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1.
Microvasc Res ; 154: 104691, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38703993

RESUMO

Neoadjuvant targeting of tumor angiogenesis has been developed and approved for the treatment of malignant tumors. However, vascular disruption leads to tumor hypoxia, which exacerbates the treatment process and causes drug resistance. In addition, successful delivery of therapeutic agents and efficacy of radiotherapy require normal vascular networks and sufficient oxygen, which complete tumor vasculopathy hinders their efficacy. In view of this controversy, an optimal dose of FDA-approved anti-angiogenic agents and combination with other therapies, such as immunotherapy and the use of nanocarrier-mediated targeted therapy, could improve therapeutic regimens, reduce the need for administration of high doses of chemotherapeutic agents and subsequently reduce side effects. Here, we review the mechanism of anti-angiogenic agents, highlight the challenges of existing therapies, and present how the combination of immunotherapies and nanomedicine could improve angiogenesis-based tumor treatment.


Assuntos
Inibidores da Angiogênese , Imunoterapia , Neoplasias , Neovascularização Patológica , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Animais , Microambiente Tumoral , Nanomedicina , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Angiogênese
2.
Cell Biochem Funct ; 42(4): e4030, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38720663

RESUMO

Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic ß-cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and transforming growth factor ß1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, Interleukin-1 beta (IL-1ß), IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.


Assuntos
Curcumina , Inflamação , NF-kappa B , Estresse Oxidativo , Transdução de Sinais , Curcumina/farmacologia , Curcumina/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , NF-kappa B/metabolismo , Animais , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Transdução de Sinais/efeitos dos fármacos , Humanos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Ratos
3.
Cell Biochem Funct ; 42(2): e3971, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38509767

RESUMO

Autophagy, as a highly conserved cellular process, participates in cellular homeostasis by degradation and recycling of damaged organelles and proteins. Besides, autophagy has been evidenced to play a dual role through cancer initiation and progression. In the early stage, it may have a tumor-suppressive function through inducing apoptosis and removing damaged cells and organelles. However, late stages promote tumor progression by maintaining stemness features and induction of chemoresistance. Therefore, identifying and targeting molecular mechanisms involved in autophagy is a potential therapeutic strategy for human cancers. Multiple transcription factors (TFs) are involved in the regulation of autophagy by modulating the expression of autophagy-related genes (ATGs). In addition, a wide array of long noncoding RNAs (lncRNAs), a group of regulatory ncRNAs, have been evidenced to regulate the function of these autophagy-related TFs through tumorigenesis. Subsequently, the lncRNAs/TFs/ATGs axis shows great potential as a therapeutic target for human cancers. Therefore, this review aimed to summarize new findings about the role of lncRNAs in regulating autophagy-related TFs with therapeutic perspectives.


Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/genética , Neoplasias/genética , Apoptose , Autofagia
4.
Chem Biodivers ; 21(4): e202301777, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38373183

RESUMO

Lawsone, a naturally occurring compound found in henna, has been used in traditional medicine for centuries due to its diverse biological activities. In recent years, its nanoparticle-based structure has gained attention in cancer and infectious disease research. This review explores the therapeutic potential of lawsone and its nanoparticles in the context of cancer and infectious diseases. Lawsone exhibits promising anticancer properties by inducing apoptosis and inhibiting cell proliferation, while its nanoparticle formulations enhance targeted delivery and efficacy. Moreover, lawsone demonstrates significant antimicrobial effects against various pathogens. The unique physicochemical properties of lawsone nanoparticles enable efficient cellular uptake and targeted delivery. Potential applications in combination therapy and personalized medicine open new avenues for cancer and infectious disease treatment. While clinical trials are needed to validate their safety and efficacy, lawsone-based nanoparticles offer hope in addressing unmet medical needs and revolutionizing therapeutic approaches.


