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Treatment with melatonin is routinely prescribed for its potent antioxidant and cognitive-promoting effects, nevertheless, it has yet to find neuromodulatory effects in normal and disease conditions. Therefore, to investigate its neuromodulatory mechanisms, melatonin was systemically administered over 10 consecutive days to both intracortical normal saline- and amyloid-ß 1-42 (Aß) peptide-injected rats. At the behavioral level, treatment with melatonin was associated with reduced efficacy in restoring Aß-induced deficit in passive-avoidance memory. Whole-cell patch-clamp recordings from CA1 pyramidal neurons revealed that melatonin treatment reduced spontaneous and evoked intrinsic excitability in control rats while exerting a reduction of spontaneous, but not evoked activity, in the Aß-injected group. Interestingly, treatment with melatonin enhances after-hyperpolarization in control, but not Aß-injected rats. In contrast, our voltage-clamp study showed that Ih current is significantly enhanced by Aß injection, and this effect is further strengthened by treatment with melatonin in Aß-injected rats. Finally, we discovered that the transcription of melatonin receptors 1 (MT1) and 2 (MT2) is significantly upregulated in the hippocampi of Aß-injected rats. Collectively, our study demonstrates that systemic treatment with melatonin has differential neuromodulation on CA1 neuronal excitability, at least in part, via differential effects on after-hyperpolarization and Ih currents due to Aß-induced neurotoxicity.
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Péptidos beta-Amiloides , Hipocampo , Melatonina , Animales , Melatonina/farmacología , Péptidos beta-Amiloides/metabolismo , Ratas , Masculino , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Receptores de Melatonina/metabolismo , Fragmentos de Péptidos/farmacología , Receptor de Melatonina MT2/metabolismo , Receptor de Melatonina MT1/metabolismo , Ratas Sprague-Dawley , Técnicas de Placa-ClampRESUMEN
Immunotherapy has lately become the most preferred cancer treatment method, and for non-small cell lung cancer (NSCLC) first-line treatment, there are many immunotherapy options. This study aimed to assess the effectiveness and toxicity of paclitaxel (PTX), docetaxel (DTX) chemotherapy, immune checkpoint inhibitor treatment (durvalumab; DVL), and their combination in NSCLC. A-549 cells were treated with DVL in combination with PTX and DTX (a quarter of the IC50 ) to investigate their anticancer effects on these cells. The MTT assay, wound healing tests, and double-staining with Annexin V/PI were used to assess the cell viability, apoptosis, and migration. The results showed that a combination of 0.35 mg/mL DVL with 6.5 µg/mL PTX and 1.75 µg/mL DTX produced a synergistic effect with CI values of 0.88, 0.37, and 0.81, respectively. Moreover, the PTX + DTX + DVL combination led to a significantly increased apoptotic rate up to 88.70 ± 3.39% in the A549 cell line compared to monotherapy (p < .001). In addition, we found that the combination therapy with these agents increased the expression level of Bax, Cas-3, p53, and Bax/Bcl-2 ratio in all experimental groups. In conclusion, the results suggest that combining anti-PD-L1 antibody therapy with chemotherapy may provide a promising approach to enhance treatment outcomes and be a potentially efficacious strategy for treating NSCLC patients. Further research and clinical investigations are needed to elucidate the underlying molecular mechanisms and validate the therapeutic potential of these compounds in vivo.
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Anticuerpos Monoclonales , Hidrocarburos Aromáticos con Puentes , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Proteína X Asociada a bcl-2 , Neoplasias Pulmonares/tratamiento farmacológico , Taxoides/farmacología , Docetaxel/farmacología , Paclitaxel/farmacologíaRESUMEN
BACKGROUND: Physical inactivity is a critical predictor of all-cause mortality and many non-communicable diseases (NCD) including coronary heart disease, diabetes, hypertension, dementia, and several cancers. The main objective of this study was to determine the main barriers to physical activity based on the STEPwise Surveillance in Iran in 2021, to guide policymakers in developing the most effective physical activity increasing strategies. METHODS: This cross-sectional study was conducted on 27,515 female and male individuals aged over 18 years from the STEPwise Surveillance 2021. The barriers to physical activity according to the modified version of barriers questionnaire and intrapersonal, interpersonal, economic, cultural, and environmental domains based on social-ecological models were determined. Association between barriers domain and physical activity level was assessed. RESULTS: Lack of time due to job commitments (31.4%) and family (19.3%) and inappropriate physical conditions including illness, pain, injury, disability, and fatigue (30.4%) were the most frequent barriers to physical activity. Interest in sedentary leisure time activities including virtual space, computer games and watching TV were the next frequent barriers to physical activity (10.01%). Intrapersonal domain had the highest frequency (62.9%) and cultural domain had the lowest frequency (2.3%). Intrapersonal and interpersonal barriers reduced the odds of engaging in physical activity (OR: 0.62, P value < 0.001, OR: 0.76, P value < 0.001). CONCLUSION: Intra- and inter-personal domain barriers might reduce the odds of being active. Developing action plans addressing these factors is suggested to increase physical activity levels.
