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1.
Sci Rep ; 14(1): 13913, 2024 06 17.
Article in English | MEDLINE | ID: mdl-38886478

ABSTRACT

Leguminous crop Tephrosia candida has high biomass production and contains a substantial quantity of nutrients within its biomass. Starting in 2019, a long-term study was done to find the best Tephrosia candida dose for mulching in guava orchards. The study had four treatments: T1 = 3.0 kg dry biomass m-2 of the plant basin, T2 = 2.0 kg, T3 = 1.0 kg, and T4 = control (no mulch). Every year, the treatments imposed in the month of August. The third year (2021-2022) results indicated that mulching with 3 kg of biomass m-2 increased trunk diameter, fruit yield, fruit weight, specific leaf area, total leaf chlorophyll, and leaf macro- and micro-nutrients. At 3.0 kg m-2, mulching improved soil properties such as EC, available nitrogen, available phosphorus, exchangeable potassium, DTPA extractable micronutrients (Fe, Zn, Cu, and Mn), total organic carbon (Ctoc), soil organic carbon (Csoc), organic carbon fractions, and microbial biomass carbon between 0-0.15 m and 0.15-0.30 m. There was an increasing trend in dehydrogenase activity (DHA) and fluorescein diacetate (FDA). The Tephrosia leaf litter exhibited decay constants of 1.27 year-1, and the carbon content was 40.11%. Therefore, applying Tephrosia biomass mulching at a rate of 3.0 kg m-2 is a viable long-term solution for enhancing soil fertility and sequestering carbon.


Subject(s)
Biomass , Fruit , Psidium , Soil , Tephrosia , Soil/chemistry , Tephrosia/metabolism , Fruit/growth & development , Plant Leaves/metabolism , Plant Leaves/growth & development , Nitrogen/analysis , Nitrogen/metabolism
3.
Med Oncol ; 41(5): 105, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38573558

ABSTRACT

Human laryngeal squamous carcinoma (LSCC) is a common malignant tumor in the head and neck. Despite the recently developed therapies for the treatment of LSCC, patients' overall survival rate still did not enhance remarkably; this highlights the need to formulate alternative strategies to develop novel treatments. The antitumor effects of antidepressant drugs such as citalopram have been reported on several cancer cells; however, they have yet to be investigated against LSCC. The current study was directed to explore the possible antitumor effects of citalopram on human laryngeal carcinoma cell lines (HEP-2). HEP-2 cells were cultured and treated with different doses of citalopram (50-400 µM) for 24, 48, and 72 h. The effects of citalopram on the viability of cancer cells were determined by the MTT assay. In addition, apoptosis and cell cycle analysis were performed by flow cytometry. Moreover, evaluation of the expression of proapoptotic and apoptotic proteins, such as cytochrome c, cleaved caspases 3 and 9, Bcl-2, and BAX, was performed by western blotting analysis. Our results revealed that citalopram significantly suppressed the proliferation of HEP-2 cells through the upregulation of p21 expression, resulting in the subsequent arrest of the cell cycle at the G0/G1 phase. Furthermore, citalopram treatment-induced HEP-2 cell apoptosis; this was indicated by the significant increase of cytochrome c, cleaved caspases 3 and 9, and BAX protein expression. On the contrary, Bcl-2 protein expression was significantly downregulated following treatment with citalopram. The ultrastructure studies were in accordance with the protein expression findings and showed clear signs of apoptosis with ring chromatin condensation upon treatment with citalopram. These findings suggest that citalopram's anti-tumor activities on HEP-2 cells entailed stimulation of the intrinsic apoptotic pathway, which was mediated via Bcl-2 suppression.


