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1.
Mol Psychiatry ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734844

RESUMO

A hallmark of fetal alcohol spectrum disorders (FASD) is neurobehavioral deficits that still do not have effective treatment. Here, we present that reduction of Apolipoprotein E (APOE) is critically involved in neurobehavioral deficits in FASD. We show that prenatal alcohol exposure (PAE) changes chromatin accessibility of Apoe locus, and causes reduction of APOE levels in both the brain and peripheral blood in postnatal mice. Of note, postnatal administration of an APOE receptor agonist (APOE-RA) mitigates motor learning deficits and anxiety in those mice. Several molecular and electrophysiological properties essential for learning, which are altered by PAE, are restored by APOE-RA. Our human genome-wide association study further reveals that the interaction of PAE and a single nucleotide polymorphism in the APOE enhancer which chromatin is closed by PAE in mice is associated with lower scores in the delayed matching-to-sample task in children. APOE in the plasma is also reduced in PAE children, and the reduced level is associated with their lower cognitive performance. These findings suggest that controlling the APOE level can serve as an effective treatment for neurobehavioral deficits in FASD.

2.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33443207

RESUMO

The developing brain is under the risk of exposure to a multitude of environmental stressors. While perinatal exposure to excessive levels of environmental stress is responsible for a wide spectrum of neurological and psychiatric conditions, the developing brain is equipped with intrinsic cell protection, the mechanisms of which remain unknown. Here we show, using neonatal mouse as a model system, that primary cilia, hair-like protrusions from the neuronal cell body, play an essential role in protecting immature neurons from the negative impacts of exposure to environmental stress. More specifically, we found that primary cilia prevent the degeneration of dendritic arbors upon exposure to alcohol and ketamine, two major cell stressors, by activating cilia-localized insulin-like growth factor 1 receptor and downstream Akt signaling. We also found that activation of this pathway inhibits Caspase-3 activation and caspase-mediated cleavage/fragmentation of cytoskeletal proteins in stress-exposed neurons. These results indicate that primary cilia play an integral role in mitigating adverse impacts of environmental stressors such as drugs on perinatal brain development.


Assuntos
Cílios/metabolismo , Células-Tronco Neurais/metabolismo , Prosencéfalo/embriologia , Animais , Animais Recém-Nascidos/metabolismo , Encéfalo/metabolismo , Dendritos/metabolismo , Feminino , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos/embriologia , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Prosencéfalo/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
3.
Arch Pharm (Weinheim) ; 357(1): e2300340, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37880869

RESUMO

Drug repurposing is an emerging field in drug development that has provided many successful drugs. In the current study, paracetamol, a known antipyretic and analgesic agent, was chemically modified to generate paracetamol derivatives as anticancer and anticyclooxygenase-2 (COX-2) agents. Compound 11 bearing a fluoro group was the best cytotoxic candidate with half-maximal inhibitory concentration (IC50 ) values ranging from 1.51 to 6.31 µM and anti-COX-2 activity with IC50 = 0.29 µM, compared to the standard drugs, doxorubicin and celecoxib. The cell cycle and apoptosis studies revealed that compound 11 possesses the ability to induce cell cycle arrest in the S phase and apoptosis in colon Huh-7 cells. These results were strongly supported by docking studies, which showed strong interactions with the amino acids of the COX-2 protein, and in silico pharmacokinetic predictions were found to be favorable for these newly synthesized paracetamol derivatives. It can be concluded that compound 11 could block cell growth and proliferation by inhibiting the COX-2 enzyme in cancer therapy.


