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1.
Cell Biol Int ; 48(2): 216-228, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38081783

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC) compared to other BC subtypes in clinical settings. Currently, there are no effective therapeutic strategies for TNBC treatment. Therefore, there is an urgent need to identify suitable biomarkers or therapeutic targets for TNBC patients. Thrombomodulin (TM) plays a role in cancer progression and metastasis in many different cancers. However, the role of TM in TNBC is not yet fully understood. First, silenced-TM in MDA-MB-231 cells caused an increase in proliferative and metastatic activity. In contrast, overexpression of TM in Hs578T cells caused a reduction in proliferation, invasion, and migration rate. Using RNA-seq analysis, we found that Integrin beta 3 (ITGB3) expression may be a downstream target of TM. Furthermore, we found an increase in ITGB3 levels in TM-KD cells by QPCR and western blot analysis but a decrease in ITGB3 levels in TM-overexpressing cells. We found phospho-smad2/3 levels were increased in TM-KD cells but decreased in TM-overexpressing cells. This implies that TM negatively regulates ITGB3 levels through the activation of the smad2/3 pathway. Silencing ITGB3 in TM-KD cells caused a decrease in proliferation and migration. Finally, we found that higher ITGB3 levels were correlated with poor overall survival and relapse-free survival in patients with TNBC. Our results indicated a novel regulatory relationship between TM and ITGB3 in TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Western Blotting , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Integrina beta3/genética , Trombomodulina/genética , Neoplasias de Mama Triplo Negativas/metabolismo
2.
AIDS Care ; 36(1): 139-145, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37723120

RESUMO

Antiretroviral therapy (ART) adherence during and after pregnancy is essential to reduce perinatal transmission of HIV. However, little is known about adherence during the intrapartum and early postpartum inpatient hospital stay. Using secondary data from a hospital-based cohort study focused on the relationship between birthweight and engagement in HIV care, we examined the magnitude of, reasons for, and factors associated with incomplete intrapartum and early postpartum ART adherence among adult women (18 years or older) living with HIV who delivered within the previous two weeks at one of five hospitals in Accra, Ghana. Of the 142 enrolled participants who had complete adherence data and reported being on ART at the time of hospital admission, 43% (61/142) reported missing at least one ART dose during labor, delivery, and postpartum, including almost 20% (28/142) missing 2 or more consecutive doses. Women who reported frequently missing ART doses during pregnancy had higher odds of reporting missed doses during their intrapartum and postpartum hospital stays. Among those with inpatient ART interruption, the most frequently cited reasons were: forgetting medication at home (42%) and challenges of being in or recovering from labor (29%). Maternal perception of infant health at birth, hospital level of care, and frequency of missing HIV medications during pregnancy were associated with incomplete ART adherence during the intrapartum and early postpartum inpatient stay. An enabling clinical environment to facilitate access to ART during inpatient stays may have positive implications for ART adherence.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Complicações Infecciosas na Gravidez , Gravidez , Adulto , Recém-Nascido , Lactente , Feminino , Humanos , Infecções por HIV/complicações , Estudos de Coortes , Complicações Infecciosas na Gravidez/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas , Gana , Pacientes Internados , Período Pós-Parto , Antirretrovirais/uso terapêutico , Adesão à Medicação , Hospitais , Fármacos Anti-HIV/uso terapêutico
3.
J Cell Biochem ; 124(6): 907-920, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37183314

RESUMO

Colorectal cancer (CRC) is the primary cause of death from gastrointestinal cancers. Aldehyde dehydrogenase 2 (ALDH2), a crucial mitochondrial enzyme for the oxidative pathway of alcohol metabolism, plays a dual role in cancer progression. In some cancers, it is tumor suppressive; in others, it drives cancer progression. However, whether targeting ALDH2 has any therapeutic implications or prognostic value in CRC is still unclear. Here, we investigated the role of ALDH2 in CRC progression by targeting its enzymatic activity rather than gene expression. We found that inhibiting ALDH2 by CVT-10216 and daidzein significantly decrease migration and stemness properties of both DLD-1 and HCT 116 cells, whereas activating ALDH2 by Alda-1 enhances migration rate. Concomitantly, ALDH2 inhibition by both CVT-10216 and daidzein downregulates the mRNA levels of fibronectin, snail, twist, MMP7, CD44, c-Myc, SOX2, and OCT-4, which are oncogenic in the advanced stage of CRC. Furthermore, Gene Set Enrichment Analysis (GSEA) on ALDH2 co-expressed genes from The Cancer Genome Atlas (TCGA) revealed that MYC target gene sets are upregulated. We found that ALDH2 inhibition decreased the nuclear protein levels of pGSK3ß serine 9 and c-Myc. This suggests that ALDH2 probably targets ß-catenin signaling in CRC cells. Together, our results demonstrate the prognostic value of ALDH2 in CRC as it regulates both CRC stemness and migration. Our findings also propose that the plant-derived isoflavone daidzein could be a potential chemotherapeutic drug targeting ALDH2 in CRC.


