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1.
Artigo em Inglês | MEDLINE | ID: mdl-38637182

RESUMO

Communication is an integral component of effective healthcare delivery to patients, and this includes breaking bad news (BBN). However, clinicians in dentistry are rarely exposed to diseases that can negatively and seriously affect an individual's view of their future and pose a mortality risk, except for oral cancer. The aim of this study was to assess clinician practices in BBN of oral cancer diagnosis in Malaysia. An exploratory sequential mixed-methods study design was used. A qualitative study was conducted among 12 clinicians to gather relevant information regarding their practices in BBN of oral cancer diagnosis using a descriptive-interpretive approach. The themes that emerged were preparation for BBN, BBN setting, communication, emotional aspects, and summarizing the session. These themes were used to develop a questionnaire with 34 items. In the quantitative study, this questionnaire was sent to 87 clinicians who had experienced BBN of oral cancer diagnosis in the past 5 years; the response rate was 100%. An arbitrary cut-off score between the third and fourth quartiles was set to distinguish 'good' and 'poor' practice in BBN among the clinicians. The data analysis was performed using IBM SPSS Statistics version 23.0. Overall, at least two-thirds of the clinicians had good practices in BBN of oral cancer diagnosis. The clinicians' designation (oral and maxillofacial surgery consultant/specialist vs dental officer) and BBN experiences were factors associated with their practices in BBN of oral cancer diagnosis.

2.
Heliyon ; 10(7): e27559, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560135

RESUMO

Ethylene Glycol (EG) and diethylene Glycol (DEG) are two contaminants known to cause various human health problems. These glycols might be present in drug syrups that are based on glycerol, sorbitol, or polyethylene glycol. In late 2022, several batches of cough, antipyretics, and antihistamine syrups were reported to contain toxic levels of EG and DEG in multiple countries; this incident concerned the World Health Organization (WHO). From an analytical perspective, several methods of glycols analysis in pharmaceuticals have been reported in the literature, with the majority being dedicated to raw material analysis. This study aims to develop a selective method capable of evaluating a wide range of paediatric syrups in order to assess the safety of commercially available paediatric syrups currently distributed in the local market. This research introduces a method for determining glycols utilizing gas chromatography-tandem mass spectrometry (GC-MS/MS), which offers significantly higher selectivity than conventional single quadrupole gas chromatography-mass spectrometry (GC-MS). The developed method meets the current International Council for Harmonisation (ICH) guidelines for validation. The absence of any interfering peaks in both the unspiked sample of promethazine syrup and the reference standard solutions proved the method's selectivity. Furthermore, 2,2,2-trichloroethanol was used as an internal standard, and a new GC-MS/MS method was developed to analyze it. The calibration curves for EG and DEG were linear within the selected concentration range of 1-10 µg/mL. The detection limit for both EG and DEG was 400 ng/mL, while the quantification limit was 1 µg/mL. Recovery values for both EG and DEG met the accuracy acceptance criterion. Thus, the developed method proved to be efficient and accurate for determining EG and DEG levels in suspected contaminated syrups.