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Ejercicio Físico , Humanos , Irán/epidemiología , Masculino , Femenino , Estudios Transversales , Adulto , Persona de Mediana Edad , Adulto Joven , Adolescente , Anciano , Conducta Sedentaria , Encuestas y Cuestionarios , Vigilancia de la PoblaciónRESUMEN
Considering the importance of inflammation and oxidative stress in the development of rheumatoid arthritis (RA) as well as anti-inflammatory and antioxidant features of N-acetylcysteine (NAC), this study was conducted to evaluate the effect of NAC supplementation on disease activity, oxidative stress, and inflammatory and metabolic parameters in RA patients. In a randomized double-masked placebo-controlled trial, 74 RA subjects were chosen and randomly divided into two groups to take 600 mg of NAC or placebo twice daily for 3 months. Before and after the study, disease activity was assessed via disease activity score-28 (DAS-28), and serum malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPX) activity, nitric oxide (NO), high-sensitivity C-reactive protein (hs-CRP), fasting blood sugar (FBS), lipid profile, and erythrocyte sedimentation rate (ESR) were measured. Seventy patients completed the trial. Compared to baseline, NAC significantly reduced morning stiffness (P < 0.001), DAS-28 (P < 0.001), ESR (P = 0.004), MDA (P < 0.001), NO (P < 0.001), hs-CRP (P = 0.006), FBS (P < 0.001), and low-density lipoprotein cholesterol (LDL-C) (P = 0.023) and significantly increased GPx activity (P = 0.015) and high-density lipoprotein cholesterol (HDL-C) level (P = 0.001). After treatment, remarkable differences were only seen between the two groups in serum NO (P = 0.003), FBS (P = 0.010), and HDL-C (P < 0.001) adjusted for baseline measures. There were no significant changes in morning stiffness, DAS-28, ESR, hs-CRP, MDA, TAC, GPx activity, triglyceride, total cholesterol, and LDL-C levels compared to the placebo group. In conclusion, NAC did not improve RA disease activity, but reduced NO and FBS and increased HDL-C levels. It appears that NAC should not be consumed as a replacement for routine medications prescribed in RA therapy, but it can be used as an adjunctive therapy.
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Acetilcisteína , Artritis Reumatoide , Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores , Proteína C-Reactiva , Suplementos Dietéticos , Método Doble Ciego , Humanos , Estrés OxidativoRESUMEN
BACKGROUND: Guillain-Barré syndrome (GBS) is the main cause of acute and subacute flaccid paralysis in western nations since the eradication of poliomyelitis. OBJECTIVE: The aim of this study is to investigate epidemiology and mortality characteristics of GBS in the north of Iran. MATERIAL AND METHODS: In this study, the hospital information system (HIS) was used to access each patient's information. The final 174 cases were examined in terms of age, sex, place of residence, the year of referral, the month of referral, the season of referral, client city, accompanying background disease, and the type of GBS. RESULTS: The mean incidence rate in Guilan province was about 0.69 in 100,000 persons, and the case fatality rate was 10.34%. The most reported type of GBS was AIDP (33.90%), and the most common symptom was upper and lower limbs paresis in 65 cases (37%). Respiratory distress (P = < 0.001), complications during hospitalization (P = 0.0001), and ICU requirement (P = 0.001) were significantly higher in dead patients. CONCLUSION: In this study, the incidence of GBS was higher in men than women and the highest number of cases was in the age group of 60 to 75 years. The significant point was the high-case fatality rate in Guilan province compared to the previous studies. The complications during hospitalization such as respiratory distress, ICU requirement, and underlying disease had a significant relation with the fatality of GBS.
