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1.
Int J Public Health ; 69: 1606554, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711785

RESUMO

Objectives: Tuberculosis (TB) is a significant public health concern in Afghanistan, with a high burden of disease in the western province of Herat. This study explored the risk factors of TB and TB's impact on the quality of life of patients in Herat. Methods: A total of 422 TB patients and 514 controls were recruited at Herat Regional Hospital and relevant TB laboratories between October 2020 and February 2021. Data was collected through interviews using a structured questionnaire and the SF-36 questionnaire. Descriptive statistics, chi-square tests, Multivariate General Linear Model, and logistic regression analysis were used to analyze the data. Results: The results showed that male sex (p = 0.023), chronic disease (p = 0.038), lower education levels (p < 0.001), and worse health status (p < 0.001) were significantly associated with higher odds of TB infection. The study also found that TB patients had significantly lower quality of life scores in almost all components (p < 0.05). Conclusion: This study provides important insights into the specific ways in which TB affects the wellbeing of patients in Afghanistan. The findings highlight the importance of addressing the psychological and social dimensions of TB.


Assuntos
Qualidade de Vida , Tuberculose , Fatores Sexuais , Tuberculose/epidemiologia , Tuberculose/patologia , Tuberculose/psicologia , Afeganistão/epidemiologia , Fatores de Risco , Estudos de Casos e Controles , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Inquéritos e Questionários
2.
J Viral Hepat ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787307

RESUMO

Hepatitis B virus is a global health concern with a high death rate in Afghanistan. Limited data exist on the disease's impact on quality of life in low-resource settings. This case-control study aims to identify potential risk factors and assess the quality of life among hepatitis B patients in Herat, Afghanistan, with a focus on sex differences. Understanding these factors can inform prevention, care, and sex-specific interventions. A cross-sectional study conducted at Herat Regional Hospital examined hepatitis B patients above 18 years old, between October 2020 and February 2021. The control group consisted of age and sex-matched individuals without a history of hepatitis B. Data were collected through a structured questionnaire covering socio-demographic characteristics, signs and symptoms of hepatitis B, and the SF-36 questionnaire for measuring the quality of life of study participants. Statistical analysis was performed using multivariate General Linear Models, and logistic regression. We identified several potential risk factors for hepatitis B infection, including male sex, younger age groups, tobacco use, lower education levels, rural residence, family history, weak social networks, specific family structures and underlying chronic diseases (p < .05). The study found that hepatitis B cases had significantly lower mean scores across all SF-36 components, indicating an overall reduced quality of life (p < .05). These differences were more pronounced in males, although females had lower scores in most components. Role limitations due to physical and emotional health were particularly affected. These findings highlight the urgent need for targeted interventions, sex-specific strategies, improved healthcare access and comprehensive policies. These findings can inform prevention efforts to improve the overall quality of life of people with hepatitis B in Afghanistan.

3.
J Am Heart Assoc ; 13(9): e030403, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38619293

RESUMO

BACKGROUND: Most studies have used cross-sectional or limited follow-up data to evaluate the relationship between social isolation (SI) and hypertension in older populations. The objective of this analysis was to examine the relationship between longitudinal SI and hypertension in a younger population. METHODS AND RESULTS: The present analysis used data from waves I to V of the National Longitudinal Study of Adolescent to Adult Health (1994-2018) and logistic regression models to describe the association of timing, duration, and transitional patterns of SI with hypertension in early middle adulthood. Models were adjusted for demographic variables and adolescent socioeconomic and health-related confounders. SI was higher across life stages among individuals with hypertension (adolescence: 38% versus 35%, young adulthood: 52% versus 44%, and early middle adulthood: 61% versus 52%). Individuals who were socially isolated in young adulthood or early middle adulthood had greater odds of hypertension in early middle adulthood than those who were not (odds ratio [OR], 1.30 [95% CI, 1.07-1.56]; OR, 1.42 [95% CI, 1.15-1.76], respectively). Early middle adulthood hypertension was significantly associated with persistent SI across all life stages and for those who moved into persistent SI after adolescence (OR, 1.40 [95% CI, 1.02-1.93]; OR, 1.61 [95% CI, 1.18-2.19], respectively). CONCLUSIONS: SI in young or early middle adulthood significantly increased the odds of hypertension, as did moving into SI and the accumulation of SI across life stages. Our analysis provides insights regarding timing for effective interventions to reduce hypertension earlier in the life course, which may prevent future adverse cardiovascular-related events.