3.
Microsc Res Tech ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581370

RESUMO

To incorporate different concentrations of Al2O9Zr3 (1%, 5%, and 10%) nanoparticles (NP) into the ER adhesive and subsequently assess the impact of this addition on the degree of conversion, µTBS, and antimicrobial efficacy. The current research involved a wide-ranging examination that merged various investigative techniques, including the application of scanning electron microscopy (SEM) for surface characterization of NP coupled with energy-dispersive x-ray spectroscopy (EDX), Fourier-transform infrared (FTIR) spectroscopy, µTBS testing, and microbial analysis. Teeth were divided into four groups based on the application of modified and unmodified three-step ER adhesive primer. Group 1 (0% Al2O9Zr3 NPs) Control, Group 2 (1% Al2O9Zr3 NPs), Group 3 (5% Al2O9Zr3 NPs), and Group 4 (10% Al2O9Zr3 NPs). EDX analysis of Al2O9Zr3 NPs was performed showing elemental distribution in synthesized NPs. Zirconium (Zr), Aluminum (Al), and Oxides (O2). After primer application, an assessment of the survival rate of Streptococcus mutans was completed. The FTIR spectra were analyzed to observe the characteristic peaks indicating the conversion of double bonds, both before and after the curing process, for the adhesive Etch and rinse containing 1,5,10 wt% Al2O9Zr3 NPs. µTBS and failure mode assessment were performed using a Universal Testing Machine (UTM) and stereomicroscope respectively. The µTBS and S.mutans survival rates comparison among different groups was performed using one-way ANOVA and Tukey post hoc (p = .05). Group 4 (10 wt% Al2O9Zr3 NPs + ER adhesive) specimens exhibited the minimum survival of S.mutans (0.11 ± 0.02 CFU/mL). Nonetheless, Group 1 (0 wt% Al2O9Zr3 NPs + ER adhesive) displayed the maximum surviving S.mutans (0.52 ± 0.08 CFU/mL). Moreover, Group 2 (1 wt% Al2O9Zr3 NPs + ER adhesive) (21.22 ± 0.73 MPa) samples displayed highest µTBS. However, the bond strength was weakest in Group 1 (0 wt% Al2O9Zr3 NPs + ER adhesive) (14.13 ± 0.32 MPa) study samples. The etch-and-rinse adhesive exhibited enhanced antibacterial activity and micro-tensile bond strength (µTBS) when 1% Al2O9Zr3 NPs was incorporated, as opposed to the control group. Nevertheless, the incorporation of Al2O9Zr3 NPs led to a decrease in DC. RESEARCH HIGHLIGHTS: 10 wt% Al2O9Zr3 NPs + ER adhesive specimens exhibited the minimum survival of S.mutans. 1 wt% Al2O9Zr3 NPs + ER adhesive samples displayed the most strong composite/CAD bond. The highest DC was observed in Group 1: 0 wt% Al2O9Zr3 NPs + ER adhesive.

4.
Front Pharmacol ; 15: 1346526, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487169

RESUMO

Excessive and imbalance of free radicals within the body lead to inflammation. The objective of the current research work was to explore the anti-inflammatory and antioxidant potential of the isolated compounds from Habenaria digitata. In this study, the isolated phenolic compounds were investigated for in vitro and in vivo anti-inflammatory potential along with the antioxidant enzyme. The anti-inflammatory and antioxidant potential of the phenolic compounds was assayed via various enzymes like COX-1/2, 5-LOX and ABTS, DPPH, and H2O2 free radical enzyme inhibitory assay. These compounds were also explored for their in vivo antioxidant activity like examining SOD, CAT, GSH-Px, and MDA levels in the brain, heart, and liver. The anti-inflammatory potential was evaluated using the carrageenan-induced pleurisy model in mice. On the basis of initial screening of isolated compounds, the most potent compound was further evaluated for the anti-inflammatory mechanism. Furthermore, the molecular docking study was also performed for the potent compound. The phenolic compounds were isolated and identified by GC-MS/NMR analysis by comparing its spectra to the library spectra. The isolated phenolic compounds from H. digitata were 5-methylpyrimidine-24,4-diol (1), 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (2), 2-isopropyl-5-methylphenol (3), 3-methoxy-4-vinylphenol (4), and 2,6-dimethoxy-4-vinylphenol (5). In in vitro antioxidant assay, the most potent compound was compound 1 having IC50 values of 0.98, 0.90, and 5 µg/mL against ABTS, DPPH, and H2O2, respectively. Similarly, against COX1/2 and 5-LOX ,compound 1 was again the potent compound with IC50 values of 42.76, 10.70, and 7.40 µg/mL. Based on the in vitro results, compound 1 was further evaluated for in vivo antioxidant and anti-inflammatory potential. Findings of the study suggest that H. digitata contains active compounds with potential anti-inflammatory and antioxidant effects. These compounds could be screened as drug candidates for pharmaceutical research, targeting conditions associated with oxidative stress and inflammatory conditions in medicinal chemistry and support their ethnomedicinal use for inflammation and oxidative stress.