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Síndrome de Guillain-Barré , Adulto , Anciano , Niño , Femenino , Síndrome de Guillain-Barré/etiología , Humanos , Incidencia , Irán/epidemiología , Masculino , Persona de Mediana Edad , Parálisis/etiología , Estaciones del AñoRESUMEN
Low-density polyethylene (LDPE) polymer is mainly used in the production of plastic bags and food packaging making up the largest volume of plastic pollutions. These polymers are potential substrates for bacteria in the bioremediation process. In this study, soil samples were collected from different plastic landfills in Iran and subsequently enriched in specific media (polyethylene as carbon source) to increase the population of LDPE-degrading bacteria. Seventeen PE-degrading bacteria, some novel, were isolated from Iranian soil samples and identified using 16S rDNA gene sequencing. These isolates were capable of degrading PE in a limited incubation period without the need for physicochemical pretreatments and comprise mostly of Actinobacteria which include the three genera of Streptomyces, Nocardia, and Rhodococcus. The isolates belonged to 17 different species of gram-positive Actinobacteria. In all, 11 species of the genus Streptomyces, 3 species of the genus Rhodococcus, and 3 species of the genus Nocardia were identified. The isolates with less than 99% 16S rRNA gene similarity to previously known species were suspected to be new species. Various analyses (weight loss, SEM, FTIR, and tensile strength test) to determine polyethylene biodegradation rate were carried out after a 60-day incubation period. Analysis of polyethylene biodegradation elucidates that Actinobacteria have a high ability for biodegradation of polyethylene-based plastics. Streptomyces sp. IR-SGS-T10 showed the highest reduction in weight of the LDPE film (1.58 mg/g/day) after 60 days of incubation without any pretreatments. Rhodococcus sp. IR-SGS-T11 shows the best reduction in the tensile property of LDPE film, while results from FTIR study for Streptomyces sp. IR-SGS-Y1 indicated a significant change in structural analysis.
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Actinobacteria/metabolismo , Plásticos/metabolismo , Polietileno/metabolismo , Actinobacteria/clasificación , Actinobacteria/genética , Actinobacteria/aislamiento & purificación , Biodegradación Ambiental , Irán , Filogenia , Polietileno/química , Microbiología del Suelo , Instalaciones de Eliminación de ResiduosRESUMEN
BACKGROUND: Despite 2.5 million infections and 169,000 deaths worldwide (as of April 20, 2020), no maternal deaths and only a few pregnant women afflicted with severe respiratory morbidity have been reported to be related to COVID-19 disease. Given the disproportionate burden of severe and fatal respiratory disease previously documented among pregnant women following other coronavirus-related outbreaks (SARS-CoV in 2003 and MERS-CoV in 2012) and influenza pandemics over the last century, the absence of reported maternal morbidity and mortality with COVID-19 disease is unexpected. OBJECTIVE: To describe maternal and perinatal outcomes and death in a case series of pregnant women with COVID-19 disease. STUDY DESIGN: We describe here a multiinstitution adjudicated case series from Iran that includes 9 pregnant women diagnosed with severe COVID-19 disease in their second or third trimester. All 9 pregnant women received a diagnosis of SARS-CoV-2 infection by reverse transcription polymerase chain reaction nucleic acid testing. Outcomes of these women were compared with their familial/household members with contact to the affected patient on or after their symptom onset. All data were reported at death or after a minimum of 14 days from date of admission with COVID-19 disease. RESULTS: Among 9 pregnant women with severe COVID-19 disease, at the time of reporting, 7 of 9 died, 1 of 9 remains critically ill and ventilator dependent, and 1 of 9 recovered after prolonged hospitalization. We obtained self-verified familial/household cohort data in all 9 cases, and in each and every instance, maternal outcomes were more severe compared with outcomes of other high- and low-risk familial/household members (n=33 members for comparison). CONCLUSION: We report herein maternal deaths owing to COVID-19 disease. Until rigorously collected surveillance data emerge, it is prudent to be aware of the potential for maternal death among pregnant women diagnosed as having COVID-19 disease in their second or third trimester.
