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Cutaneous malignant melanoma (cMM) can develop at any site, but one-third of cases primarily affect the lower extremities, with ankle and foot lesions representing 3-15% of all cases. However, cMM may become a clinical conundrum when it presents as chronic ulceration that is clinically indiscernible from other lower extremity ulcers in patients with diabetes. We present the case of a 71-year-old female patient with a longstanding history of diabetes, hypertension, obesity, chronic kidney disease and heart failure who presented to our hospital with a fungating heel ulcer. The lesion was initially managed in another hospital as a neuropathic diabetic foot ulcer (DFU), treated by multiple local wound debridement. However, the ulcer progressed into a fungating heel lesion that interfered with the patient's mobility and quality of life. Consequently, the patient was referred to our specialist diabetic foot service for further management. Excisional biopsy of the lesion disclosed a cMM. Positron emission tomography/computed-tomography scanning revealed hypermetabolic ipsilateral inguinal lymphadenopathy, and a right cerebral metastasis for which palliative chemotherapy was initiated. Immunotherapy was considered, but the patient died before it was started. Atypical foot ulcers in patients with diabetes warrant a careful diagnostic approach, especially for recalcitrant cutaneous lesions not responding to standard therapies. Conscientious management, without undue delay in obtaining a histopathological diagnosis, might lead to early diagnosis of melanoma and potentially more favourable outcomes. This case highlights the importance of consideration of atypical foot lesions, in general practice in addition to referral centres, to try to identify alarming features and act accordingly.
Assuntos
Pé Diabético , Calcanhar , Melanoma , Neoplasias Cutâneas , Humanos , Feminino , Idoso , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Melanoma/diagnóstico , Melanoma/patologia , Pé Diabético/diagnóstico , Pé Diabético/terapia , Diagnóstico Diferencial , Evolução Fatal , Melanoma Maligno Cutâneo , Úlcera do Pé/diagnóstico , Úlcera do Pé/terapia , Úlcera do Pé/patologiaRESUMO
The aim of this study was to evaluate the effects of two forms of tobacco smoking, cigarettes and water pipe smoking (WPS), on the expression of a panel of salivary proteins in healthy adults. Three groups of age and gender-matched participants were enrolled in the study: never-smokers, cigarette smokers and WPS (N = 55 per group). Expression of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), endothelin and transferrin in unstimulated whole saliva was estimated using enzyme-linked immunosorbent assays. Statistical analysis consisted of one-way ANOVA and Tukey's post hoc tests, in addition to bioinformatics analysis. VEGF expression was the least in WPS (51.1 ± 14.5 pg/ml) compared to both controls (150.1 ± 13.8 pg/ml) and cigarette smokers (93 ± 9.9 pg/ml), with a significant difference in WPS (p < 0.001) and cigarette smokers (p < 0.01) compared to controls. Furthermore, transferrin showed the weakest expression in the WPS group (1238 ± 261.4 pg/ml) compared to controls (2205.6 ± 298.6 pg/ml) (p = 0.05) and cigarette smokers (1805.4 ± 244 pg/ml). Neither EGF nor endothelin expression showed any statistical difference between the groups (p > 0.05). Gene-gene interaction network demonstrated that FLT1, TFRC, KDR, VEGFB and PGF genes had the highest potential for interaction with the studied proteins. Further functional annotations on the identified markers in the interaction network were performed to identify HIF-1 pathways among the most relevant pathways. In conclusion, smoking habits alter the expression of salivary VEGF and transferrin, which may correspond to early sub-clinical changes in the oral mucosa. The clinical relevance of these salivary changes requires further research.
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Prostate cancer (PCa) is a significant global contributor to mortality, predominantly affecting males aged 65 and above. The field of omics has recently gained traction due to its capacity to provide profound insights into the biochemical mechanisms underlying conditions like prostate cancer. This involves the identification and quantification of low-molecular-weight metabolites and proteins acting as crucial biochemical signals for early detection, therapy assessment, and target identification. A spectrum of analytical methods is employed to discern and measure these molecules, revealing their altered biological pathways within diseased contexts. Metabolomics and proteomics generate refined data subjected to detailed statistical analysis through sophisticated software, yielding substantive insights. This review aims to underscore the major contributions of multi-omics to PCa research, covering its core principles, its role in tumor biology characterization, biomarker discovery, prognostic studies, various analytical technologies such as mass spectrometry and Nuclear Magnetic Resonance, data processing, and recent clinical applications made possible by an integrative "omics" approach. This approach seeks to address the challenges associated with current PCa treatments. Hence, our research endeavors to demonstrate the valuable applications of these potent tools in investigations, offering significant potential for understanding the complex biochemical environment of prostate cancer and advancing tailored therapeutic approaches for further development.