5.
Glob Health Res Policy ; 9(1): 10, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38486301

RESUMO

The COVID-19 pandemic has dramatically threatened the Gulf Cooperation Council (GCC) countries which have a large proportion of foreign workers. The governments of GCC countries have proactively implemented a comprehensive set of policy measures, and up to our knowledge, a systematic analysis of qualitative and quantitative evidence on the government response is still lacking. We summarized the GCC countries' government response and quantitatively measured that response using four indexes-the Government Response Index, the Stringency Index, the Vaccine Index, and the Initial Response Index, to analyse their response for future pandemic preparedness. Overall, the government response of all the GCC countries to the COVID-19 pandemic has been comprehensive, stringent, and timely. Notably, the GCC countries have implemented comprehensive vaccine policies. In addition, they have worked actively to protect foreign workers to improve their access to health services and secure their essential living conditions, regardless of their immigrant status. All the GCC countries dynamically adjusted their response to the evolving COVID-19 epidemiological burden and started to relax the stringency of the control policies after the Omicron wave, though the governments had different response magnitudes as measured by the four indexes. These findings have provided several important lessons for future pandemic response and preparedness for countries with similar economic, demographic, and health contexts in (1) prompt actions of containment and closure policies with dynamic adjusting, (2) strengthening health system policies, (3) comprehensive vaccination policies with universal access, (4) equitable and free access to testing, diagnosis, and treatment for all, and (5) strengthening the resilience of health systems.


Assuntos
COVID-19 , Vacinas , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Governo , Política de Saúde
6.
PLoS One ; 19(3): e0300504, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38484005

RESUMO

Direct recycling of aluminum waste is crucial in sustainable manufacturing to mitigate environmental impact and conserve resources. This work was carried out to study the application of hot press forging (HPF) in recycling AA6061 aluminum chip waste, aiming to optimize operating factors using Response Surface Methodology (RSM), Artificial Neural Network (ANN) and Genetic algorithm (GA) strategy to maximize the strength of recycled parts. The experimental runs were designed using Full factorial and RSM via Minitab 21 software. RSM-ANN models were employed to examine the effect of factors and their interactions on response and to predict output, while GA-RSM and GA-ANN were used for optimization. The chips of different morphology were cold compressed into billet form and then hot forged. The effect of varying forging temperature (Tp, 450-550°C), holding time (HT, 60-120 minutes), and chip surface area to volume ratio (AS:V, 15.4-52.6 mm2/mm3) on ultimate tensile strength (UTS) was examined. Maximum UTS (237.4 MPa) was achieved at 550°C, 120 minutes and 15.4 mm2/mm3 of chip's AS: V. The Tp had the largest contributing effect ratio on the UTS, followed by HT and AS:V according to ANOVA analysis. The proposed optimization process suggested 550°C, 60 minutes, and 15.4 mm2 as the optimal condition yielding the maximum UTS. The developed models' evaluation results showed that ANN (with MSE = 1.48%) outperformed RSM model. Overall, the study promotes sustainable production by demonstrating the potential of integrating RSM and ML to optimize complex manufacturing processes and improve product quality.


Assuntos
Alumínio , Redes Neurais de Computação , Temperatura , Temperatura Baixa , Software
7.
Cureus ; 16(3): e55967, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38469368

RESUMO

BACKGROUND: Vitamin D deficiency is a major global health problem. Most previous studies focused attention on the significant role of sunlight exposure in the homeostasis of vitamin D and calcium blood levels. Magnesium is pivotal in the proper functioning of vitamin D, and the physiologic functions of different organs require a balanced vitamin D and magnesium status. The relationship between sunlight exposure and blood levels of vitamin D and magnesium has often been overlooked. The aim of this study was to evaluate vitamin D and magnesium status based on sunlight exposure and ethnicity in Bahraini and expatriate workers. METHODS: A cross-sectional study was conducted between October 2018 and September 2019. One hundred and seventy-four subjects participated in this study were subdivided based on their ethnicity and work environment-dependent exposure to sunlight into four groups: (1) Bahraini exposed (n=94), (2) Bahraini non-exposed (n=25), (3) expatriate exposed (n=31), and (4) expatriate non-exposed (n=24). Blood levels of vitamin D and magnesium were evaluated for all the participants. RESULTS:  Independent of ethnicity, vitamin D levels were insignificantly different among the studied groups and were all below the normal reference range. Yet, there was still a sunlight-dependent increase in vitamin D level that could be seen only in Bahraini workers. Magnesium levels were significantly higher in expatriates when compared to Bahraini workers. Sunlight-exposed expatriates had significantly higher magnesium levels than their Bahraini counterparts, while there was no significant difference between both ethnicities in the non-exposed groups. CONCLUSION: Country- and ethnic-specific definitions for vitamin D status and sunlight exposure are recommended. The assessment of magnesium status is pivotal in the overall assessment of vitamin D status.

