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1.
Tob Induc Dis ; 21: 06, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36721860

RESUMO

INTRODUCTION: Smoking cessation has significant health benefits. The purpose of this study is to assess the efficacy and related factors of smoking cessation therapies in the Jazan Region of Saudi Arabia. METHODS: This is a cross-sectional study that took place at smoking cessation clinics in primary healthcare centers between January 2019 and January 2020. RESULTS: This study enrolled a total of 103 people. The success rate for quitting smoking was 36% at three months, with a 13% relapse rate at six months. Age (p=0.017), occupation (p=0.046), daily cigarette intake (p=0.015), and number of visits (p=0.001) were all found to be significant determinants of smoking cessation. In the multivariate analysis, only the number of visits increased the likelihood to quit smoking (AOR=0.31; 95% CI: 0.15-0.63). Self-efficacy was cited as the primary reason for quitting smoking by 71% of the participants, whereas family support, smoking cessation therapies, and friends' support were cited as predictive variables by 18%, 10%, and 1% of the participants, respectively. CONCLUSIONS: Smokers who received the smoking cessation intervention package were three times more likely to succeed in giving up smoking when compared to those who received the routine service. Regular follow-up during smoking cessation interventions significantly enhanced the quit rate. It is recommended that pharmacotherapy strategies and intense therapy performed face-to-face with a cessation counselor be combined to improve the quit rate.

2.
Biotechnol Genet Eng Rev ; : 1-14, 2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36617893

RESUMO

Metastatic melanoma has less frequency, but considered as the most dreaded cancer. The combination of nivolumab & ipilimumab is proving their mettle in treating metastatic melanoma. The patients when administered with the combination of nivolumab & ipilimumab have shown improved median progression free survival, objective response rate and overall survival rate compared with nivolumab and ipilimumab monotherapy. The combination shrinks the tumor cells by attacking different checkpoints viz. CTLA-4 and PD-L1, respectively. The combination treatment reveals reduced disease progression and suggests nivolumab's non-cross resistant nature. The median progression free survival in "nivolumab plus ipilimumab" group has shown an increase of 66.7% and 296.6% in comparison to nivolumab and ipilimumab monotherapy. The other parameter viz. objective response rate improvement is equivalent to almost 14% and 38.6% when compared to nivolumab and ipilimumab monotherapy, respectively.

3.
J Med Virol ; 95(1): e28412, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36527332

RESUMO

Considering the global trend to confine the COVID-19 pandemic by applying various preventive health measures, preprocedural mouth rinsing has been proposed to mitigate the transmission risk of SARS-CoV-2 in dental clinics. The study aimed to investigate the effect of different mouth rinses on salivary viral load in COVID-19 patients. This study was a single-center, randomized, double-blind, six-parallel-group, placebo-controlled clinical trial that investigated the effect of four mouth rinses (1% povidone-iodine, 1.5% hydrogen peroxide, 0.075% cetylpyridinium chloride, and 80 ppm hypochlorous acid) on salivary SARS-CoV-2 viral load relative to the distilled water and no-rinse control groups. The viral load was measured by quantitative reverse transcription PCR (RT-qPCR) at baseline and 5, 30, and 60 min post rinsing. The viral load pattern within each mouth rinse group showed a reduction overtime; however, this reduction was only statistically significant in the hydrogen peroxide group. Further, a significant reduction in the viral load was observed between povidone-iodine, hydrogen peroxide, and cetylpyridinium chloride compared to the no-rinse group at 60 min, indicating their late antiviral potential. Interestingly, a similar statistically significant reduction was also observed in the distilled water control group compared to the no-rinse group at 60 min, proposing mechanical washing of the viral particles through the rinsing procedure. Therefore, results suggest using preprocedural mouth rinses, particularly hydrogen peroxide, as a risk-mitigation step before dental procedures, along with strict adherence to other infection control measures.