Assuntos
Neoplasias Colorretais , beta Catenina , Humanos , Linhagem Celular Tumoral , beta Catenina/genética , beta Catenina/metabolismo , Neoplasias Colorretais/patologia , Transdução de Sinais , Células HCT116 , Regulação Neoplásica da Expressão Gênica , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/metabolismo
4.
J Transl Med ; 21(1): 505, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37496011

RESUMO

BACKGROUND: Colorectal cancer (CRC) is highly prevalent and lethal globally, and its prognosis remains unsatisfactory. Drug resistance is regarded as the main cause of treatment failure leading to tumor recurrence and metastasis. The overexpression of fucosylated epitopes, which are usually modifications of glycoproteins, was reported to occur in various epithelial cancers. However, the effects of treatments that target these antigens in colorectal cancer remain unclear. METHODS: This study investigated the expression of heavily fucosylated glycans (HFGs) in 30 clinical samples from patients with CRC and other normal human tissues. The complement-dependent cytotoxicity was explored in vitro through treatment with anti-HFG monoclonal antibody (mAb) alone or in combination with chemotherapeutic agents. In vivo inhibitory effects were also examined using a xenograft mouse model. RESULTS: Immunohistochemistry staining and western blotting revealed that HFG expression was higher in human colorectal cancer tissues than in normal tissues. In DLD-1 and SW1116 cells, which overexpress fucosylated epitopes, anti-HFG mAb produced observable cytotoxic effects, especially when it was combined with chemotherapeutic agents. The xenograft model also demonstrated that anti-HFG mAb had potent and dose-dependent inhibitory effects on colorectal tumor growth. CONCLUSIONS: As a novel cancer antigen, HFGs are a promising treatment target, and the implementation of anti-HFG mAb treatment for CRC warrants further investigation.


Assuntos
Neoplasias Colorretais , Recidiva Local de Neoplasia , Humanos , Animais , Camundongos , Imuno-Histoquímica , Antígenos , Modelos Animais de Doenças , Epitopos , Polissacarídeos/farmacologia , Neoplasias Colorretais/patologia , Linhagem Celular Tumoral
5.
Int J Mol Sci ; 24(12)2023 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-37373155

RESUMO

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality worldwide. Even with advances in therapy, CRC mortality remains high. Therefore, there is an urgent need to develop effective therapeutics for CRC. PCTAIRE protein kinase 1 (PCTK1) is an atypical member of the cyclin-dependent kinase (CDK) family, and the function of PCTK1 in CRC is poorly understood. In this study, we found that patients with elevated PCTK1 levels had a better overall survival rate in CRC based on the TCGA dataset. Functional analysis also showed that PCTK1 suppressed cancer stemness and cell proliferation by using PCTK1 knockdown (PCTK1-KD) or knockout (PCTK1-KO) and PCTK1 overexpression (PCTK1-over) CRC cell lines. Furthermore, overexpression of PCTK1 decreased xenograft tumor growth and knockout of PCTK1 significantly increased in vivo tumor growth. Moreover, knockout of PCTK1 was observed to increase the resistance of CRC cells to both irinotecan (CPT-11) alone and in combination with 5-fluorouracil (5-FU). Additionally, the fold change of the anti-apoptotic molecules (Bcl-2 and Bcl-xL) and the proapoptotic molecules (Bax, c-PARP, p53, and c-caspase3) was reflected in the chemoresistance of PCTK1-KO CRC cells. PCTK1 signaling in the regulation of cancer progression and chemoresponse was analyzed using RNA sequencing and gene set enrichment analysis (GSEA). Furthermore, PCTK1 and Bone Morphogenetic Protein Receptor Type 1B (BMPR1B) in CRC tumors were negatively correlated in CRC patients from the Timer2.0 and cBioPortal database. We also found that BMPR1B was negatively correlated with PCTK1 in CRC cells, and BMPR1B expression was upregulated in PCTK1-KO cells and xenograft tumor tissues. Finally, BMPR1B-KD partially reversed cell proliferation, cancer stemness, and chemoresistance in PCTK1-KO cells. Moreover, the nuclear translocation of Smad1/5/8, a downstream molecule of BMPR1B, was increased in PCTK1-KO cells. Pharmacological inhibition of Smad1/5/8 also suppressed the malignant progression of CRC. Taken together, our results indicated that PCTK1 suppresses proliferation and cancer stemness and increases the chemoresponse of CRC through the BMPR1B-Smad1/5/8 signaling pathway.