Assuntos
Doenças Transmissíveis , Naftoquinonas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Naftoquinonas/química , Gerenciamento Clínico
5.
Pestic Biochem Physiol ; 197: 105701, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38072556

RESUMO

BACKGROUND: Aluminum phosphide (AlP) is a well-known toxic compound used as an agricultural pesticide to prevent insect damage to stored crops. However, even if just a small amount was consumed, it caused lasting harm to the human body and, in acute concentrations, death. The current study employed cerium oxide nanoparticles (CeO2 NPs) to reduce oxidative stress and various harmful outcomes of AlP poisoning. METHODS: Following finding effective concentrations of CeO2 NPs via MTT assay, Human Cardiac Myocyte (HCM) cells were pre-treated with CeO2 NPs for 24 h. After that, they were exposed to 2.36 µM AlP. The activity of oxidative stress and mitochondrial biomarkers, including mitochondrial swelling, mitochondrial membrane potential, and cytochrome c release, were evaluated in HCM cells. Finally, the population of apoptotic and necrotic cells was assessed via flow cytometry. RESULTS: After 24 h, data revealed that all tested concentrations of CeO2 NPs were safe, and 25 and 50 µM of that were selected as effective concentrations. Oxidative stress markers (malondialdehyde, protein carbonyl, superoxide dismutase, and catalase) showed that CeO2 NPs could successfully decrease AlP poisoning due to their antioxidant characteristics. Mitochondrial markers were also recovered by pre-treatment of HCM cells with CeO2 NPs. Furthermore, pre-treating with CeO2 NPs could compensate for the reduction of live cells with AlP and cause a diminishing in the population of early and late apoptotic cells. CONCLUSION: As a result, it is evident that CeO2 NPs, through the recovery of oxidative stress and mitochondrial damages caused by AlP, reduce apoptosis and have therapeutic potentials on HCM cells.


Assuntos
Nanopartículas , Praguicidas , Humanos , Praguicidas/toxicidade , Estresse Oxidativo
6.
Neurol Sci ; 42(8): 3135-3143, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34014397

RESUMO

BACKGROUND: Mavoglurant (AFQ056), a selective metabotropic glutamate receptor 5 (mGluR5) inhibitor, was tested for t levodopa-induced dyskinesia (LID) in patients with Parkinson's Disease (PD). However, clinical trials showed inconsistent results regarding the efficacy of mavoglurant in treating LID in patients with Parkinson's disease (PD). METHODS: A computer literature search of PubMed, Scopus, Web of science, and Cochrane CENTRAL was conducted until March 2021. We selected relevant randomized controlled trials comparing mavoglurant to placebo. Study data were extracted and pooled as mean difference (MD) in the meta-analysis model. RESULTS: Six RCTs were included in this meta-analysis with a total of 485 patients. Mavoglurant was not significantly superior to placebo in terms of the "off-time" (MD -0.27 h, 95% CI -0.65 to 0.11), "on time" (MD 0.29 h, 95% CI -0.09 to 0.66), Lang-Fahn activities of daily living dyskinesia scale (MD -0.95, 95% CI -1.98 to 0.07), UPDRS-III (MD -0.51, 95% CI -1.66 to 0.65), or UPDRS-IV (MD -0.41, 95% CI -0.85 to 0.03). However, the pooled modified abnormal involuntary movement scale favored the mavoglurant group than the placebo group (MD -2.53, 95% CI -4.23 to -0.82). CONCLUSIONS: This meta-analysis provides level one evidence that mavoglurant is not effective in treating the LID in patients with PD.


Assuntos
Discinesias , Doença de Parkinson , Atividades Cotidianas , Antiparkinsonianos/efeitos adversos , Humanos , Indóis , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológico
7.
J Viral Hepat ; 27(11): 1190-1201, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32564500

