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Inflammation is a complex defense process that maintains tissue homeostasis. However, this complex cascade, if lasts long, may contribute to pathogenesis of several diseases. Chronic inflammation has been exhaustively studied in the last few decades, for its contribution in development and progression of cancer. The intrinsic limitations of conventional anti-inflammatory and anti-cancer therapies triggered the development of nanomedicines for more effective and safer therapies. Targeting inflammation and tumor cells by nanoparticles, encapsulated with active therapeutic agents, offers a promising outcome with patient survival. Considerable technological success has been achieved in this field through exploitation of tumor microenvironment, and recognition of molecules overexpressed on endothelial cells or macrophages, through enhanced vascular permeability, or by rendering biomimetic approach to nanoparticles. This review focusses on the inflammatory pathways in progression of a tumor, and advancement in nanotechnologies targeting these pathways. We also aim to identify the gaps that hinder the successful clinical translation of nanotherapeutics with further clinical studies that will allow oncologist to precisely identify the patients who may be benefited from nanotherapy at time when promotion or progression of tumor initiates. It is postulated that the nanomedicines, in near future, will shift the paradigm of cancer treatment and improve patient survival.
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Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Nanomedicina , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/metabolismo , Sistemas de Liberação de Medicamentos , Células Endoteliais/metabolismo , Neoplasias/metabolismo , Inflamação/tratamento farmacológico , Microambiente TumoralRESUMO
This study aimed to determine the chemical composition of the essential oils (EOs) of Ocimum basilicum L., as well as to evaluate the antibacterial, antidiabetic, dermatoprotective, and anti-inflammatory properties, and the EOs and aqueous extracts of O. basilicum. The antibacterial activity was evaluated against bacterial strains, Gram-positive and Gram-negative, using the well diffusion and microdilution methods, whereas the antidiabetic activity was assessed in vitro using two enzymes involved in carbohydrate digestion, α-amylase and α-glucosidase. On the other hand, the dermatoprotective and anti-inflammatory activities were studied by testing tyrosinase and lipoxygenase inhibition activity, respectively. The results showed that the chemical composition of O. basilicum EO (OBEO) is dominated by methyl chavicol (86%) and trans-anethol (8%). OBEO exhibited significant antibacterial effects against Gram-negative and Gram-positive strains, demonstrated by considerable diameters of the inhibition zones and lower MIC and MBC values. In addition, OBEO exhibited significant inhibition of α-amylase (IC50 = 50.51 ± 0.32 µg/mL) and α-glucosidase (IC50 = 39.84 ± 1.2 µg/mL). Concerning the anti-inflammatory activity, OBEO significantly inhibited lipoxygenase activity (IC50 = 18.28 ± 0.03 µg/mL) compared to the aqueous extract (IC50 = 24.8 ± 0.01 µg/mL). Moreover, tyrosinase was considerably inhibited by OBEO (IC50 = 68.58 ± 0.03 µg/mL) compared to the aqueous extract (IC50 = 118.37 ± 0.05 µg/mL). The toxicological investigations revealed the safety of O. basilicum in acute and chronic toxicity. The finding of in silico analysis showed that methyl chavicol and trans-anethole (main compounds of OBEO) validate the pharmacokinetics of these compounds and decipher some antibacterial targets.