Assuntos
Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Humanos , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Quinases Ciclina-Dependentes/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais
6.
BMC Pregnancy Childbirth ; 20(1): 398, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32677910

RESUMO

BACKGROUND: Maternal retention in HIV care is lower for women in the postpartum period than during pregnancy, but the reasons are poorly understood. We examined key differences in barriers to retention in HIV care during and after pregnancy. METHODS: We conducted semi-structured, in-depth interviews with 30 postpartum women living with HIV. Participants were recruited from two tertiary facilities implementing Option B+ for prevention of mother-to-child HIV transmission in Accra, Ghana. We collected data from mothers who had disengaged from HIV care and those who were still engaged in care. The interviews were analyzed using principles adapted from grounded theory. RESULTS: Participants' experiences and narratives showed that retention in HIV care was more challenging during the postpartum period than during pregnancy. Poor maternal physical health (from birth complications and cesarean section), socio-cultural factors (norms about newborn health and pregnancy), and economic difficulties linked to childbirth (such as unemployment, under-employment, and debt) made the costs of retention in HIV care more economically and socially expensive in the postpartum period than during pregnancy. Some participants also shared that transportation costs and resulting dependence on a partner to pay increased during the postpartum period because of a strong shift in maternal preference for private modes of transportation due to HIV stigma and the desire to protect the newborn. These factors played a larger role in the postpartum period than during pregnancy and created a significant barrier to retention. A conceptual model of how these factors interrelate, the synergy between them, and how they affect retention in the postpartum period is presented. CONCLUSIONS: In Ghana, lower retention in HIV care in the postpartum period compared to in pregnancy may be primarily driven by social, economic, and newborn health factors. Multifaceted economic-based and stigma-reduction interventions are needed to increase retention in maternal HIV care after childbirth.


Assuntos
Infecções por HIV/terapia , Período Pós-Parto/psicologia , Retenção nos Cuidados , Adulto , Feminino , Gana , Humanos , Lactente , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/psicologia , Pesquisa Qualitativa , Estigma Social , Fatores Socioeconômicos , Adulto Jovem
7.
AIDS Behav ; 23(2): 433-444, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29968140

RESUMO

Care for low birthweight (LBW) infants can contribute to psychological difficulties and stigma among mothers living with HIV, creating challenges for antiretroviral therapy (ART) adherence and retention in HIV care. We explored how caring for LBW infants affects maternal ART adherence and retention in care. We conducted 30 in-depth interviews with postpartum women living with HIV in Accra, Ghana: 15 with LBW infants and 15 with normal birthweight (NBW) infants. Compared to mothers with NBW infants, mothers with LBW infants described how caring for their newborns led to increased caregiver burden, prolonged hospital stays, and stigma-contributing to incomplete ART adherence and missed clinical appointments. For a few women, care for LBW infants created opportunities for re-engagement in HIV care and motivation to adhere to ART. Results suggest women living with HIV and LBW babies in Ghana face increased challenges that impact their adherence to care and ART.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Cuidado do Lactente/psicologia , Adesão à Medicação/psicologia , Mães/psicologia , Período Pós-Parto/psicologia , Adulto , Feminino , Gana , Infecções por HIV/psicologia , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Tempo de Internação , Gravidez , Complicações Infecciosas na Gravidez , Pesquisa Qualitativa , Estigma Social , Adulto Jovem
8.
Chin J Physiol ; 62(6): 231-240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31793458

