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1.
Mol Biol Rep ; 51(1): 1039, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39367097

RESUMO

BACKGROUND: Lung cancer (LC) is the most common form of cancer in the world. Of the proteins involved in cell differentiation and proliferation, the epidermal growth factor receptor (EGFR) is among the most significant. Amino acids play a crucial role in cell physiology as metabolic regulators. The benefits of liquid biopsies are their non-invasive nature, ease of collection, and ability to depict the entire tumor's status. The present study is designed to detect the relation between the EGFR exon 19 747-750 deletion mutation and lung cancer and investigate the patterns of alterations of plasma-free amino acids (PFAA) in lung cancer patients of different histopathological types and stages as biomarkers for early detection of lung cancer. METHODS: The study sample comprised 60 lung cancer patients and 60 age- and sex-matched healthy individuals as the control group. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to examine the EGFR exon 19 747-750 deletion mutation, and an AA analyzer was used to quantify the plasma free amino acid (PFAA) profile. RESULTS: Compared with controls, LC patients had significantly higher levels of three AAs and significantly lower levels of fifteen AAs. Thirteen AAs varied significantly between stages I and II. In the lung cancer group, the percentage of cases of mutant EGFR exon-19 deletion increased to 30% from 13.3% in the control group. The histological forms of lung cancer did not significantly differ in this rise. Valine and citrulline plasma levels were substantially greater in the mutant than in the wild-type. Lysine, histidine, and methionine were the independent predictors of the LC group in multivariate analysis. CONCLUSION: Lung cancer development is influenced by the EGFR exon 19 747-750 deletion mutation, and the prognosis and early prediction of lung cancer are greatly affected by the amino acid profile concentrations.


Assuntos
Aminoácidos , Receptores ErbB , Éxons , Neoplasias Pulmonares , Deleção de Sequência , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Receptores ErbB/genética , Receptores ErbB/sangue , Éxons/genética , Feminino , Masculino , Pessoa de Meia-Idade , Aminoácidos/sangue , Deleção de Sequência/genética , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Adulto , Estudos de Casos e Controles
2.
Int J Mol Sci ; 25(19)2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39409094

RESUMO

Glioblastoma is known to be one of the most aggressive and fatal human cancers, with a poor prognosis and resistance to standard treatments. In the last few years, many solid tumor treatments have been revolutionized with the help of immunotherapy. However, this type of treatment has failed to improve the results in glioblastoma patients. Effective immunotherapeutic strategies may be developed after understanding how glioblastoma achieves tumor-mediated immune suppression in both local and systemic landscapes. Biomarkers may help identify patients most likely to benefit from this type of treatment. In this review, we discuss the use of immunotherapy in glioblastoma, with an emphasis on immune checkpoint inhibitors and the factors that influence clinical response. A Pubmed data search was performed for all existing information regarding immune checkpoint inhibitors used for the treatment of glioblastoma. All data evaluating the ongoing clinical trials involving the use of ICIs either as monotherapy or in combination with other drugs was compiled and analyzed.


Assuntos
Glioblastoma , Inibidores de Checkpoint Imunológico , Imunoterapia , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/imunologia , Biomarcadores Tumorais
3.
Cureus ; 16(8): e67578, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39310480

RESUMO

The intracranial development of breast metastasis inside a meningioma is a rare entity known as tumor-to-tumor metastasis or tumor-to-meningioma metastasis. Although rare such cases have been reported in the scientific literature, most of them are from breast and lung cancer, and even rarer from the genitourinary tract, while meningioma is the most cited to harbor these metastases. A thorough histopathological analysis represents the cornerstone of the diagnosis of these lesions. The current article presents a case of breast cancer metastasis developed inside a meningioma in a female patient, which is a rare metastatic presentation. Although hormonal causes have been incriminated, the pathophysiology of this phenomenon is still unclear.