Assuntos
COVID-19 , Antissépticos Bucais , Humanos , Antissépticos Bucais/uso terapêutico , SARS-CoV-2 , Peróxido de Hidrogênio , Povidona-Iodo/uso terapêutico , Cetilpiridínio/uso terapêutico , Pandemias , Carga Viral , Água
4.
Cureus ; 14(12): e32854, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36578857

RESUMO

Introduction Patient rights are an essential part of healthcare practice. In fact, patients are one of the most vulnerable members of society. As a result, improving the rights of patients is considered a priority in medical services. Aim The purpose of this study is to measure the level of patients' awareness of their rights. Subjects and methods This is a cross-sectional study conducted among patients living in Al-Ahsa, Saudi Arabia. A self-administered questionnaire was distributed among Al-Ahsa patients using an online survey. The questionnaire was composed of socio-demographic variables (i.e., age, gender, education, etc.), sources of patient information regarding patients, means of increasing awareness toward patients' rights, and a 15-item questionnaire to measure the awareness about patient rights and responsibilities. Results Among the 295 patients, 59.7% were males and 39% were aged between 31 and 40 years old. The overall mean awareness score was 54.6 (SD 7.44). 53.2% of the patients were categorized as having moderate awareness levels, 44.1% were good and only 2.7% were categorized as having poor levels of awareness. Factors associated with increased awareness were being older, hospital admission, hospital visitation for the last three months, and healthcare providers as the sources of the patient's right information. Conclusion There was sufficient awareness of patient rights and responsibilities in our region. Increasing age, frequent hospital visitation, and education given by healthcare providers could effectively improve awareness of patient rights and responsibilities. A multicenter study is required to shed more light on the awareness of patients regarding their rights and responsibilities.

5.
Healthcare (Basel) ; 10(11)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36360499

RESUMO

BACKGROUND: Traumatic brain injury (TBI) is a serious issue and a leading cause of death and disability worldwide. Caregivers of TBI patients experience psychological distress and a variety of social and financial issues. The present study aims to investigate the caregiver's burden and the factors that influence this burden. Furthermore, the present study will find out the association of religious practice, religious coping relations and psychological distress among caregivers of children affected with TBI. METHODS: A cross-sectional survey was conducted on 302 caregivers of children with TBI using Duke University Religion Index (DURL) for religious practice. General Health Questionaire-12 (GHQ-12) was used for anxiety and depression and Brief Religious Coping Scale (RCOPE) was used for coping strategies. The caregivers were conveniently chosen from different regions of Khyber Pakhtunkhwa province and data was collected from different tertiary care hospitals in Peshawar. RESULTS: Forty-nine (49) % of caregivers score ≥ 3 on GHQ suffer from psychological distress with a Mean of 20.957 ± 4.175). Positive coping methods were mostly used by caregivers than negative coping have a low level of distress with a Mean Positive Coping (P-COPE ) of 6.93 ± 0.41, Mean of Negative Coping (N-COPE) 0.486 ± 1.023. In religious practice, caregivers mostly participate in Organized Reliogious Activities (ORA) or some Non-Organized Reliogious Activities (NORA) with a Mean ORA of 4.20 ± 1.27, and NORA Mean of 4.17 ± 1.37 used by the caregivers. Coping methods were related to Caregiver psychological distress (GHQ-12 and P-COPE co-relation scores are (ρ -0.022, p b 0.05); GHQ-12 scores and N-COPE (ρ + 0.221=, p b 0.001). There is a negative correlation between GHQ 12 and PCOPE, while GHQ12 is positively correlated with NCOPE. CONCLUSION: According to this study, there is a significant association between religious coping methods, religious practice, and psychological distress among caregivers of children with traumatic brain injury.

