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1.
Heliyon ; 10(10): e31286, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38803860

RESUMEN

Bladder carcinoma (BLCA) is a widespread urological malignancy causing significant global mortality, often hindered by delayed diagnosis and limited treatments. BLCA frequently exhibits TP53 mutations, playing a pivotal role in its pathogenesis and underscoring the potential of targeting TP53 as a therapeutic approach for this prevalent urological malignancy. Tumor tissues from 50 bladder cancer patients were used for mutational analysis in TP53's mutation-rich exons (5, 7, & 8). The gene expression of the TP53 gene, along with a TP53-target gene B-cell translocation gene 2 (BTG2) was also assessed in the cDNA samples from the same BLCA tissues and 15 urine controls of healthy people. The analysis revealed 22 % of patients with somatic hotspot mutations, 18 % with pathogenic missense mutations, and 12 % with intronic variants. Patients with somatic mutations exhibited the worst prognosis, supported by survival analysis from The Cancer Genome Atlas (TCGA) BLCA data. Interestingly, H296Y missense mutation correlated with higher TP53 expression and improved survival, while intronic SNPs were linked to worse outcomes. Additionally, upregulated BTG2 expression in mutated patients was observed which was correlated with poor prognosis, emphasizing the role of TP53 mutations in bladder cancer progression. The multivariate analysis highlighted the predictive power of TP53 mutations, with a high frequency of high-grade tumors (78.57 %) in mutated patients, underscoring their role in cancer progression. In conclusion, this study emphasizes the crucial role of TP53 mutations in bladder cancer patients from Bangladesh.

2.
Biochem Biophys Rep ; 38: 101703, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38596408

RESUMEN

The urea transporter UT-B1, encoded by the SLC14A1 gene, has been hypothesized to be a significant protein whose deficiency and dysfunction contribute to the pathogenesis of bladder cancer and many other diseases. Several studies reported the association of genetic alterations in the SLC14A1 (UT-B1) gene with bladder carcinogenesis, suggesting a need for thorough characterization of the UT-B1 protein's coding and non-coding variants. This study used various computational techniques to investigate the commonly occurring germ-line missense and non-coding SNPs (ncSNPs) of the SLC14A1 gene (UT-B1) for their structural, functional, and molecular implications for disease susceptibility and dysfunctionality. SLC14A1 missense variants, primarily identified from the ENSEMBL genome browser, were screened through twelve functionality prediction tools leading to two variants D280Y (predicted detrimental by maximum tools) and D280N (high global MAF) for rs1058396. Subsequently, the ConSurf and NetSurf tools revealed the D280 residue to be in a variable site and exposed on the protein surface. According to I-Mutant2.0 and MUpro, both variants are predicted to cause a significant effect on protein stability. Analysis of molecular docking anticipated these two variants to decrease the binding affinity of UT-B1 protein for the examined ligands to a significant extent. Molecular dynamics also disclosed the possible destabilization of the UT-B1 protein due to single nucleotide polymorphism compared to wild-type protein which may result in impaired protein function. Furthermore, several non-coding SNPs were estimated to affect transcription factor binding and regulation of SLC14A1 gene expression. Additionally, two ncSNPs were found to affect miRNA-based post-transcriptional regulation by creating new seed regions for miRNA binding. This comprehensive in-silico study of SLC14A1 gene variants may serve as a springboard for future large-scale investigations examining SLC14A1 polymorphisms.

3.
Cureus ; 16(3): e56319, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38629022

RESUMEN

The liver, which presents as a focal point for tuberculosis in pediatric cases, is rarely encountered, and reported instances are scarce. This atypical manifestation underscores the management of tuberculosis affecting this particular organ in the context of pediatric patients. The treatment of solitary tubercular liver abscesses in children necessitates a collaborative approach, engaging pediatricians, infectious disease specialists, and interventional radiologists. It also needs awareness among physicians to explore and treat early and to complete further assessments for a better outcome. In our instance, investigating the cause of fever led us to diagnose a tubercular liver abscess in a previously healthy 10-year-old male. The substantiation of this diagnosis was accomplished through a meticulous liver biopsy, wherein immunohistochemistry was employed to detect tubercular pathogens. Following the confirmation of the diagnosis, the initiation of a targeted therapeutic regimen resulted in the subsequent resolution of the fever.