Subject(s)
Antipsychotic Agents , Carcinoma , Humans , Citalopram/pharmacology , Resting Phase, Cell Cycle , Cytochromes c , Apoptosis , G1 Phase Cell Cycle Checkpoints , Proto-Oncogene Proteins c-bcl-2
5.
Cureus ; 16(1): e51637, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38313892

ABSTRACT

BACKGROUND: Coronary heart disease (CHD) is a leading cause of death globally, and psychological factors are increasingly recognized as playing a significant role in its prognosis. This study aimed to assess the public's awareness of psychological factors affecting CHD prognosis in Makkah, Saudi Arabia. METHODS: A cross-sectional online survey was conducted with 385 participants recruited randomly. The survey collected data on sociodemographic characteristics and respondents' opinions regarding the effects of negative and positive psychological factors on CHD prognosis, including differences based on age and gender. RESULTS: The majority of participants (96.9%) agreed that negative psychological factors, such as stress (80.5%), anxiety (76.9%), and depression (67.5%), influence CHD prognosis. Positive factors like satisfaction (79.2%) and happiness (75.6%) were also recognized as influential. Participants aged 30-50 and over 50 demonstrated higher awareness of the link between psychological factors and CHD compared to those under 30. No significant gender differences were observed in knowledge levels. CONCLUSION: This study suggests that the Makkah population has a good understanding of the impact of psychological factors on CHD prognosis. Integrating this knowledge into comprehensive health education programs could benefit CHD prevention, management, and prognosis in the region. Future research should explore broader populations and utilize diverse methodologies to refine and generalize these findings.

6.
Article in English | MEDLINE | ID: mdl-38091079

ABSTRACT

Scientists are seeking to find an effective treatment for tumors that has no side effects. N-Acetyl-l-cysteine (NAC) is a thiol compound extracted from garlic. Current study explores the potential of NAC-loaded niosomes (NAC-NIO) for tumor treatment in mice. NAC-loaded niosomes' efficiency, morphology, UV absorption, size distribution, zeta potential, release, and FTIR analysis were evaluated. For vivo study, 25 male BALB/c mice were divided to five groups: gp1 negative control (receive saline), gp2 positive control (tumor group), gp3 treated with NAC, gp4 treated with NAC-NIO at the same time of tumor injection, and gp5 treated with NAC-NIO after tumor growth (day 14). The impact of NAC-NIO on the tumor treatment was evaluated by measuring tumor size progress, comet assay, oxidative stress parameters (GSH, nitric oxide, MDA), western blot analysis, and histopathological investigation of tissues. NAC-NIO showed 72 ± 3% encapsulation efficiency and zeta potential - 5.95 mV with spherical shape. It was found that oral administration of NAC-NIO in a dose of 50 mg/kg provided significant protection against tumor cells. Our formulation decreases DNA injury significantly (P < 0.05). It was noticed that NAC-NIO can increase oxidative stress levels in tumor tissue. On the other hand, the caspase 3 and caspase 9 gene expression were upregulated significantly (P < 0.001) in mice administrated NAC-NIO compared with all other groups. Histological studies confirmed the protective effect of NAC-NIO against tumor especially for treatment during tumor growth protocol. The results suggested that oral delivery of NAC-NIO formulation improved antioxidant effect.

7.
Clin Lab ; 69(12)2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38084686

ABSTRACT

BACKGROUND: COVID-19 is no longer a global public health emergency, but it still affects numerous diseases and needs further research. Diabetic COVID-19 patients with major complications or intensive care had high mortality rates. This review provides pathophysiological descriptive data on diabetes mellitus type 2 and shows how COVID-19 infection in Saudi Arabia predicts disease severity and prognosis. METHODS: This review was conducted through online research on MEDLINE/PubMed databases, Scopus, and Web of Science based on links between COVID-19 and diabetes mellitus type 2 patients. By using the keywords 'COVID-19', 'diabetes', ' correlation', and impact on 'population' from December 2022 to February 2023. The full texts of the articles that were retrieved were accessed. RESULTS: The COVID-19 epidemic has affected the community, especially diabetics, and their daily life. According to our research on prior studies, most COVID-19 patients in Saudi Arabia had diabetes as a comorbidity. CONCLUSIONS: We underline the necessity of thorough study to better understand COVID-19 and its association with diabetes to design and implement evidence-based initiatives and policies in Saudi Arabia, where diabetes is a major health issue.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , COVID-19/epidemiology , Comorbidity , Prognosis , Saudi Arabia/epidemiology
8.
eNeurologicalSci ; 33: 100486, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38053652