6.
NPJ Breast Cancer ; 8(1): 118, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335120

RESUMO

This nonrandomized, open-label, multi-cohort Phase 1b study (NCT02779751) investigated the safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) without prior CDK4 and 6 inhibitor exposure. Patients were divided into two cohorts: treatment naïve (cohort 1) and pretreated (cohort 2). Patients received abemaciclib plus pembrolizumab with (cohort 1) or without (cohort 2) anastrozole over 21-day cycles. The primary objective was safety, and secondary objectives included efficacy and pharmacokinetics (PK). Cohort 1/2 enrolled 26/28 patients, respectively. Neutropenia (30.8/28.6%), AST increase (34.6/17.9%), ALT increase (42.3/10.7%), and diarrhea (3.8/10.7%) were the most frequent grade ≥3 adverse events in cohort 1/2, respectively. A total of two deaths occurred, which investigators attributed to treatment-related adverse events (AEs), both in cohort 1. Higher rates of all grade and grade ≥3 interstitial lung disease (ILD)/pneumonitis were observed compared to previously reported with abemaciclib and pembrolizumab monotherapy. The PK profiles were consistent between cohorts and with previous monotherapy studies. In cohorts 1/2, the overall response rate and disease control rate were 23.1/28.6% and 84.6/82.1%, respectively. Median progression-free survival and overall survivals were 8.9 (95% CI: 3.9-11.1) and 26.3 months (95% CI: 20.0-31.0) for cohort 2; cohort 1 data are immature. Abemaciclib plus pembrolizumab demonstrated antitumor activity, but high rates of ILD/pneumonitis and severe transaminase elevations occurred with/without anastrozole compared to the previous reporting. Benefit/risk analysis does not support further evaluation of this combination in the treatment of HR+, HER2- MBC.

7.
Cureus ; 14(9): e29692, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36321042

RESUMO

Background "Bounce back" patients is a term used to refer to patients returning to the emergency department within 72 hours after the first visit. This can be attributed to various factors related to diagnosis, management, or the health care system. Objective This study sought to evaluate the extent of bounce-back patients in the emergency department of King Abdullah Medical City (KAMC), Makkah, Saudi Arabia, and then explore the possible relationship between shock index (SI) and bounce-back patients. Methods This is a retrospective chart review of the electronic system among patients who have returned to the emergency department within 72 hours from the index visit. All records were reviewed from May 2019 to May 2021. Vital signs were collected to calculate the shock index (heart rate/systolic blood pressure). The data were analyzed by SPSS Statistics v.27.0 (IBM Corp., Armonk, NY).  Results A total of (506) responses were analyzed. The median age was 56 years with an IQR of 40-67, and males represented 55.3%. Around three-quarters of the second complaints (76.9%) were related to the index visit. The durations between the visits were as follows: 51.8% within 24 hours, 30.2% within 25-48 hours, and 18% within 49-72 hours. The median and IQR for shock index were 0.67 and 0.59-0.80 respectively, while the median and IQR for reverse shock index were 1.49 and 1.25-1.71 respectively. Diabetes and the duration between the two visits were associated with the complaints (p-value=0.005, p-value=0.011) respectively. Conclusion The majority of bounce-back cases occurred within the first 24 hours in our sample. Hypertension, diabetes, and ischemic heart diseases were the most prevalent comorbidities among the bounce-back patients. The majority of bounce-back patients (76.9%) presented with complaints related to the index visit.