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Ocimum basilicum , Óleos Voláteis , Ocimum basilicum/química , Monofenol Mono-Oxigenase , alfa-Glucosidases , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , LipoxigenasesRESUMO
Cardiovascular diseases (CVD) cause significant global morbidity, mortality and public health burden annually. CVD alters richness, diversity, and composition of Gut microbiota along with RAS and histopathological differences. Present study explores Metformin role in mitigating doxorubicin induced cardiovascular toxicity/remodeling. Animals were divided into 4 groups with n=6: Group I (N. Control) free access to diet and water; Group II (MET. Control) on oral Metformin (250â¯mg/kg) daily; Group III (DOX. Control) alternate day intraperitoneal Doxorubicin (3â¯mg/kg) totaling 18â¯mg/kg; Group IV (DOX. MET. Control) received both daily oral Metformin (250â¯mg/kg) and alternate day Doxorubicin (3â¯mg/kg). Gut microbial analysis was made from stool before animals were sacrificed for biochemical and histopathological analysis. Significant alterations were observed in É and ß-diversity with new genus from Firmicutes, specifically Clostridia_UCG-014, Eubacterium ruminantium, and Tunicibacter, were prevalent in both the DOX. Control and DOX.MET groups. Proteobacteria, represented by Succinivibrio, were absent in all groups. Additionally, Parabacteroides from the Bacteroidia phylum was absent in all groups except the N. control. In the DOX.MET Control group, levels of Angiotensin II ( 7.75± 0.49 nmol/min, p<0.01) and Renin (2.60±0.26â¯ng/ml/hr) were significantly reduced. Conversely, levels of CK-MB, Fibrinogen, Troponin, CRP ( p < 0.0001), and TNFÉ (p < 0.05) were elevated. Histopathological examination revealed substantial cardiac changes, including Fibrinogen and fat deposition and eosinophilic infiltration, as well as liver damage characterized by binucleated cells and damaged hepatocytes, along with altered renal tissues in the DOX.MET.Control group. The findings suggest that MET. significantly modifies gut microbiota, particularly impacting the Firmicutes and Proteobacteria phyla. The reduction in Angiotensin II levels, alongside increased inflammatory markers and myocardial damage, highlights the complex interactions and potential adverse effects associated with MET therapy on cardiovascular health.
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Microbioma Gastrointestinal , Metformina , Microbioma Gastrointestinal/efeitos dos fármacos , Metformina/farmacologia , Animais , Masculino , Doxorrubicina , Doenças Cardiovasculares/induzido quimicamente , Ratos , Bactérias/efeitos dos fármacos , Bactérias/classificação , Fezes/microbiologiaRESUMO
BACKGROUND: Clinical endocrinology has observed emerging endocrine complications following COVID-19 vaccination, amidst successful reductions in COVID-19 hospitalizations and deaths. The Pfizer-BioNTech and Moderna mRNA vaccines have demonstrated efficacy. Reports indicate a potential association between SARS-CoV-2 vaccination and diabetes, exploring interactions with ACE-2 receptors and molecular mimicry. Additionally, altered liver and kidney function tests post-vaccination prompt investigation into their role in predicting type 2 diabetes. This study aims to explore these biochemical abnormalities in a case-control, single-centre prospective study. MATERIALS AND METHODS: This prospective study aimed to evaluate a total of five hundred healthy donors, out of which 203 qualified for final analysis. Participants were selected based on their vaccination status with a COVID-19 vaccine and prior exposure to the SARS-CoV-2 virus. Donors without prior SARS-CoV-2 infection were excluded from the study. Included participants were adults who had received three doses of the COVID-19 vaccine. RESULTS: A total of 203 individuals were included in the study, comprising 104 with type 2 diabetes mellitus (T2DM) and 99 without. Demographic characteristics including age, sex, nationality, Rh factors, ABO blood groups, liver function tests (LFT), kidney function tests (KFT), lactate dehydrogenase (LDH), and mineral ion levels were analysed. Among the participants, the distribution based on HbA1c levels showed 47.8% with HbA1c <7% classified as normal, 38.48% with HbA1c 8-10% classified as high, and 16.64% with HbA1c <10% classified as uncontrolled diabetes. Significant findings included a decrease in magnesium levels to 0.77±0.82 mmol/L (p<0.04*), an increase in LDH levels to 420.70±356.26 µL (p<0.01*), and elevated levels of alkaline phosphatase (143.22 ± 142.62 µL, p<0.001), gamma-glutamyl transferase (GGT) (55.70 ± 32.20 µL, p<0.001), and serum bilirubin (9.23 ± 4.87 µmol/L, p<0.001). Creatinine levels were significantly lower at 116.75 ± 101.94 µmol/L (p#60;0.001), while uric acid levels were significantly elevated at 305.92 ± 145.04 µmol/L (p<0.001) in individuals with uncontrolled HbA1c <10%. A majority of these individuals belonged to the O+ blood group. CONCLUSION: This study underscores significant shifts in serum biomarkers and their complex interplay with mRNA-based SARS-CoV-2 vaccination and diabetes, particularly in uncontrolled cases. The findings suggest potential autoimmune reactions triggered by the self-adjuvant properties of mRNA and polyethylene glycol lipid conjugates. Variations observed among different blood groups may correspond to racial disparities influencing molecular mimicry mechanisms. Despite these insights, the underlying pathophysiological mechanisms remain unclear, highlighting the critical need for further research to validate and expand upon these findings.