4.
Cureus ; 16(8): e67353, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39310566

RESUMO

Giant dissecting aneurysms of the internal carotid artery are extremely uncommon, particularly in young adults. In this report, we provide a case of a 35-year-old male patient who experienced severe headaches, double vision, paralysis of the left abducens nerve, trigeminal neuralgia, nausea, and vomiting. The cerebral MRI showed an intensely gadolinophilic lesion following the left internal carotid artery route from the petrous canal; it also caused an internal deviation of the cavernous route of the internal carotid artery with a fluid heterogeneous area that pushed the cavernous dura mater (including the Gasser ganglion) on the free cisternal route of the trigeminal nerve. Furthermore, the cerebral angiography revealed a giant dissecting aneurysm at the C2-C4 junction of ICA, anteriorly oriented with perilesional stenoses. The interdisciplinary medical team determined that the most optimal therapeutic strategy would involve coil embolization, and the giant left ICA aneurysm was occluded along with the left ICA, with 15 giant platinum coils. Following the successful intervention, the patient experienced a remarkable clinical outcome, characterized by an immediate reversal of the majority of the symptoms. Although we were not certain of the alleviation of symptoms after the endovascular treatment, fortunately, the results were beyond expectations.

5.
Curr Issues Mol Biol ; 46(9): 9881-9894, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39329940

RESUMO

The race to find an effective treatment for glioblastoma (GBM) remains a critical topic, because of its high aggressivity and impact on survival and the quality of life. Currently, due to GBM's high heterogeneity, the conventional treatment success rate and response to therapy are relatively low, with a median survival rate of less than 20 months. A new point of view can be provided by the comprehension of the tumor microenvironment (TME) in pursuance of the development of new therapeutic strategies to aim for a longer survival rate with an improved quality of life and longer disease-free interval (DFI). The main components of the GBM TME are represented by the extracellular matrix (ECM), glioma cells and glioma stem cells (GSCs), immune cells (microglia, macrophages, neutrophils, lymphocytes), neuronal cells, all of them having dynamic interactions and being able to influence the tumoral growth, progression, and drug resistance thus being a potential therapeutic target. This paper will review the latest research on the GBM TME and the potential therapeutic targets to form an up-to-date strategy.

6.
Medicina (Kaunas) ; 60(8)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39202515

RESUMO

Background and Objectives: Notwithstanding the major progress in the management of cancerous diseases in the last few decades, glioblastoma (GBM) remains the most aggressive brain malignancy, with a dismal prognosis, mainly due to treatment resistance and tumoral recurrence. In order to diagnose this disease and establish the optimal therapeutic approach to it, a standard tissue biopsy or a liquid biopsy can be performed, although the latter is currently less common. To date, both tissue and liquid biopsy have yielded numerous biomarkers that predict the evolution and response to treatment in GBM. However, despite all such efforts, GBM has the shortest recorded survival rates of all the primary brain malignancies. Materials and Methods: We retrospectively reviewed patients with a confirmed histopathological diagnosis of glioblastoma between June 2011 and June 2023. All the patients were treated in the Third Neurosurgical Department of the Clinical Emergency Hospital "Bagdasar-Arseni" in Bucharest, and their outcomes were analyzed and presented accordingly. Results: Out of 518 patients in our study, 222 (42.8%) were women and 296 (57.14%) were men. The most common clinical manifestations were headaches and limb paralysis, while the most frequent tumor locations were the frontal and temporal lobes. The survival rates were prolonged in patients younger than 60 years of age, in patients with gross total tumoral resection and less than 30% tumoral necrosis, as well as in those who underwent adjuvant radiotherapy. Conclusions: Despite significant advancements in relation to cancer diseases, GBM is still a field of great interest for research and in great need of new therapeutic approaches. Although the multimodal therapeutic approach can improve the prognosis, the survival rates are still short and the recurrences are constant.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/cirurgia , Glioblastoma/mortalidade , Glioblastoma/terapia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/mortalidade , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento , Idoso de 80 Anos ou mais , Lituânia/epidemiologia
7.
Curr Issues Mol Biol ; 46(7): 6903-6939, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39057054