RESUMO

Lung harbors the growth of primary and secondary tumors. Even though numerous factors regulate the complex signal transduction and cytoskeletal remodeling toward the progression of lung cancer, cyclin-dependent kinase 5 (Cdk5), a previously known kinase in the central nervous system, has raised much attention in the recent years. Patients with aberrant Cdk5 expression also lead to poor survival. Cdk5 has already been employed in various cellular processes which shape the fate of cancer. In lung cancer, Cdk5 mainly regulates tumor suppressor genes, carcinogenesis, cytoskeletal remodeling, and immune checkpoints. Inhibiting Cdk5 by using drugs, siRNA or CRISP-Cas9 system has rendered crucial therapeutic advantage in the combat against lung cancer. Thus, the relation of Cdk5 to lung cancer needs to be addressed in detail. In this review, we will discuss various cellular events modulated by Cdk5 and we will go further into their underlying mechanism in lung cancer.


Assuntos
Neoplasias Pulmonares , Quinase 5 Dependente de Ciclina , Humanos , Transdução de Sinais
9.
Int J Mol Sci ; 20(16)2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31395805

RESUMO

Cyclin-dependent kinase 5 (CDK5) is a unique member of the cyclin-dependent kinase family. CDK5 is activated by binding with its regulatory proteins, mainly p35, and its activation is essential in the development of the central nervous system (CNS) and neurodegeneration. Recently, it has been reported that CDK5 plays important roles in regulating various biological and pathological processes, including cancer progression. Concerning prostate cancer, the androgen receptor (AR) is majorly involved in tumorigenesis, while CDK5 can phosphorylate AR and promotes the proliferation of prostate cancer cells. Clinical evidence has also shown that the level of CDK5 is associated with the progression of prostate cancer. Interestingly, inhibition of CDK5 prevents prostate cancer cell growth, while drug-triggered CDK5 hyperactivation leads to apoptosis. The blocking of CDK5 activity by its small interfering RNAs (siRNA) or Roscovitine, a pan-CDK inhibitor, reduces the cellular AR protein level and triggers the death of prostate cancer cells. Thus, CDK5 plays a crucial role in the growth of prostate cancer cells, and AR regulation is one of the important pathways. In this review paper, we summarize the significant studies on CDK5-mediated regulation of prostate cancer cells. We propose that the CDK5-p35 complex might be an outstanding candidate as a diagnostic marker and potential target for prostate cancer treatment in the near future.


Assuntos
Quinase 5 Dependente de Ciclina/metabolismo , Neoplasias da Próstata/patologia , Androgênios/análise , Androgênios/metabolismo , Animais , Apoptose , Carcinogênese/metabolismo , Carcinogênese/patologia , Quinase 5 Dependente de Ciclina/análise , Humanos , Masculino , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/terapia , Receptores Androgênicos/análise , Receptores Androgênicos/metabolismo , Fator de Transcrição STAT3/análise , Fator de Transcrição STAT3/metabolismo
10.
BMC Infect Dis ; 15: 217, 2015 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-26022703

RESUMO

BACKGROUND: Lassa fever is a potentially fatal acute viral illness caused by Lassa virus which is carried by rodents and is endemic in some West African countries. Importation of emerging infections such as Lassa fever, Ebola Virus Disease and other viral hemorrhagic fevers into non endemic regions is a growing threat particularly as international travel and commitments in resolving conflicts in endemic countries in the West Africa sub-region continue. CASE PRESENTATION: We report the first two recorded imported cases of Lassa fever among Ghanaian Peace keepers in rural Liberia, who became ill while on Peace keeping mission. They were subsequently evacuated to the UN level IV hospital in Accra, where their illnesses were laboratory confirmed. One of the patients recovered with ribavirin treatment and supportive therapy. No secondary clinical cases occurred in Ghana. CONCLUSIONS: Healthcare providers at all levels of care should thus have a high index of suspicion for these infectious diseases and adopt standard infection control measures when treating patients in endemic regions or returning travelers from an endemic region with a febrile illness even of a known etiology.