8.
Medicina (Kaunas) ; 58(11)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36422197

RESUMO

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a condition usually caused by a single gene mutation and manifested by both renal and extrarenal features, eventually leading to end-stage renal disease (ESRD) by the median age of 60 years worldwide. Approximately 89% of ADPKD patients had either PKD1 or PKD2 gene mutations. The majority (85%) of the mutations are in the PKD1 gene, especially in the context of family history. Objectives: This study investigated the genetic basis and the undiscovered genes that are involved in ADPKD development among the Saudi population. Materials and Methods: In this study, 11 patients with chronic kidney disease were enrolled. The diagnosis of ADPKD was based on history and diagnostic images: CT images include enlargement of renal outlines, renal echogenicity, and presence of multiple renal cysts with dilated collecting ducts, loss of corticomedullary differentiation, and changes in GFR and serum creatinine levels. Next-generation whole-exome sequencing was conducted using the Ion Torrent PGM platform. Results: Of the 11 Saudi patients diagnosed with chronic kidney disease (CKD) and ADPKD, the most common heterozygote nonsynonymous variant in the PKD1 gene was exon15: (c.4264G > A). Two missense mutations were identified with a PKD1 (c.1758A > C and c.9774T > G), and one patient had a PKD2 mutation (c.1445T > G). Three detected variants were novel, identified at PKD1 (c.1758A > C), PKD2L2 (c.1364A > T), and TSC2 (deletion of a'a at the 3'UTR, R1680C) genes. Other variants in PKD1L1 (c.3813_381 4delinsTG) and PKD1L2 (c.404C > T) were also detected. The median age of end-stage renal disease for ADPK patients in Saudi Arabia was 30 years. Conclusion: This study reported a common variant in the PKD1 gene in Saudi patients with typical ADPKD. We also reported (to our knowledge) for the first time two novel missense variants in PKD1 and PKD2L2 genes and one indel mutation at the 3'UTR of the TSC2 gene. This study establishes that the reported mutations in the affected genes resulted in ADPKD development in the Saudi population by a median age of 30. Nevertheless, future protein-protein interaction studies to investigate the influence of these mutations on PKD1 and PKD2 functions are required. Furthermore, large-scale population-based studies to verify these findings are recommended.


Assuntos
Falência Renal Crônica , Rim Policístico Autossômico Dominante , Insuficiência Renal Crônica , Adulto , Humanos , Regiões 3' não Traduzidas , Proteínas de Membrana/genética , Mutação/genética , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/diagnóstico , Arábia Saudita , Canais de Cátion TRPP/genética
9.
Front Immunol ; 13: 944452, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311781

RESUMO

Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor of the central nervous system and has a very poor prognosis. The current standard of care for patients with GBM involves surgical resection, radiotherapy, and chemotherapy. Unfortunately, conventional therapies have not resulted in significant improvements in the survival outcomes of patients with GBM; therefore, the overall mortality rate remains high. Immunotherapy is a type of cancer treatment that helps the immune system to fight cancer and has shown success in different types of aggressive cancers. Recently, healthcare providers have been actively investigating various immunotherapeutic approaches to treat GBM. We reviewed the most promising immunotherapy candidates for glioblastoma that have achieved encouraging results in clinical trials, focusing on immune checkpoint inhibitors, oncolytic viruses, nonreplicating viral vectors, and chimeric antigen receptor (CAR) immunotherapies.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Receptores de Antígenos Quiméricos , Humanos , Glioblastoma/patologia , Imunoterapia/métodos , Neoplasias Encefálicas/patologia , Prognóstico , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/uso terapêutico , Fatores Imunológicos/uso terapêutico
10.
Mymensingh Med J ; 31(4): 1183-1191, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36189570