ABSTRACT

Background: Dandy-Walker malformation or syndrome is the most common posterior fossa malformation. It is commonly associated with other congenital anomalies such as cardiac defects; however, association with a giant occipital meningocele is extremely rare, as only around 34 cases have been described. Case description: We report a case of a 2-month-old female infant who presented with a midline, gigantic mass in the back of the head. It was first discovered on a prenatal ultrasound. The mass measured about 15 × 5 cm, extending to the midback, not changing in size with crying, not attached to the back, and with a positive transillumination test. The diagnosis was confirmed after doing a brain computed tomography, which revealed hypoplasia of the vermis with an enlarged posterior fossa as well as cystic dilation of both ventricles with herniation through a bone defect. Conclusion: Our case highlights a rare association between giant occipital meningocele and Dandy-Walker syndrome that is rarely discussed or reported in the medical literature. By reporting this extremely rare case of Dandy-Walker syndrome associated with a giant occipital meningocele, we hope to contribute to the creation of a database for future research so that a management protocol can be established for use by clinicians and neurosurgeons for better management of the condition.

10.
Int J Mol Sci ; 24(2)2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36674859

ABSTRACT

Colorectal cancer (CRC) is one of the most common malignancies worldwide; it is the fourth leading cause of cancer-related deaths. CRC arises due to mutations that can affect oncogenes, tumour suppressor genes and DNA repair genes. The lack of novel diagnostic and therapeutic targets and the development of chemoresistance are some of the major issues when dealing with CRC. The overexpression of ATP-binding cassette (ABC) transporters is considered one facilitating mechanism for chemoresistance. Furthermore, ABC transporters have additional roles in cancer development beyond multidrug resistance. In CRC, lipid dysregulation has a key role in tumour development and progression, as cancer cells rely on lipids for energy and rapid cell proliferation. ABC subfamily A (ABCA) contains the largest members of ABC proteins, mainly known for their role in lipid transport, mostly membrane lipids such as cholesterol and phospholipids. Although the exact mechanism of action of these members is not confirmed, their expression is usually correlated with tumour progression and therapy resistance, probably due to their role in lipid homeostasis. CRC shows alteration in the expression of ABCA transporters, which is usually linked to poor prognosis and overall survival. Therefore, as lipid transporters, their role in CRC is investigated, and their diagnostic and prognostic potential is evaluated. This minireview presents evidence from various studies suggesting that ABCA transporters might have an active role in CRC and can be utilized as potential diagnostic and therapeutic targets.


Subject(s)
ATP-Binding Cassette Transporters , Colorectal Neoplasms , Humans , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , ATP Binding Cassette Transporter, Subfamily A , Phospholipids , Colorectal Neoplasms/pathology , Adenosine Triphosphate
11.
Chem Biol Drug Des ; 101(2): 245-270, 2023 02.
Article in English | MEDLINE | ID: mdl-36305722

ABSTRACT

This study aimed to synthesize new potent quinoline derivatives based on hydrazone moieties and evaluate their antimicrobial activity. The newly synthesized hydrazono-quinoline derivatives 2, 5a, 9, and 10b showed the highest antimicrobial activity with MIC values ≤1.0 µg/ml against bacteria and ≤8.0 µg/ml against the fungi. Further, these derivatives exhibited bactericidal and fungicidal effects with MBC/MIC and MFC/MIC ratio ≤4. Surprisingly, the most active compounds displayed good inhibition to biofilm formation with MBEC values ranging between (40.0 ± 10.0 - 230.0 ± 31.0) and (67.0 ± 24.0 - 347.0 ± 15.0) µg/ml against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. The hemolytic assays confirmed that the hydrazono-quinoline derivatives are non-toxic with low % lysis values ranging from 4.62% to 14.4% at a 1.0 mg/ml concentration. Besides, compound 5a exhibited the lowest hemolytic activity value of ~4.62%. Furthermore, the study suggests that the hydrazono-quinoline analogs exert their antibacterial activity as dual inhibitors for DNA gyrase and DNA topoisomerase IV enzymes with IC50 values ranging between (4.56 ± 0.3 - 21.67 ± 0.45) and (6.77 ± 0.4 - 20.41 ± 0.32) µM, respectively. Additionally, the recent work advocated that compound 5a showed the reference SAL at the É£-radiation dose of 10.0 kGy in the sterilization process without affecting its chemical structure. Finally, the in silico drug-likeness, toxicity properties, and molecular docking simulation were performed. Besides, the result exhibited good oral-bioavailability, lower toxicity prediction, and lower binding energy with good binding mode rather than the positive control.