Assuntos
Antivirais/uso terapêutico , Busca de Comunicante , Febre Lassa/tratamento farmacológico , Militares , Ribavirina/uso terapêutico , Viagem , Adulto , Doenças Transmissíveis Emergentes , Gana , Humanos , Febre Lassa/diagnóstico , Febre Lassa/transmissão , Vírus Lassa/genética , Libéria , Masculino , Saúde Pública
11.
Int J Dev Disabil ; 70(3): 458-468, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699501

RESUMO

Proper treatment of developmental disabilities requires health workers to have adequate knowledge of etiology and referral procedures. There is a dearth of research on knowledge of developmental disabilities among health workers in Ghana. The purpose of this study was to document knowledge about developmental disorders, causes, and referral procedures among health workers. Researchers used a successive free-listing method to interview 37 health workers. Developmental disabilities which present with physical symptoms were the most salient disorders identified among health workers, while learning disabilities and attention deficit disorder were largely overlooked. The most commonly listed developmental disabilities were cerebral palsy, Down syndrome, and autism spectrum disorder. Respondents had limited knowledge about the causes of and referral resources for developmental disabilities. Results show the need for continuing medical education, public awareness, and enhanced resources to support the identification and care of children with developmental disabilities in Ghana.

12.
Anticancer Res ; 44(2): 543-553, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307563

RESUMO

BACKGROUND/AIM: Bladder cancer remains a significant global health concern, necessitating a deeper understanding of the molecular mechanisms underlying its progression. Cyclin-Dependent Kinase 5 (CDK5) has recently emerged as a potential player in bladder cancer pathogenesis. This study investigated the involvement of CDK5 in bladder cancer, emphasizing its potential as a therapeutic target. MATERIALS AND METHODS: The expression levels of CDK5 and p35 (CDK5 regulatory protein) and their roles in the tumor grade and malignancy of patient samples were evaluated using western blot analysis and immunohistochemistry. In addition, tumor cancer genome atlas (TCGA) was utilized to evaluate survival rate in patients with bladder cancer. We further confirmed the role of CDK5 with in vitro experiments using western blot analysis, immunocytochemistry, cell culture-based proliferation and migration assays. RESULTS: Higher CDK5 and p35 were associated with a higher tumor grade and poor survival rate in patients with bladder cancer. To confirm the role of CDK5 in vitro, we over-expressed CDK5 in bladder cancer cells. The results showed that the over-expression of CDK5 enhanced bladder cancer cell proliferation and migration. In addition, CDK5 inhibition by a pan-CDK inhibitor, Roscovitine (RV), significantly reduced proliferation of bladder cancer cells. Indeed, the migration and adhesion of bladder cancer cells were inhibited by RV treatment. CONCLUSION: CDK5 might play important roles in bladder cancer progression and be a potential diagnostic and therapeutic target in the near future.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Proliferação de Células , Quinase 5 Dependente de Ciclina/genética , Quinase 5 Dependente de Ciclina/metabolismo , Roscovitina , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
13.
Chemosphere ; 358: 142124, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38677614

RESUMO

Metformin, the most commonly prescribed drug for the treatment of diabetes, is increasingly used during pregnancy to address various disorders such as diabetes, obesity, preeclampsia, and metabolic diseases. However, its impact on neocortex development remains unclear. Here, we investigated the direct effects of metformin on neocortex development, focusing on ERK and p35/CDK5 regulation. Using a pregnant rat model, we found that metformin treatment during pregnancy induces small for gestational age (SGA) and reduces relative cortical thickness in embryos and neonates. Additionally, we discovered that metformin inhibits neural progenitor cell proliferation in the sub-ventricular zone (SVZ)/ventricular zone (VZ) of the developing neocortex, a process possibly mediated by ERK inactivation. Furthermore, metformin induces neuronal apoptosis in the SVZ/VZ area of the developing neocortex. Moreover, metformin retards neuronal migration, cortical lamination, and differentiation, potentially through p35/CDK5 inhibition in the developing neocortex. Remarkably, compensating for p35 through in utero electroporation partially rescues metformin-impaired neuronal migration and development. In summary, our study reveals that metformin disrupts neocortex development by inhibiting neuronal progenitor proliferation, neuronal migration, cortical layering, and cortical neuron maturation, likely via ERK and p35/CDK5 inhibition. Consequently, our findings advocate for caution in metformin usage during pregnancy, given its potential adverse effects on fetal brain development.