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BACKGROUND: Much increasing evidence has suggested that long-term complications post vaccination of SARS-CoV-2 experience a wide range of complication including diabetes. The risk and burden of type 1 diabetes is extensively reported, but type 2 diabetes mellitus (T2D) has yet to be characterized. To address this gap, we aimed to examine trends of long-term complications post SARS-CoV-2 infection and vaccination in diabetes incidence among the Saudi population. METHODS: In this cross-sectional hospital-based study, we analyzed the blood profile of first-time blood donors from the University Hospital of King Abdulaziz University, Jeddah. Saudi Arabia. Various blood parameters, HbA1c was measured in the month of May 2023. All the donors were non-diabetic and were never diagnosed with T2D before the current blood donation. 203 healthy subjects donated their blood, out of which 104 had abnormally high HbA1c tending towards diagnosis of T2D and 99 had with blood profiles. The study followed the STROBE reporting guidelines. RESULTS: Out of 203 donors 104 (male 50(48.1%), female 54(51.9%)) were diagnosed with increased HbA1c (8.24 in males) compared to 7.61 of HbA1c in females. 35.6% were above Ë65 years, with 52.9% with O+ from the ABO blood group. Liver functions indicated significant pË0.05, 0.04, increased amount of GGT (46.47 U/L), Alkaline phosphatase (99.93 ±64.26 uL) respectively in HbA1c elevated donors KFT represented significant pË0.05, 0.02 elevated levels of urea (6.73 ±5.51 mmol/L), creatinine (129.97 ±195.17 umol/L) respectively along with elevated values of Lactate dehydrogenase (LDH) (263.72± 196.70 uL) and triglycerides (1.66 ±0.74mmol/L) when compared to normal value of HbA1c donors. DISCUSSION: In the present cross-sectional study, significant increase in HbA1c, trending towards increased cases of T2D post SARS-CoV-2 infection and vaccination. Males are much affected compared to females. Further maximum number of cases were from donors above the age of 65 years with altered partial LFT (GGT, Alkaline phosphatase), KFT (urea, creatinine), lipid profile (TG) and LDH in post SARS-CoV-2 and vaccination blood donors. CONCLUSION: Increase in HbA1c in 50% of donors, irrespective of gender, is an alarming figure for health authorities, with altered LFT, KFT and LDH tests and, in the near future, may increase the incidence of T2D. Large-scale population-based studies are required to prevent future incidences of T2D in young children who will be vaccinated.
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Doadores de Sangue , Vacinas contra COVID-19 , COVID-19 , Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , SARS-CoV-2 , Humanos , Masculino , Feminino , COVID-19/prevenção & controle , COVID-19/epidemiologia , COVID-19/sangue , Doadores de Sangue/estatística & dados numéricos , Arábia Saudita/epidemiologia , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobinas Glicadas/análise , Pessoa de Meia-Idade , Vacinação/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Gliomas are the most frequent, heterogeneous group of tumors arising from glial cells, characterized by difficult monitoring, poor prognosis, and fatality. Tissue biopsy is an established procedure for tumor cell sampling that aids diagnosis, tumor grading, and prediction of prognosis. MATERIALS AND METHODS: We studied and compared the levels of liquid biopsy markers in patients with different grades of glioma. Also, we tried to prove the potential association between glioma and specific blood group antigens. RESULTS: 78 patients were found, among whom the maximum percentage with glioblastoma had blood group O+ (53.8%). The second highest frequency had blood group A+ (20.4%), followed by B+ (9.0%) and A- (5.1%), and the least with O-. Liquid biopsy biomarkers included Alanine Aminotransferase (ALT), Lactate Dehydrogenase (LDH), lymphocytes, Urea, Alkaline phosphatase (AST), Neutrophils, and C-Reactive Protein (CRP). The levels of all the components increased significantly with the severity of the glioma, with maximum levels seen in glioblastoma (grade IV), followed by grade III and grade II, respectively. CONCLUSION: Gliomas have significant clinical challenges due to their progression with heterogeneous nature and aggressive behavior. A liquid biopsy is a non-invasive approach that aids in setting up the status of the patient and figuring out the tumor grade; therefore, it may show diagnostic and prognostic utility. Additionally, our study provides evidence to prove the role of ABO blood group antigens in the development of glioma. However, future clinical research on liquid biopsy will improve the sensitivity and specificity of these tests and confirm their clinical usefulness to guide treatment approaches.