Assuntos
Antineoplásicos , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/química , Acetaminofen/farmacologia , Relação Estrutura-Atividade , Ciclo-Oxigenase 2/metabolismo , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/química , Proliferação de Células , Simulação de Acoplamento Molecular , Estrutura Molecular
4.
BMC Med Educ ; 24(1): 737, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982353

RESUMO

BACKGROUND: The importance of including bioethics in the medical curricula has been recognized globally. Certain countries including Pakistan continue to lag behind although some developments have occurred recently. OBJECTIVES: The research aimed to provide a snapshot of bioethics education in undergraduate medical colleges in Karachi, Pakistan. The secondary objectives included identifying factors promoting or inhibiting integration of bioethics into the curriculum. METHODS: A two-pronged strategy was used to collect data including a website review of medical colleges, in existence for more than ten years, recognized by the Pakistan Medical and Dental Council (PMDC), the regulating body for undergraduate medical education in Pakistan. The other arm employed in-depth interviews with medical educationists in colleges fulfilling inclusion criteria. Data from the website was analyzed and presented as frequencies. Qualitative data was analyzed using content analysis method which involved coding of transcripts, multiple readings and arriving at subthemes and themes iteratively. RESULTS: Thirteen medical colleges were included for the website review, of which four were from public sector. Three medical colleges used the word "ethics" in their vision and mission statement and four had provided a detailed curriculum for ethics on their website. Thematic framework included four broad themes: 1) Need for Bioethics Education, 2) Current Status of Bioethics Education 3) Challenges in integration of bioethics in medical curriculum and 4) Recommendations for integration of bioethics in the Curriculum. Participants were in agreement that bioethics was important in development of future physicians. Participants identified various challenges, foremost being shortage of trained faculty, lack of institutional buy-in and overcrowded curriculum. CONCLUSION: The study identified sporadic inclusion of bioethics in undergraduate medical curricula, left to the discretion of individual institutions. Since Karachi is a cosmopolitan city, the findings may reasonably reflect the situation in other parts of the country. While bioethics is recognized as an important field, it will continue to remain an orphan subject in the curricula unless the regulatory and accreditation bodies make it compulsory for institutions to include ethics in their curricula.


Assuntos
Bioética , Currículo , Educação de Graduação em Medicina , Paquistão , Humanos , Bioética/educação , Pesquisa Qualitativa
5.
Proteomics ; 22(22): e2200148, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36066285

RESUMO

Entamoeba histolytica is responsible for dysentery and extraintestinal disease in humans. To establish successful infection, it must generate adaptive response against stress due to host defense mechanisms. We have developed a robust proteomics workflow by combining miniaturized sample preparation, low flow-rate chromatography, and ultra-high sensitivity mass spectrometry, achieving increased proteome coverage, and further integrated proteomics and RNA-seq data to decipher regulation at translational and transcriptional levels. Label-free quantitative proteomics led to identification of 2344 proteins, an improvement over the maximum number identified in E. histolytica proteomic studies. In serum-starved cells, 127 proteins were differentially abundant and were associated with functions including antioxidant activity, cytoskeleton, translation, catalysis, and transport. The virulence factor, Gal/GalNAc-inhibitable lectin subunits, was significantly altered. Integration of transcriptomic and proteomic data revealed that only 30% genes were coordinately regulated at both transcriptional and translational levels. Some highly expressed transcripts did not change in protein abundance. Conversely, genes with no transcriptional change showed enhanced protein abundance, indicating post-transcriptional regulation. This multi-omics approach enables more refined gene expression analysis to understand the adaptive response of E. histolytica during growth stress.


Assuntos
Entamoeba histolytica , Humanos , Entamoeba histolytica/metabolismo , Proteômica/métodos , Proteoma/metabolismo , Lectinas/metabolismo , Espectrometria de Massas , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo
6.
Mediators Inflamm ; 2022: 7423537, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35153624

RESUMO

The COVID-19 pandemic is rapidly spreading, and health care systems are being overwhelmed with the huge number of cases, with a good number of cases requiring intensive care. It has become imperative to develop safe and effective treatment strategies to improve survival. In this regard, understanding the pathogenesis of COVID-19 is highly important. Many hypotheses have been proposed, including the ACE/angiotensin-II/angiotensin receptor 1 pathway, the complement pathway, and the angiotensin-converting enzyme 2/mitochondrial assembly receptor (ACE2/MasR) pathway. SARS-CoV-2 binds to the ACE2 on the cell surface, downregulating the ACE2, and thus impairs the inactivation of bradykinin and des-Arg9-bradykinin. Bradykinin, a linear nonapeptide, is extensively distributed in plasma and different tissues. Kininogens in plasma and tissue are the main sources of the two vasoactive peptides called bradykinin and kallidin. However, the role of the dysregulated bradykinin pathway is less explored in the pathogenesis of COVID-19. Understanding the pathogenesis of COVID-19 is crucial for the development of new effective treatment approaches which interfere with these pathways. In this review, we have tried to explore the interaction between SARS-CoV-2, ACE2, bradykinin, and its metabolite des-Arg9-bradykinin in the pathogenesis of COVID-19.