RESUMO

Accounting for 48% of malignant brain tumors in adults, glioblastoma has been of great interest in the last decades, especially in the biomolecular and neurosurgical fields, due to its incurable nature and notable neurological morbidity. The major advancements in neurosurgical technologies have positively influenced the extent of safe tumoral resection, while the latest progress in the biomolecular field of GBM has uncovered new potential therapeutical targets. Although GBM currently has no curative therapy, recent progress has been made in the management of this disease, both from surgical and molecular perspectives. The main current therapeutic approach is multimodal and consists of neurosurgical intervention, radiotherapy, and chemotherapy, mostly with temozolomide. Although most patients will develop treatment resistance and tumor recurrence after surgical removal, biomolecular advancements regarding GBM have contributed to a better understanding of this pathology and its therapeutic management. Over the past few decades, specific biomarkers have been discovered that have helped predict prognosis and treatment responses and contributed to improvements in survival rates.

8.
Cureus ; 16(6): e61949, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38855489

RESUMO

Duplication 20p or partial trisomy 20 is a rare chromosomal anomaly characterized by duplication of the short arm of chromosome 20, with various clinical abnormalities. Despite complete trisomy 20, which usually leads to prenatal death, partial trisomy 20 can manifest with variable phenotypes, from mild to severe manifestations. Here, we present a rare case of an 8-year-old boy diagnosed with trisomy 20, epilepsy with focal seizures of genetic origin, craniosynostosis, type 1 diabetes, and autism spectrum disorder. Duplication 20p is a complex diagnostic and presents a therapeutic challenge due to its diverse clinical manifestations. To succeed in the intricacy of such a unique and challenging case, a comprehensive clinical and genetic assessment must be performed.

9.
Mol Biol Rep ; 51(1): 401, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457071

RESUMO

BACKGROUND: Gastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved. METHODS: An ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done. RESULTS: The ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group. CONCLUSIONS: Aloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.


Assuntos
Preparações de Plantas , Úlcera Gástrica , Ratos , Masculino , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Proteína 3 que Contém Domínio de Pirina da Família NLR , Etanol/efeitos adversos , Úlcera/tratamento farmacológico , Gastrinas/uso terapêutico , Piroptose , Ratos Wistar , Extratos Vegetais/farmacologia , Transdução de Sinais
10.
Int J Biol Macromol ; 265(Pt 2): 130950, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38513911

RESUMO

Due to its outstanding qualities, particularly when it takes the shape of hydrogels, chitosan is a well-known biological macromolecule with many applications. When chitosan hydrogels are modified with other polymers, the desirable function as skin regeneration hydrogels is compromised; nevertheless, the mechanical properties can be improved, which is crucial for commercialization. In this study, for the first time, bimetallic zinc silver metal-organic frameworks (ZAg MOF) loaded with ascorbic acid were added to chitosan/polyethylene oxide (PEO) based interpenetrating polymer network (IPN) hydrogels that were crosslinked with biotin to improve their antimicrobial activity, mechanical characteristics, and sustainable treatment of wounds. Significant changes in the microstructure, hydrophilicity level, and mechanical properties were noticed. Ascorbic acid release patterns were upregulated in an acidic environment pH (5.5) that mimics the initial wound pH. Impressive cell viability (98 %), antimicrobial properties, and almost full skin healing in a short time were achieved for the non-replaceable chitosan/PEO developed hydrogels. Enhancing the wound healing of the treated animals using the prepared CS/PEO hydrogel dressing was found to be a result of the inhibition of dermal inflammation via decreasing IL-1ß, suppressing ECM degradation (MMP9), stimulating proliferation through upregulation of TGF-ß and increasing ECM synthesis as it elevates collagen 1 and α-SMA contents. The findings support the implementation of developed hydrogels as antimicrobial hydrogels dressing for fast skin regeneration.