4.
PLoS One ; 19(1): e0296361, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38165846

RESUMEN

Genome-wide association studies (GWAS) identified a coding single nucleotide polymorphism, MYNN rs10936599, at chromosome 3q. MYNN gene encodes myoneurin protein, which has been associated with several cancer pathogenesis and disease development processes. However, there needed to be a more detailed characterization of this polymorphism's (and other coding and non-coding polymorphisms) structural, functional, and molecular impact. The current study addressed this gap and analyzed different properties of rs10936599 and non-coding SNPs of MYNN via a thorough computational method. The variant, rs10936599, was predicted functionally deleterious by nine functionality prediction approaches, like SIFT, PolyPhen-2, and REVEL, etc. Following that, structural modifications were estimated through the HOPE server and Mutation3D. Moreover, the mutation was found in a conserved and active residue, according to ConSurf and CPORT. Further, the secondary structures were predicted, followed by tertiary structures, and there was a significant deviation between the native and variant models. Similarly, molecular simulation also showed considerable differences in the dynamic pattern of the wildtype and mutant structures. Molecular docking revealed that the variant binds with better docking scores with ligand NOTCH2. In addition to that, non-coding SNPs located at the MYNN locus were retrieved from the ENSEMBL database. These were found to disrupt the transcription factor binding regulatory regions; nonetheless, only two affect miRNA target sites. Again, eight non-coding variants were detected in the testes with normalized expression, whereas HaploReg v4.1 unveiled annotations for non-coding variants. In summary, in silico comprehensive characterization of coding and non-coding single nucleotide polymorphisms of MYNN gene will assist researchers to work on MYNN gene and establish their association with certain types of cancers.


Asunto(s)
Proteínas de Unión al ADN , Polimorfismo de Nucleótido Simple , Factores de Transcripción , Estudio de Asociación del Genoma Completo , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Mutación , Humanos , Proteínas de Unión al ADN/genética , Factores de Transcripción/genética
5.
Sci Rep ; 14(1): 368, 2024 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172584

RESUMEN

Being a frequent malignant tumor of the genitourinary system, Bladder Urothelial Carcinoma (BLCA) has a poor prognosis. This study focused on identifying and validating prognostic biomarkers utilizing methylation, transcriptomics, and clinical data from The Cancer Genome Atlas Bladder Urothelial Carcinoma (TCGA BLCA) cohort. The impact of altered differentially methylated hallmark pathway genes was subjected to clustering analysis to observe changes in the transcriptional landscape on BLCA patients and identify two subtypes of patients from the TCGA BLCA population where Subtype 2 was associated with the worst prognosis with a p-value of 0.00032. Differential expression and enrichment analysis showed that subtype 2 was enriched in immune-responsive and cancer-progressive pathways, whereas subtype 1 was enriched in biosynthetic pathways. Following, regression and network analyses revealed Epidermal Growth Factor Receptor (EGFR), Fos-related antigen 1 (FOSL1), Nuclear Factor Erythroid 2 (NFE2), ADP-ribosylation factor-like protein 4D (ARL4D), SH3 domain containing ring finger 2 (SH3RF2), and Cadherin 3 (CDH3) genes to be the most significant prognostic gene markers. These genes were used to construct a risk model that separated the BLCA patients into high and low-risk groups. The risk model was also validated in an external dataset by performing survival analysis between high and low-risk groups with a p-value < 0.001 and the result showed the high group was significantly associated with poor prognosis compared to the low group. Single-cell analyses revealed the elevated level of these genes in the tumor microenvironment and associated with immune response. High-grade patients also tend to have a high expression of these genes compared to low-grade patients. In conclusion, this research developed a six-gene signature that is pertinent to the prediction of overall survival (OS) and might contribute to the advancement of precision medicine in the management of bladder cancer.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Pronóstico , Perfilación de la Expresión Génica , Metilación , Microambiente Tumoral , Proteínas Portadoras , Proteínas Oncogénicas
6.
BMC Psychiatry ; 23(1): 884, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-38017407