Assuntos
Bradicinina/fisiologia , COVID-19/etiologia , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/fisiologia , Humanos , Sistema Calicreína-Cinina/fisiologia , Receptores da Bradicinina/fisiologia , Tratamento Farmacológico da COVID-19
7.
Hemoglobin ; 46(5): 277-284, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36369918

RESUMO

The National Premarital Screening Program, which includes sickle cell disease and thalassemia, was made mandatory in 2004 by the Kingdom of Saudi Arabia (KSA), and the earlier studies have shown a poor knowledge and negative attitude toward this program in the different study groups. This study was conducted to assess the knowledge and attitudes toward premarital screening (PMS) in a randomly selected national sample of the Saudi population, 18 years and above. This was a cross-sectional study conducted in the Saudi population in the western region between July and December 2021. Valid and reliable questionnaire and data were collected from 893 participants aged ≥18 years. The χ2 test was used to ascertain if there is an association between categorical variables. Multivariate logistic regression was used to determine factors predicting satisfactory knowledge. All 893 study participants had heard about PMS with 625 (70.0%), 244 (27.3%) and 24 (2.7%) having satisfactory, fair and poor knowledge, respectively. Participants aged 26-35 years (p =0 .038), females (p < 0.001), those with higher education (p = 0.003) and employed (p = 0.004), had a better knowledge compared to other groups. Most of the participants had a positive attitude toward PMS. There is a changing trend in the knowledge and attitude toward PMS with a greater number of people wanting to go for PMS. There is also an improvement in the number of participants opting out of marriage in case of incompatibility with their future partner. However, the health education programs need to be improved regarding the hemoglobinopathies.


Assuntos
Hemoglobinopatias , Exames Pré-Nupciais , Feminino , Humanos , Adolescente , Adulto , Arábia Saudita/epidemiologia , Estudos Transversais , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/genética , Atitude , Conhecimentos, Atitudes e Prática em Saúde
8.
Cereb Cortex ; 30(12): 6444-6457, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-32780108

RESUMO

The development of the cerebral cortex is directed by a series of methodically precise events, including progenitor cell proliferation, neural differentiation, and cell positioning. Over the past decade, many studies have demonstrated the critical contributions of Notch signaling in neurogenesis, including that in the developing telencephalon. However, in vivo evidence for the role of Notch signaling in cortical development still remains limited partly due to the redundant functions of four mammalian Notch paralogues and embryonic lethality of the knockout mice. Here, we utilized the conditional deletion and in vivo gene manipulation of Rbpj, a transcription factor that mediates signaling by all four Notch receptors, to overcome these challenges and examined the specific roles of Rbpj in cortical development. We report severe structural abnormalities in the embryonic and postnatal cerebral cortex in Rbpj conditional knockout mice, which provide strong in vivo corroboration of previously reported functions of Notch signaling in neural development. Our results also provide evidence for a novel dual role of Rbpj in cell type-specific regulation of two key developmental events in the cerebral cortex: the maintenance of the undifferentiated state of neural progenitor cells, and the radial and tangential allocation of neurons, possibly through stage-dependent differential regulation of Ngn1.


Assuntos
Movimento Celular , Córtex Cerebral/crescimento & desenvolvimento , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/fisiologia , Células-Tronco Neurais/fisiologia , Neurônios/fisiologia , Animais , Diferenciação Celular , Córtex Cerebral/citologia , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células-Tronco Neurais/citologia
9.
Pak J Med Sci ; 33(2): 380-382, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28523041