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Infecciones por Coronavirus/mortalidad , Mortalidad Materna , Neumonía Viral/mortalidad , Complicaciones Infecciosas del Embarazo/mortalidad , Adulto , Betacoronavirus , COVID-19 , Femenino , Humanos , Recién Nacido , Irán/epidemiología , Persona de Mediana Edad , Pandemias , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Milk has a high nutritional value and can affect human health. Therefore, it is important to know the factors affecting its quality. The purpose of this study was to evaluate the raw milk microbial quality and factors affecting it. A total of 4260 raw cow milk samples, which were collected from villages around Garmsar city, Iran, and their microbial load were registered at Garmsar Dairy Cow Association between 2013 and 2014, was used in the present study. The total average ± SD of microbial load concentration was 3.02 × 105 ± 2.75 × 105 (CFU/ml). The average concentration of total bacteria in 2013 was 2.73 × 105 ± 1.58 × 105 (CFU/ml) and in 2014 it was 3.32 × 105 ± 3.93 × 105(CFU/ml). Seasonally, it was 2.94 × 105 ± 1.72 × 105 (CFU/ml), 3.69 × 105 ± 4.55 × 105 (CFU/ml), 2.91 × 105 ± 1.62 × 105 (CFU/ml), and 2.63 × 105 ± 1.67 × 105 (CFU/ml) for spring, summer, autumn, and winter, respectively. There was a significant difference in seasonal average microbial concentration of milk samples (p < 0.05). The present study concludes that microbial load of milk can be affected by environmental and hygienic conditions. Ranchers need to pay more attention to hygiene especially in warm seasons. Because in case of high microbial load in raw milk, even after milk pasteurization, it is not possible to have a high-quality and desirable product. Milk producers and distributors need also awareness in order to reduce the incidence of secondary contamination. But, the main correction is to establish direct supervision of the Ministry of Health onto the health of dairy cow farmers by structural integrity of Veterinary Medical Organization as the global one health.
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Bacterias/aislamiento & purificación , Bovinos/microbiología , Recuento de Colonia Microbiana/veterinaria , Leche/microbiología , Animales , Femenino , Irán , Leche/químicaRESUMEN
BACKGROUND: Endometriosis is a chronic and progressive gynecological disorder and is manifest by dysmenorrhea and a major cause of infertility and chronic pelvic pain. The study was designed to compare the value of cervico-vaginal fluid of interleukin-1α (IL-1α) in patients with and without endometriosis. MATERIALS AND METHODS: Fifty women were assessed in this case control study. The case group included 25 patients with endometriosis. The control group included 25 women without any evidence of endometriosis or any other genital disease. Endometriosis was confirmed by laparoscopy and histopathological examination. Cervico-vaginal fluid samples were obtained from patients during the follicular phase and preup surgery to assess the levels of IL-1α in cervico-vaginal fluid. The level of IL-1α was assessed using commercially available Avi Bionhuman Enzyme-Linked Immunosorbent Assay kits (FIN-01720, Vantaa, Finland) for IL-1α. Receiver-operator curve analysis was used to estimate the power of IL-1α to distinguish subjects with endometriosis from controls. RESULTS: The cervico-vaginal fluid level of IL-1α in cases was 210.44 ± 40.11 pg/mL and in controls was 54.28 ± 25.73 pg/mL, the differences between two groups was statistically significant (P < 0.0001). The cut-off point for cervico-vaginal fluid IL-1 for endometriosis was 105 pg/mL, with a sensitivity of 100% (95% confidence interval [CI]: 86.2-100), and specificity of 100% (95% CI: 86.2-100). CONCLUSION: Results show a significant increase in the cervico-vaginal fluid levels of IL-1α, in women with endometriosis, that it can be a useful marker in the diagnosis of endometriosis.