Assuntos
Quitosana , Animais , Quitosana/farmacologia , Quitosana/química , Polietilenoglicóis/farmacologia , Antibacterianos/química , Hidrogéis/farmacologia , Hidrogéis/química , Polímeros , Ácido Ascórbico
11.
Cell Biochem Funct ; 42(2): e3958, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38396357

RESUMO

Iron accumulation in the brain causes oxidative stress, blood-brain barrier (BBB) breakdown, and neurodegeneration. We examined the preventive effects of acetylated oligopeptides (AOP) from whey protein on iron-induced hippocampal damage compared to N-acetyl cysteine (NAC). This 5-week study used 40 male albino rats. At the start, all rats received 150 mg/kg/day of oral NAC for a week. The 40 animals were then randomly divided into four groups: Group I (control) received a normal diet; Group II (iron overload) received 60 mg/kg/day intraperitoneal iron dextran 5 days a week for 4 weeks; Group III (NAC group) received 150 mg/kg/day NAC and iron dextran; and Group IV (AOP group) received 150 mg/kg/day AOP and iron dextran. Enzyme-linked immunosorbent assay, spectrophotometry, and qRT-PCR were used to measure MMP-9, tissue inhibitor metalloproteinase-1 (TIMP-1), MDA, reduced glutathione (GSH) levels, and nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) gene expression. Histopathological and immunohistochemical detection of nestin, claudin, caspase, and GFAP was also done. MMP-9, TIMP-1, MDA, caspase, and GFAP rose in the iron overload group, while GSH, Nrf2, HO-1, nestin, and claudin decreased. The NAC and AOP administrations improved iron overload-induced biochemical and histological alterations. We found that AOP and NAC can protect the brain hippocampus from iron overload, improve BBB disruption, and provide neuroprotection with mostly no significant difference from healthy controls.


Assuntos
Acetilcisteína , Sobrecarga de Ferro , Oligopeptídeos , Animais , Masculino , Ratos , Acetilcisteína/farmacologia , Acetilcisteína/metabolismo , Caspases/metabolismo , Claudinas/genética , Giro Denteado/metabolismo , Giro Denteado/patologia , Dextranos/metabolismo , Dextranos/farmacologia , Regulação para Baixo , Glutationa/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Ferro/metabolismo , Ferro/farmacologia , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/tratamento farmacológico , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/farmacologia , Nestina/genética , Nestina/metabolismo , Nestina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-1/farmacologia , Regulação para Cima , Oligopeptídeos/farmacologia , Heme Oxigenase-1/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo
12.
Biomedicines ; 11(9)2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37760926

RESUMO

BACKGROUND: While acknowledging the generally poor prognostic features of brain metastases from renal cell carcinoma (BM RCC), it is important to be aware of the fact that neurosurgery still plays a vital role in managing this disease, even though we have entered an era of targeted therapies. Notwithstanding their initial high effectiveness, these agents often fail, as tumors develop resistance or relapse. METHODS: The authors of this study aimed to evaluate patients presenting with BM RCC and their outcomes after being treated in the Neurosurgical Department of Clinical Emergency Hospital "Bagdasar-Arseni", and the Neurosurgical Department of the National Institute of Neurology and Neurovascular Diseases, Bucharest, Romania. The study is based on a thorough appraisal of the patient's demographic and clinicopathological data and is focused on the strategic role of neurosurgery in BM RCC. RESULTS: A total of 24 patients were identified with BM RCC, of whom 91.6% had clear-cell RCC (ccRCC) and 37.5% had a prior nephrectomy. Only 29.1% of patients harbored extracranial metastases, while 83.3% had a single BM RCC. A total of 29.1% of patients were given systemic therapy. Neurosurgical resection of the BM was performed in 23 out of 24 patients. Survival rates were prolonged in patients who underwent nephrectomy, in patients who received systemic therapy, and in patients with a single BM RCC. Furthermore, higher levels of hemoglobin were associated in our study with a higher number of BMs. CONCLUSION: Neurosurgery is still a cornerstone in the treatment of symptomatic BM RCC. Among the numerous advantages of neurosurgical intervention, the most important is represented by the quick reversal of neurological manifestations, which in most cases can be life-saving.