RESUMEN

BACKGROUND: Local humanitarian workers in low and middle-income countries must often contend with potentially morally injurious situations, often with limited resources. This creates barriers to providing sustainable mental health and psychosocial support (MHPSS) to displaced individuals. Clinical supervision is an often neglected part of ensuring high-quality, sustainable care. The Caring for Carers (C4C) project aims to test the effectiveness and acceptability of online group-based supportive supervision on the well-being of MHPSS practitioners, as well as service-user-reported service satisfaction and quality when working with displaced communities in Türkiye, Syria, and Bangladesh. This protocol paper describes the aim, design, and methodology of the C4C project. METHOD: A quasi-experimental, mixed-method, community-based participatory research study will be conducted to test the effectiveness of online group-based supportive clinical supervision provided to 50 Syrian and 50 Bangladeshi MHPSS practitioners working with Syrian and Rohingya displaced communities. Monthly data will be collected from the practitioners and their beneficiaries during the active control (six months) and supervision period (16 months over two terms). Outcomes are psychological distress (Kessler-6), burnout (the Copenhagen Burnout Inventory), compassion fatigue, compassion satisfaction, and secondary traumatic stress (Professional Quality of Life Scale), perceived injustice, clinical self-efficacy (Counseling Activity Self-Efficacy Scale), service satisfaction, and quality (Client Satisfaction Questionnaire and an 18-item measure developed in this project). A realist evaluation framework will be used to elucidate the contextual factors, mechanisms, and outcomes of the supervision intervention. DISCUSSION: There is a scarcity of evidence on the role of clinical supervision in improving the well-being of MHPSS practitioners and the quality of service they provide to displaced people. By combining qualitative and quantitative data collection, the C4C project will address the long-standing question of the effectiveness and acceptability of clinical supervision in humanitarian settings.


Asunto(s)
Agotamiento Profesional , Desgaste por Empatía , Humanos , Salud Mental , Cuidadores , Calidad de Vida , Agotamiento Profesional/prevención & control , Agotamiento Profesional/psicología
7.
Glob Ment Health (Camb) ; 10: e59, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37854431

RESUMEN

Background: Mental illness stigma is universally prevalent and a significant barrier to achieving global mental health goals. Mental illness stigma in Bangladesh has gained little attention despite its widespread impact on seeking mental health care in rural and urban areas. This study aimed to investigate mental illness stigma and the associated factors in rural and urban areas of Bangladesh. Methods: The study areas were divided into several clusters from which 325 participants (≥18 years) were recruited with systematic random sampling. The Bangla version of the Days' Mental Illness Stigma Scale was used to collect data. Independent-samples t-test, ANOVA, and multiple regression were performed. Results: Results suggest that gender, age, geographical location, socioeconomic status, and occupation significantly differed across subscales of stigma. Age, gender, seeking treatment of mental illness, having knowledge on mental health, and socioeconomic status were predictive factors of mental illness stigma. The results also showed a high treatment gap in both rural and urban areas. Conclusion: This study supports that mental illness stigma is prevalent in Bangladesh, requiring coordinated efforts. Results can inform the development of contextually tailored mental health strategies to reduce stigma and contribute to the promotion of mental health of individuals and communities across Bangladesh.

8.
BMC Psychol ; 11(1): 216, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37525224

RESUMEN

BACKGROUND: Mental illnesses stigma is a universal and transcultural phenomenon. While mental illnesses stigma is pervasive in Bangladesh, very little research exists on stigma toward mental illnesses among indigenous communities. This study aimed to investigate the prevailing stigma and the risk factors among different indigenous communities in the Chattogram Hill Tracts (CHT) in Bangladesh. METHODS: A cross-sectional survey was carried out and participants were recruited purposively from Rangamati, a South-Eastern district of Bangladesh in the CHT. Participants from various indigenous communities including Chakma, Marma, Rakhine, Tripura, and Pangkhua were recruited. The 28- item Bangla translated version of the Mental Illnesses Stigma Scale was used. Independent-samples t-test, ANOVA, and multiple regression were performed. RESULTS: The results indicate evidence of a gender difference with females reporting more stigma than their male counterparts. Age, gender, socioeconomic status, and monthly income are associated with stigma among indigenous people. Further analyses of the subscales indicated significant differences among sociodemographic variables. CONCLUSIONS: The results provide an insight into the prevailing stigma and associate risk factors among indigenous communities. The results may help inform anti-stigma interventions targeting indigenous communities in Bangladesh.