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A tumor represents a highly intricate tissue entity, characterized by an exceptionally complex microenvironment that starkly contrasts with the typical physiological surroundings of healthy tissues. Within this tumor microenvironment (TME), every component and factor assume paramount importance in the progression of malignancy and exerts a pivotal influence on a patient's clinical outcome. One of the remarkable aspects of the TME is its remarkable heterogeneity, not only across different types of cancers but even within the same histological category of tumors. In-depth research has illuminated the intricate interplay between specific immune cells and molecules and the dynamic characteristics of the TME. Recent investigations have yielded compelling evidence that several mutations harbored by tumor cells possess the capacity to instigate substantial alterations in the TME. These mutations, often acting as drivers of tumorigenesis, can orchestrate a cascade of events that remodel the TME, thereby influencing crucial aspects of cancer behavior, including its invasiveness, immune evasion, and response to therapies. It is within this nuanced context that the present study endeavors to provide a concise yet comprehensive summary of how specific mutations, within the genetic landscape of cancer cells, can instigate profound changes in TME features. By elucidating the intricate relationship between genetic mutations and the TME, this research aims to contribute to a deeper understanding of cancer biology. Ultimately, the knowledge gained from this study holds the potential to inform the development of more targeted and effective treatments, thereby offering new hope to patients grappling with the complexities of cancer.
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Neoplasias , Humanos , Neoplasias/genética , Carcinogénesis , Biología , Medios de Contraste , Mutación , Microambiente Tumoral/genéticaRESUMEN
OBJECTIVE: Gastric cancer is a prevalent cancer type worldwide, and significant research efforts are focused on finding effective treatments. Recent studies have highlighted the importance of plasma membrane carriers, particularly solute carriers, in cancer progression. The SLC16A family, notably the SLC16A13 gene, plays a critical role in cancer development and tumor growth. This study aims to explore the impact of reducing SLC16A13 expression in gastric cancer cells on their survival, proliferation, and metastatic potential. METHODS: Gastric cancer cells (KATO2) were cultured in RPMI medium supplemented with 10% fetal bovine serum. The cells were then transfected with SLC16A13 si-RNA to lower gene expression. The effects of this si-RNA on cell death and apoptosis were assessed using MTT and flow cytometry assays. Cell migration capabilities were evaluated using the scratch test. Western blot and Real-Time PCR were employed to measure SLC16A13 expression levels and protein detection. Additionally, RT-PCR was used to analyze changes in genes related to apoptosis and cell migration. RESULTS: The reduction of SLC16A13 expression following si-RNA transfection significantly increased apoptosis and cell death in the KATO2 cell line after 72 hours (P < 0.0001). Furthermore, the study revealed that decreased SLC16A13 expression did not impact cancer cell migration. Cell viability, assessed by MTT assay, showed a significant decrease at 48 and 72 hours post-transfection (P < 0.0001). CONCLUSION: The findings indicate that targeting SLC16A13 can effectively increase cell death and apoptosis in gastric cancer cells, making it a viable therapeutic target.
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Apoptosis , Biomarcadores de Tumor , Movimiento Celular , Proliferación Celular , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Células Tumorales Cultivadas , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , ARN Interferente Pequeño/genéticaRESUMEN
The concentration of polycyclic aromatic hydrocarbons (PAHs) in the air inside residential houses in Iran along with measuring the amount of 1-OHpyrene metabolite in the urine of the participants in the study was investigated by gas chromatography-mass spectrometry (GC-MS). Demographic characteristics (including age, gender, and body composition), equipment affecting air quality, and wealth index were also investigated. The mean ± standard error (SE) concentration of particulate matter 10 (PM10) and ∑PAHs in the indoor environment was 43.2 ± 1.98 and 1.26 ± 0.15 µg/m3, respectively. The highest concentration of PAHs in the indoor environment in the gaseous and particulate phase related to Naphthalene was 1.1 ± 0.16 µg/m3 and the lowest was 0.01 ± 0. 0.001 µg/m3 Pyrene, while the most frequent compounds in the gas and particle phase were related to low molecular weight hydrocarbons. 30% of the samples in the indoor environment have BaP levels higher than the standards provided by WHO guidelines. 