RESUMO

Hypertensive kidney damage results in glomerular as well as tubular dysfunction. Albuminuria is a well-known marker of glomerular damage. On the other hand, urinary uromodulin is increasingly considered as a potential biomarker of early tubular dysfunction. The aim of the study was to assess glomerular and tubular function of the kidney by measuring urinary albumin and uromodulin excretion in hypertensive subjects. This cross-sectional study was conducted from July 2018 to June 2019 in Hypertension Clinic of Dhaka Medical College Hospital, Dhaka and Kidney Care and Research Centre, Sonargaon, Narayanganj, Bangladesh. In this study 122 hypertensive subjects with age >30 years, duration of hypertension <5 years, without accelerated or malignant BP, absence of dipstick proteinuria and eGFR >60ml/min were included. There were also 33 normotensive individuals included as healthy controls. Albumin-creatinine ratio (uACR mg/g), urine uromodulin-creatinine ratio (uUMODµg/g), urinary sodium-creatinine ratio (mEq/g) and potassium-creatinine ratio (mEq/g) were measured from single morning spot urine sample. Urinary uromodulin levels were measured by ELISA method. The hypertensive and normotensive subjects were age matched 49.0±12.0 vs. 48.0±11.0, years (p=NS). The mean uACR was 29.0±65.0 versus 5.6±2.7mg/g, (p<0.001) respectively. The median uUMOD in hypertensive subjects was 3.38 (1.73-9.06) and in normotensives 3.85(2.28-5.69) µg/g (p=non significant). Multivariate analysis showed significant inverse association between diastolic blood pressure and urinary uromodulin excretion. A uUMOD cut-off of 2.9 (25th percentile) showed eGFR, urinary sodium and potassium excretions were significantly lower at low uromodulin group. The glomerular involvement was found in 21.0% of hypertensive subjects as evidenced by albuminuria. No difference was observed in urinary uromodulin level between hypertensive and normotensive subjects. Low urinary uromodulin level was associated with lower eGFR, Na+ and K+ excretion which indicate simultaneous tubular and glomerular involvement.


Assuntos
Hipertensão , Nefropatias , Adulto , Albuminas , Albuminúria , Bangladesh , Biomarcadores , Creatinina/urina , Estudos Transversais , Hipertensão Essencial/complicações , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Potássio , Sódio , Uromodulina/urina
11.
Front Aging Neurosci ; 14: 977411, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158539

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive loss of cognitive functions like thinking, memory, reasoning, behavioral abilities, and social skills thus affecting the ability of a person to perform normal daily functions independently. There is no definitive cure for this disease, and treatment options available for the management of the disease are not very effective as well. Based on histopathology, AD is characterized by the accumulation of insoluble deposits of amyloid beta (Aß) plaques and neurofibrillary tangles (NFTs). Although several molecular events contribute to the formation of these insoluble deposits, the aberrant post-translational modifications (PTMs) of AD-related proteins (like APP, Aß, tau, and BACE1) are also known to be involved in the onset and progression of this disease. However, early diagnosis of the disease as well as the development of effective therapeutic approaches is impeded by lack of proper clinical biomarkers. In this review, we summarized the current status and clinical relevance of biomarkers from cerebrospinal fluid (CSF), blood and extracellular vesicles involved in onset and progression of AD. Moreover, we highlight the effects of several PTMs on the AD-related proteins, and provide an insight how these modifications impact the structure and function of proteins leading to AD pathology. Finally, for disease-modifying therapeutics, novel approaches, and targets are discussed for the successful treatment and management of AD.

12.
Polymers (Basel) ; 14(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36080654

RESUMO

Colon cancer (CC) is one of major causes of mortality and affects the socio-economic status world-wide. Therefore, developing a novel and efficient delivery system is needed for CC management. Thus, in the present study, lipid polymer hybrid nanoparticles of apigenin (LPHyNPs) was prepared and characterized on various parameters such as particle size (234.80 ± 12.28 nm), PDI (0.11 ± 0.04), zeta potential (-5.15 ± 0.70 mV), EE (55.18 ± 3.61%), etc. Additionally, the DSC, XRD, and FT-IR analysis determined drug entrapment and affinity with the selected excipient, demonstrating a promising drug affinity with the lipid polymer. Morphological analysis via SEM and TEM exhibited spherical NPs with a dark color core, which indicated drug entrapment inside the core. In vitro release study showed significant (p < 0.05) sustained release of AGN from LPHyNPs than AGN suspension. Further, the therapeutic efficacy in terms of apoptosis and cell cycle arrest of developed LPHyNPs against CC was estimated by performing flow cytometry and comparing its effectiveness with blank LPHyNPs and AGN suspension, which exhibited remarkable outcomes in favor of LPHyNPs. Moreover, the mechanism behind the anticancer attribute was further explored by estimating gene expression of various signaling molecules such as Bcl-2, BAX, NF-κB, and mTOR that were involved in carcinogenic pathways, which indicated significant (p < 0.05) results for LPHyNPs. Moreover, to strengthen the anticancer potential of LPHyNPs against chemoresistance, the expression of JNK and MDR-1 genes was estimated. Outcomes showed that their expression level reduced appreciably when compared to blank LPHyNPs and AGN suspension. Hence, it can be concluded that developed LPHyNPs could be an efficient therapeutic system for managing CC.

