , Endotelina-1/sangue , Exposição Ambiental , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Adulto , Biomarcadores/sangue , Monitoramento Ambiental , Feminino , Sangue Fetal/química , Humanos , Recém-Nascido , Irã (Geográfico) , Masculino , Gravidez , Análise de Regressão , Cordão Umbilical/metabolismo , Adulto Jovem
20.
J Pharm Pharm Sci ; 19(1): 72-81, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27096694

RESUMO

PURPOSE: Statins are widely prescribed drugs for lowering cholesterol. Some studies have suggested that statins can prevent breast cancer recurrence and reduce mortality rate. However they are not conclusive. Present systematic review and meta-analysis of published cohort studies was conducted to determine the effects of statins intake and risk of breast cancer recurrence and mortality rate. METHODS: Online databases (PubMed, Embase, Scopus, EBSCO and Cochrane Collaboration) were searched through October 2014. Pooled relative risks and 95 % confidence intervals were calculated with random-effects. RESULTS: A total of 8 cohort studies (4 for recurrence 2 for mortality and 2 for both) involving 124669 participants with breast cancer were eligible. Our results suggest a significant reduction in recurrence (OR= 0.79. I2= 38%) and death (OR = 0.84, I2 = 8.58 %) among statin users. CONCLUSION: Our meta-analysis suggests that breast cancer patients will benefit from statin intake, however from these cohorts we are unable to differentiate between various statins in terms of effectiveness and duration of use. We highly propose conducting randomized clinical trials.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Estudos Observacionais como Assunto , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Fatores de Risco , Análise de Sobrevida
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