RESUMO

OBJECTIVES: To describe the efficacy of Functional Endoscopic Sinus Surgery(FESS) in our set up in comparison with other published studies to treat primary and recurrent nasal polyposis. METHOD: This descriptive study was conducted in 02 years at Ear Nose Throat Department Combined Military Hospital (CMH) Multan from October 2013 to October 2015. Convenient sample comprising 116 patients of both sexes of age group from 18 to 60 years were selected from ENT Out Patient Department, with documented diagnosis of nasal polyposis that underwent functional endoscopic sinus surgery. Out of 116 patients, 15 (12.9%) had recurrent nasal polyposis while 101 (87.1%) had primary nasal polyposis. Patients were assessed clinically. Preoperative nasal endoscopy and CT scan of nose and paranasal sinuses were performed in every patient to assess the extent of disease and evaluate the surgical anatomy. Patients were followed up 03 monthly, 06 monthly and after 01 year. Clinical signs of nasal polyposis were evaluated by nasal endoscopy at each follow up visit. RESULTS: There were 116 patients with documented diagnosis of nasal polyposis. Among these, 75 (64.7%) were male and 41 (35.3%) were female patients. Mean age of presentation in males was 39.1 years and that of females was 36.7 years. Only 15 patients (12.9%) developed recurrent disease within a year. CONCLUSION: Functional endoscopic sinus surgery is preferred as a primary treatment modality for primary and recurrent nasal polyposis. Mucosal polyps can be carefully debrided, the natural ostia enlarged, the ethmoid sinuses are unroofed, and sphenoid sinuses are opened in nasal cavity and sinus nasal mucosa is mostly preserved due to excellent visualization and surgical technique. Improvement in symptoms with minimal chance of recurrence may be expected in more than 90% patients.

10.
Orbit ; 33(4): 314-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24831817

RESUMO

Castleman disease is a non-neoplastic cause of lymphadenopathy, first described in 1956 by Dr. Benjamin Castleman. Orbital involvement in Castleman disease is extremely rare. We report a case of bilateral orbital Castleman disease in a 48-year-old Asian male who presented with bilateral inferior dystopia. MRI revealed bilateral extraconal superior orbital mass. Histopathology and immunohistochemistry of the mass revealed features of Castleman disease of hyaline vascular type. Castleman disease should be a differential in suspected idiopathic orbital inflammatory disease and lymphoproliferative disorders.


Assuntos
Hiperplasia do Linfonodo Gigante/diagnóstico , Doenças Orbitárias/diagnóstico , Biomarcadores/metabolismo , Hiperplasia do Linfonodo Gigante/metabolismo , Exoftalmia/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Orbitárias/metabolismo
11.
Appl Biochem Biotechnol ; 196(2): 1079-1088, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37318688

RESUMO

To explore and analyze the correlation between LncRNA TDRG1 expression degree and the prognosis of cervical carcinoma tissues. The cervical cancer tissues and para-carcinoma tissues of 106 patients with cervical carcinoma surgically removed in our hospital were chosen as specimens. LncRNA TDRG1 expression in cervical carcinoma tissues and para-carcinoma tissues was inspected by real-time fluorescence quantitative PCR, and the correlation between LncRNA TDRG1 and the clinicopathological parameters and disease prognosis was analyzed. The relative expression of LncRNA TDRG1 in cervical carcinoma tissues was critically gone up (P < 0.05) compared to para-carcinoma tissues. The relative expression of LncRNA TDRG1 in cervical carcinoma was correlated with FIGO staging, lymph node metastasis, infiltrating depth of cervical basal, and the differentiation of cancer cells (P < 0.05). According to the results of the Kaplan-Meier curve and Log-rank test, the overall survival conditions of subjects with low-lncRNA TDRG1 were superior to that of those with high-lncRNA TDRG1 expression (P < 0.05). The expression of LncRNA TDRG1 in cervical carcinoma tissues and the clinicopathological features in predicting the overall survival (OS) in sufferers with cervical carcinoma were investigated by the Cox regression model. LncRNA TDRG1 expression in cervical carcinoma tissues is tightly associated with the progression and prognosis of cervical carcinoma, which may be a latent biological indicator for clinical diagnosis and prognosis of cervical carcinoma.