8.
Cureus ; 16(2): e53549, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38445128

RESUMO

BACKGROUND:  This study in Jazan, Saudi Arabia aims to identify anxiety-related factors associated with symptom severity in irritable bowel syndrome (IBS). IBS is a common gastrointestinal disorder causing abdominal pain and altered bowel habits. The prevalence of IBS in Saudi Arabia is estimated to be 10%-20% among the general population. Therefore, the present study aimed to determine anxiety-related factors associated with symptom severity in irritable bowel syndrome in Jazan, Saudi Arabia. Understanding these factors will provide insights into the overall impact of IBS on patients' quality of life. METHODS: The study utilized a cross-sectional, descriptive observational design to examine the general population in Jazan, Saudi Arabia. The sample size of 385 individuals was calculated based on the population size and desired error margin. A convenience sampling technique was employed to select participants who met the inclusion criteria. A validated anonymous self-administered electronic survey was distributed through social media channels. The survey consisted of four sections gathering demographic information, personal risk factors, IBS types with anxiety and risk factors, and a questionnaire to determine the level of anxiety. A pilot study was conducted to improve the survey's clarity. Ethical considerations were followed, and data were analyzed using Statistical Package for Social Sciences (SPSS; IBM Corp., Armonk, NY, USA). Descriptive statistics and significance tests were performed. RESULT: A study with 637 participants found a 31.08% prevalence of IBS, which was more common in females. Participants with IBS had a higher rate of chronic disease. There were no significant differences in demographic factors between IBS and non-IBS participants. The duration of IBS diagnosis varied, with the majority of IBS with diarrhea (IBS-D) sufferers being diagnosed five years prior. Symptom severity differed among IBS types, with those with an unspecified type reporting the highest percentage of severe symptoms. IBS types were also correlated with anxiety levels, with IBS-D sufferers reporting moderate anxiety and those with an unspecified type reporting severe anxiety. CONCLUSION: A study with 637 participants found the prevalence of IBS to be 31.08%, with higher rates in females. IBS was associated with chronic diseases and higher anxiety levels. The findings emphasize the need for comprehensive management of IBS, including psychological interventions and dietary modifications, to improve patients' overall health and quality of life. Further research on genetic and modifiable risk factors is needed.

10.
Pharmaceuticals (Basel) ; 17(2)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38399423

RESUMO

Breast cancer begins in the breast cells, mainly impacting women. It starts in the cells that line the milk ducts or lobules responsible for producing milk and can spread to nearby tissues and other body parts. In 2020, around 2.3 million women across the globe received a diagnosis, with an estimated 685,000 deaths. Additionally, 7.8 million women were living with breast cancer, making it the fifth leading cause of cancer-related deaths among women. The mutational changes, overexpression of drug efflux pumps, activation of alternative signalling pathways, tumour microenvironment, and cancer stem cells are causing higher levels of drug resistance, and one of the major solutions is to identify multitargeted drugs. In our research, we conducted a comprehensive screening using HTVS, SP, and XP, followed by an MM/GBSA computation of human-approved drugs targeting HER2/neu, BRCA1, PIK3CA, and ESR1. Our analysis pinpointed IRESSA (Gefitinib-DB00317) as a multitargeted inhibitor for these proteins, revealing docking scores ranging from -4.527 to -8.809 Kcal/mol and MM/GBSA scores between -49.09 and -61.74 Kcal/mol. We selected interacting residues as fingerprints, pinpointing 8LEU, 6VAL, 6LYS, 6ASN, 5ILE, and 5GLU as the most prevalent in interactions. Subsequently, we analysed the ADMET properties and compared them with the standard values of QikProp. We extended our study for DFT computations with Jaguar and plotted the electrostatic potential, HOMO and LUMO regions, and electron density, followed by a molecular dynamics simulation for 100 ns in water, showing an utterly stable performance, making it a suitable drug candidate. IRESSA is FDA-approved for lung cancer, which shares some pathways with breast cancers, clearing the hurdles of multitargeted drugs against breast and lung cancer. This has the potential to be groundbreaking; however, more studies are needed to concreate IRESSA's role.