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Biomarcadores Tumorais , Metabolômica , Neoplasias da Próstata , Proteômica , Humanos , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/diagnóstico , Metabolômica/métodos , Proteômica/métodos , Biomarcadores Tumorais/metabolismo , Análise de Dados , Espectrometria de Massas/métodosRESUMO
Background and Objectives: Human papillomavirus (HPV) was previously investigated in lung cancer with wide inter-geographic discrepancies. p16INK4a has been used as a surrogate for detecting high-risk HPV (HR-HPV) in some cancer types. This study assessed the evidence of HPV in non-small-cell lung cancer (NSCLC) among Jordanian patients, investigated the expression of p16INK4a, and evaluated its prognostic value and association with HPV status. Materials and Methods: The archived samples of 100 patients were used. HPV DNA detection was performed by real-time polymerase chain reaction (RT-PCR). p16INK4a expression was assessed by immunohistochemistry (IHC). The Eighth American Joint Committee on Cancer protocol (AJCC) of head and neck cancer criteria were applied to evaluate p16INK4a positivity considering a moderate/strong nuclear/cytoplasmic expression intensity with a distribution in ≥75% of cells as positive. Results: HPV DNA was detected in 5% of NSCLC cases. Three positive cases showed HR-HPV subtypes (16, 18, 52), and two cases showed the probable HR-HPV 26 subtype. p16INK4a expression was positive in 20 (20%) NSCLC cases. None of the HPV-positive tumors were positive for p16INK4a expression. A statistically significant association was identified between p16INK4a expression and the pathological stage (p = 0.029) but not with other variables. No survival impact of p16INK4a expression was detected in NSCLC cases as a group; however, it showed a statistically significant association with overall survival (OS) in squamous cell carcinoma (SqCC) cases (p = 0.033). Conclusions: This is the first study to assess HPV and p16INK4a expression in a Jordanian population. HPV positivity is rare in NSCLC among a Jordanian subpopulation. P16 INK4a reliability as a surrogate marker for HPV infection in lung cancer must be revisited.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Inibidor p16 de Quinase Dependente de Ciclina , Neoplasias Pulmonares , Infecções por Papillomavirus , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/virologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA Viral/análise , Papillomavirus Humano , Imuno-Histoquímica , Jordânia/epidemiologia , Neoplasias Pulmonares/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Prognóstico , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: Chronic inflammation is a hallmark of cancer, and it can be stimulated by many factors. Substance P (SP), through binding to neurokinin 1 receptor (NK1R), and pyruvate kinase M2 (PKM2) play critical roles in cancer development and progression via modulating the tumor microenvironment. This study aimed to investigate the prognostic significance of SP and PKM2 in combination with NK1R and Ki-67 in hormone receptor negative (HR-ve) breast cancer. METHODS: Immunohistochemical expression levels of SP, NK1R, PKM2, and Ki-67 were measured in 144 paraffin-embedded breast cancer tissues (77 h -ve and 67 h + ve). SP, NK1R, and PKM2 were scored semiquantitatively, while Ki-67 was obtained by the percentage of total number of tumor cells with nuclear staining. The optimal cutoff value for SP, NK1R, PKM2, and Ki-67 were assessed by Cutoff Finder. RESULTS: High SP expression in HR -ve breast cancer was associated with TNM stage (p = 0.020), pT stage (p = 0.035), pN stage (p = 0.002), axillary lymph node metastasis (p = 0.003), and NK1R expression level (p = 0.010). In HR + ve breast cancer, SP expression was associated with HER2 status (p = 0.001) and PKM2 expression level (p = 0.012). Regarding PKM2 expression level, it significantly associated with HER2 status (p = 0.001) and history of DCIS (p = 0.046) in HR-ve tumors, and with HER2 status (p < 0.001) and SP expression level (p = 0.012) in HR + ve tumors. Survival analysis revealed that high SP level negatively impacted overall survival in HR-ve tumors that had low NK1R level (p = 0.021). Moreover, high SP negatively impacted overall survival in HR-ve tumors that had low Ki-67 level (p = 0.005). High PKM2 negatively impacted overall survival in HR-ve cases with low SP (p = 0.047). CONCLUSION: Combined expression levels of SP with NK1R or Ki-67, and PKM2 with SP could be used to predict survival in breast cancer patients with HR-ve tumors. Our findings suggest a role of SP/NK1R pathway and PKM2 in HR-ve breast cancer pathogenesis which should be further investigated to unveil the underlying molecular mechanisms.
Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/patologia , Substância P , Receptores da Neurocinina-1/metabolismo , Antígeno Ki-67/metabolismo , Piruvato Quinase , Hormônios , Microambiente TumoralRESUMO
BACKGROUND: Spontaneous idiopathic testicular hemorrhage is an extremely rare entity with few published reports in the literature. CASE PRESENTATION: We report a case of a 15-year-old boy who had been experiencing intense, left scrotal pain for the previous twelve hours. No previous history of trauma or bleeding disorders. The left testis was enlarged and tender. Left orchiectomy was performed. The entire testis was dusty and dark grossly. Microscopic sections show diffuse intratesticular bleeding with intact seminiferous tubules and spermatogenesis. CONCLUSIONS: Spontaneous idiopathic testicular hemorrhage should be considered when evaluating patients with acute scrotal pain. Clinical and ultrasonographic findings and histopathologic evaluation are mandatory to diagnose it.
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Doenças dos Genitais Masculinos , Doenças Testiculares , Anormalidades Urogenitais , Masculino , Humanos , Adolescente , Diagnóstico Diferencial , Testículo/diagnóstico por imagem , Testículo/patologia , Orquiectomia , Doenças Testiculares/diagnóstico por imagem , Doenças Testiculares/patologia , Escroto/diagnóstico por imagem , Escroto/patologia , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Dor Pélvica/diagnósticoRESUMO
Cirsimaritin is a dimethoxy flavon that has different biological activities such as antiproliferative, antimicrobial, and antioxidant activities. This study aims to investigate the anti-diabetic effects of cirsimaritin in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with cirsimaritin (50 mg/kg) or metformin (200 mg/kg) for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. Cirsimaritin reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p < 0.001). Cirsimaritin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p < 0.01). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with cirsimaritin compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 (p < 0.01 and p < 0.05, respectively) and pAMPK-α1 (p < 0.05) were upregulated following treatment with cirsimaritin. Cirsimaritin was able to upregulate GLUT2 and AMPK protein expression in the liver (p < 0.01, <0.05, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with cirsimaritin compared to the vehicle controls (p < 0.001). Cirsimaritin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.001) in diabetic rats compared to the vehicle control. Cirsimaritin could represent a promising therapeutic agent to treat T2D.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Metformina , Ratos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Metformina/efeitos adversos , Dieta Hiperlipídica , Glicemia/metabolismo , Resistência à Insulina/fisiologia , Hipoglicemiantes/efeitos adversos , Estreptozocina/efeitos adversosRESUMO
Untargeted multi-omics analysis of plasma is an emerging tool for the identification of novel biomarkers for evaluating disease prognosis, and for developing a better understanding of molecular mechanisms underlying human disease. The successful application of metabolomic and proteomic approaches relies on reproducibly quantifying a wide range of metabolites and proteins. Herein, we report the results of untargeted metabolomic and proteomic analyses from blood plasma samples following analyte extraction by two frequently-used solvent systems: chloroform/methanol and methanol-only. Whole blood samples were collected from participants (n = 6) at University Hospital Sharjah (UHS) hospital, then plasma was separated and extracted by two methods: (i) methanol precipitation and (ii) 4:3 methanol:chloroform extraction. The coverage and reproducibility of the two methods were assessed by ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). The study revealed that metabolite extraction by methanol-only showed greater reproducibility for both metabolomic and proteomic quantifications than did methanol/chloroform, while yielding similar peptide coverage. However, coverage of extracted metabolites was higher with the methanol/chloroform precipitation.