RESUMO

The aim of this study was to assess the efficacy and safety of two protocols for retreatment of a cohort of Egyptian patients with chronic hepatitis C (CHC) who relapsed after NS5A inhibitor-based therapy. We conducted a prospective cohort study to assess the safety and efficacy of 12 weeks' retreatment with either combination of sofosbuvir/daclatasvir/simeprevir plus ribavirin (SOF/DCV/SMV/RBV, n = 45) or sofosbuvir/ombitasvir/paritaprevir/ritonavir plus ribavirin (SOF/OBV/PTV/r/RBV, n = 163) in patients who had previously failed NS5A inhibitors-based regimens. The primary end point was SVR 12 weeks after the end of treatment (SVR12). Safety follow-up data were recorded for 60 weeks after the end of treatment. Two hundred-eight patients were included in the study. Of them, 53.4% of patients were females and 40.4% had liver cirrhosis. The most common prior drug combinations were sofosbuvir/daclatasvir (n = 94) and sofosbuvir/daclatasvir plus ribavirin (n = 109). The overall SVR12 rates were 98.1%. In SOF/DCV/SMV/RBV group, 95.6% achieved SVR12, while in SOF/OBV/PTV/r/RBV group, the SVR12 rates were 98.8%. SVR12 was higher in cirrhotic patients (84/84) than noncirrhotic (120/124), P value = .0149. Regarding the safety outcomes, anaemia and fatigue were significantly higher in SOF/OBV/PTV/r/RBV group. Hepatocellular carcinoma (HCC) was reported in eight (3.8%) patients (four in each group). Of them, death was confirmed in four patients. Retreatment of Egyptian CHC relapsed patients with either sofosbuvir/daclatasvir/simeprevir plus ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir plus ribavirin is highly effective and well-tolerated for both noncirrhotic and compensated cirrhotic patients. Incidental de novo HCC and hepatic decompensation are comparable in the two groups.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Quimioterapia Combinada , Egito , Feminino , Genótipo , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Estudos Prospectivos , Retratamento , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resultado do Tratamento
8.
Eur J Orthop Surg Traumatol ; 29(7): 1383-1393, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31165917

RESUMO

PURPOSE: Both sliding hip screws (SHS) and cancellous screws are used in the surgical management of intracapsular femoral neck fracture. However, there is paucity of information as to which is the superior treatment modality. We performed this systematic review and meta-analysis study to compare the clinical outcomes of SHS and cancellous screws for the treatment of femoral neck fractures in adult patients. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL, up to December 2017. Randomized controlled trials (RCTs) directly comparing the clinical outcomes of SHS and cancellous screws for femoral neck fractures were retrieved with no language or publication year restrictions. Data retrieved included operative details, nonunion rate, avascular necrosis, reoperation, infection and mortality, hip pain, functional hip scores, and medical complications. These were pooled as risk ratio or mean difference (MD) with their corresponding 95% confidence interval (CI). Heterogeneity was assessed by Chi-square test. RESULTS: Ten RCTs involving 1934 patients were included in the final analysis. The pooled estimate showed that the SHS group was associated with more intraoperative blood loss (MD = 110.01 ml, 95% CI [52.42, 167.60], p = 0.00002) than the cancellous screws. There was no significant difference in terms of operative time, postoperative hip function, nonunion, avascular necrosis, reoperation rate, infection, fracture healing, hip pain, medical complications, and mortality rate. CONCLUSION: Based on our study, the cancellous screws group was associated with less intraoperative blood loss in comparison with the SHS group. No other significant differences were found between the two interventions.


Assuntos
Parafusos Ósseos , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/instrumentação , Perda Sanguínea Cirúrgica , Fraturas do Colo Femoral/fisiopatologia , Necrose da Cabeça do Fêmur/etiologia , Fixação Interna de Fraturas/métodos , Fraturas não Consolidadas/etiologia , Articulação do Quadril/fisiopatologia , Humanos , Duração da Cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação , Resultado do Tratamento
9.
Neurol Sci ; 39(1): 31-44, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28942578