13.
Cancer Cell Int ; 22(1): 279, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071488

RESUMO

Cancer is a major health concern and accounts for one of the main causes of death worldwide. Innovative strategies are needed to aid in the diagnosis and treatment of different types of cancers. Recently, there has been an evolving interest in utilizing nanobodies of camel origin as therapeutic tools against cancer. Nanotechnology uses nanobodies an emerging attractive field that provides promises to researchers in advancing different scientific sectors including medicine and oncology. Nanobodies are characteristically small-sized biologics featured with the ability for deep tissue penetration and dissemination and harbour high stability at high pH and temperatures. The current review highlights the potential use of nanobodies that are naturally secreted in camels' biological fluids, both milk and urine, in the development of nanotechnology-based therapy for treating different typesQuery of cancers and other diseases. Moreover, the role of nano proteomics in the invention of novel therapeutic agents specifically used for cancer intervention is also illustrated.

14.
Biotechnol Genet Eng Rev ; : 1-22, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123822

RESUMO

Bacterial co-infections are typically associated with viral respiratory tract infections and pose a significant public health problem around the world. COVID-19 infection damages tissues lining the respiratory track and regulates immune cells/cytokines leading to microbiome dysbiosis and facilitating the area to be colonized by pathogenic bacterial agents. There have been reports of different types of bacterial co-infection in COVID-19 patients. Some of these reports showed despite geographical differences and differences in hospital settings, bacterial co-infections are a major cause of morbidity and mortality in COVID-19 patients. The inappropriate use of antibiotics for bacterial infections, particularly broad-spectrum antibiotics, can also further complicate the infection process, often leading to multi drug resistance, clinical deterioration, poor prognosis, and eventually death. To this end, researchers must establish a new therapeutic approach to control SARS-CoV-2 and the associated microbial coinfections. Hence, the aim of this review is to highlight the bacterial co-infection that has been recorded in COVID-19 patients and the status of antimicrobial resistance associated with the dual infections.

15.
PLoS One ; 17(9): e0274412, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36129901

RESUMO

Dietary supplements are products containing dietary elements including vitamins, minerals, amino acids, herbs, or botanicals. They can aid consumers with low dietary intake and quality, as well as those with high demands, by boosting nutritious value. A cross-sectional study was conducted among adults living in Saudi Arabia aged between 18-60 years old using online self-administered questionnaire. Information regarding sociodemographic characteristics, use and type of dietary supplements, and attitude toward and patterns of dietary supplement use was collected. The chi-square test, Pearson correlations, and the independent t-test were used. In total, 531 participants (115 men and 416 women) were included. Approximately half of the participants (51.8%, n = 275) used dietary supplements. Participants who were using dietary supplements were significantly younger (29.16 ± 9.32 years), more highly educated (85.5%, n = 235), and worked in the health sector (63.7%, n = 100). Herbal supplement use was associated with older age and female sex. Single mineral supplements were used more frequently by married, female, pregnant, or breastfeeding participants and those not working in the health sector. Fatty supplements were used more frequently by participants with a higher level of education. Regarding the attitude toward dietary supplement use, women, single participants, and health care workers showed a significant positive attitude. In-depth investigation into the amount of and reasons for dietary supplement use in the health sector is required. Additionally, educating pregnant and breastfeeding women on the importance of dietary supplements is necessary.