Assuntos
Metanol , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Metanol/química , Clorofórmio , Reprodutibilidade dos Testes , ProteômicaRESUMO
Skin cancer, including malignant melanoma (MM) and keratinocyte carcinoma (KC), historically named non-melanoma skin cancers (NMSC), represents the most common type of cancer among the white skin population. Despite decades of clinical research, the incidence rate of melanoma is increasing globally. Therefore, a better understanding of disease pathogenesis and resistance mechanisms is considered vital to accomplish early diagnosis and satisfactory control. The "Omics" field has recently gained attention, as it can help in identifying and exploring metabolites and metabolic pathways that assist cancer cells in proliferation, which can be further utilized to improve the diagnosis and treatment of skin cancer. Although skin tissues contain diverse metabolic enzymes, it remains challenging to fully characterize these metabolites. Metabolomics is a powerful omics technique that allows us to measure and compare a vast array of metabolites in a biological sample. This technology enables us to study the dermal metabolic effects and get a clear explanation of the pathogenesis of skin diseases. The purpose of this literature review is to illustrate how metabolomics technology can be used to evaluate the metabolic profile of human skin cancer, using a variety of analytical platforms including gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR). Data collection has not been based on any analytical method.
Assuntos
Metaboloma , Neoplasias Cutâneas , Humanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas/métodos , Metabolômica/métodos , Neoplasias Cutâneas/diagnósticoRESUMO
Background: Isorhamnetin is a flavonoid that is found in medical plants. Several studies showed that isorhamnetin has anti-inflammatory and anti-obesity effects. This study aims to investigate the anti-diabetic effects of isorhamnetin in a high-fat diet and Streptozotocin-(HFD/STZ)-induced mice model of type 2 diabetes. Materials and Methods: Mice were fed with HFD followed by two consecutive low doses of STZ (40 mg/kg). HFD/STZ diabetic mice were treated orally with isorhamnetin (10 mg/kg) or (200 mg/kg) metformin for 10 days before sacrificing the mice and collecting plasma and soleus muscle for further analysis. Results: Isorhamnetin reduced the elevated levels of serum glucose compared to the vehicle control group (p < 0.001). Isorhamnetin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control mice (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in diabetic mice treated with isorhamnetin compared to the vehicle controls. Fasting glucose level was significantly lower in diabetic mice treated with isorhamnetin during the intraperitoneal glucose tolerance test (IPGTT) (p < 0.001). The skeletal muscle protein contents of GLUT4 and p-AMPK-α were upregulated following treatment with isorhamnetin (p > 0.01). LDL, triglyceride, and cholesterol were reduced in diabetic mice treated with isorhamnetin compared to vehicle control (p < 0.001). Isorhamnetin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.05) in diabetic mice compared to vehicle control. Conclusions: Isorhamnetin ameliorates insulin resistance, oxidative stress, and inflammation. Isorhamnetin could represent a promising therapeutic agent to treat T2D.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina/fisiologia , Dieta Hiperlipídica/efeitos adversos , Estreptozocina/farmacologia , Diabetes Mellitus Experimental/metabolismo , Inflamação/tratamento farmacológico , Modelos Animais de Doenças , Estresse Oxidativo , Glucose/farmacologia , Glicemia , Hipoglicemiantes/uso terapêuticoRESUMO
Background and Objectives: Type two diabetes mellitus (T2DM) is a chronic disease with debilitating complications and high mortality. Evidence indicates that good glycemic control delays disease progression and is hence a target of disease management protocols. Nonetheless, some patients cannot maintain glycemic control. This study aimed to investigate the association between serum leptin levels and several SNPs of the LEP gene with the lack of glycemic control in T2DM patients on metformin therapy. Materials and Methods: In a hospital-based case-control study, 170 patients with poor glycemic control and 170 patients with good glycemic control were recruited. Serum leptin was measured. Patients were genotyped for three SNPs in the LEP gene (rs7799039, rs2167270, and rs791620). Results: Serum leptin was significantly lower in T2DM patients with poor glycemic control (p < 0.05). In multivariate analysis, serum leptin levels significantly lowered the risk of having poor glycemic control (OR = 0.985; CI: 0.976-0.994; p = 0.002); moreover, the GA genotype of rs2167270 was protective against poor glycemic control compared to the GG genotype (OR = 0.417; CI: 0.245-0.712; p = 0.001). Conclusions: Higher serum leptin and the GA genotype of the rs2167270 SNP of the LEP gene were associated with good glycemic control in T2DM patients on metformin therapy. Further studies with a larger sample size from multiple institutions are required to validate the findings.