Assuntos
RNA Longo não Codificante , Neoplasias do Colo do Útero , Feminino , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Diferenciação Celular , Regulação Neoplásica da Expressão Gênica , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética
12.
Data Brief ; 52: 109997, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38226037

RESUMO

Biochar production is an effective approach to managing abundant agricultural wastes. Pruning wastes from trimming the branches of trees such as carambola and mango, as well as coconut shells, are among the agricultural wastes that have reutilisation potential, which would simultaneously reduce the space required for disposal. In this study, the potential use of these wastes by converting them into biochar was investigated. The data presented in this study highlight the design of a pyrolysis system for a low-temperature slow pyrolysis process, as well as the characterisation data of the biochar produced using this system. The data collected included the elemental composition, porosity, as well as surface and adsorption characteristics of the biochar. These data indicate that the biochar produced had certain qualities that would enable its use for specific agricultural and industrial purposes. Meanwhile, the design indicated that it could facilitate small farms with specific outputs. In brief, these data can be used as references for developing a small-scale system for agricultural waste management using different types of crops.

13.
Curr Pharm Des ; 30(14): 1115-1127, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38561612

RESUMO

BACKGROUND: Cardiovascular diseases (CVDs) continue to exert a substantial global influence in specific areas due to population growth, aging, microbiota, and genetic/environmental factors. Drinking water has a strong impact on the health of an individual. Further, emerging evidence has highlighted the therapeutic potential and benefits of Zamzam water (Zam). OBJECTIVE: We investigated the influence of Zam on doxorubicin-induced cardiac toxicity, elucidating its consequential effects on GUT microbiota dysbiosis and hepatic and renal functions. METHODS: Male rats were categorized into four groups: Group 1 as Normal control (NC), Group 2 as Zamzam control (ZC), Group 3 Disease control (DC) and Group 4 as Therapeutic control (DZ) treated with Zam against doxorubicin-induced disease at a dose of 1mg/kg boy weight) intraperitoneally (i.p). RESULTS: Significant dysbiosis in the composition of GM was observed in the DC group along with a significant decrease (p < 0.05) in serum levels of Zinc, interleukin-10 (IL-10), IL-6 and Angiotensin II (Ang II), while C-reactive protein (CRP), fibrinogen, and CKMB increased significantly (restoration of Zinc ions (0.72 ± 0.07 mcg/mL) compared to NC. Treatment with Zamzam exhibited a marked abundance of 18-times to 72% in Romboutsia, a genus of firmicutes, along with lowering of Proteobacteria in DZ followed by significant restoration of Zinc ions (0.72 ± 0.07 mcg/mL), significant (p ˂ 0.05) reduction in CRP (7.22 ± 0.39 mg/dL), CKMB (118.8 ± 1.02 U/L) and Fibrinogen (3.18 ± 0.16 mg/dL), significant (p < 0.05) increase in IL-10 (7.22 ± 0.84 pg/mL) and IL-6 (7.18 ± 0.40 pg/ml), restoration of Ang II (18.62 ± 0.50 nmol/mL/min), marked increase in renin with normal myocyte architecture and tissue orientation of kidney, and restoration of histological architecture of hepatocyte. CONCLUSION: Zam treatment mitigated cardiac toxicity risk through the modulation of GUT microbiota and the renin-angiotensin system and tissue histology effectively.


Assuntos
Microbioma Gastrointestinal , Sistema Renina-Angiotensina , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Ratos , Sistema Renina-Angiotensina/efeitos dos fármacos , Doxorrubicina/farmacologia , Água/química
14.
J Physiol ; 591(5): 1295-312, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23266937