11.
Healthcare (Basel) ; 12(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338202

RESUMO

BACKGROUND: Migraine is a common health condition in both men and women. Premenstrual syndrome (PMS) affects many women during their menstrual cycle, with around 50-60% of women with migraine attacks experiencing menstrual headaches. Most have mild symptoms, but 5-8% suffer from moderate to severe symptoms, causing distress and functional issues. Pure menstrual migraine (PMM) occurs in about 50% of women with migraine, and it can be debilitating in terms of frequency and severity. This information is crucial for Saudi Arabian medical professionals to provide better care and support, improving the quality of life for women with PMS and menstrual migraine (MM) attacks. OBJECTIVES: To estimate the prevalence of MM in women, to evaluate the severity and frequency of MM in women with PMS, and to identify potential risk factors aggravating MM in women with PMS in Saudi Arabia. METHODOLOGY: A cross-sectional community-based study was conducted on reproductive-aged (18-50 years) women who had regular menstrual cycles and were diagnosed with PMS, using a self-administered questionnaire between December 2022 to May 2023 in Saudi Arabia. RESULTS: Out of the 2130 female participants, 397 (18.6%) had migraine. Among these 397 migraine sufferers, 230 (57.9%) experienced MM, while 167 (42.1%) had non-MM. In reproductive women in general, MM occurred in 10.7% of cases, while non-MM was observed in 7.8%. There is a correlation between increasing BMI and an increased incidence of MM. About one-third of the participants experienced moderate disability due to migraine attacks, with 134 (33.8%) individuals affected. Additionally, most MM sufferers missed at least 3 days of work in the last 3 months due to their condition. CONCLUSIONS: Migraine attacks occurring during the menstrual cycle impair the ability to engage in social, physical, household, and academic activities, often hindering the fulfillment of professional commitments. To gain a deeper understanding of menstrual and non-menstrual migraine attacks, it is essential to conduct extensive prospective studies aimed at developing effective management strategies.

12.
Cureus ; 16(1): e51976, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38344534

RESUMO

BACKGROUND: Tinnitus may directly or indirectly influence professional, personal, and leisure activities and disrupt family and social relationships in severe cases. This study aimed to explore the impact of tinnitus on the quality of life (QoL) and psychological well-being among Saudi Arabian adults. METHODS: This study used a cross-sectional design to collect data from adults experiencing tinnitus. Data collection took place between September 5, 2023 and October 7, 2023 at King Khalid University, Abha, Saudi Arabia. The study involved adults aged 18 to 65 with tinnitus. Participants were recruited from audiology clinics. A multi-stage stratified random sampling method was used to recruit the study participants. The severity of tinnitus handicap was assessed using the 25-item Tinnitus Handicap Inventory (THI) questionnaire. THI consists of 25 items divided into functional, emotional, and catastrophic subscales. The total score ranges from 0 to 100, with higher scores indicating greater tinnitus-related handicap. THI scores are categorized into 0-16, 18-36, 38-56, 58-76, and 78-100. RESULTS:  A total of 163 participants were included in this study. The largest age group category was 18-29 years, comprising 57.05% (n = 93) of the sample. The study included a slightly higher percentage of female participants (65.03%, n = 106). More than three-fifths (61.96% ) of the participants were from the Western Region (n = 101), 91.40% (n = 149) were Saudi nationals, 55.21% (n = 90) were single, 67.5% (n = 110) had university education, 46.0% (n = 75) had income less than 500 SAR, 44.78% (n =73) was employed, and 74.23% (n = 121) did not smoke. Tinnitus hurts emotions and QoL. The largest proportion of the studied patients with tinnitus faced catastrophic handicaps (24.5%, n = 40), and nearly equal proportions experienced mild and moderate handicaps (23.3%, n = 38 and 23.9%, n =39, respectively). Severe handicap was reported in 15.3% (n = 25), while a slight effect was reported in (12.9%, n = 21). Tinnitus affected their hearing (36.81%, n = 60); interfered with daily life (33.74%, n = 55), social activities (30.06%, n = 49), social relationships (29.45%, n = 48), and concentration (37.42%, n = 61); caused fatigue (38.04%, n = 62) and sleep disturbances (36.81%, n = 60); and prevented them from enjoying life (25.77%, n = 42). Tinnitus caused anger (47.85%, n = 78), confusion (42.94%, n = 70), anxiety (43.56%, n = 71), feeling unsafe (33.74%, n = 55), desperation (36.81%, n = 60), frustration (30.06%, n = 49), being upset (38.04%, n = 62), experiencing depression (30.67%), and challenges in coping with stress (31.29%). There was a significant association between the THI score and region of residence (p = 0.02), income (p = 0.041), occupation (p = 0.013), and smoking (p = 0.014). CONCLUSIONS: Our research underscored the profound impact of tinnitus on the QoL among adults in Saudi Arabia. A significant portion of the studied patients faced catastrophic handicaps, emphasizing the severity of the condition. These findings underscore the multifaceted and far-reaching consequences of tinnitus, highlighting the need for comprehensive support and management strategies tailored to the unique sociodemographic factors influencing individuals' experiences.