68% of low molecular weight hydrocarbons were in the gas phase and 73 and 75% of medium and high molecular weight hydrocarbons were in the particle phase. There was a significant relationship between the concentration of some PAH compounds with windows, evaporative coolers, printers, and copiers (p < 0.05). The concentration of PAHs in houses with low economic status was higher than in houses with higher economic status. The average concentration of 1-hydroxypyrene metabolite in the urine of people was 7.10 ± 0.76 µg/L, the concentration of this metabolite was higher in men than in women, and there was a direct relationship between the amount of this metabolite in urine and the amount of some hydrocarbon compounds in the air, PM10, visceral fat and body fat. This relationship was significant for age (p = 0.01). The concentration of hydrocarbons in the indoor environment has been above the standard in a significant number of non-smoking indoor environments, and the risk assessment of these compounds can be significant. Also, various factors have influenced the amount of these compounds in the indoor air, and paying attention to them can be effective in reducing these hydrocarbons in the air.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Monitoreo Biológico , Material Particulado , Hidrocarburos Policíclicos Aromáticos , Contaminación del Aire Interior/análisis , Contaminación del Aire Interior/estadística & datos numéricos , Hidrocarburos Policíclicos Aromáticos/análisis , Hidrocarburos Policíclicos Aromáticos/orina , Humanos , Irán , Masculino , Femenino , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/orina , Adulto , Material Particulado/análisis , Persona de Mediana Edad , Monitoreo del Ambiente , Pirenos/análisis , Pirenos/orina , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Adulto Joven , Vivienda , Cromatografía de Gases y Espectrometría de MasasRESUMEN
Exposure to metal(loid)s can cause adverse health effects. This study evaluated the concentrations of aluminum, arsenic, cadmium, chromium, mercury, nickel, and lead in particulate matter <10 µm (PM10) and in the urine of 100 participants from urban residential areas in Iran. A total of 100 residential buildings (one adult from each household) in six cities across Iran were recruited for this study. The levels of metal(loid)s in PM10 and the urine of participants were measured using acid digestion followed by inductively coupled plasma mass spectrometry (ICP-MS). The average (±SE) PM10 concentration in the buildings was 51.7 ± 3.46 µg/m3. Aluminum and cadmium had the highest and lowest concentrations among the metal(loid)s, averaging 3.74 ± 1.26 µg/m3 and 0.01 ± 0.001 µg/m3, respectively. In 85 % of the samples, the concentration of metal(loid)s in indoor air exceeded WHO air quality standards. Cadmium and lead had the highest and lowest numbers of indoor air samples exceeding the recommended standards, respectively. A significant correlation was found between the concentration of metal(loid)s in urine samples and indoor PM10 levels, as well as the wealth index of participants. There was also a significant direct relationship between the concentrations of nickel, arsenic, lead, and mercury in urine and the age of participants. Factors such as building location, type of cooling systems, use of printers at home, and natural ventilation influenced the concentration and types of metal(loid)s in the indoor air.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Monitoreo Biológico , Exposición a Riesgos Ambientales , Contaminación del Aire Interior/análisis , Contaminación del Aire Interior/estadística & datos numéricos , Irán , Humanos , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Adulto , Material Particulado/análisis , Ciudades , Metales/análisis , Metales/orina , Masculino , Monitoreo del Ambiente/métodos , Femenino , Arsénico/análisis , Persona de Mediana EdadRESUMEN
In this work, we have reported the design, synthesis, in vitro, and in silico enzymatic evaluation of new bis-4-hydroxycoumarin-based phenoxy-1,2,3-triazole-N-phenylacetamide derivatives 5a-m as potent α-glucosidase inhibitors. All the synthesized analogues showed high inhibition effects against α-glucosidase (IC50 values ranging between 6.0 ± 0.2 and 85.4 ± 2.3 µM) as compared to the positive control acarbose (IC50 = 750.0 ± 0.6 µM). Among the newly synthesized compounds 5a-m, 2,4-dichloro-N-phenylacetamide derivative 5i with inhibition effect around 125-folds more than the acarbose was identified as the most potent entry. A structure-activity relationship (SAR) study about the title compounds 5a-m demonstrated that the inhibition effects of these compounds depend on the pattern of substitution on the N-phenylacetamide ring. The interaction modes and binding energies in the active site of enzyme of the important analogues (in term of SAR study) were evaluated through molecular docking study. Molecular dynamics and prediction of pharmacokinetic properties and toxicity of the most potent compound 5i also evaluated and the obtained data was compared with the acarbose.