Subject(s)
Anti-Infective Agents , DNA Gyrase , Molecular Docking Simulation , DNA Gyrase/metabolism , DNA Topoisomerase IV/metabolism , Topoisomerase II Inhibitors/pharmacology , Topoisomerase II Inhibitors/chemistry , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Microbial Sensitivity Tests , Structure-Activity Relationship , Molecular Structure
12.
Arch Psychiatr Nurs ; 41: 214-220, 2022 12.
Article in English | MEDLINE | ID: mdl-36428052

ABSTRACT

BACKGROUND: Clinical hospital stressors during the COVID-19 pandemic are one of the problems that affect the quality of education among first-year nursing students, particularly in the first 6 months of their practice. OBJECTIVE: Assess the types and severity of clinical hospital stressors among first-year nursing students and investigate the relationship between students' clinical stressors and their level of worry from COVID-19. DESIGN: A descriptive correlational research design. The study was conducted at the Faculty of Nursing, Alexandria's main university hospital. The study included a convenience sample of 200 first-year nursing students. TOOLS: Socio-demographic and academic data of nursing students. The Perceived Stress Scale (PSS) is used to assess the degree and type of stressors. RESULTS: The highest reported types of stressors were stress from the clinical hospital (M = 13.54) and stress from a lack of professional knowledge and skills (M = 13). Concerning the overall stressors, all students experienced a severe degree of stress (M = 116.87). Furthermore, students' age, sex, number of study hours/week, number of assignments/week, and worry from COVID 19 were highly statistically significant with degrees of perceived stress as (p = 0.000, 0.030). CONCLUSION: Clinical hospital stressors had a significant negative impact on the majority of students' education in the hospital. As well as worrying about COVID 19, positively increased the perceived stressors of nursing students. RECOMMENDATIONS: Implement an educational program for the first-year nursing students about clinical hospital stressors during COVID-19 and trained them how they can cope with these stressors by using stress management.


Subject(s)
COVID-19 , Students, Nursing , Humans , Pandemics , Stress, Psychological , Hospitals
13.
Front Oncol ; 12: 918340, 2022.
Article in English | MEDLINE | ID: mdl-35747793

ABSTRACT

Background: Numerous clinical and experimental observations have alluded to the substantial anti-neoplastic role of vitamin D in breast cancer (BC), primarily by inducing apoptosis and affecting metastasis. Tumor progression and resistance to chemotherapy have been linked to vasculogenic mimicry (VM), which represents the endothelial-independent formation of microvascular channels by cancer cells. However, the effect of vitamin D on VM formation in BC has not been thoroughly investigated. This study examined the impact of 1α,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D, on the expression of major factors involved in BC migration, invasion, and VM formation. Experimental Methods: Publicly available transcriptomic datasets were used to profile the expression status of the key VM markers in vitamin D-treated BC cells. The in silico data were validated by examining the expression and activity of the key factors that are involved in tumor progression and MV formation in hormone-positive MCF-7 and aggressive triple-negative MDA-MB-231 BC cells after treatment with calcitriol. Results and Discussions: The bioinformatics analysis showed that tumor VM formation-enriched pathways were differentially downregulated in vitamin D-treated cells when compared with control counterparts. Treatment of BC cells with calcitriol resulted in increased expression of tissue inhibitors of metalloproteinases (TIMPs 1 and 2) and decreased content and gelatinolytic activity of matrix metalloproteinases (MMPs 2 and 9). Furthermore, calcitriol treatment reduced the expression of several pro-MV formation regulators including vascular endothelial growth factor (VEGF), tumor growth factor (TGF-ß1), and amphiregulin. Eventually, this process resulted in a profound reduction in cell migration and invasion following the treatment of BC cells with calcitriol when compared to the controls. Finally, the formation of VM was diminished in the aggressive triple-negative MDA-MB-231 cancer cell line after calcitriol treatment. Conclusion: Our findings demonstrate that vitamin D mediates its antitumor effects in BC cells by inhibiting and curtailing their potential for VM formation.