Assuntos
Diabetes Mellitus Tipo 2 , Leptina , Metformina , Humanos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Genótipo , Controle Glicêmico , Leptina/genética , Metformina/uso terapêutico , Polimorfismo de Nucleotídeo ÚnicoRESUMO
In a previous report, we described the discovery of (E)-5-((8-hydroxyquinolin-5-yl)diazenyl)-2-methylbenzenesulfonamide as a potent inhibitor of GLO-I enzyme with IC50 of 1.28 ± 0.12 µM. Herein, lead optimization of this compound was achieved through targeting the central zinc atom and hydrophilic amino acid residues in the active site of the enzyme. Among the synthesized compounds, compound TS010 showed the most potent inhibitory activity with IC50 of 0.57 ± 0.04 µM. Compound TS013 also showed comparable activity to that of the lead compound with IC50 of 1.14 ± 0.03 µM. Molecular docking studies disclosed the binding mode of the compounds inside the active side of GLO-I enzyme.
Assuntos
Antineoplásicos , Lactoilglutationa Liase , Antineoplásicos/química , Antineoplásicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Lactoilglutationa Liase/química , Lactoilglutationa Liase/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Oxytocin produces an excitatory effect on gastric muscle through the activation of receptors present on stomach smooth muscle cells. However, the intracellular mechanisms that mediate oxytocin excitatory effects are still largely unknown. Therefore, we aimed to investigate the signaling pathways involved in oxytocin-induced contractions in gastric smooth muscle, shedding light on phospholipase C (PLC)-ß1 signaling and its downstream molecules, including inositol 1,4,5- trisphosphate (IP3) and myosin light chain kinase (MLCK). The contractions of gastric smooth muscle from male rats were measured in an organ bath set up in response to exogenous oxytocin 10-7 M, in the presence and absence of inhibitors of the indicated signaling molecules. Oxytocin (10-9-10-5 M) induced dose-dependent stomach smooth muscle contraction. Pre-incubation with atosiban, an oxytocin receptor inhibitor, abolished the oxytocin-induced contraction. Moreover, PLC ß1 inhibitor (U73122) and IP3 inhibitor Xestospongin C inhibited oxytocin-induced muscle contraction to various degrees. Verapamil, a calcium channel blocker, inhibited oxytocin-induced contraction, and pre-incubation of the strips, with both verapamil and Xestospongin C, further inhibited the excitatory effect of oxytocin. Chelation of intracellular calcium with BAPT-AM (1,2-bis-(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid) significantly inhibited the effect of oxytocin on muscle contraction. Finally, pre-incubation of the strips with the Ca2+/calmodulin-dependent protein kinase selective inhibitor STO-609 significantly inhibited the contraction induced by oxytocin. These results suggest that oxytocin directly stimulates its cell surface receptor to activate PLC ß1, which in turn liberates IP3, which eventually elevates intracellular calcium, the prerequisite for smooth muscle contraction.
Assuntos
Cálcio , Ocitocina , Ratos , Masculino , Animais , Ocitocina/farmacologia , Ocitocina/metabolismo , Cálcio/metabolismo , Fosfolipase C beta/metabolismo , Fosfolipases Tipo C/metabolismo , Músculo Liso/metabolismo , Estômago , Contração Muscular/fisiologia , Verapamil/farmacologiaRESUMO
Glioblastoma (GB) is a primary malignancy of the central nervous system that is classified by the WHO as a grade IV astrocytoma. Despite decades of research, several aspects about the biology of GB are still unclear. Its pathogenesis and resistance mechanisms are poorly understood, and methods to optimize patient diagnosis and prognosis remain a bottle neck owing to the heterogeneity of the malignancy. The field of omics has recently gained traction, as it can aid in understanding the dynamic spatiotemporal regulatory network of enzymes and metabolites that allows cancer cells to adjust to their surroundings to promote tumor development. In combination with other omics techniques, proteomic and metabolomic investigations, which are a potent means for examining a variety of metabolic enzymes as well as intermediate metabolites, might offer crucial information in this area. Therefore, this review intends to stress the major contribution these tools have made in GB clinical and preclinical research and highlights the crucial impacts made by the integrative "omics" approach in reducing some of the therapeutic challenges associated with GB research and treatment. Thus, our study can purvey the use of these powerful tools in research by serving as a hub that particularly summarizes studies employing metabolomics and proteomics in the realm of GB diagnosis, treatment, and prognosis.