RESUMO

Cholecystokinin (CCK) is a hypothetical controller for suckling and infancy body weight, although the underlying mechanisms remain unclear. Therefore, the present study analysed the mechanisms using mice lacking the CCK-1 receptor (CCK1R-/-). Although CCK1R-/- mice displayed normal weights at birth and adulthood, CCK1R-/- pups had enlarged adipocytes and were overweight from the first to second week after birth, regardless of maternal genotype. The lacZ reporter gene assay and/or calcium imaging analysis demonstrated that CCK-1 receptors were abundant in satiety-controlling regions such as the hypothalamus, brainstem, nodose ganglion and pylorus in adults, whereas these signals were few to lacking at pre-weanling stages. At postnatal day (PD) 6, the increase in cFos expression in the medullary nucleus tractus solitarius was similarly triggered by gastrointestinal milk- or saline filling in both genotypes, further indicating immature CCK-1 receptor function in an ascending satiety-controlling system during infancy. Conversely, third ventricle ependymal tanycyte-like cells expressed CCK-1 receptors with expression peaking at PD6. At PD6, wild-type but not CCK1R-/- mice had increased cFos immunoreactivity in ependymal cells following gastrointestinal milk filling whereas the response became negligible at PD12. In addition, ependymal cFos was not increased by saline filling, indicating that these responses are dependent on CCK-1 receptors, developmental stage and nutrients. Furthermore, body weights of wild-type pups were transiently increased by blocking ependymal CCK receptor function with microinjection of a CCK-1 antagonist, but not a CCK-2 antagonist. Hence, we demonstrate de novo functions of ependymal CCK-1 receptors and reveal a new aspect of infant satiety-controlling mechanisms.


Assuntos
Epêndima/metabolismo , Receptores da Colecistocinina/metabolismo , Resposta de Saciedade , Terceiro Ventrículo/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Fatores Etários , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Animais Lactentes , Peso ao Nascer , Cálcio/metabolismo , Tamanho Celular , Quimiocinas CC , Ingestão de Alimentos , Epêndima/efeitos dos fármacos , Comportamento Alimentar , Feminino , Genótipo , Antagonistas de Hormônios/administração & dosagem , Injeções Intraventriculares , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microinjeções , Sobrepeso/metabolismo , Sobrepeso/fisiopatologia , Fenótipo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores da Colecistocinina/antagonistas & inibidores , Receptores da Colecistocinina/deficiência , Receptores da Colecistocinina/genética , Resposta de Saciedade/efeitos dos fármacos , Transdução de Sinais , Terceiro Ventrículo/efeitos dos fármacos , Aumento de Peso
15.
J Biol Chem ; 287(47): 39391-401, 2012 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-23038256

RESUMO

Cholecystokinin (CCK) and its receptor subtypes CCK-1 and -2 have diverse homeostatic functions. CCK-1 and -2 receptors share a common phosphatidylinositol signaling pathway, yet little is known regarding their possible functional coupling. We focused on CCK-mediated Ca(2+) signaling in parvocellular paraventricular nucleus (PVN) cells, which control satiety and other autonomic functions. Analysis of mouse hypothalamic slices demonstrated that the general CCK receptor agonist CCK-8s (10 nM) triggered Ca(2+) transients most significantly in the posterior subregion of the PVN (PaPo). This 10 nM CCK-8s-induced response was absent in CCK-1 receptor knock-out (CCK1R(-/-)) slices, showing that the response is mediated by CCK-1 receptors. CCK-8s concentrations higher than 30 nM triggered a Ca(2+) rise similarly in wild-type and CCK1R(-/-) slices. The large CCK-8s (100 nM)-induced Ca(2+) responses in CCK1R(-/-) slices were blocked by a CCK-2 receptor antagonist (CI-988), whereas those in wild-type slices required a mixture of CI-988 and lorglumide (a CCK-1 receptor antagonist) for complete antagonism. Therefore, CCK-1 and -2 receptors may function synergistically in single PaPo neurons and deletion of CCK-1 receptors may facilitate CCK-2 receptor signaling. This hypothesis was supported by results of real-time RT-PCR, immunofluorescence double labeling and Western blotting assays, which indicated CCK-2 receptor overexpression in PaPo neurons of CCK1R(-/-) mice. Furthermore, behavioral studies showed that intraperitoneal injections of lorglumide up-regulated food accesses in wild-type but not in CCK1R(-/-) mice, whereas CI-988 injections up-regulated food accesses in CCK1R(-/-) but not in wild-type mice. Compensatory CCK signaling via CCK-2 receptors in CCK1R(-/-) mice shed light on currently controversial satiety-controlling mechanisms.