14.
Anemia ; 2022: 9104209, 2022.
Article in English | MEDLINE | ID: mdl-35310133

ABSTRACT

Aims: The review explores the findings of previous studies to elucidate the association between levels of D-dimer and COVID-19 severity and prognosis. In addition, we assessed the efficiency of anticoagulant therapies in reducing COVID-19 severity and improving the prognosis of the patients. Materials and Methods: A comprehensive literature review was conducted using MEDLINE/PubMed databases, Scopus, and Web of Science with the help of keywords "COVID-19," "D-Dimer," "Thrombosis," "Fibrin network," "Anticoagulant therapy," "Inflammation," and "disease severity." Based on all these articles and clinical experience, a scoping review was constructed and the full texts of the articles that were retrieved were accessed. Results: A D-dimer is a complex protein molecule that is formed during plasmin-mediated degradation of the fibrin network. Thus, it serves as a marker of thrombotic activity. On the other hand, in addition to severe respiratory distress and reduction in pulmonary gas exchange, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also triggers prothrombotic changes in the infected individuals. The levels of D-dimer have been postulated to be positively associated with the degree of disease severity among COVID-19 patients. Conclusions: It has been postulated that D-dimer could potentially be used as a biomarker to predict the prognosis and outcome of COVID-19 patients at the time of admission to hospitals and facilitate more personalized and efficient clinical management that could significantly reduce the mortality rate of such patients and allow more rapid recovery.

15.
J Int Med Res ; 50(2): 3000605221076975, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35209724

ABSTRACT

OBJECTIVE: To determine the prevalence of Helicobacter pylori infection in a Saudi Arabian population and its association with the body mass index (BMI) and serum 8-hydroxy deoxyguanine (8-OHdG) levels as biomarker for oxidative stress. METHODS: This cross-sectional study enrolled patients that had experienced epigastric discomfort or dyspepsia for > 1 month and had undergone diagnostic upper endoscopy. Patients with a body mass index (BMI) ≥30 kg/m2 were defined as obese. The presence of anti-H. pylori antibodies was confirmed using an H. pylori immunoglobulin G (IgG) antibody enzyme-linked immunosorbent assay. The levels of 8-OHdG were measured using a competitive inhibition enzyme immunoassay. RESULTS: A total of 298 patients were enrolled in the study. Of these, 186 (62.4%) patients were H. pylori-positive and 112 (37.6%) patients were H. pylori-negative. The mean ± SD age of the overall study cohort was 47.17 ± 9.27 years. The H. pylori-positive patients had significantly higher levels of H. pylori IgG antibodies than H. pylori-negative patients. H. pylori prevalence linearly correlated with BMI quantile. The 8-OHdG levels were strongly associated with the BMI of the patients in the H. pylori-positive group. CONCLUSION: Obese individuals exhibited higher H. pylori prevalence than individuals with a lean BMI (BMI < 25.00 kg/m2).


Subject(s)
Helicobacter Infections , Helicobacter pylori , Adult , Antibodies, Bacterial , Body Mass Index , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Helicobacter Infections/complications , Helicobacter Infections/diagnosis , Helicobacter Infections/epidemiology , Helicobacter pylori/genetics , Humans , Middle Aged , Obesity/complications , Obesity/epidemiology , Oxidative Stress , Saudi Arabia/epidemiology
16.
Saudi Med J ; 43(2): 177-186, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35110343