RESUMO

We performed this systematic review and meta-analysis to evaluate the tolerability and efficacy of intranasal sumatriptan, a selective serotonin agonist, compared to placebo or other migraine therapeutics for the treatment of acute migraine attacks. We searched PubMed, SCOPUS, Embase, and Cochrane CENTRAL for relevant randomized controlled trials (RCTs). Data were extracted from eligible studies and pooled as risk ratios (RR), using RevMan software. We performed subgroup and meta-regression analyses for different doses and treatment endpoints. Sixteen RCTs (n = 5925 patients) matched our inclusion criteria. The overall effect-estimate showed that intranasal sumatriptan was superior to placebo in terms of pain relief (RR = 1.70, 95% CI [1.31, 2.21], p < 0.0001) and headache relief (RR = 1.58, 95% CI [1.35, 1.84], p < 0.00001) at 2 h. Although sumatriptan was superior to placebo in terms of headache relief at 30 min (RR = 1.31, 95% CI [1.08, 1.59], p = 0.005), no significant difference was found between both groups in terms of the frequency of pain-free participants at 30 min (RR = 1.18, 95% CI [0.49, 2.88], p = 0.71). Subgroup analysis and meta-regression models showed that increasing the dose of sumatriptan reduced the time needed for headache relief; however, this clinical improvement with higher doses was associated with more frequent adverse events in comparison to smaller doses. In conclusion, intranasal sumatriptan is effective for the treatment of acute migraine attacks. However, it was associated with a six-fold increase in the risk of taste disturbance, compared to the placebo. Future RCTs are recommended to provide head-to-head comparison of different administration routes and drug formulations of sumatriptan.


Assuntos
Transtornos de Enxaqueca/tratamento farmacológico , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , Sumatriptana/uso terapêutico , Doença Aguda , Administração Intranasal , Humanos , Manejo da Dor/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sumatriptana/administração & dosagem , Resultado do Tratamento
10.
Ann Hepatol ; 17(1): 18-32, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29311409

RESUMO

BACKGROUND AND AIM: Grazoprevir is an NS3/4A protease inhibitor (PI), while elbasvir is an NS5A inhibitor. We performed this meta-analysis to directly compare grazoprevir plus elbasvir and ribavirin regimen vs. grazoprevir and elbasvir without ribavirin in the treatment of hepatitis C virus genotype 1 infection and to precisely evaluate the efficacy of the latter regimen in cirrhotic, IL28 CC genotype patients and those coinfected with human immunodeficiency virus. MATERIAL AND METHODS: A computer literature search of PubMed, Scopus, EBSCO, Embase, and Cochrane central was conducted. Studies were screened for eligibility. Sustained virologic response (SVR) rates were pooled using OpenMeta[Analyst] software for windows. A subgroup analysis was performed to stratify the treatment efficacy according to the different baseline characteristics of HCV patients. RESULTS: Eight randomized controlled trials (n = 1,297 patients) were pooled in the final analysis. The overall SVR rate was 96.6% with 95% CI [95.5% to 98%]. For cirrhotic patients, the SVR rate was 95.7% with 95% CI [93.9% to 97.5%] and for non-cirrhotic patients, the SVR rate was 97% with 95% CI [95.9% to 98.4%]. Furthermore, the addition of ribavirin (RBV) to the treatment regimen did not significantly improve the SVR (RR 1.003, 95% CI [0.944 to 1.065]). The dual regimen was effective in patient populations with NS3 resistance-associated (RAS). However, this regimen achieved lower SVR rates (< 90%) in patients with NS5A RAS. CONCLUSIONS: We conclude that the 12-week treatment regimen of the fixed dose combination of grazoprevir plus elbasvir achieved high SVR rates in patients with HCV genotype 1 infection. The addition of ribavirin to this regimen did not add a significant benefit.