Asunto(s)
Trastornos Mentales , Femenino , Humanos , Masculino , Estudios Transversales , Bangladesh , Estigma Social , Renta
9.
Front Genet ; 14: 955631, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36959829

RESUMEN

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., "Critical-Exon Genes (CEGs)"] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package. Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients' pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability. Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients.

10.
Heliyon ; 9(1): e12776, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36632115

RESUMEN

Background: Breastfeeding requires additional diversified foods for the nutritional requirements of mothers and children, especially in preventing micronutrient deficiencies. The minimum dietary diversity for women (MDD-W) is a proxy indicator of micronutrient adequacy for women. Objectives: This study aimed to identify the determinants associated with MDD in lactating women. Methods: A community-based cross-sectional study was conducted among lactating mothers having at least one live birth in last three years from two districts of Bangladesh between 31st May 2021 and 9th June 2021. Dietary and socio-demographic information was obtained using a single 24-h recall and socio-economic status questionnaires. MDD was defined as at least four food groups consumed in the last 24 hours. In binary logistic regression, adjusted models were used to assess the relationship between MDD and socio-economic factors. Results: The mean Dietary Diversity Score (DDS) was 3.9 ± 1.2. The MDD was met by 29.7% of women. Respondent's ages 20-24 years [Adjusted Odds Ratio (AOR) = 0.5; 95% CI: 0.3-0.9], 25-34 years [AOR = 0.5; 95% CI: 0.3-0.8], and 35-49 years [AOR = 0.5; 95% CI: 0.2-0.9], husband's academic qualifications more than 12 years [AOR = 1.9; 95% CI: 1.0-3.7], family income more than 15000 BDT per month [AOR = 2.3; 95% CI: 1.2-4.3], and husband's profession as a day labor [AOR = 0.5; 95% CI: 0.3-0.7] were significant factors to have MDD. Conclusions: DDS and MDD were very poor among the mothers, whereas women's age, husband's education, and the family's monthly income were independent determinants of MDD. Special interventions may be needed to improve MDD.

11.
Cell Rep ; 40(10): 111309, 2022 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-36070693

RESUMEN

Dysfunctional dopamine signaling is implicated in various neuropsychological disorders. Previously, we reported that dopamine increases D1 receptor (D1R)-expressing medium spiny neuron (MSN) excitability and firing rates in the nucleus accumbens (NAc) via the PKA/Rap1/ERK pathway to promote reward behavior. Here, the results show that the D1R agonist, SKF81297, inhibits KCNQ-mediated currents and increases D1R-MSN firing rates in murine NAc slices, which is abolished by ERK inhibition. In vitro ERK phosphorylates KCNQ2 at Ser414 and Ser476; in vivo, KCNQ2 is phosphorylated downstream of dopamine signaling in NAc slices. Conditional deletion of Kcnq2 in D1R-MSNs reduces the inhibitory effect of SKF81297 on KCNQ channel activity, while enhancing neuronal excitability and cocaine-induced reward behavior. These effects are restored by wild-type, but not phospho-deficient KCNQ2. Hence, D1R-ERK signaling controls MSN excitability via KCNQ2 phosphorylation to regulate reward behavior, making KCNQ2 a potential therapeutical target for psychiatric diseases with a dysfunctional reward circuit.


Asunto(s)
Dopamina , Canal de Potasio KCNQ2 , Trastornos Mentales , Proteínas del Tejido Nervioso , Animales , Dopamina/metabolismo , Canal de Potasio KCNQ2/metabolismo , Trastornos Mentales/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Fosforilación , Receptores de Dopamina D1/metabolismo , Recompensa
13.
Mol Psychiatry ; 27(8): 3479-3492, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35665767