13.
Curr Issues Mol Biol ; 45(9): 7680-7704, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37754269

RESUMO

The most commonly diagnosed malignancy of the urinary system is represented by renal cell carcinoma. Various subvariants of RCC were described, with a clear-cell type prevailing in about 85% of all RCC tumors. Patients with metastases from renal cell carcinoma did not have many effective therapies until the end of the 1980s, as long as hormonal therapy and chemotherapy were the only options available. The outcomes were unsatisfactory due to the poor effectiveness of the available therapeutic options, but then interferon-alpha and interleukin-2 showed treatment effectiveness, providing benefits but only for less than half of the patients. However, it was not until 2004 that targeted therapies emerged, prolonging the survival rate. Currently, new technologies and strategies are being developed to improve the actual efficacy of available treatments and their prognostic aspects. This article summarizes the mechanisms of action, importance, benefits, adverse events of special interest, and efficacy of immunotherapy in metastatic renal cell carcinoma, with a focus on brain metastases.

14.
Int J Mol Sci ; 24(13)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37446288

RESUMO

Despite all of the progress in understanding its molecular biology and pathogenesis, glioblastoma (GBM) is one of the most aggressive types of cancers, and without an efficient treatment modality at the moment, it remains largely incurable. Nowadays, one of the most frequently studied molecules with important implications in the pathogenesis of the classical subtype of GBM is the epidermal growth factor receptor (EGFR). Although many clinical trials aiming to study EGFR targeted therapies have been performed, none of them have reported promising clinical results when used in glioma patients. The resistance of GBM to these therapies was proven to be both acquired and innate, and it seems to be influenced by a cumulus of factors such as ineffective blood-brain barrier penetration, mutations, heterogeneity and compensatory signaling pathways. Recently, it was shown that EGFR possesses kinase-independent (KID) pro-survival functions in cancer cells. It seems imperative to understand how the EGFR signaling pathways function and how they interconnect with other pathways. Furthermore, it is important to identify the mechanisms of drug resistance and to develop better tailored therapeutic agents.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Transdução de Sinais
15.
Sci Rep ; 13(1): 5790, 2023 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-37031209

RESUMO

Simvastatin (SV) is a poorly soluble drug; its oral administration is associated with a significant problem: Myopathy. The present study aims to formulate SV microsponges that have the potential to minimize the myotoxicity accompanying the oral administration of the drug. SV microsponges were prepared by exploiting the emulsion solvent evaporation technique. The % entrapment efficiency (%EE) of the drug approached 82.54 ± 1.27%, the mean particle size of SV microsponges ranged from 53.80 ± 6.35 to 86.03 ± 4.79 µm in diameter, and the % cumulative drug release (%CDR) of SV from microsponges was significantly higher than that from free drug dispersion much more, the specific surface area of the optimized microsponges formulation was found to be 16.6 m2/g revealed the porosity of prepared microsponges. Histological and glycogen histochemical studies in the skeletal muscles of male albino rats revealed that microsponges were safer than free SV in minimizing myotoxicity. These findings were proven by Gene expression of Mitochondrial fusion and fission (Mfn1) & (Fis1) and (Peroxisome proliferator-activated receptor gamma co-activator 1α) PGC-1α. Finally, our study ascertained that SV microsponges significantly decreased the myotoxicity of SV.


Assuntos
Sistemas de Liberação de Medicamentos , Miotoxicidade , Masculino , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Emulsões , Porosidade , Sinvastatina/efeitos adversos , Animais , Ratos
16.
Appl Biochem Biotechnol ; 195(8): 5053-5071, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36947366

RESUMO

Multiple organs, including the testes, are damaged by iron overload. It has been shown that N-acetyl cysteine (NAC) influences oxidative stress in iron overload. The present study aimed to evaluate the roles of acetylated peptide (AOP) and NAC in the inhibition of iron-overload induced-testicular damage. At the beginning of the experiment, NAC (150 mg /kg) was given for a week to all 40 rats. Then, four groups were formed by dividing the animals (10 rats/group). Group I included healthy control rats. Group II (iron overload) was given intraperitoneal iron dextran (60 mg/kg/day) 5 days a week for 4 weeks. Group III (NAC) was given NAC orally at a dose of 150 mg/kg/day for 4 weeks in addition to iron dextran. Group IV (AOP) was given AOP orally at a dose of 150 mg/kg/day for 4 weeks besides iron dextran. When the experiment time was over, testosterone serum level, testicular B cell lymphoma-2 (BCL-2) and protein kinase B (PKB) protein levels, nuclear factor kappa-B (NF-κB), and Beclin1 mRNA expression levels, and malondialdehyde (MDA), and reduced glutathione (GSH) were determined by ELISA, quantitative reverse transcription-PCR, and chemical methods. Finally, histopathological examinations and immunohistochemical detection of claudin-1 and CD68 were performed. The iron overload group exhibited decreased testosterone, BCL-2, PKB, claudin-1, and GSH and increased MDA, NF-κB, Beclin1, and CD68, while both NAC and AOP treatments protected against the biochemical and histopathological disturbances occurring in the iron overload model. We concluded that NAC and AOP can protect against testes damage by iron overload via their antioxidant, anti-inflammatory, antiapoptotic, and ant-autophagic properties. The NAC and AOP may be used as preventative measures against iron overload-induced testicular damage.