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Astrocitoma , Glioblastoma , Humanos , Proteômica/métodos , Glioblastoma/diagnóstico , Glioblastoma/metabolismo , Metabolômica/métodosRESUMO
The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has captivated the globe's attention since its emergence in 2019. This highly infectious, spreadable, and dangerous pathogen has caused health, social, and economic crises. Therefore, a worldwide collaborative effort was made to find an efficient strategy to overcome and develop vaccines. The new vaccines provide an effective immune response that safeguards the community from the virus' severity. WHO has approved nine vaccines for emergency use based on safety and efficacy data collected from various conducted clinical trials. Herein, we review the safety and effectiveness of the WHO-approved COVID-19 vaccines and associated immune responses, and their impact on improving the public's health. Several immunological studies have demonstrated that vaccination dramatically enhances the immune response and reduces the likelihood of future infections in previously infected individuals. However, the type of vaccination and individual health status can significantly affect immune responses. Exposure of healthy individuals to adenovirus vectors or mRNA vaccines causes the early production of antibodies from B and T cells. On the other hand, unhealthy individuals were more likely to experience harmful events due to relapses in their existing conditions. Taken together, aligning with the proper vaccination to a patient's case can result in better outcomes.
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COVID-19 , Vacinas Virais , Humanos , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2 , Pandemias/prevenção & controle , COVID-19/prevenção & controle , Anticorpos Antivirais , ImunidadeRESUMO
Cancer of the central nervous system (CNS) is ranked as the 19th most prevalent form of the disease in 2020. This study aims to identify candidate biomarkers and metabolic pathways affected by paclitaxel and etoposide, which serve as potential treatments for glioblastoma, and are linked to the pathogenesis of glioblastoma. We utilized an untargeted metabolomics approach using the highly sensitive ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) for identification. In this study, 92 and 94 metabolites in U87 and U373 cell lines were profiled, respectively. The produced metabolites were then analyzed utilizing t-tests, volcano plots, and enrichment analysis modules. Our analysis revealed distinct metabolites to be significantly dysregulated (nutriacholic acid, L-phenylalanine, L-arginine, guanosine, ADP, hypoxanthine, and guanine), and to a lesser extent, mevalonic acid in paclitaxel and/or etoposide treated cells. Furthermore, both urea and citric acid cycles, and metabolism of polyamines and amino acids (aspartate, arginine, and proline) were significantly enriched. These findings can be used to create a map that can be utilized to assess the antitumor effect of paclitaxel and/or etoposide within the studied cancer cells.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Etoposídeo/farmacologia , Paclitaxel/farmacologia , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Neoplasias Encefálicas/tratamento farmacológicoRESUMO
Silver nanoparticles (AgNPs) are widely used commercially due to their antimicrobial effects. Little is known about the effect of AgNPs on neural transmission and pain response. The aim of this study was to assess the anti-nociceptive activity of AgNPs. AgNPs were prepared at 16 ug/mL, white albino rats were injected with various doses of AgNPs, and challenged using a hot-plate test and paw withdrawal latency (PWL) was measured. The chronic constriction injury (CCI) model was utilized to evaluate the pedal withdrawal reflex and tail withdrawal reflex. An electrophysiological study was conducted utilizing colon longitudinal muscle strips. AgNPs increased the latency of PWL in a dose-dependent matter over the duration of 6 h. The paw withdrawal threshold in animals with CCI significantly increased after AgNPs administration. In isolated colon longitudinal muscle strips, AgNPs significantly reduced the colonic migrating motor complexes (MMCs) and contraction. This action was completely reversed after removing the AgNPs and adding acetylcholine to the preparation. In this study, AgNPs showed significant anti-nociception properties. To our knowledge, this is the first report to describe this pharmacological action of AgNPs.