13.
Front Genet ; 15: 1292280, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370514

RESUMO

Background: The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide, and vaccination efficacy has been decreasing with each lineage, necessitating the need for alternative antiviral therapies. Predicting host-virus protein-protein interactions (HV-PPIs) is essential for identifying potential host-targeting drug targets against SARS-CoV-2 infection. Objective: This study aims to identify therapeutic target proteins in humans that could act as virus-host-targeting drug targets against SARS-CoV-2 and study their interaction against antiviral inhibitors. Methods: A structure-based similarity approach was used to predict human proteins similar to SARS-CoV-2 ("hCoV-2"), followed by identifying PPIs between hCoV-2 and its target human proteins. Overlapping genes were identified between the protein-coding genes of the target and COVID-19-infected patient's mRNA expression data. Pathway and Gene Ontology (GO) term analyses, the construction of PPI networks, and the detection of hub gene modules were performed. Structure-based virtual screening with antiviral compounds was performed to identify potential hits against target gene-encoded protein. Results: This study predicted 19,051 unique target human proteins that interact with hCoV-2, and compared to the microarray dataset, 1,120 target and infected group differentially expressed genes (TIG-DEGs) were identified. The significant pathway and GO enrichment analyses revealed the involvement of these genes in several biological processes and molecular functions. PPI network analysis identified a significant hub gene with maximum neighboring partners. Virtual screening analysis identified three potential antiviral compounds against the target gene-encoded protein. Conclusion: This study provides potential targets for host-targeting drug development against SARS-CoV-2 infection, and further experimental validation of the target protein is required for pharmaceutical intervention.

14.
Neurol Sci ; 45(4): 1409-1418, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38082050

RESUMO

Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/uso terapêutico , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Neurônios/metabolismo , Doenças Neurodegenerativas/metabolismo , Neuroglia
15.
Pathol Res Pract ; 253: 154957, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38000201

RESUMO

The long non-coding RNA (lncRNA) HOTAIR occupies a central position in the complex domain of cancer biology, particularly concerning its intricate interplay with the Wnt/ß-catenin signaling pathway. This comprehensive review explores the multifaceted interactions between HOTAIR and the Wnt/ß-catenin cascade, elucidating their profound function in cancer growth, progression, and therapeutic strategies. The study commences by underscoring the pivotal role of the Wnt/ß-catenin cascade in governing essential cellular activities, emphasizing its dysregulation as a linchpin in cancer initiation and advancement. It introduces HOTAIR as a crucial regulatory entity, influencing gene expression in both healthy and diseased. The core of this review plunges into the intricacies of HOTAIR's engagement with Wnt/ß-catenin signaling. It unravels how HOTAIR, through epigenetic modifications and transcriptional control, exerts its influence over key pathway constituents, including ß-catenin, Wnt ligands, and target genes. This influence drives unchecked cancer cell growth, invasion, and metastasis. Furthermore, the review underscores the clinical significance of the HOTAIR-Wnt/ß-catenin interplay, elucidating its associations with diverse cancer subtypes, patient prognoses, and prospects as a therapy. It provides insights into ongoing research endeavors to develop HOTAIR-targeted treatments and initiatives to facilitate aberrant Wnt/ß-catenin activation. Concluding on a forward-looking note, the article accentuates the broader implications of HOTAIR's involvement in cancer biology, including its contributions to therapy resistance and metastatic dissemination. It underscores the importance of delving deeper into these intricate molecular relationships to pave the way for groundbreaking cancer treatment.


Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Processos Neoplásicos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Via de Sinalização Wnt/genética
16.
Chemistry ; 30(3): e202302714, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-37983723

RESUMO

Metal imine-thiolate complexes, M(NS)2 are known to undergo imine C-C bond formation to give M(N2 S2 ) complexes (M=Co, Ni) containing a redox-active ligand. Although these transfor-mations are not typically quantitative, we demonstrate here that the one-electron reduction of a related Ni bis(imine-thiolate) complex affords the corresponding paramagnetic [Ni(N2 S2 )]- anion (2⋅- ) exclusively; subsequent oxidation with [Cp2 Fe]BF4 then affords a high yield of neutral 2 (Cp=η5 -cyclopentadienyl). Moreover, electrochemical studies indicate that a second one-electron reduction affords the diamagnetic dianion. Both anionic products were isolated and characterized by SC-XRD and their electronic structures were investigated by UV-vis spectro-electrochemistry, EPR and NMR spectroscopy, and DFT studies. These studies show that reduction proceeds primarily on the ligand, with (N2 S2 )4- containing both thiolate and ring-delocalized anions.

17.
Clin Lab ; 69(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38084679

RESUMO

BACKGROUND: Inherited hemoglobinopathies are common in Jazan Province, Saudi Arabia, and some patients may frequently require a blood transfusion. Therefore, the provision of compatible units using extended phenotypes is necessary to preclude the risk of alloimmunization. This study aimed to investigate the frequencies of the Lewis (LE), Lutheran (LU), and P1 antigens, as well as determine the prevalence of LE and LU phenotypes. METHODS: This study collected 150 blood samples from Saudi Arabian anonymous volunteering blood donors at Prince Muhammed bin Nasser Hospital in Jazan Province, Saudi Arabia. Serotyping was performed using antigen profile-II based on gel card technology to determine LE, LU, and P1 antigens. RESULTS: The prevalence of antigens was as follows: Lea (n = 37, 24.6%), Leb (n = 87, 58%), Lua (n = 6, 4%), Lub (n = 150, 100%), and P1 (n = 120, 80%). Regarding the LE phenotypes, Le (a+b-) was 24.7%, Le (a-b+) was 58%, and Le (a-b-) was 17.3%. The frequencies of only observed LU phenotypes Lu (a-b+) and Lu (a+b+) were 96% and 4%, respectively. CONCLUSIONS: In summary, this study reports LE, LU, and P1 antigen prevalence. Moreover, LE and LU phenotype frequencies were investigated. This study may help establish a national database of blood group antigens in Jazan Province, Saudi Arabia. Additionally, it may provide better transfusion practice to avoid the alloimmunization risk.


Assuntos
Antígenos de Grupos Sanguíneos , Protestantismo , Humanos , Arábia Saudita/epidemiologia , Prevalência , Antígenos de Grupos Sanguíneos/genética , Fenótipo , Antígenos
18.
PLoS One ; 18(12): e0295714, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38100507