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4-Hidroxicumarinas , Diseño de Fármacos , Inhibidores de Glicósido Hidrolasas , Simulación del Acoplamiento Molecular , alfa-Glucosidasas , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/síntesis química , Relación Estructura-Actividad , alfa-Glucosidasas/metabolismo , alfa-Glucosidasas/química , 4-Hidroxicumarinas/química , 4-Hidroxicumarinas/farmacología , 4-Hidroxicumarinas/síntesis química , Simulación por Computador , Dominio Catalítico , Simulación de Dinámica MolecularRESUMEN
This study aimed to investigate the estimated burden attributed to lead exposure (LE), at the national and subnational levels from 1990 to 2019 in Iran. The burden attributed to LE was determined through the estimation of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs) and years lived with disability (YLDs) using the comparative risk assessment method of Global Burden of Disease (GBD) study presenting as age-standardized per 100,000 person year (PY) with 95% uncertainty intervals (95% UI). Furthermore, the burden of each disease were recorded independently. Eventually, the age-standardized YLLs, DALYs, deaths and YLDs rates attributed to LE demonstrated a decrease of 50.7%, 48.9%, 38.0%, and 36.4%, respectively, from 1990 to 2019. The most important causes of LE burden are divided into two acute and chronic categories: acute, mainly causes mental disorders (DALYs rate of 36.0 in 2019), and chronic, results in cardiovascular diseases (CVDs) (DALYs rate of 391.8) and chronic kidney diseases (CKDs) (DALYs rate of 26.6), with CVDs bearing the most significant burden. At the sub-national level, a decrease in burden was evident in most provinces; moreover, low and low-middle SDI provinces born the highest burden. The burden increased mainly by ageing and was higher in males than females. It was concluded that although the overall decrease in the burden; still it is high, especially in low and low-middle SDI provinces, in advanced ages and in males. Among IDID, CKDs and CVDs that are the most important causes of LE-attributed burden in Iran; CVDs bear the highest burden.
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Esperanza de Vida , Unionidae , Masculino , Femenino , Animales , Humanos , Carga Global de Enfermedades , Años de Vida Ajustados por Calidad de Vida , Plomo , Irán/epidemiología , Salud Global , Factores de RiesgoRESUMEN
BACKGROUND: This study measured the concentrations of arsenic (As), aluminum (Al), cadmium (Cd), chromium (Cr), mercury (Hg), nickel (Ni), and lead (Pb) in the urine samples of the Iranian adult population. METHODS: This nationally representative study was conducted on 490 participants in six provinces of Iran who were selected based on the clustering method. Participants included healthy Iranian adults aged above 25 years without a history of illness and non-smokers. Fasting urine sampling, body composition, and demographic measurements were performed for each participant. Urine samples were analyzed by acid digesting method using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The analysis included descriptive statistics and multiple linear regression using Python programming language. RESULTS: The geometrical mean (with corresponding reference values, µg/l) concentrations of metal(loid)s in urine for women, men, and both were 198.2 (625.3), 163.5 (486.1), and 192.5(570.4) for Al, 15.6(51.7), 28.8(71.1), and 21.9 (61.64) for As, 18.5(55.2), 20.7(56.5), and 19.22(55.75) for Pb, 17.9(57.6), 17.9 (53.9), and 17.9(56) for Ni, 13.95(47.5), 20.3(62.2) and 16(51.6) for Cr, 3.5(12.2), 2.9(11.5), and 3.3(12) for Hg, 0.74(2.7), 0.95 (3.6), and 0.81(3.1) for Cd. There was a direct relationship between the concentration of metal(loid)s and demographic indicators and body composition (P<0.05). Moreover, there was a direct relationship between the concentration of As, Cr, Hg, Ni, and Pb with age and wealth index (P<0.05). CONCLUSIONS: The concentrations found could be used as the reference range for As, Al, Cd, Cr, Hg, Ni, and Pb for human biomonitoring studies on the Iranian adult population.