Assuntos
Sinalização do Cálcio/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Receptor de Colecistocinina B/metabolismo , Receptores da Colecistocinina/metabolismo , Animais , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Quimiocinas CC , Relação Dose-Resposta a Droga , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/genética , Neurônios/citologia , Nootrópicos/farmacologia , Núcleo Hipotalâmico Paraventricular/citologia , Receptor de Colecistocinina B/agonistas , Receptor de Colecistocinina B/genética , Receptores da Colecistocinina/agonistas , Receptores da Colecistocinina/genética , Sincalida/análogos & derivados , Sincalida/farmacologia
16.
Commun Biol ; 6(1): 736, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37460609

RESUMO

Fetal alcohol spectrum disorders (FASD) show behavioral problems due to prenatal alcohol exposure (PAE). A previous study reports changes in gene expressions linked to fatty acid (FA) metabolism in the cerebral cortex of the PAE mouse model. We find an increase of palmitic acid and arachidonic acid in phospholipid in the cerebral cortex of PAE at postnatal day 30. The increase of palmitic acid is consistent with increase of the producing enzyme, Fasn (fatty acid synthase). Decrease of 26:6 FA is also consistent with the increase of the enzyme which uses 26:6 as a substrate for making very long chain FAs, Elovl4 (elongation of very long chain fatty acids protein 4). However, there is no increase in the elongated products. Rather, lipid droplets (LDs) accumulated in the brain. Although FA-associated metabolic measurements are not affected by PAE, the abundance of FA-related gut microbiota is altered. This suggests that the gut microbiome could serve as a tool to facilitate uncovering the brain pathophysiology of FASD and a potential target to mitigate neurobehavioral problems.


Assuntos
Transtornos do Espectro Alcoólico Fetal , Efeitos Tardios da Exposição Pré-Natal , Humanos , Camundongos , Animais , Feminino , Gravidez , Transtornos do Espectro Alcoólico Fetal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Modelos Animais de Doenças , Ácidos Palmíticos , Ácidos Graxos
17.
Diagnostics (Basel) ; 13(4)2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36832079

RESUMO

BACKGROUND: Laboratory errors arise at any stage of testing. Detecting these inaccuracies before results are revealed might delay diagnosis and treatment, causing patient distress. Here, we studied the preanalytical errors in a hematology laboratory. METHODS: This one-year retrospective analysis was conducted at the laboratory of a tertiary care hospital and included information on blood samples that were taken for hematology tests from both outpatients and inpatients. Laboratory records included sample collection and rejection information. The type and frequency of preanalytical errors were expressed as a proportion of total errors and sample number. Microsoft Excel was utilized to enter data. The results were presented in the form of frequency tables. RESULTS: This research included 67,892 hematology samples. For preanalytical errors, 886 samples (1.3%) were discarded. The most common preanalytical error was insufficient sample (54.17%), and the least common was an empty/damaged tube (0.4%). Erroneous samples in the emergency department were mostly insufficient and clotted, whereas pediatric sample errors were caused by insufficient and diluted samples. CONCLUSION: Inadequate samples and clotted samples account for the vast majority of preanalytical factors. Insufficiency and dilutional errors were most frequent from pediatric patients. Adherence to best laboratory practices can drastically cut down on preanalytical errors.

18.
Indian J Pathol Microbiol ; 66(4): 848-851, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38084546

RESUMO

Teratomas are germ cell tumors occurring usually in gonadal organs. They are neoplasms composed of one or more of the three germ layers. Extragonadal teratomas are uncommonly reported in the literature. The liver is an extremely rare site for teratoma, constituting < 1% of all teratomas. The majority of the liver teratomas are found in the pediatric population with only a dozen cases reported in adults to the best of our knowledge. We present a case of a 27-year-old male with a history of abdominal pain of 5 months duration. CT scan revealed liver mass suggesting teratoma. The patient underwent cholecystectomy and segmental liver resection. Histopathology revealed mature cystic teratoma. Complete resection remains the best treatment option. Teratomas of the liver are extremely rare, constituting < 1% of all teratomas. An extensive review of the literature yielded < 50 cases of primary hepatic teratomas with only a dozen cases in adults and only two cases in males.