Assuntos
Acetilcisteína , Sobrecarga de Ferro , Masculino , Ratos , Animais , Acetilcisteína/farmacologia , Acetilcisteína/metabolismo , Testículo , NF-kappa B/metabolismo , Proteína Beclina-1/metabolismo , Claudina-1/metabolismo , Dextranos/metabolismo , Estresse Oxidativo , Antioxidantes/farmacologia , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Glutationa/metabolismo , Morte Celular , Testosterona/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ferro/metabolismo
17.
BMC Chem ; 17(1): 3, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36782310

RESUMO

In this study, Superparamagnetic magnetite nanoparticles (SPMNPs) are used in a new way as direct nanocarrier for Doxorubicin hydrochloride (DOX) via the functionalization of their surface with tri-sodium citrate through ligand exchange to conjugate DOX with imine bond to form tri-sodium citrate functionalized magnetite loaded DOX nanoparticles (DOX/Cit-MNPs). The DOX/Cit-MNPs were coated with chitosan to form chitosan coated citrate functionalized magnetite loaded DOX nanoparticles (Cs/DOX/Cit-MNPs) to offer biodegradability and pH-sensitive drug release features. The Fourier transform infrared spectroscopy (FTIR) analysis confirmed functionalization of SPMNPs, DOX-conjugation, and chitosan coating. The trans electron microscopy (TEM) show spherical nanostructures with average size 40 nm for coated nanocarriers. The saturation magnetization value of carrier was 59 emu/g.The in-vitro release of DOX from the chitosan coated tri-sodium citrate functionalized magnetite loaded DOX nanoparticles (Cs/DOX/Cit-MNPs) was studied to be 75% at pH 5.5 and 28.6% at pH 7.4 which proves the pH sensitivity of encapsulated Cs/DOX/Cit-MNPs. The effect of Cs/DOX/Cit-MNPs toward Human Breast Cancer Cell lines (MCF7) was studied and found to be 76% without magnet and 98% with external magnet after 72 h. With increasing DOX concentration and treatment time, the cell inhibition (IR%) of DOX solution and Cs/DOX-Cit-MNPs suspension to all cells is increased. Cs/DOX/Cit-MNPs showed sustained release and good inhibition to cancer cells and offer a protective mode for normal cells (WISH) compared to the free DOX.

18.
Biology (Basel) ; 11(12)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36552217

RESUMO

Chronic obstructive pulmonary disease (COPD) is a major cause of death and morbidity; it may be accompanied by oxidative stress and inflammation with or without underlying genetic etiology. Finding circulating biomarkers for COPD that can help early diagnosis and predict exacerbation and association with respiratory functions has been challenging. There were 40 healthy participants and 60 COPD patients in this research. The rs2070600 gene variant was examined by PCR-RFLP. Circulating sRAGE and annexin A1 levels were determined by ELISA. GSH and MDA were determined by spectrophotometry. In COPD patients, sRAGE serum levels were substantially lower, but conversely, annexin A1 levels were much greater than in controls. The rs2070600 gene polymorphism's strong association with COPD was demonstrated by genotyping and allelic frequency distribution. The GA genotype was most distributed in COPD, and it was strongly linked to lower serum sRAGE levels. The interrelation between annexin A1, sRAGE, and COPD could be explained through effects on inflammatory mediators' pathways. The rs2070600 gene polymorphism was found to significantly enhance the risk of COPD. Serum sRAGE and annexin A1 may be considered potential diagnostic tools for COPD. Through impacts on GSH and MDA levels that alter the release of inflammatory factors and, therefore, lung damage, it is possible to explain the relationship between annexin A1, sRAGE, and COPD.