RESUMEN

Acetylcholine is a neuromodulator critical for learning and memory. The cholinesterase inhibitor donepezil increases brain acetylcholine levels and improves Alzheimer's disease (AD)-associated learning disabilities. Acetylcholine activates striatal/nucleus accumbens dopamine receptor D2-expressing medium spiny neurons (D2R-MSNs), which regulate aversive learning through muscarinic receptor M1 (M1R). However, how acetylcholine stimulates learning beyond M1Rs remains unresolved. Here, we found that acetylcholine stimulated protein kinase C (PKC) in mouse striatal/nucleus accumbens. Our original kinase-oriented phosphoproteomic analysis revealed 116 PKC substrate candidates, including Rac1 activator ß-PIX. Acetylcholine induced ß-PIX phosphorylation and activation, thereby stimulating Rac1 effector p21-activated kinase (PAK). Aversive stimulus activated the M1R-PKC-PAK pathway in mouse D2R-MSNs. D2R-MSN-specific expression of PAK mutants by the Cre-Flex system regulated dendritic spine structural plasticity and aversive learning. Donepezil induced PAK activation in both accumbal D2R-MSNs and in the CA1 region of the hippocampus and enhanced D2R-MSN-mediated aversive learning. These findings demonstrate that acetylcholine stimulates M1R-PKC-ß-PIX-Rac1-PAK signaling in D2R-MSNs for aversive learning and imply the cascade's therapeutic potential for AD as aversive learning is used to preliminarily screen AD drugs.


Asunto(s)
Acetilcolina , Quinasas p21 Activadas , Animales , Ratones , Proteína Quinasa C , Donepezilo/farmacología , Encéfalo
14.
BMC Psychiatry ; 22(1): 201, 2022 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-35303810

RESUMEN

BACKGROUND: Adequate good quality of sleep is essential for physical fitness during pregnancy as well as being a depressive symptoms-free mind. However, there is little evidence of the relationship between depressive symptoms and poor sleep quality among pregnant women in Bangladesh. This study aimed to find the association between depressive symptoms and poor sleep quality among pregnant women in northern rural Bangladesh. METHODS: A community-based cross-sectional study was carried out from May 2021 to June 2021 among 481 pregnant women tested positive in the pregnancy test of Jaldhaka and Dimla Upazila of Nilphamari district, Rangpur Division. Data were collected with a structured questionnaire including socio-demographic conditions, sleep quality, and depressive symptoms, comprising the Pittsburgh Sleep Quality Index (PSQI) and the Patient Health Questionnaire- 9 (PHQ-9). RESULTS: 8.94% of the women had depressive symptoms, whereas 38.88% of the participants were bad sleepers. However, women who had depressive symptoms [Adjusted odds ratio (AOR) = 2.55; 95% CI 1.33-4.9] and educational qualifications above 10 years [AOR = 0.60; 95% CI: 0.39-0.92] were associated with poor sleep quality. CONCLUSIONS: A higher percentage of pregnant women had poor sleep quality, whereas depressive symptoms and academic background of the participants were significantly associated with poor sleep quality. Ensuring adequate sleep time and better quality could be helpful to prevent depressive symptoms.


Asunto(s)
Mujeres Embarazadas , Trastornos del Inicio y del Mantenimiento del Sueño , Bangladesh/epidemiología , Estudios Transversales , Depresión/complicaciones , Depresión/epidemiología , Femenino , Humanos , Embarazo , Sueño , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Calidad del Sueño
15.
Chem Rec ; 22(7): e202100319, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35189015

RESUMEN

Recently, nanostructured carbon-based soft bioelectronics and biosensors have received tremendous attention due to their outstanding physical and chemical properties. The ultrahigh specific surface area, high flexibility, lightweight, high electrical conductivity, and biocompatibility of 1D and 2D nanocarbons, such as carbon nanotubes (CNT) and graphene, are advantageous for bioelectronics applications. These materials improve human life by delivering therapeutic advancements in gene, tumor, chemo, photothermal, immune, radio, and precision therapies. They are also utilized in biosensing platforms, including optical and electrochemical biosensors to detect cholesterol, glucose, pathogenic bacteria (e. g., coronavirus), and avian leucosis virus. This review summarizes the most recent advancements in bioelectronics and biosensors by exploiting the outstanding characteristics of nanocarbon materials. The synthesis and biocompatibility of nanocarbon materials are briefly discussed. In the following sections, applications of graphene and CNTs for different therapies and biosensing are elaborated. Finally, the key challenges and future perspectives of nanocarbon materials for biomedical applications are highlighted.