Assuntos
Hipertensão , Isolamento Social , Humanos , Hipertensão/epidemiologia , Hipertensão/psicologia , Masculino , Feminino , Adulto , Estudos Longitudinais , Adolescente , Adulto Jovem , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Fatores Etários , Pressão Sanguínea/fisiologia , Medição de Risco , Fatores de Tempo
4.
Front Neuroinform ; 18: 1331220, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444756

RESUMO

Spiking neural network simulations are a central tool in Computational Neuroscience, Artificial Intelligence, and Neuromorphic Engineering research. A broad range of simulators and software frameworks for such simulations exist with different target application areas. Among these, PymoNNto is a recent Python-based toolbox for spiking neural network simulations that emphasizes the embedding of custom code in a modular and flexible way. While PymoNNto already supports GPU implementations, its backend relies on NumPy operations. Here we introduce PymoNNtorch, which is natively implemented with PyTorch while retaining PymoNNto's modular design. Furthermore, we demonstrate how changes to the implementations of common network operations in combination with PymoNNtorch's native GPU support can offer speed-up over conventional simulators like NEST, ANNarchy, and Brian 2 in certain situations. Overall, we show how PymoNNto's modular and flexible design in combination with PymoNNtorch's GPU acceleration and optimized indexing operations facilitate research and development of spiking neural networks in the Python programming language.

5.
Int J Dev Neurosci ; 84(2): 99-108, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38178780

RESUMO

BACKGROUND: Many clinical evidences have reported the higher risk of seizure in young children and infants after exposure to hyperthermia, which more likely can cause brain damage and affect cognitive function, so, many researches were focused on prevention or treatment of febrile seizure (FS) with minimal adverse effects. Considering the potential effects of oxidative stress as a prominent trigger in FS, and demonstrating the anti-oxidant effects of metformin, the present study aimed to investigate the protective effect of metformin administration in prenatal and lactation periods in rat pups exposed to hyperthermia by which induced seizure. METHOD AND MATERIALS: Pregnant rats were divided into six groups: (1) vehicle: pregnant rats received normal saline during pregnancy and lactation; (2) FS: pregnant rats received normal saline during pregnancy and lactation; (3-5) FS-Met50/100/150 mg/kg: pregnant rats received different doses of metformin including 50, 100 and 150 mg/kg during pregnancy and lactation; (6) Met150 mg/kg: pregnant rats received Met150 mg/kg during pregnancy and lactation. The male pups born to mothers received in all FS groups exposed to hyperthermia. All experimental groups were allowed to grow up, and after the lactation period, they were subjected for behavioural tests and biochemical analysis. RESULTS: According to the present findings, the prenatal and lactation exposure to the highest dose of metformin demonstrated significant difference with FS group in both behavioural and biochemical test analyses. Although the remaining doses of metformin were also effective, the much better results were reported with the highest dose of metformin (150 mg/kg). Interestingly, the highest dose of metformin administered alone demonstrated better result than vehicle in probe trial test. CONCLUSION: Considering the present research and related study in relation to metformin in ameliorating the epilepsy symptoms, there are numerous evidences on positive effect of metformin on seizure. Although the exact mechanism is unclear, the anti-oxidant effect of metformin is strongly supported.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Convulsões Febris , Animais , Feminino , Masculino , Gravidez , Ratos , Antioxidantes , Lactação , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/prevenção & controle , Estresse Oxidativo , Efeitos Tardios da Exposição Pré-Natal/psicologia , Solução Salina , Convulsões Febris/tratamento farmacológico , Convulsões Febris/etiologia
6.
Curr Pharm Des ; 29(31): 2461-2476, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37921135