Assuntos
Suplementos Nutricionais , Vitaminas , Adolescente , Adulto , Aminoácidos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minerais , Gravidez , Prevalência , Arábia Saudita , Adulto Jovem
16.
J Cell Physiol ; 237(11): 4021-4036, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36063496

RESUMO

Extracellular vehicles (EVs) are nanoscale lipid bilayer vesicles that carry biologically active biomolecule cargos like proteins, lipids, and nucleic acids (DNA, RNA) outside of the cell. Blood (serum/plasma), urine, and bronchoalveolar lavage fluid are all examples of biofluids from which they may be collected. EVs play a vital role in intracellular communication. The molecular signature of EVs largely depends on the parental cell's status. EVs are classified into two groups, (1) exosomes (originated by endogenous route) and (2) microvesicles (originated from the plasma membrane, also known as ectosomes). The quantity and types of EV cargo vary during normal conditions compared to pathological conditions (chronic inflammatory lung diseases or lung cancer). Consequently, EVs contain novel biomarkers that differ based on the cell type of origin and during lung diseases. Small RNAs (e.g., microRNAs) are transported by EVs, which is one of the most rapidly evolving research areas in the field of EVs biology. EV-mediated cargos transport small RNAs that can result in reprograming the target/recipient cells. Multiple chronic inflammatory lung illnesses, such as chronic obstructive pulmonary disease, asthma, pulmonary hypertension, pulmonary fibrosis, cystic fibrosis, acute lung injury, and lung cancer, have been demonstrated to be regulated by EV. In this review, we will consolidate the current knowledge and literature on the novel role of EVs and their small RNAs concerning chronic lung diseases (CLDs). Additionally, we will also provide better insight into the clinical and translational impact of mesenchymal stem cells-derived EVs as novel therapeutic agents in treating CLDs.


Assuntos
Exossomos , Vesículas Extracelulares , Pneumopatias , Neoplasias Pulmonares , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Exossomos/genética , Exossomos/metabolismo , Pneumopatias/genética , Neoplasias Pulmonares/metabolismo
17.
Discov Oncol ; 13(1): 94, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36169772

RESUMO

Glioblastoma multiforme (GBM) is one of the most aggressive glial cell tumors in adults. Although current treatment options for GBM offer some therapeutic benefit, median survival remains poor and does not generally exceed 14 months. Several genes, such as isocitrate dehydrogenase (IDH) enzyme and O6-methylguanine-DNA methyltransferase (MGMT), have been implicated in pathogenesis of the disease. Treatment is often adapted based on the presence of IDH mutations and MGMT promoter methylation status. Recent GBM cell line studies have associated Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) expression with high-grade tumors. Increased Nrf2 expression is often found in tumors with IDH-1 mutations. Nrf2 is an important transcription factor with anti-apoptotic, antioxidative, anti-inflammatory, and proliferative properties due to its complex interactions with multiple regulatory pathways. In addition, evidence suggests that Nrf2 promotes  GBM cell survival in hypoxic environment,by up-regulating hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Downregulation of Nrf2 has been shown to improve GBM sensitivity to chemotherapy drugs such as Temozolomide. Thus, Nrf2 could be a key regulator of GBM pathways and potential therapeutic target.  Further research efforts exploring an interplay between Nrf2 and major molecular signaling mechanisms could offer novel GBM drug candidates with a potential to significantly improve patients prognosis.

18.
Vaccines (Basel) ; 10(8)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36016218

RESUMO

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that can transmit from dromedary camels to humans, causing severe pneumonia, with a 35% mortality rate. Vaccine candidates have been developed and tested in mice, camels, and humans. Previously, we developed a vaccine based on the modified vaccinia virus Ankara (MVA) viral vector, encoding a full-length spike protein of MERS-CoV, MVA-MERS. Here, we report the immunogenicity of high-dose MVA-MERS in prime-boost vaccinations in mice and camels. METHODS: Three groups of mice were immunised with MVA wild-type (MVA-wt) and MVA-MERS (MVA-wt/MVA-MERS), MVA-MERS/MVA-wt, or MVA-MERS/MVA-MERS. Camels were immunised with two doses of PBS, MVA-wt, or MVA-MERS. Antibody (Ab) responses were evaluated using ELISA and MERS pseudovirus neutralisation assays. RESULTS: Two high doses of MVA-MERS induced strong Ab responses in both mice and camels, including neutralising antibodies. Anti-MVA Ab responses did not affect the immune responses to the vaccine antigen (MERS-CoV spike). CONCLUSIONS: MVA-MERS vaccine, administered in a homologous prime-boost regimen, induced high levels of neutralising anti-MERS-CoV antibodies in mice and camels. This could be considered for further development and evaluation as a dromedary vaccine to reduce MERS-CoV transmission to humans.