Assuntos
Cisto Dermoide , Neoplasias Embrionárias de Células Germinativas , Teratoma , Adulto , Humanos , Masculino , Hepatectomia , Fígado/diagnóstico por imagem , Fígado/cirurgia , Fígado/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Teratoma/diagnóstico , Teratoma/cirurgia , Teratoma/patologia
19.
Vaccines (Basel) ; 11(3)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36992148

RESUMO

BACKGROUND: Coronavirus disease 2019 has become a global health threat resulting in a catastrophic spread and more than 3.8 million deaths worldwide. It has been suggested that there is a negative influence of diabetes mellites (DM), which is a complex chronic disease, on COVID-19 severe outcomes. Other factors in diabetic patients may also contribute to COVID-19 disease outcomes, such as older age, obesity, hyperglycaemia, hypertension, and other chronic conditions. METHODS: A cohort study was conducted on the demographics, clinical information, and laboratory findings of the hospitalised COVID-19 with DM and non-DM patients were obtained from the medical records in King Faisal Specialist Hospital and Research Centre, Saudi Arabia. RESULTS: Among the study population, 108 patients had DM, and 433 were non-DM patients. Patients with DM were more likely to present symptoms such as fever (50.48%), anorexia (19.51%), dry cough (47.96%), shortness of breath (35.29%), chest pain (16.49%), and other symptoms. There was a significant decrease in the mean of haematological and biochemical parameters, such as haemoglobin, calcium, and alkaline phosphate in people with diabetes compared to non-diabetics and a considerable increase in other parameters, such as glucose, potassium, and cardiac troponin. CONCLUSIONS: According to the findings of this study, patients who have diabetes have a greater risk of developing more severe symptoms associated with COVID-19 disease. This could result in more patients being admitted to the intensive care unit as well as higher mortality rates.

20.
Cureus ; 15(12): e50046, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38186469

RESUMO

INTRODUCTION: Iron deficiency anemia is the most common type of anemia according to the World Health Organization. Females are more likely to be affected than males. There are several factors causing iron deficiency anemia, such as increased loss of iron, decreased intake of iron, and increased utilization of iron. There are limited research studies evaluating the risk factors that cause anemia among female medical students in Saudi Arabia. For this, the study aimed to identify the prevalence of undiagnosed iron deficiency anemia (IDA) among young female university students and to identify if there is any correlation between IDA and several factors including dietary habits, psychological stress, anxiety status, and body mass index. MATERIALS AND METHODS: A cross-sectional observational study was performed between October 2022 and December 2022 with a sample of 100 healthy female students aged between 19 and 23 years, who were studying at the medical colleges of Umm Al-Qura University, Saudi Arabia. Blood samples were collected to perform complete blood count and iron profile tests. Also, a survey was done to find correlation between iron deficiency anemia and dietary intake, drinks, stress, anxiety, and body mass index (BMI). Independent t-test or Mann-Whitney U test were used to compare values for non-anemic with anemic participants, and linear regression tests were used to analyze differences between non-anemic and anemic participants' dietary intake factors and stress and anxiety scores. The level of significance was set at p<0.05. RESULTS: The findings represent an overall prevalence of iron deficiency anemia in female medical students based on the lab finding results. Thus, students were divided into two following groups: anemic (13%) with hemoglobin (Hb) concentration <12 g/dL and non-anemic (84%) with Hb concentration ≥12 g/dL. When comparing the two groups, results showed significant differences in the majority of RBC indices (hematocrit {HCT}, mean corpuscular volume {MCV}, mean corpuscular hemoglobin {MCH}, red cell distribution width {RDW}) and iron profiles, p-value was <0.05. On evaluation of the different types of food consumption, the mean iron intake was around 7 mg/day, and in 65% of the participants, it was below the estimated average requirement (EAR) of iron (8.1 mg/dL). The perceived stress scale (PSS) shows that 63% of the participants experienced moderate stress and 58% reported severe anxiety by the generalized anxiety disorder (GAD) scale. In multiple linear regression, iron was positively associated with hemoglobin concentrations, whereas stress scores were negatively associated with hemoglobin concentrations. CONCLUSION: There is a relatively low prevalence of anemia and most of it was found of the microcytic type, indicating that this condition is a common health issue among local female college students. There was no independent association between stress or anxiety and hemoglobin levels.

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