Assuntos
Antivirais/uso terapêutico , Benzofuranos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Imidazóis/uso terapêutico , Quinoxalinas/uso terapêutico , Adulto , Idoso , Antivirais/efeitos adversos , Benzofuranos/efeitos adversos , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Combinação de Medicamentos , Farmacorresistência Viral , Inibidores Enzimáticos/efeitos adversos , Feminino , Genótipo , Hepacivirus/enzimologia , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/virologia , Humanos , Imidazóis/efeitos adversos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Quinoxalinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ribavirina/uso terapêutico , Resposta Viral Sustentada , Resultado do Tratamento , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Adulto Jovem
11.
Arch Virol ; 162(8): 2181-2190, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28361290

RESUMO

Atazanavir (ATZ) is a well-tolerated protease inhibitor that can be boosted with ritonavir (r) to treat infection with resistant strains of human immunodeficiency virus 1 (HIV-1). The aim of this meta-analysis was to compare the efficacy, safety, and metabolic effects of ATZ/r regimen versus commonly used antiretroviral drugs such as lopinavir (LPV) and darunavir (DRV) in HIV-1-infected patients. We searched PubMed, Scopus, Embase and Cochrane CENTRAL, using relevant keywords. Data were extracted from eligible randomized trials and pooled as risk ratios (RR) or standardized mean differences (SMD) in a meta-analysis model using RevMan software. Nine randomized controlled trials (RCTs) (3292 patients) were eligible for the final analysis. After 96 weeks of treatment, the pooled effect estimate did not favor either ATZ/r or LPV/r in terms of virological failure rate (RR 1.11, 95% CI [0.74, 1.66]). However, ATZ/r was marginally superior to LPV/r in terms of increasing the proportion of patients with HIV RNA <50 copies/ml (RR 1.09, 95% CI [1.01, 1.17]). The pooled effect estimate did not favor ATZ/r over DRV/r regarding the change in plasma levels of total cholesterol, triglycerides, or high-density lipoprotein at 24, 48, and 96 weeks. Moreover, no significant difference was found between the two regimens (ATZ/r and DRV/r) in terms of change in visceral (SMD -0.06, 95%CI [-0.33, 0.21]) or subcutaneous adipose tissue (SMD 0.12, 95% CI [-0.15, 0.39]). The ATZ/r regimen was generally as effective and well-tolerated as the LPV/r regimen for the treatment of HIV-1 patients. Compared to the DRV/r regimen, ATZ/r has no favorable effect on the plasma lipid profile or adipose tissue distribution.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Sulfato de Atazanavir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Ritonavir/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Sulfato de Atazanavir/efeitos adversos , Contagem de Linfócito CD4 , Darunavir/efeitos adversos , Darunavir/uso terapêutico , HIV-1/efeitos dos fármacos , Humanos , Lopinavir/efeitos adversos , Lopinavir/uso terapêutico , RNA Viral/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/efeitos adversos , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
12.
Neurol Sci ; 38(11): 1913-1920, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28780707

RESUMO

Parkinson's disease (PD) is a globally prevalent neurodegenerative disorder, characterized by progressive neuronal loss in the substantia nigra and formation of Lewy bodies. These pathological characteristics are clinically translated into motor symptoms, such as bradykinesia, rigidity, resting tremors, and postural instability. Emerging data from epidemiological studies suggest a possible association between PD and hepatitis C virus (HCV) infection, which affects up to 71 million individuals worldwide. Preclinical studies have shown that HCV can penetrate and replicate within the brain macrophages and microglial cells, increasing their production of pro-inflammatory cytokines that can directly cause neuronal toxicity. Other studies reported that interferon, previously used to treat HCV infection, can increase the risk of PD through inhibition of the nigrostriatal dopaminergic transmission or induction of neuroinflammation. In this article, we provide a comprehensive review on the possible association between HCV infection and PD and highlight recommendations for further research and practice in this regard.


Assuntos
Hepacivirus , Hepatite C/complicações , Doença de Parkinson/complicações , Doença de Parkinson/virologia , Animais , Hepatite C/epidemiologia , Hepatite C/fisiopatologia , Hepatite C/terapia , Humanos , Doença de Parkinson/epidemiologia , Doença de Parkinson/fisiopatologia
13.
Rheumatol Int ; 37(7): 1053-1064, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28236221