RESUMO

INTRODUCTION: Several successful attempts have been recorded with PD-L1 blockade via atezolizumab monotherapy or combination therapy with chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). Due to the lack of a large-scale study, we present a meta-analysis aimed at evaluating the safety and efficacy of this promising strategy in patients with mTNBC. METHODS: A comprehensive literature search was conducted using electronic databases to identify eligible RCTs. Twelve studies, including 2479 mTBNC patients treated with atezolizumab monotherapy or in combination with chemotherapy, were included up to January 2022. The PRISMA checklist protocol and the I2 statistic were applied for quality assessment and heterogeneity tests of the selected trials, respectively. Fixed and random-effects models were estimated based on the heterogeneity tests, and statistical analysis was performed using CMA. RESULTS: Our pooled findings demonstrated that the median overall survival (OS) and progression-free survival (PFS) were 16.526 and 5.814 months in mTNBC patients, respectively. Furthermore, when comparing efficacy indicators between PD-L1-positive and PD-L1-negative groups, mTNBC patients with PD-L1 had better OS, PFS, and ORR than PD-L1-negative patients. Also, the immune-related adverse event incident for alopecia was higher (51.9%) than other complications across atezolizumab therapy. CONCLUSION: Moreover, the pooled analysis indicated that the overall rate of lung metastasis following atezolizumab therapy was 42.8%, which was higher than the rates of metastasis in bone (26.9%), brain (5.4%), and lymph node (6.5%). Atezolizumab showed a manageable safety profile and had promising and durable anti-tumor efficacy in TMBC patients. Higher PD-L1 expression may be closely correlated with better clinical efficacy.


Assuntos
Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
7.
Caspian J Intern Med ; 14(4): 676-680, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38024162

RESUMO

Background: Helicobacter pylori (H. pylori) has infected about 50% of the world's population and it is the main cause for peptic ulcer, gastric adenocarcinoma and even a major cause for gastric MALT lymphoma. Methods: This study was performed in Mazandaran, Sari, situated in North of Iran. Three-hundred and twenty-eight adult patients with endoscopically approved gastric or duodenal ulcers or erosions and H. pylori infection were randomly divided into 2 groups to receive either 14 days PABT (Pantoprazole 40 mg, Amoxicillin 1 g, Bismuth 425 mg (all twice daily) and Tetracycline 500 mg four times a day) and PACM (Pantoprazole 40 mg, Amoxicillin 1g, Clarithromycin 500 mg, and Metronidazole 500 mg, all twice daily). To evaluate H. pylori eradication, fecal H. pylori antigen test was performed 8 weeks after treatment. Results: The eradication rates were 94.51% in the PABT and 91.46% in PACM group based on the intention to treat analysis. Moreover, the eradication rates were 95.58% and 92.72% according to per-protocol analysis, respectively. Also, both groups had very low rates of severe side effects. Conclusion: Regarding the ideal eradication rates achieved by both treatment groups and the low rates of severe side effects, both treatment protocols can be prescribed for H. pylori eradication in North of Iran.

8.
J Biomol Struct Dyn ; : 1-14, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37705281

RESUMO

Chemotherapeutic treatment of colorectal cancer (CRC) has not been satisfactory until now; therefore, the discovery of more efficient medications is of great significance. Based on available knowledge, the CXCL12/CXCR4 axis plays a significant role in tumorigenesis, and inhibition of CXCR4 chemokine receptor with AMD3100 is one of the most known therapeutic modalities in cancer therapy. Herein, N, N''-thiocarbonylbis(N'-(3,4-dimethylphenyl)-2,2,2-trifluoroacetimidamide) (A1) was synthesized as a potent CXCR4 inhibitor. A1 inhibitory activity was first evaluated employing Molecular Docking simulations in comparison with the most potent CXCR4 inhibitors. Then, the antiproliferative and cytotoxic effect of A1 on CT26 mouse CRC cells was investigated by MTT assay technique and compared with those of the control molecule, AMD3100. The impact of the target compounds IC50 on apoptosis, cell cycle arrest, and CXCR4 expression was determined by flow cytometry technique. Our finding demonstrated that A1 induces a cytotoxic effect on CT26 cells at 60 µg/mL concentration within 72 h and provokes cell apoptosis and G2/M cell cycle arrest in comparison with the untreated cells, while AMD3100 did not show a cytotoxic effect up to 800 µg/mL dose. The obtained results show that A1 (at a concentration of 40 µg/mL) significantly reduced the proliferation of CT26 cells treated with 100 ng/mL of CXCL12 in 72 h. Moreover, treatment with 60 µg/mL of A1 and 100 ng/mL of CXCL12 for 72 h significantly decreased the number of cells expressing the CXCR4 receptor compared to the control group treated with CXCL12. Eventually, the obtained results indicate that A1, as a dual-function fluorinated small molecule, may benefit CRC treatment through inhibition of CXCR4 and exert a cytotoxic effect on tumor cells.Communicated by Ramaswamy H. Sarma.