19.
Anal Bioanal Chem ; 414(29-30): 8379-8388, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36287223

RESUMO

Nowadays, in the clinical, pharmaceutical, and environmental sectors, the development of facile and sensitive analytical methods and/or innovative devices for the follow-up and detection of antibiotics and pharmaceutical formulations, in general, are urgently needed and still challenging. This work declared three vital applications for broad-spectrum nitrofurantoin (macrofuran) antibiotic detection and quantification: A colorimetric method, a coated paper strip-based nano-lanthanum complex prototype and fabrication of smart electronic color sensor device-based coated paper strips. The colorimetric method showed a significant response upon increasing the concentration of the nitrofurantoin in a range between (1.0-100.0 ng/mL) via a visual color change from orange-yellow to red colors degree with detection and quantification limits of 0.175 and 0.53 ng/mL, respectively, whereas the nano-lanthanum complex coated paper strip prototype showed qualitative on-site sensing for nitrofurantoin via naked eye color changes which can be detected anywhere. Moreover, a smart prototype for detecting macrofuran in the means of paper color change in the RGB color component extraction algorithm and the grayscale projection value processing algorithm was fabricated. The change in RGB color on the coated paper strip was detected using an electronic color sensor device. The developed colorimetric method, coated paper strip, and the electronic color sensor device prototype exhibited fast, simple, costless, and selective towards macrofuran over the competing analyzed. As well as, showed good applicability in the different real samples spiked with different concentrations of macrofuran.


Assuntos
Colorimetria , Nitrofurantoína , Colorimetria/métodos , Eletrônica , Preparações Farmacêuticas
20.
Asian Pac J Cancer Prev ; 23(6): 2079-2087, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35763651

RESUMO

Transitional cell carcinoma is considered the most predominant type of bladder cancer. Bladder can cer can also be found as squamous cell carcinoma that accounts for 5% of the total bladder cancer due to its etiology. The biomarkers associated with grade, prognosis, and stage of the disease are not well proved and known however, many studies have pointed to the association between SNAL/SLUG and Twist2 to the overall survival in patients with bladder cancer. These biomarkers were found to have a crucial role in inhibiting cadherin mediators specifically E-cadherin which are found normally in high level to integrate cell adhesion and normal function of the bladder. This research aims to detect SNAL/SLUG and Twist2 biomarkers in specimens of patients with bladder cancer and to detect their impact on E-cadherin, a tumor suppressor mediator responsible for improving survival and prevent metastasis. MATERIALS AND METHODS: Using 150 archival tissue blocks from human bladder cancer cases to detect expression of SNAIL/SLUG and Twist2 in relation to loss of E-cadherin by immunohistochemical method. RESULTS: Our results have revealed that in squamous cell carcinoma 40 specimens showed marked Twist 2 expression, and 30 specimens showed marked snail/slug biomarkers expression while poorly differentiated cancer cases showed marked expression of Twist 2 in 60 specimens and marked expression of Snail/slug marked expression in 50 specimens. Both were associated with E-cadherin loss. Among the 100 specimens with transitional cell carcinoma, 70 specimens showed divergent differentiation with 7 subtypes each showed different medium to high expression of Snail/Slug and Twist 2 biomarkers with the loss of E-cadherin. E-cadherin was strongly associated with the inverse increase in SNAL/SLUG and Twist2 biomarkers in urothelial carcinoma. CONCLUSION: Detection of SNAIL/SLUG and Twist 2 biomarkers in urothelial cancer is an important predictor for the loss of E-cadherin, a cornerstone in urinary bladder cell adhesion and its loss in urothelial carcinoma may contribute to cancer invasion and poor prognosis. 
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Assuntos
Carcinoma de Células Escamosas , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Biomarcadores , Caderinas , Transição Epitelial-Mesenquimal , Humanos , Bexiga Urinária
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