19.
Front Cell Infect Microbiol ; 12: 964265, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034704

RESUMO

An outbreak of coronavirus disease 2019 (COVID-19) emerged in China in December 2019 and spread so rapidly all around the globe. It's continued and spreading more dangerously in India and Brazil with higher mortality rate. Understanding of the pathophysiology of COVID-19 depends on unraveling of interactional mechanism of SARS-CoV-2 and human immune response. The immune response is a complex process, which can be better understood by understanding the immunological response and pathological mechanisms of COVID-19, which will provide new treatments, increase treatment efficacy, and decrease mortality associated with the disease. In this review we present a amalgamate viewpoint based on the current available knowledge on COVID-19 which includes entry of the virus and multiplication of virus, its pathological effects on the cellular level, immunological reaction, systemic and organ presentation. T cells play a crucial role in controlling and clearing viral infections. Several studies have now shown that the severity of the COVID-19 disease is inversely correlated with the magnitude of the T cell response. Understanding SARS-CoV-2 T cell responses is of high interest because T cells are attractive vaccine targets and could help reduce COVID-19 severity. Even though there is a significant amount of literature regarding SARS-CoV-2, there are still very few studies focused on understanding the T cell response to this novel virus. Nevertheless, a majority of these studies focused on peripheral blood CD4+ and CD8+ T cells that were specific for viruses. The focus of this review is on different subtypes of T cell responses in COVID-19 patients, Th17, follicular helper T (TFH), regulatory T (Treg) cells, and less classical, invariant T cell populations, such as δγ T cells and mucosal-associated invariant T (MAIT) cells etc that could influence disease outcome.


Assuntos
COVID-19 , Brasil , Linfócitos T CD8-Positivos , Humanos , SARS-CoV-2 , Subpopulações de Linfócitos T
20.
Infect Drug Resist ; 15: 4127-4136, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937784

RESUMO

Purpose: This study was conducted to investigate antibody immune responses induced by BNT162b2 and AZD1222 human COVID-19 vaccines in Riyadh city, Saudi Arabia. Patients and Methods: ELISA was used to evaluate antibodies, against the SARS-CoV-2 spike S1 protein, in serum samples from 432 vaccinated individuals at six time points: pre-vaccination (baseline), post-prime, post-boost, 6-months, and 1 year post-vaccination, and 3 weeks post a third dose. Virus microneutralization assay was used to confirm antibody responses in a subset of samples. Results: Anti-SARS-CoV-2 spike IgG were detected in most subjects post-prime, reached a peak level post-boost, and remained at high level at the 6-month follow-up. At 1 year post-vaccine, the antibody levels were low but increased to a significant level higher than the peak following a third dose. The third dose was given at an average of 250 days after the second dose. The virus microneutralization assay confirmed the neutralization activity of the induced SARS-CoV-2 IgG antibodies. The vaccines induced higher IgG titres at post-prime (p=0.0001) and 6 months (p=0.006) in previously infected individuals. An increased interval between prime and boost, more than recommended time, appeared to enhance the IgG levels (p=0004). Moreover, the vaccines induced higher IgG levels in younger subjects (p=0.01). Conclusion: These data provide insights and build on the current understanding of immune responses induced by these two vaccines; and support a third boosting dose for these COVID-19 vaccines.

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