9.
Addict Health ; 15(2): 112-118, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37560395

RESUMO

Background: Addiction is a global public health problem, with over 36 million people suffering from drug-use disorders. Afghanistan, the world's leading opium producer, has high rates of drug use owing to the easy access to drugs in this country. This study aimed to investigate drug users' quality of life in Herat, Afghanistan, and identify the factors affecting it. Methods: This cross-sectional study examined health-related quality of life at six rehabilitation camps in Herat, Afghanistan, from March to July 2019, using the short form-36 questionnaire (SF-36). Data collected through interviews were analyzed using SPSS software (version 25). Findings: A total of 240 participants from six rehabilitation camps in Herat, Afghanistan participated in this study. The majority of participants (80%) rated their overall health as "good" or "very good". Men had higher average scores for mental health and vitality than women and those aged 30-39 had the highest quality of life. Statistically significant differences were found in bodily pain (P=0.038), vitality (P=0.042), and social functioning (P=0.046) among users of different types of drugs. Opium abusers had the highest scores for the physical and mental components, followed by heroin, methamphetamine, hashish, and crack abusers. Conclusion: This study explored the relationship between drug addiction and quality of life in Herat, Afghanistan. The findings showed that young adults were more vulnerable to drug use and male addicts and opium users had the highest quality of life. This study can inform the development of effective rehabilitation programs but more research is needed for addiction treatment strategies.

10.
Cancer Rep (Hoboken) ; 6(9): e1873, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37574721

RESUMO

BACKGROUND: Afghanistan is in an epidemiological transition, as cancer is the second leading cause of mortality due to non-communicable diseases. This study is the first to provide a comprehensive perspective on the overall cancer situation in Afghanistan by discussing the top five most common cancers, their incidence variations, risk factors, and preventive measures. The limited number of cancer studies conducted in Afghanistan highlights the importance of the present review. RECENT FINDINGS: This article provides an overview of cancer burden in Afghanistan in 2020. It utilizes IARC-generated GLOBOCAN 2020 data for one, three, and five-year prevalence rates, the estimated number of new cancer cases, and mortality rates by age group in Afghanistan. According to GLOBOCAN, the top five common cancers in both sexes in Afghanistan were breast (n = 3173, 14.3%), stomach (n = 2913, 7.8%), lung (n = 1470, 6.6%), cervix uteri (n = 1200, 5.4%), and colorectum (n = 1084, 4.9%). CONCLUSION: This study provides a brief overview of the general cancer situation in Afghanistan, and a more in-depth analysis of the five common cancers identified. Effective therapies, awareness, and prevention initiatives targeting lifestyle, immunization, early diagnosis, and environmental risk factors are essential for addressing the impact of population growth and aging on cancer incidence in Afghanistan. Further research and extensive studies are needed to better understand cancer burden in the country.


Assuntos
Neoplasias , Masculino , Feminino , Humanos , Incidência , Prevalência , Afeganistão , Distribuição por Sexo , Neoplasias/terapia
11.
Int Immunopharmacol ; 122: 110470, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37433246

RESUMO

Researchers have tried to find novel strategies for cancer treatment in the past decades. Among the utilized methods, administering oncolytic viruses (OVs) alone or combined with other anticancer therapeutic approaches has had promising outcomes, especially in solid tumors. Infecting the tumor cells by these viruses can lead to direct lysis or induction of immune responses. However, the immunosuppressive tumor microenvironment (TME) is considered a significant challenge for oncolytic virotherapy in treating cancer. Based on OV type, hypoxic conditions in the TME can accelerate or repress virus replication. Therefore, genetic manipulation of OVs or other molecular modifications to reduce hypoxia can induce antitumor responses. Moreover, using OVs with tumor lysis capability in the hypoxic TME may be an attractive strategy to overcome the limitations of the therapy. This review summarizes the latest information available in the field of cancer virotherapy and discusses the dual effect of hypoxia on different types of OVs to optimize available related therapeutic methods.