RESUMO

Cervical cancer poses a substantial worldwide health challenge, especially in low- and middle-income nations, caused by high-risk types of human papillomavirus. It accounted for a significant percentage of cancer-related deaths among women, particularly in areas with limited healthcare resources, necessitating innovative therapeutic approaches, and single-targeted studies have produced significant results, with a considerable chance of developing resistance. Therefore, the multitargeted studies can work as a beacon of hope. This study is focused on performing the multitargeted molecular docking of FDA-approved drugs with the three crucial proteins TBK1, DNA polymerase epsilon, and integrin α-V ß-8 of cervical cancer. The docking studies using multisampling algorithms HTVS, SP, and XP reveal Pixantrone Maleate (DB06193) as a multitargeted inhibitor with docking scores of -8.147, -8.206 and -7.31 Kcal/mol and pose filtration with MM\GBSA computations with scores -40.55, -33.67, and -37.64 Kcal/mol. We also have performed QM-based DFT and pharmacokinetics studies of the compound and compared it with the standard values, which results in the compound being entirely suitable against cervical cancer proteins. The interaction fingerprints have revealed that PHE, VAL, SER and ALA are the residues among most interactions. We also explore the stability of the multitargeted potential of Pixantrone Maleate through 100ns MD simulations and investigate the RMSD, RMSF and intermolecular interactions between all three proteins-ligand complexes. All computational studies favour Pixantrone Maleate as a multitargeted inhibitor of the TBK1, DNA polymerase epsilon, and integrin α-V ß-8 and can be validated experimentally before use.


Assuntos
Simulação de Dinâmica Molecular , Neoplasias do Colo do Útero , Feminino , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Neoplasias do Colo do Útero/tratamento farmacológico , DNA Polimerase II , Integrinas , Maleatos
19.
Micromachines (Basel) ; 14(12)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38138350

RESUMO

This paper presents a miniaturized broadband Bi-Yagi antenna array that covers a bandwidth from 1.79 GHz to 2.56 GHz. The proposed antenna achieves a tradeoff between maximizing bandwidth, effective area, and gain while minimizing physical dimensions. The antenna design considers the coupling between the radiator and director elements, resulting in increased bandwidth as the resonating modes shift apart. Additionally, the proposed design optimizes element spacing and dimensions to achieve high gain, wide bandwidth, efficient radiation, and a minimum aperture size. The proposed antenna, with physical dimensions of 138.6 mm × 47.7 mm × 1.57 mm, demonstrates gains ranging from 6.2 dBi to 9.34 dBi across the frequency range, with a total efficiency between 88% and 98%. The proposed design is experimentally validated by measuring the reflection coefficients, input impedance, gain, and normalized radiation pattern. These features make the antenna well suited for capturing and harvesting electromagnetic waves in mobile wireless and Wi-Fi applications.

20.
Polymers (Basel) ; 15(24)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38139930

RESUMO

Fiber sizing is one of the most important components in manufacturing composites by affecting mechanical properties, including strength and stiffness. The sizing of manmade fibers offers many advantages, such as improving fiber/matrix adhesion and bonding properties, protecting fiber surfaces from damage during the processing and weaving stages, and enhancing the surface wettability of polymer matrices. In this work, the influence of fiber sizing levels on carbon fibers' (CFs) mechanical properties is reported at room temperature using single fiber tensile testing (Favimat+), single fiber pullout testing (SFPO), and interfacial elemental analysis by X-ray photoelectron spectroscopy (XPS). Standard modulus CFs (7 ± 0.2 µm in diameter) were sized using two commercially available Michelman sizing formulations. The average solid content for each sizing formulation was 26.3 ± 0.2% and 34.1 ± 0.2%, respectively. HEXION RIMR 135 with curing agent RIMH 137 was used as a model thermoset epoxy matrix during SFPO measurements. A predictive engineering fiber sizing methodology was also developed. Sizing amounts of 0.5, 1, and 2 wt.% on the fiber surface were achieved for both sizing formulations. For each fiber size level, 50 single-fiber tensile testing experiments and 20 single-fiber pull-out tests were conducted. The ultimate tensile strength (σult) of the carbon fibers and the interfacial shear strength (τapp) of the single fiber composite were analyzed. The sizing levels' effect on interfacial shear stress and the O/C (Oxygen/Carbon) surface composition ratio was investigated. Based on our experimental findings, an increase of 6% in fiber performance was recorded for ultimate tensile and interfacial shear strengths. As a result, generalized fiber sizing and characterization methods were established. These developed methods can be used to characterize the strength and interfacial shear strength of manmade fibers with different sizing formulations and solid contents irrespective of the matrix, i.e., thermoset or thermoplastic.

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