Assuntos
Proliferação de Células , Quinase 5 Dependente de Ciclina , Metformina , Neocórtex , Metformina/farmacologia , Animais , Feminino , Gravidez , Neocórtex/efeitos dos fármacos , Quinase 5 Dependente de Ciclina/metabolismo , Ratos , Proliferação de Células/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Ratos Sprague-Dawley , Diferenciação Celular/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
14.
Biomedicines ; 11(5)2023 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-37239055

RESUMO

Estrogen and estrogen receptors (ER) play a key role in breast cancer progression, which can be treated with endocrine therapy. Nevertheless, resistance to endocrine therapies is developed over time. The tumor expression of thrombomodulin (TM) is correlated with favorable prognosis in several types of cancer. However, this correlation has not yet been confirmed in ER-positive (ER+) breast cancer. This study aims to evaluate the role of TM in ER+ breast cancer. Firstly, we found that lower TM expression correlates to poor overall survival (OS) and relapse-free survival (RFS) rates in ER+ breast cancer patients through Kaplan-Meier survival analysis (p < 0.05). Silencing TM in MCF7 cells (TM-KD) increased cell proliferation, migration, and invasion ability. Additionally, TM-KD MCF7 cells showed higher sensitivity (IC50 15 µM) to the anti-cancer agent curcumin than the scrambled control cells. Conversely, overexpression of TM (TM-over) in T47D cells leads to decreased cell proliferation, migration, and invasion ability. Furthermore, TM-over T47D cells showed more resistance (IC50 > 40 µM) to the curcumin treatment. The PI staining, DAPI, and tunnel assay also confirmed that the curcumin-induced apoptosis in TM-KD MCF7 cells was higher (90.34%) than in the scrambled control cells (48.54%). Finally, the expressions of drug-resistant genes (ABCC1, LRP1, MRP5, and MDR1) were determined by qPCR. We found that the relative mRNA expression levels of ABCC1, LRP1, and MDR1 genes after curcumin treatment were higher in scrambled control cells than in TM-KD cells. In conclusion, our results demonstrated that TM plays a suppressive role in the progression and metastasis of ER+ breast cancer, and it regulates curcumin sensitivity by interfering with ABCC1, LRP1, and MDR1 gene expression.

15.
BMC Public Health ; 12: 957, 2012 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-23137234

RESUMO

BACKGROUND: Influenza A viruses that cause highly pathogenic avian influenza (HPAI) also infect humans. In many developing countries such as Ghana, poultry and humans live in close proximity in both the general and military populations, increasing risk for the spread of HPAI from birds to humans. Respiratory infections such as influenza are especially prone to rapid spread among military populations living in close quarters such as barracks making this a key population for targeted avian influenza surveillance and public health education. METHOD: Twelve military barracks situated in the coastal, tropical rain forest and northern savannah belts of the country were visited and the troops and their families educated on pandemic avian influenza. Attendants at each site was obtained from the attendance sheet provided for registration. The seminars focused on zoonotic diseases, influenza surveillance, pathogenesis of avian influenza, prevention of emerging infections and biosecurity. To help direct public health policies, a questionnaire was used to collect information on animal populations and handling practices from 102 households in the military barracks. Cloacal and tracheal samples were taken from 680 domestic and domesticated wild birds and analysed for influenza A using molecular methods for virus detection. RESULTS: Of the 1028 participants that took part in the seminars, 668 (65%) showed good knowledge of pandemic avian influenza and the risks associated with its infection. Even though no evidence of the presence of avian influenza (AI) infection was found in the 680 domestic and wild birds sampled, biosecurity in the households surveyed was very poor. CONCLUSION: Active surveillance revealed that there was no AI circulation in the military barracks in April 2011. Though participants demonstrated good knowledge of pandemic avian influenza, biosecurity practices were minimal. Sustained educational programs are needed to further strengthen avian influenza surveillance and prevention in military barracks.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Vírus da Influenza A , Influenza Aviária/prevenção & controle , Influenza Humana/epidemiologia , Instalações Militares , Militares/educação , Animais , Aves , Estudos Transversais , Feminino , Gana/epidemiologia , Humanos , Vírus da Influenza A/isolamento & purificação , Influenza Aviária/epidemiologia , Influenza Humana/prevenção & controle , Masculino , Militares/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Vigilância da População , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sensibilidade e Especificidade
16.
Acad Med ; 97(8): 1151-1157, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35385402