Assuntos
Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Neoplasias/patologia , Vírus Oncolíticos/genética , Microambiente Tumoral , Replicação Viral
12.
Subst Abuse Treat Prev Policy ; 18(1): 7, 2023 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-36683028

RESUMO

Tobacco Harm Reduction (THR) offers a promising approach to addressing the significant burden of smoking in Afghanistan. Over three million Afghans smoke daily, making it a leading cause of preventable deaths in the country. While the previous Afghan government implemented various tobacco cessation policies and strategies, these measures were only partially effective in reducing the number of smokers or smoking-related deaths. In 2021, community-based initiatives in Kabul and Herat started advocating for Tobacco Harm Reduction (THR) as a novel, realistic, and practical approach proven to promote smoking abstinence and minimize tobacco harm. However, implementing THR strategies in Afghanistan faces numerous challenges, including a lack of governmental support, funding issues, unfavorable market conditions, the high cost-effectiveness of THR products, and misconceptions about these products. To effectively promote THR in Afghanistan and overcome these challenges, it will be necessary to implement THR policies that support THR products for smokers, regulate the market for these products, produce them locally with healthcare professional oversight, conduct more engaging advocacy campaigns, and secure domestic sponsors.


Assuntos
Nicotiana , Abandono do Hábito de Fumar , Humanos , Fumantes , Redução do Dano , Afeganistão/epidemiologia
13.
Front Immunol ; 13: 1018962, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389779

RESUMO

Tumor-infiltrating lymphocytes (TILs), frontline soldiers of the adaptive immune system, are recruited into the tumor site to fight against tumors. However, their small number and reduced activity limit their ability to overcome the tumor. Enhancement of TILs number and activity against tumors has been of interest for a long time. A lack of knowledge about the tumor microenvironment (TME) has limited success in primary TIL therapies. Although the advent of engineered T cells has revolutionized the immunotherapy methods of hematologic cancers, the heterogeneity of solid tumors warrants the application of TILs with a wide range of specificity. Recent advances in understanding TME, immune exhaustion, and immune checkpoints have paved the way for TIL therapy regimens. Nowadays, TIL therapy has regained attention as a safe personalized immunotherapy, and currently, several clinical trials are evaluating the efficacy of TIL therapy in patients who have failed conventional immunotherapies. Gaining favorable outcomes following TIL therapy of patients with metastatic melanoma, cervical cancer, ovarian cancer, and breast cancer has raised hope in patients with refractory solid tumors, too. Nevertheless, TIL therapy procedures face several challenges, such as high cost, timely expansion, and technical challenges in selecting and activating the cells. Herein, we reviewed the recent advances in the TIL therapy of solid tumors and discussed the challenges and perspectives.


Assuntos
Melanoma , Neoplasias Ovarianas , Feminino , Humanos , Linfócitos do Interstício Tumoral , Imunoterapia , Linfócitos T/patologia , Microambiente Tumoral
14.
Int Immunopharmacol ; 113(Pt A): 109325, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36252475

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is cause of the novel coronavirus disease (COVID-19). In the last two years, SARS-CoV-2 has infected millions of people worldwide with different waves, resulting in the death of many individuals. The evidence disclosed that the host immune responses to SARS-CoV-2 play a pivotal role in COVID-19 pathogenesis and clinical manifestations. In addition to inducing antiviral immune responses, SARS-CoV-2 can also cause dysregulated inflammatory responses characterized by the noticeable release of proinflammatory mediators in COVID-19 patients. Among these proinflammatory mediators, chemokines are considered a subset of cytokines that participate in the chemotaxis process to recruit immune and non-immune cells to the site of inflammation and infection. Researchers have demonstrated that monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor (CCR2) are involved in the recruitment of monocytes and infiltration of these cells into the lungs of patients suffering from COVID-19. Moreover, elevated levels of CCL2 have been reported in the bronchoalveolar lavage fluid (BALF) obtained from patients with severe COVID-19, initiating cytokine storm and promoting CD163+ myeloid cells infiltration in the airways and further alveolar damage. Therefore, CCL2/CCR axis plays a key role in the immunopathogenesis of COVID-19 and targeted therapy of involved molecules in this axis can be a potential therapeutic approach for these patients. This review discusses the biology of the CCL2/CCR2 axis as well as the role of this axis in COVID-19 immunopathogenesis, along with therapeutic options aimed at inhibiting CCL2/CCR2 and modulating dysregulated inflammatory responses in patients with severe SARS-CoV-2 infection.