ABSTRACT

OBJECTIVES: To analyze the impact and distribution of blood groups in different ethnicities and the extent of susceptibility to infection with COVID-19 in Makkah, Saudi Arabia. METHODS: A retrospective study was performed on 4,609 COVID-19 patients from five ethnic groups to assess the impact and distribution of different blood types and susceptibility to COVID-19 infection. The study was carried out between November 2020 and June 2021 in the College of Medicine, Umm Al-Qura University in collaboration with the General Directorate of Health Affairs, Makkah, Saudi Arabia. RESULTS: Blood group (A, B, and O) distributions in 2,617 COVID-19 patients with local control populations was done. Our study found that in both Saudi and non-Saudi populations, blood groups O and A were associated with higher infection rates, whereas blood group AB was associated with lower infection rates (p=0.0001). COVID-19 seems to be associated with blood groups A, B, and AB (RR=3.23, 95% CI=2.702-3.821, p=0.0001). COVID-19 risk was lower in people with O blood group (RR=0.783, 95% CI=0.733-0.836, p=0.0001). South Asians had higher odds of COVID-19 infection when compared to Saudi cases and other ethnic groups (OR=1.12, 95 % CI: 1.074-1.24, p=0.04). CONCLUSION: We emphasize that COVID-19 infection is not proportional among ethnically related blood groups. Notably, RhD-negative protect against COVID-19, whereas A and O blood types are more susceptible. Thus, when assessing COVID-19 prognosis and vaccination priority, blood groups A and O are critical.


Subject(s)
Blood Group Antigens , COVID-19 , Ethnicity , Humans , Retrospective Studies , SARS-CoV-2 , Saudi Arabia/epidemiology
17.
Skeletal Radiol ; 51(4): 765-775, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34324016

ABSTRACT

OBJECTIVE: To compare ultrasound- (US), fluoroscopy- (FL), and palpation-guided contrast injection techniques used for dorsal radio-carpal wrist MRA. MATERIALS AND METHODS: Patients with chronic wrist pain were randomized as to which injection technique they underwent into three groups of 50 participants. Dorsal radio-carpal contrast injection was performed under US, FL guidance (one radiologist for each), or palpation guidance by an orthopedic surgeon. The three techniques were compared by procedure time, success rate, number of attempts needed, frequency and grade of extravasation, joint distension, and MRA image quality. Additionally, any change from baseline wrist pain was recorded using the visual analog scale (VAS) at five time points (immediately, 8 h, 24 h, 48 h, and 1 week) after injection. RESULTS: One hundred and fifty patients (83 males and 67 females; mean age 29 ± 6.5 years) were included. Success rates for US- and FL-guided injections were 100%, while palpation-guided approach was significantly less successful (72%) (P = 0.02) with significantly more frequent extravasation (56%)(P < 0.001). US guidance was the least time-consuming (6.5 ± 1.6 min) compared to FL guidance (12.5 ± 1.9 min) and palpation guidance (8 ± 1.2 min) (all P < 0.001). The mean number of joint puncture attempts was significantly lower with imaging-guided techniques (1.1 ± 0.24 and 1.2 ± 0.4 for US and FL, P = 0.23) compared to palpation-guided one (1.6 ± 0.8) (P = 0.007). The largest increases in baseline-pain were 8-h post-injection, and US guidance was the least painful at all-time points (all P < 0.05). Joint distension and image quality were significantly better with imaging-guided techniques (P < 0.001 and P = 0.003). CONCLUSIONS: US-guided radio-carpal injection is a less time-consuming, more tolerable, and successful radiation-free method when compared to FL guidance. Palpation-guided injections require multiple attempts to enter the joint with high failure rates and frequent extravasation.


Subject(s)
Arthrography , Wrist , Adult , Arthrography/methods , Female , Fluoroscopy , Humans , Injections, Intra-Articular/methods , Male , Palpation , Ultrasonography, Interventional/methods , Young Adult
18.
Int J Mol Sci ; 22(21)2021 Oct 28.
Article in English | MEDLINE | ID: mdl-34769131