Assuntos
Nanopartículas Metálicas , Prata , Animais , Prata/farmacologia , RatosRESUMO
This study examined the effects of ischemic preconditioning (IP) on the ischemia/reperfusion (I/R) induced injury in normal and hypertrophied hearts. Cardiac hypertrophy in rabbits was induced by L-thyroxine (0.5 mg/kg/day for 16 days). Hearts with or without IP (3 cycles of 5 min ischemia and 10 min reperfusion) were subjected to I/R (60 min ischemia followed by 60 min reperfusion). IP reduced the I/R-induced infarct size from 68% to 24% and 57% to 33% in the normal and hypertrophied hearts, respectively. Leakage of creatine phosphokinase in the perfusate from the hypertrophied hearts due to I/R was markedly less than that form the normal hearts; IP prevented these changes. Although IP augmented the increase in phosphorylated p38-mitogen-activated protein kinase (p38-MAPK) content due to I/R, this effect was less in the hypertrophied than in the normal heart. These results suggest that reduced cardioprotection by IP of the I/R-induced injury in hypertrophied hearts may be due to reduced activation of p38-MAPK in comparison with normal hearts.
Assuntos
Precondicionamento Isquêmico Miocárdico , Infarto do Miocárdio/complicações , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/terapia , Animais , Masculino , Traumatismo por Reperfusão Miocárdica/complicações , Coelhos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
AIMS OF THE STUDY: The purpose of this study was to assess pharmacists' knowledge and attitude towards early detection of colorectal cancer (CRC) in Jordan and to explore potential predictor variables of such knowledge and attitude. METHODS USED TO CONDUCT THE STUDY: An electronic, self-reported questionnaire was used to collect data about demographics, knowledge and attitude regarding early detection of CRC. Both content and face validity were tested in a panel of experts. The participants' responses were analysed using descriptive statistics and multiple linear regressions. RESULTS OF THE STUDY: The 352 pharmacists (78% females, 94% Jordanian) had a median age of 28 years and graduated mostly (83%) from public universities. Surprisingly, 90% were not able to identify carcinoembryonic antigen (CEA) as a non-accurate diagnostic method and almost one-third did not identify the correct screening tests. On a scale of 5, the majority of participants (59%) had moderate knowledge scores (3 or 4) in case scenarios. The median knowledge Percent of Maximum Possible (POMP) score was 67% and higher scores were associated with more years since graduation, pharmacists with MSc degree and higher, working in urban areas, studying oncology course and received oncology training (P < .05). Most participants showed a positive attitude towards early detection of CRC (median attitude POMP score was 78%). However, none of the analysed variables predicted their level of attitude. CONCLUSIONS DRAWN FROM THE STUDY AND CLINICAL IMPLICATIONS: Although the majority of pharmacists demonstrated a positive attitude towards early detection of CRC, their knowledge was inadequate. The study highlighted the importance of optimising the education programmes to improve the pharmacists' knowledge about CRC early detection and preparing the pharmacists for participating in future national screening initiatives.
Assuntos
Neoplasias Colorretais , Farmacêuticos , Adulto , Atitude do Pessoal de Saúde , Neoplasias Colorretais/diagnóstico , Estudos Transversais , Feminino , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Jordânia , Masculino , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND OBJECTIVES: Blood transfusion is inherently associated with risks, and little is known regarding the available quality and safety measures in developing countries. No studies or census has been carried out, and therefore, no data on this compelling issue are available. MATERIALS AND METHODS: Data emanating from eight Arabic eastern/southern Mediterranean countries who responded to five surveys were collected and tabulated. RESULTS: Asepsis during phlebotomy, screening for serological and immuno-haematological parameters and appropriate storage conditions are maintained across all countries. Variations in blood component processing exist. Universal leucoreduction is systematically applied in Lebanon. Nucleic acid testing is only performed in Egypt. Aphaeresis procedure, leucoreduction and quality control for blood components are virtually inexistent in Mauritania. Written donor questionnaire is absent in Algeria and Tunisia. Most donor deferral periods for infectious agents are inconsistent with international standards. CONCLUSION: Gaps in the processing and in the quality/safety measures applied to the manufacture of blood components are quite evident in most eastern/southern Mediterranean countries. The decision of establishing an effective collaboration network and an independent body - aside from WHO - composed of specialists that oversees all transfusion activities in these countries is certainly a crucial step towards ensuring an optimum level of blood safety.