Assuntos
Tratamento Farmacológico da COVID-19 , Quimiocina CCL2 , Humanos , SARS-CoV-2 , Síndrome da Liberação de Citocina , Monócitos , Receptores CCR2
15.
Epigenomics ; 14(16): 965-986, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-36043685

RESUMO

Aging as an inevitable phenomenon is associated with pervasive changes in physiological functions. There is a relationship between aging and the increase of several chronic diseases. Most age-related disorders are accompanied by an underlying chronic inflammatory state, as demonstrated by local infiltration of inflammatory cells and greater levels of proinflammatory cytokines in the bloodstream. Within inflammaging, many epigenetic events, especially DNA methylation, change. During the aging process, due to aberrations of DNA methylation, biological processes are disrupted, leading to the emergence or progression of a variety of human diseases, including cancer, neurodegenerative disorders, cardiovascular disease and diabetes. The focus of this review is on DNA methylation, which is involved in inflammaging-related activities, and how its dysregulation leads to human disorders.


Aging as a natural process is associated with variation in physiological functions. One of the hallmarks of aging is epigenetic changes, which are directly involved in the aging process and aging-related diseases. DNA methylation is one of the epigenetic changes during aging. Consequently, changes in DNA methylation affect various cellular processes and cause age-related diseases. This review discusses the role of DNA methylation in aging processes and age-related diseases.


Assuntos
Metilação de DNA , Doenças Neurodegenerativas , Envelhecimento/genética , Citocinas/genética , Humanos , Inflamação/genética , Doenças Neurodegenerativas/genética
16.
J Chem Theory Comput ; 18(9): 5539-5558, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36001344

RESUMO

Molecular assembly processes are generally driven by thermodynamic properties in solutions. Atomistic modeling can be very helpful in designing and understanding complex systems, except that bulk solvent is very inefficient to treat explicitly as discrete molecules. In this work, we develop and assess two multiscale solvation models for computing solvation thermodynamic properties. The new SLIC/CDC model combines continuum solvent electrostatics based on the solvent layer interface condition (SLIC) with new statistical thermodynamic models for hydrogen bonding and nonpolar modes: cavity formation, dispersion interactions, combinatorial mixing (CDC). Given the structures of 500 solutes, the SLIC/CDC model predicts Gibbs energies of solvation in water with an average accuracy better than 1 kcal/mol, when compared to experimental measurements, and better than 0.8 kcal/mol, when compared to explicit-solvent molecular dynamics simulations. The individual SLIC/CDC energy mode values agree quantitatively with those computed from explicit-solvent molecular dynamics. The previously published SLIC/SASA multiscale model combines the SLIC continuum electrostatic model with the solvent-accessible surface area (SASA) nonpolar energy mode. With our new, improved parametrization method, the SLIC/SASA model now predicts Gibbs energies of solvation with better than 1.4 kcal/mol average accuracy in aqueous systems, compared to experimental and explicit-solvent molecular dynamics, and better than 1.6 kcal/mol average accuracy in ionic liquids, compared to explicit-solvent molecular dynamics. Both models predict solvation entropies, and are the first implicit-solvation models capable of predicting solvation heat capacities.


Assuntos
Líquidos Iônicos , Soluções , Solventes/química , Termodinâmica , Água/química
17.
Nutr Res ; 105: 33-52, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35797732

RESUMO

Various reports show the beneficial effect of naringenin on the development of cancer. We hypothesized that naringenin suppresses cancer cells by activating intrinsic and extrinsic apoptosis pathways. This systematic review and meta-analysis was performed to reveal the effect of naringenin on cancer inhibition in vitro and in vivo by altering apoptotic factors. Literature search was carried out using electronic databases including PubMed, Web of Science, Scopus, Google Scholar, and Embase up to February 2021. The heterogeneity test of the included studies was performed using the PRISMA checklist protocol and I2 statistic, respectively. Pooled standard mean difference and effect size (ES) with 95% confident interval (CI) were used to evaluate each relationship. A total of 32 articles were enrolled in our final analysis. Meta-analysis of the pooled findings for apoptosis, viability percentage, and apoptotic factors determined that treatment with naringenin affects viability and apoptosis in cancer cells in vitro and in vivo. Moreover, the results of in vitro experiments showed that naringenin increases the activity of caspase-3 (ES, 5.04; 95% CI, 2.61-7.47; I2 = 99.9), caspase-9 (ES, 2.99; 95% CI, 2.47-3.51; I2 = 93.7%), caspase-8 (ES, 2.86; 95% CI, 1.11-4.61; I2 = 99.7%), and Bax expression (ES, 2.73; 95% CI, 1.91-3.55; I2 = 99.4%) in cancer cells. It also increased the apoptotic rate and the activity of caspase-3 and caspase-9 in tumor-bearing animals. Overall, our findings highlight the potential therapeutic effects of naringenin in cancer inhibition through caspases cascade.