Asunto(s)
Técnicas Biosensibles , Grafito , Nanoestructuras , Nanotubos de Carbono , Grafito/química , Humanos , Nanoestructuras/química , Nanotubos de Carbono/química
16.
Int J Mol Sci ; 24(1)2022 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-36613848

RESUMEN

The N-methyl-D-aspartate receptor (NMDAR)-mediated structural plasticity of dendritic spines plays an important role in synaptic transmission in the brain during learning and memory formation. The Rho family of small GTPase RhoA and its downstream effector Rho-kinase/ROCK are considered as one of the major regulators of synaptic plasticity and dendritic spine formation, including long-term potentiation (LTP). However, the mechanism by which Rho-kinase regulates synaptic plasticity is not yet fully understood. Here, we found that Rho-kinase directly phosphorylated discs large MAGUK scaffold protein 2 (DLG2/PSD-93), a major postsynaptic scaffold protein that connects postsynaptic proteins with NMDARs; an ionotropic glutamate receptor, which plays a critical role in synaptic plasticity. Stimulation of striatal slices with an NMDAR agonist induced Rho-kinase-mediated phosphorylation of PSD-93 at Thr612. We also identified PSD-93-interacting proteins, including DLG4 (PSD-95), NMDARs, synaptic Ras GTPase-activating protein 1 (SynGAP1), ADAM metallopeptidase domain 22 (ADAM22), and leucine-rich glioma-inactivated 1 (LGI1), by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among them, Rho-kinase increased the binding of PSD-93 to PSD-95 and NMDARs. Furthermore, we found that chemical-LTP induced by glycine, which activates NMDARs, increased PSD-93 phosphorylation at Thr612, spine size, and PSD-93 colocalization with PSD-95, while these events were blocked by pretreatment with a Rho-kinase inhibitor. These results indicate that Rho-kinase phosphorylates PSD-93 downstream of NMDARs, and suggest that Rho-kinase mediated phosphorylation of PSD-93 increases the association with PSD-95 and NMDARs to regulate structural synaptic plasticity.


Asunto(s)
Receptores de N-Metil-D-Aspartato , Quinasas Asociadas a rho , Quinasas Asociadas a rho/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Cromatografía Liquida , Espectrometría de Masas en Tándem , Plasticidad Neuronal/fisiología , Transmisión Sináptica/fisiología , Homólogo 4 de la Proteína Discs Large/metabolismo , Sinapsis/metabolismo , Hipocampo/metabolismo
17.
J Neurochem ; 160(3): 325-341, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34878647

RESUMEN

The nucleus accumbens (NAc) plays critical roles in emotional behaviors, including aversive learning. Aversive stimuli such as an electric foot shock increase acetylcholine (ACh) in the NAc, and muscarinic signaling appears to increase neuronal excitability and aversive learning. Muscarinic signaling inhibits the voltage-dependent potassium KCNQ current which regulates neuronal excitability, but the regulatory mechanism has not been fully elucidated. Phosphorylation of KCNQ2 at threonine 217 (T217) and its inhibitory effect on channel activity were predicted. However, whether and how muscarinic signaling phosphorylates KCNQ2 in vivo remains unclear. Here, we found that PKC directly phosphorylated KCNQ2 at T217 in vitro. Carbachol and a muscarinic M1 receptor (M1R) agonist facilitated KCNQ2 phosphorylation at T217 in NAc/striatum slices in a PKC-dependent manner. Systemic administration of the cholinesterase inhibitor donepezil, which is commonly used to treat dementia, and electric foot shock to mice induced the phosphorylation of KCNQ2 at T217 in the NAc, whereas phosphorylation was suppressed by an M1R antagonist. Conditional deletion of Kcnq2 in the NAc enhanced electric foot shock induced aversive learning. Our findings indicate that muscarinic signaling induces the phosphorylation of KCNQ2 at T217 via PKC activation for aversive learning.


Asunto(s)
Reacción de Prevención/fisiología , Canal de Potasio KCNQ2/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Núcleo Accumbens/metabolismo , Sistema Nervioso Parasimpático/fisiología , Proteína Quinasa C/metabolismo , Receptores Muscarínicos/fisiología , Animales , Carbacol/farmacología , Inhibidores de la Colinesterasa/farmacología , Donepezilo/farmacología , Canal de Potasio KCNQ2/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Agonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/farmacología , Proteínas del Tejido Nervioso/genética , Fosforilación , Receptor Muscarínico M2/efectos de los fármacos
18.
Glob Chall ; 5(9): 2100002, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34504715