ABSTRACT

Lung cancer is the leading cause of cancer mortality in both genders, with non-small cell lung cancer (NSCLC) accounting for about 85% of all lung cancers. At the time of diagnosis, the tumour is usually locally advanced or metastatic, shaping a poor disease outcome. NSCLC includes adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Searching for novel therapeutic targets is mandated due to the modest effect of platinum-based therapy as well as the targeted therapies developed in the last decade. The latter is mainly due to the lack of mutation detection in around half of all NSCLC cases. New therapeutic modalities are also required to enhance the effect of immunotherapy in NSCLC. Identifying the molecular signature of NSCLC subtypes, including genetics and epigenetic variation, is crucial for selecting the appropriate therapy or combination of therapies. Epigenetic dysregulation has a key role in the tumourigenicity, tumour heterogeneity, and tumour resistance to conventional anti-cancer therapy. Epigenomic modulation is a potential therapeutic strategy in NSCLC that was suggested a long time ago and recently starting to attract further attention. Histone acetylation and deacetylation are the most frequently studied patterns of epigenetic modification. Several histone deacetylase (HDAC) inhibitors (HDIs), such as vorinostat and panobinostat, have shown promise in preclinical and clinical investigations on NSCLC. However, further research on HDIs in NSCLC is needed to assess their anti-tumour impact. Another modification, histone methylation, is one of the most well recognized patterns of histone modification. It can either promote or inhibit transcription at different gene loci, thus playing a rather complex role in lung cancer. Some histone methylation modifiers have demonstrated altered activities, suggesting their oncogenic or tumour-suppressive roles. In this review, patterns of histone modifications in NSCLC will be discussed, focusing on the molecular mechanisms of epigenetic modifications in tumour progression and metastasis, as well as in developing drug resistance. Then, we will explore the therapeutic targets emerging from studying the NSCLC epigenome, referring to the completed and ongoing clinical trials on those medications.


Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Epigenesis, Genetic , Histone Code , Histones/metabolism , Molecular Targeted Therapy , Animals , Carcinoma, Non-Small-Cell Lung/therapy , Humans
19.
Front Cell Dev Biol ; 9: 766978, 2021.
Article in English | MEDLINE | ID: mdl-34820382

ABSTRACT

Background: Vitamin D deficiency associates with high risk of breast cancer (BRCA) and increased cellular iron. Vitamin D exerts some of its anti-cancer effects by regulating the expression of key iron regulatory genes (IRGs). The association between vitamin D and cellular iron content in BRCA remains ambiguous. Herein, we addressed whether vitamin D signaling exerts a role in cellular iron homeostasis thereby affecting survival of breast cancer cells. Methods: Expression profile of IRGs in vitamin D-treated breast cancer cells was analyzed using publicly available transcriptomic datasets. After treatment of BRCA cell lines MCF-7 and MDA-MB-231 with the active form of vitamin D, labile iron content, IRGs protein levels, oxidative stress, and cell survival were evaluated. Results: Bioinformatics analysis revealed several IRGs as well as cellular stress relates genes were differentially expressed in BRCA cells. Vitamin D treatment resulted in cellular iron depletion and differentially affected the expression of key IRGs protein levels. Vitamin D treatment exerted oxidative stress induction and alteration in the cellular redox balance by increasing the synthesis of key stress-related markers. Collectively, these effects resulted in a significant decrease in BRCA cell survival. Conclusion: These findings suggest that vitamin D disrupts cellular iron homeostasis leading to oxidative stress induction and cell death.

20.
Adv Emerg Nurs J ; 43(4): 331-343, 2021.
Article in English | MEDLINE | ID: mdl-34699423

ABSTRACT

Efforts to minimize the impact of prescribed opioids on future adverse outcomes are reliant on emergency care providers' ability to screen and detect opioid use disorder (OUD). Many prescriptions are initiated in the emergency department (ED) for acute pain; thus, validated measures are especially needed. Our systematic review describes the available opioid-related screening measures identified through search of the available literature. Measures were categorized by intent and applied clinical setting. We found 44 articles, identifying 15 screening measures. Of these, nine were developed to screen for current opioid misuse and five to screen for risk of future opioid misuse. None were created for use outside of a chronic pain setting. Many measures were applied differently from intended purpose. Although several measures are available, screening for adverse opioid outcomes in the ED is hampered by lack of validated instruments. Development of clarified conceptual models and ED-specific research is necessary to limit OUD.


Subject(s)
Chronic Pain , Opioid-Related Disorders , Analgesics, Opioid/adverse effects , Emergency Service, Hospital , Emergency Treatment , Humans , Opioid-Related Disorders/diagnosis , Opioid-Related Disorders/drug therapy
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