RESUMO

Discussion surrounding the role of the humanities as an important analytic epistemology within medical education is generally less robust than literature supporting its value in building empathy and promoting personal reflection and wellness. As such, the humanities have not been considered to be as relevant when teaching medical reasoning or technical skills. Yet, might the humanities offer value in emboldening the analytic thinking of medical learners? This article proposes an integrative conceptual model that links the thought process defining medicine-clinical reasoning-with humanistic analysis in an effort to advance the argument that the humanities offer a complementary and innovative platform that can be used within traditional medical education. The article then discusses preliminary findings from a pilot curriculum based on this model, implemented during internal medicine morning report at the University of North Carolina at Chapel Hill School of Medicine. Preliminary qualitative analysis of transcripts from the pilot curriculum demonstrates that a thought process analogous to that of clinical reasoning can be identified within guided group analyses of humanities works. Participants simultaneously used thought processes that were analytic and intuitive. The emergence of ambiguity/intuition as a theme in the pilot curriculum suggests the humanities could be a powerful tool for exploring and embracing ambiguity in clinical practice. Through the development of an integrative conceptual model, this article helps to demonstrate more explicitly the theoretical link between the reasoning pathways of the humanities and clinical medicine. Though a refined curriculum and more rigorous analysis are needed before arguing for the incorporation of the humanities into traditional graduate medical education on a larger scale, the preliminary findings here support the feasibility and promise of a curriculum based on the proposed integrative conceptual model.


Assuntos
Educação de Graduação em Medicina , Educação Médica , Raciocínio Clínico , Currículo , Educação de Pós-Graduação em Medicina , Ciências Humanas/educação , Humanos
17.
J Food Sci ; 87(2): 686-698, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35067922

RESUMO

The effect of carbon dioxide-argon radio frequency cold plasma treatment on the in vitro digestion and structural characteristics of granular and non-granular waxy maize, potato, and rice starches was investigated in this study. The effect on the fine structure of waxy potato was very minimal after plasma treatment irrespective of their granular or non-granular form. The short chain length (SCL) of waxy maize and rice (granular and non-granular) starches was reduced leading to subsequent increases in the long chain length (LCL). In vitro digestibility studies showed that cold plasma treatment enhanced (p < 0.05) the amount of slowly digestible starches (5.62%; 10.24%) and resistant starches (0.28%; 85.66%) in non-granular waxy maize (WMS NG) and granular waxy potato starches (WPS G), respectively. The amount of rapidly digestible starches increased in granular waxy maize starch (WMS G) (85.08%) but was unaffected in non-granular waxy rice (WRS NG), WPS G, and non-granular waxy potato starches after plasma treatment. FTIR-ATR data confirmed the ability of cold plasma to induce cross-linking in waxy starches specifically in WMS NG, WRS G, WRS NG, and WPS G. Overall, the unit and internal chain structure of the waxy starches were mostly unaffected by radio frequency plasma treatment. Cross-linking served as the dominant mechanism by which plasma altered the structure and digestibility of these starches. PRACTICAL APPLICATION: Cold plasma technology has been suggested as a green technique for starch modification. More research is, however, needed to facilitate the industrial scale up of this technology. In this study, we utilized a carbon dioxide-argon radio frequency cold plasma to modify waxy maize, rice and potato starches. Cold plasma treatment resulted in starches that were resistant to digestion and were highly cross-linked. The cross-linking would give the starches the ability to possibly withstand the high temperatures and shear that can be applied during industrial processing.