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BACKGROUND: Cardiovascular diseases (CVDs) continue to exert a substantial global influence in specific areas due to population growth, aging, microbiota, and genetic/environmental factors. Drinking water has a strong impact on the health of an individual. Further, emerging evidence has highlighted the therapeutic potential and benefits of Zamzam water (Zam). OBJECTIVE: We investigated the influence of Zam on doxorubicin-induced cardiac toxicity, elucidating its consequential effects on GUT microbiota dysbiosis and hepatic and renal functions. METHODS: Male rats were categorized into four groups: Group 1 as Normal control (NC), Group 2 as Zamzam control (ZC), Group 3 Disease control (DC) and Group 4 as Therapeutic control (DZ) treated with Zam against doxorubicin-induced disease at a dose of 1mg/kg boy weight) intraperitoneally (i.p). RESULTS: Significant dysbiosis in the composition of GM was observed in the DC group along with a significant decrease (p < 0.05) in serum levels of Zinc, interleukin-10 (IL-10), IL-6 and Angiotensin II (Ang II), while C-reactive protein (CRP), fibrinogen, and CKMB increased significantly (restoration of Zinc ions (0.72 ± 0.07 mcg/mL) compared to NC. Treatment with Zamzam exhibited a marked abundance of 18-times to 72% in Romboutsia, a genus of firmicutes, along with lowering of Proteobacteria in DZ followed by significant restoration of Zinc ions (0.72 ± 0.07 mcg/mL), significant (p Ë 0.05) reduction in CRP (7.22 ± 0.39 mg/dL), CKMB (118.8 ± 1.02 U/L) and Fibrinogen (3.18 ± 0.16 mg/dL), significant (p < 0.05) increase in IL-10 (7.22 ± 0.84 pg/mL) and IL-6 (7.18 ± 0.40 pg/ml), restoration of Ang II (18.62 ± 0.50 nmol/mL/min), marked increase in renin with normal myocyte architecture and tissue orientation of kidney, and restoration of histological architecture of hepatocyte. CONCLUSION: Zam treatment mitigated cardiac toxicity risk through the modulation of GUT microbiota and the renin-angiotensin system and tissue histology effectively.
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Microbioma Gastrointestinal , Sistema Renina-Angiotensina , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Ratos , Sistema Renina-Angiotensina/efeitos dos fármacos , Doxorrubicina/farmacologia , Água/químicaRESUMO
Neoplasm (Glioblastoma) and Alzheimer's disease (AD) comprise two of the most chronic psychological ailments. Glioblastoma is one of the aggressive and prevalent malignant diseases characterized by rapid growth and invasion resulting from cell migration and degradation of extracellular matrix. While the latter is characterized by extracellular plaques of amyloid and intracellular tangles of tau proteins. Both possess a high degree of resistance to treatment owing to the restricted transport of corresponding drugs to the brain protected by the blood-brain barrier (BBB). Development of optimized therapies using advanced technologies is a great need of today. One such approach is the designing of nanoparticles (NPs) to facilitate the drug delivery at the target site. The present article elaborates the advances in nanomedicines in treatment of both AD as well as Gliomas. The intention of this review is to provide an overview of different types of NPs with their physical properties emphasizing their importance in traversing the BBB and hitting the target site. Further, we discuss the therapeutic applications of these NPs along with their specific targets. Multiple overlapping factors with a common pathway in development of AD and Glioblastoma are discussed in details that will assist the readers in developing the conceptual approach to target the NP for an aging population in the given circumstances with limitations of currently designed NPs, and the challenges to meet and the future perspectives.