Assuntos
Apoptose , Neoplasias , Animais , Caspase 3 , Caspase 9 , Flavanonas , Neoplasias/tratamento farmacológico , Transdução de Sinais
18.
Inflamm Res ; 71(10-11): 1127-1142, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35804246

RESUMO

BACKGROUND/OBJECTIVE: Naringenin is a member of the flavonoid family that can perform many biological processes to treat a wide range of inflammatory diseases and pathological conditions related to oxidative stress (OS). Naringenin immunomodulatory activities have been the subject of recent research as an effective alternative treatment for autoimmune disorders. The effects of naringenin on the levels of inflammatory biomarkers and OS factors in animal models of autoimmune disorders (ADs) were studied in this meta-analysis. METHODS: Up until January 2022, electronic databases such as Cochrane Library and EMBASE, PubMed, Web of Science, and Scopus were used to conduct a comprehensive literature search in English language. To evaluate the effect of naringenin on inflammatory mediators, such as TNF-α, IL-6, IL-ß, IFN-γ, NF-κB, and nitric oxide, and OS biomarkers, such as CAT, SOD, GPx, GSH and MDA, in AD models, we measured the quality assessment and heterogeneity test using the PRISMA checklist protocol and I2 statistic, respectively. A random-effects model was employed based on the heterogeneity test, and then pooled data were standardized as mean difference (SMD) with a 95% confident interval (CI). RESULTS: We excluded all clinical trials, cell experiment studies, animal studies with different parameters, non-autoimmune disease models, and an inadequate series of studies for quantitative synthesis. Finally, from 627 potentially reports, 12 eligible studies were included in the meta-analysis. Data were collected from several groups. Of these, 153 were in the naringenin group and 149 were in the control group. Our meta-analysis of the pooled data for the parameters of inflammation and OS indicated that naringenin significantly reduced the levels of NF-κB (SMD - 3.77, 95% CI [- 6.03 to - 1.51]; I2 = 80.1%, p = 0.002), IFN-γ (SMD - 6.18, 95% CI [- 8.73 to - 3.62]; I2 = 53.7%, p = 0.115), and NO (SMD - 3.97, 95% CI [- 5.50 to - 2.45]; I2 = 73.4%, p = 0.005), IL-1ß (SMD - 4.23, 95% CI [- 5.09 to - 3.37]; I2 = 0.0%, p = 0.462), IL-6 (SMD - 5.84, 95% CI [- 7.83 to - 3.85]; I2 = 86.5%, p < 0.001), and TNF-α (SMD - 5.10, 95% CI [- 6.34 to - 3.86]; I2 = 74.7%, p < 0.001). These findings also demonstrated the efficacy of naringenin on increasing the levels of CAT (SMD 4.19, 95% CI [1.33 to 7.06]; I2 = 79.9%, p = 0.007), GSH (SMD 4.58, 95% CI [1.64 to 7.51]; I2 = 90.5%, p < 0.001), and GPx (SMD 9.65, 95% CI [2.56 to 16.74]; I2 = 86.6%, p = 0.001) and decreasing the levels of MDA (SMD - 3.65, 95% CI [- 4.80 to - 2.51]; I2 = 69.4%, p = 0.001) than control groups. However, treatment with naringenin showed no statistically difference in SOD activity (SMD 1.89, 95% CI [- 1.11 to 4.89]; I2 = 93.6%, p < 0.001). CONCLUSION: Overall, our findings revealed the immunomodulatory potential of naringenin as an alternative treatment on inhibition of inflammation and OS in several autoimmune-related diseases. Nevertheless, regarding the limitation of clinical trials, strong preclinical models and clinical settings in the future are needed that address the effects of naringenin on ADs. Before large-scale clinical studies, precise human pharmacokinetic investigations are required to determine the dosage ranges and evaluate the initial safety profile of naringenin.