Assuntos
Gases em Plasma , Amilopectina , Hidrólise , Amido , Ceras , Zea mays
18.
Curr Res Food Sci ; 5: 1668-1675, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193040

RESUMO

High amylose and waxy starches from maize and potato were incubated with plasma-activated water (PAW) at 25 °C, 60 °C, and 80 °C temperatures to investigate PAW treatment effects on the starches' properties. At 60 °C incubation temperature, the starches were basically annealed with PAW. Annealing starches with PAW significantly increased (p < 0.05) the gelatinization parameters except for the enthalpy of gelatinization of waxy potato starch. Furthermore, starch swelling power significantly decreased while the water absorption capacity and solubility increased significantly when incubated at 80 °C. X-ray photoelectron spectroscopy (XPS) analysis showed the oxidation of C-C/C-H and C-O into carboxyl groups in waxy and high amylose maize starches incubated with PAW at 60 °C and 80 °C, respectively. In addition, cross-linking was observed in waxy maize and high amylose potato incubated with PAW at 80 °C and 25 °C, respectively. Overall, the results indicated PAW temperature is an important factor in modifying cereals and tuber starches with PAW.

19.
J Food Sci ; 87(8): 3496-3512, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35781707

RESUMO

In this study, the effects of extrusion conditions such as feed moisture content (20%, 24%, and 28%), screw speed (200, 300, and 400 rpm), and extrusion temperature (130, 150, and 170°C) on the physical and functional properties (moisture content, expansion ratio, bulk density, hardness, water absorption index [WAI], water solubility index [WSI]) of intermediate wheatgrass (IWG) were investigated for the first time. Response surface methodology was used to model and optimize the extrusion conditions to produce expanded IWG. The model coefficient of determination (R2 ) was high for all the responses (0.87-0.98). All the models were found to be significant (p < 0.05) and were validated with independent experiments. Generally, all the extrusion conditions were found to have significant effects on the IWG properties measured. Increasing the screw speed and decreasing the extrusion temperature resulted in IWG extrudates with a high expansion ratio. This also resulted in IWG extrudates with generally low hardness and bulk density. Screw speed was found to have the most significant effect on the WAI and WSI, with increasing screw speed resulting in a significant (p < 0.05) decrease in WAI and a significant (p < 0.05) increase in WSI. The optimum conditions for obtaining an IWG extrudate with a high expansion ratio and WAI were found to be 20% feed moisture, 200 -356 rpm screw speed, and 130-154°C extrusion temperature. PRACTICAL APPLICATION: Extrusion cooking was employed in the production of expanded IWG. This research could provide a foundation to produce expanded IWG, which can potentially be used as breakfast cereals and snacks. This is critical in the efforts to commercialize IWG for mainstream food applications.


Assuntos
Culinária , Manipulação de Alimentos , Fenômenos Químicos , Culinária/métodos , Manipulação de Alimentos/métodos , Poaceae , Solubilidade , Água
20.
PLOS Glob Public Health ; 2(12): e0001331, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36962893

RESUMO

Children with neurodevelopmental disabilities in low- and middle-income countries (LMICs) experience profound health and social inequities. While challenges faced by children living with disabilities and their caregivers have been widely documented, little is known about barriers faced by healthcare providers (HCPs) who serve these children. This study seeks to understand the barriers to testing, diagnosing, referral, and treatment of children living with cerebral palsy (CLWCP) from the perspectives of HCPs in Ghana. This qualitative study was conducted in the Greater Accra region of Ghana. A snowball sampling strategy was used to recruit HCPs from major hospitals, education centers, and health facilities. Data were collected through 11 semi-structured in-depth interviews (IDIs) with HCPs. Using an adapted version of the Sweat & Denison socio-ecological framework (SDSF), barriers to providing healthcare to CLWCPs were organized into superstructural, structural, environmental, relational, individual, and technological levels. We found that barriers to providing healthcare to CLWCPs exist at all levels of the adapted framework. The most salient barriers were identified at the superstructural, structural, and environmental levels. All HCPs expressed frustration with Ghana's health insurance policies and inadequacies of the health systems infrastructures, such as patient assessment rooms, health information systems, and pharmaceutical products for CP care. HCPs also reported that disability-related stigma often discourages providers in training from specializing in the area of developmental disabilities. HCPs emphasized critical challenges related to local perceptions of disability, gender norms and ideologies, and health system policies and infrastructure. Findings highlight the importance of identifying multi-level factors that can influence testing, diagnosing, referral, treatment, and provision of care for CLWCPs in Ghana. Addressing identified challenges from each level of influence may improve CLWCP's experiences throughout the care continuum.

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