RESUMEN

This study investigates the efficacy of chemically modified bone adhesive as a formaldehyde-free binder for wood-based industries. Two different types of adhesive are formulated after chemical modification of bone powder using sulfuric acid (0.5 m) and polyvinyl acetate (PVA). Gel time, solid content, Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), viscosity, and single lap joint test for shear strength are analyzed in order to assess the adhesive properties. To analyze the efficacy of the formulated adhesive, particleboards are fabricated using boiled and unboiled sugarcane bagasse. The physical and mechanical properties of the fabricated panels are measured following ASTM standards. It is found that adhesive Type C (T-C) has the shortest gel time of 4.2 min for the highest shear strength, i.e., 5.31 MPa. The particleboard (BTC-2) fabricated using T-C adhesive shows a highest density of 0.73 g cm-3, a modulus of elasticity (MOE) of 1975 N mm-2, and a modulus of rupture (MOR) of 11.80 N mm-2. The dimensional stability of the fabricated particleboards does not follow the standard requirements; however, further study might be helpful for using the chemically modified bone adhesive as a biobased adhesive.

19.
Artículo en Inglés | MEDLINE | ID: mdl-34527262

RESUMEN

BACKGROUND: The mental health status of indigenous people in Bangladesh has attracted little or no attention. The objective of the present study is to determine the extent of symptoms of anxiety and depression in the two largest indigenous communities in Bangladesh. METHODS: In total, 240 participants were recruited, 120 from each of the Marma and Chakma communities with an overall mean age of 44.09 years (s.d. 15.73). Marma people were older (mean ages 48.92 v. 39.25, p < 0.001). Participants completed the Anxiety Scale (AS) and Depression Scale (DS) that have been developed and standardised in Bangladesh in the Bangla (Bengali) language. RESULTS: Results indicated that anxiety and depression scores were elevated in both communities, 59.2% of the participants scoring above the cut-off for clinical significance on AS and 58.8% of the participants scoring above the cut-off for clinical significance on DS. Marma people compared to Chakma people were more anxious (M = 59.49 v. 43.00, p < 0.001) and more depressed (M = 106.78 v. 82.30, p < 0.001). The demographic variables of age, sex and socioeconomic status were weakly or inconsistently related to scores. In the Marma people, females scored higher on both AS and DS, but in the Chakma community, males scored higher on AS and the same on DS. CONCLUSION: The finding of significant anxiety and depression in communities with such limited mental health services is a matter of concern and emphasises the need to formulate and implement appropriate mental health policies for indigenous people in Bangladesh and other parts of the world.

20.
Artículo en Inglés | MEDLINE | ID: mdl-34367649

RESUMEN

BACKGROUND: Subjective wellbeing in terms of objective outcome can be useful to determine the level of progress in clinical practice as well as research studies in Bangladesh. Besides, cultural understanding of well-being for Bangladeshi population is also equally important to report. A valid Bangla version of the five-item WHO Well-being Index can be a suitable measure to achieve the purposes. Therefore, the present study aimed at validating the WHO-5 Well-being Index for general population in Bangladesh. METHODS: After following the standard procedures for translation, back-translation, and committee translation, the initial Bangla version of the scale was developed and pretested. Based on the feedback during pretesting, a slight modification was made and the final version was developed. This final version was administered to 269 participants of different socioeconomic backgrounds to find out the reliability and validity of the scale from March 2019 to May 2019. The data analysis was conducted using SPSS 24. RESULTS: The scale demonstrated acceptable internal consistency (α = 0.754) and test-retest reliability (r = 0.713), divergent validity (r = -0.443, p < 0.01 with the Bangla version of Perceived Stress Scale-10) and convergent validity (r = 0.542, p < 0.01 with the Bangla version of Warwick-Edinburgh Mental Well-Being Scale). The data also yielded one-factor structure for the scale in exploratory factor analysis explaining 38.68% of total variance. The factor-structure was further supported in the confirmatory factor analysis (χ2 = 295.852, χ2/df = 2.017, RMSEA = 0.062, CFI = 0.986, TLI = 0.964, and SRMR = 0.0255). CONCLUSION: The findings suggested the Bangla version of the WHO-5 Well-being Index is a psychometrically valid and reliable tool for general adult population in Bangladeshi when it comes to measuring subjective well-being both in clinical practice and research studies.

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