Assuntos
Doenças Autoimunes , Flavanonas , Animais , Humanos , Doenças Autoimunes/tratamento farmacológico , Biomarcadores/metabolismo , Inflamação/tratamento farmacológico , Interleucina-6/metabolismo , NF-kappa B , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase , Fator de Necrose Tumoral alfa/metabolismo , Flavanonas/farmacologia
19.
Front Psychol ; 13: 810775, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35651557

RESUMO

Action research (AR) and reflective thinking (RT) can enhance learning since both processes provide students with the opportunities to step back and think about how they actually solve problems. While there is a robust academic inquiry on reflection practices and AR in the educational setting, investigating learners' reflections through AR practices can shed more light on related research. This study implemented reflective journal writing through AR and aimed to investigate (1) the participants' views about reflective journal writing, (2) the effects of journal writing on RT development, and (3) the learners' grammar use in writing. Eighty language learners formed the two experimental and control groups of the study. The possible relationship between the RT level and participants' final exam was checked. Analyses of the participants' journals, the semi-structured interview, the questionnaires' results, and the final exam scores were considered. The findings showed that the participants had positive views about journal writing, and they could enhance their level of RT as well as their grammar use in writing; nevertheless, no relationship between the RT level and final exam scores of the participants was found. The methodology and the results of the study could be conducive to welcoming alternative methods of teaching and assessment that encourage the learners' reflective practices and active engagements in language classes.

20.
Inflammopharmacology ; 30(4): 1259-1276, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35661071

RESUMO

BACKGROUND/OBJECTIVE: Apigenin is a member of the flavonoid family that can regulate various biological processes, which is characterized as a treatment of different inflammatory disorders and pathological problems associated with oxidative stress (OS). Recent research has focused on apigenin immunomodulatory properties as a potential treatment for different types of lung injuries. This meta-analysis was designed to determine the impact of apigenin treatment on inflammatory markers and OS parameters in animal models of lung injuries. METHODS: The comprehensive literature search was conducted using electronic databases such as Google Scholar, PubMed, Web of Science, Scopus, and Embase up to August 2021. To assess apigenin's effect on inflammatory mediators and OS biomarkers in lung injury animal models, we used the I2 statistic to determine the heterogeneity. We then pooled data as standardized mean difference (SMD) with a 95% confidence interval (CI). RESULTS: Our meta-analysis of the pooled data for inflammatory biomarkers demonstrated that the apigenin administration significantly decreased the NF-κB expression (SMD - 1.60, 95% CI [- 2.93 to - 0.26]; I2 = 89.0%, p < 0.001), IL-1ß (SMD - 4.30, 95% CI [- 6.24 to - 2.37]; I2 = 67.3%, p = 0.047), IL-6 (SMD - 4.10, 95% CI [- 5.04 to - 3.16]; I2 = 72.6%, p < 0.001), TNF-α (SMD - 3.74, 95% CI [- 4.67 to - 2.82]; I2 = 84.1%, p < 0.001), and TNF-α gene expression (SMD - 3.44, 95% CI [- 4.44 to - 2.43]; I2 = 0.0%, p = 0.622). This study also indicated the efficacy of apigenin in increasing the level of CAT (SMD 4.56, 95% CI [3.57 to 5.55]; I2 = 15.3%, p = 3.15), GSH (SMD 5.12, 95% CI [3.53 to 6.70]; I2 = 77.6%, p < 0.001), and SOD (SMD 3.45, 95% CI [2.50 to 4.40]; I2 = 79.2%, p < 0.001), and decreasing the level of MDA (SMD - 3.87, 95% CI [- 5.25 to - 2.49]; I2 = 80.3%, p < 0.001) and MPO (SMD - 4.02, 95% CI [- 5.64 to - 2.40]; I2 = 88.9%, p < 0.001), TGF- ß (SMD - 3.81, 95% CI [- 4.91 to - 2.70]; I2 = 73.4%, p = 0.001) and W/D level (SMD - 3.22, 95% CI [- 4.47 to - 1.97]; I2 = 82.1%, p < 0.001) than control groups. CONCLUSION: Overall, our findings showed the immunomodulatory potential of apigenin as an alternative treatment for the suppression of inflammatory responses and OS in different types of lung injury diseases. Nevertheless, due to the paucity of clinical studies, reliable preclinical models, and clinical settings, evaluating the influence of apigenin on lung injury is required in the future. Before conducting large-scale clinical trials, detailed human pharmacokinetic studies are also needed to establish dosage ranges and determine the initial safety and tolerability of apigenin.


Assuntos
Apigenina , Lesão Pulmonar , Animais , Apigenina/farmacologia , Apigenina/uso terapêutico , Biomarcadores/metabolismo , Humanos , Lesão Pulmonar/tratamento farmacológico , Estresse Oxidativo , Fator de Necrose Tumoral alfa/metabolismo
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