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Monitoreo Biológico , Mercurio , Humanos , Adulto , Irán , Femenino , Masculino , Valores de Referencia , Persona de Mediana Edad , Mercurio/orina , Plomo/orina , Cadmio/orina , Metales/orina , Níquel/orina , Arsénico/orina , Aluminio/orina , Cromo/orinaRESUMEN
Gill histological changes were used as a biomarker to evaluate the health of yellowfin seabream, Acanthopagrus latus (A. latus), collected from different sites in Musa Creeks including: (A) Petrochemical, (B) Jaafari, (C) Ghazaleh, (D) Majidieh, and (E) Zangi creeks. Also Genaveh with relatively clean water was selected as reference. The gills of 60 A. latus were fixed in Bouin's solution for 12 hr, dehydrated in a graded series of ethanol, and embedded in paraffin. Five micrometer thick sections were stained in H&E and Periodic Acid Schiff for microscopic examination. Also, the presence of gill histological alterations was assessed by the histopathologic alteration index (HAI). The gill morphological abnormalities include mucus secretion increase, debris, blood plaque, and shortening of filaments. The gill pathological changes included lamellar cells hyperplasia, aneurysm, lamellar fusion, and epithelial lifting. The HAI means were varied from moderate to severe in sites A and B, thus these sites are considered as being of low quality. Some severe pathological alterations were observed in site D, but their distribution was lower than sites A and B. The least HAI means of sites C and E demonstrated their good environmental quality. The results suggest that there is close relation between amounts of pathological alterations and environmental contamination.
Asunto(s)
Branquias/efectos de los fármacos , Branquias/patología , Dorada , Contaminantes Químicos del Agua/envenenamiento , Contaminación Química del Agua/análisis , Análisis de Varianza , Animales , Biomarcadores/análisis , Femenino , Branquias/química , Branquias/citología , Histología , Océano Índico , Masculino , FotomicrografíaRESUMEN
Testicular germ cell tumors (TGCTs) are a common malignancy occurring in young adult men. The various genetic risk factors have been suggested to contribute to TGCT pathogenesis, however, they have a distinct mutational profile with a low rate of somatic point mutations, more frequent chromosomal gains, and aneuploidy. The most frequently mutated oncogenes in human cancers are RAS oncogenes, while their impact on testicular carcinogenesis and refractory disease is still poorly understood. In this mini-review, we summarize current knowledge on genetic alternations of RAS signaling-associated genes (the single nucleotide polymorphisms and point mutations) in this particular cancer type and highlight their link to chemotherapy resistance mechanisms. We also mention the impact of epigenetic changes on TGCT progression. Lastly, we propose a model for RAS-dependent signaling networks, regulation, cross-talks, and outcomes in TGCTs.
Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Adulto Joven , Genómica , Seminoma/patología , Neoplasias Testiculares/patología , Proteínas ras/metabolismoRESUMEN
Tuberculous (TB) pericarditis is a well-known manifestation of tuberculosis, particularly in endemic regions. The progression to constrictive pericarditis, while under anti-tuberculosis treatment, is reported to be as high as 30%. This report presents a case of a 56-year-old female patient who complained of cough, pleuritic chest pain, night sweats, and fever, followed by orthopnea, dyspnea, and peripheral edema. Transthoracic echocardiography revealed the early stages of constrictive pericarditis and a small pericardial effusion. Chest computed tomography (CT) showed a thickened pericardium, small pericardial and pleural effusions, and multiple mediastinal lymphadenopathies. Due to a high suspicion of tuberculous pericarditis, the patient was administered empirical anti-TB treatment. A follow-up after two months showed complete resolution of symptoms and echocardiographic findings. Empirical antimicrobial treatment in endemic areas is a well-established strategy for managing tuberculous infection and proved successful in this patient. The early presentation and the significant improvement in signs and symptoms following the medical anti-TB regimen, without the need for pericardiectomy, were unique aspects of this case.
RESUMEN
The Spence Children's Anxiety Scale (SCAS) is a tool for measuring anxiety symptoms in children and adolescents. In this study, the psychometric properties of the Persian version of SCAS were investigated in an Iranian adolescents. This study was conducted on a sample of 684 adolescents. For standardization of SCAS, first- and second-order confirmatory factor analyses wereperformed. Also, to evaluate convergent and divergent validity, Fornell and Larcker criteria (1994), along with the Revised Children's Manifest Anxiety Scale (RCMAS)and Children's Depression Inventory (CDI), was used. A receiver operating characteristic (ROC) curve analysis was also performedto determine the cut-off point. The model fit of the correlated six-factor model was good however, a second-order model provided a statistically superior fit to the data. The reliability coefficients for the total scale and its dimensions were satisfactory (α > 0.7). Therefore, it can be concluded that the Persian version of SCAS has acceptable reliability and validity and can be used as a useful tool for early screening of anxiety in Iranian adolescents due to its easy use and specific design for children and adolescents.