RESUMO

We conducted this systematic reviews and meta-analysis to investigate the safety and efficacy of ocrelizumab in patients with active rheumatoid arthritis (RA) who exhibited resistance or intolerance to methotrexate or biological therapy. We performed a web-based literature search of PubMed, Google Scholar, EBSCO, Scopus, Embase, and Web of science for studies that compared ocrelizumab plus methotrexate versus methotrexate plus placebo in RA patients. Data were extracted from eligible studies and pooled as risk ratios (RR), using RevMan software. Pooling data from four RCTs (2230 patients) showed that ocrelizumab plus methotrexate were superior to methotrexate plus placebo at 24 weeks in terms of improvement on the American college of rheumatology (ACR20, ACR50, and ACR70) criteria (p < 0.00001), disease activity score 28-ESR (RR = 3.77, 95% CI [2.47, 5.74], p < 0.00001), and Sharp/van der Heijde radiological score (RR = 1.63, 95% CI [1.43, 1.85], p < 0.00001). These effects were consistent among all ocrelizumab doses. The rates of serious adverse events were comparable between the ocrelizumab and placebo containing groups (RR = 1, 95% CI [0.78, 1.28], p = 0.98). However, infusion related reactions were significantly higher in ocrelizumab group (RR = 2.13, 95% CI [1.69, 2.68], p < 0.00001), compared to placebo group. The combination of ocrelizumab plus methotrexate was superior to methotrexate plus placebo on all clinical and radiographic improvement scales. The incidence of adverse events, including serious adverse events, was comparable between both groups. Future trials should investigate the efficacy of ocrelizumab alone and develop strategies to alleviate its related infusion reactions.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Metotrexato/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Produtos Biológicos/efeitos adversos , Distribuição de Qui-Quadrado , Resistência a Medicamentos , Substituição de Medicamentos , Quimioterapia Combinada , Humanos , Reação no Local da Injeção/etiologia , Metotrexato/efeitos adversos , Razão de Chances , Fatores de Risco , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia
14.
Pathol Res Pract ; 256: 155189, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38452581

RESUMO

When the expression levels of metastasis suppressor-1 (MTSS1) were discovered to be downregulated in a metastatic cancer cell line in 2002, it was proposed that MTSS1 functioned as a suppressor of metastasis. The 755 amino acid long protein MTSS1 connects to actin and organizes the cytoskeleton. Its gene is located on human chromosome 8q24. The suppressor of metastasis in metastatic cancer was first found to be MTSS1. Subsequent reports revealed that MTSS1 is linked to the prevention of metastasis in a variety of cancer types, including hematopoietic cancers like diffuse large B cell lymphoma and esophageal, pancreatic, and stomach cancers. Remarkably, conflicting results have also been documented. For instance, it has been reported that MTSS1 expression levels are elevated in a subset of melanomas, hepatocellular carcinoma associated with hepatitis B, head and neck squamous cell carcinoma, and lung squamous cell carcinoma. This article provides an overview of the pathological effects of lncRNA MTSS1 dysregulation in cancer. In order to facilitate the development of MTSS1-based therapeutic targeting, we also shed light on the current understanding of MTS1.


Assuntos
Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Movimento Celular/genética , Neoplasias Hepáticas/genética , Proteínas dos Microfilamentos/metabolismo , Invasividade Neoplásica/patologia , Proteínas de Neoplasias/metabolismo , RNA Longo não Codificante/genética
15.
Microsc Res Tech ; 87(3): 411-423, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37877737

RESUMO

This paper reports on the findings from a study that aimed to identify and characterize the constituents of Ocimum basilicum extract using gas chromatography-mass spectrometry (GC-MS) analysis, as well as assess the physicochemical properties and stability of nanoemulsions formulated with O. basilicum extract. The GC-MS analysis revealed that the O. basilicum extract contained 22 components, with Caryophyllene and Naringenin identified as the primary active constituents. The nanoemulsion formulation demonstrated excellent potential for use in the biomedical field, with a small and uniform particle size distribution, a negative zeta potential, and high encapsulation efficiency for the O. basilicum extract. The nanoemulsions exhibited spherical morphology and remained physically stable for up to 6 months. In vitro release studies indicated sustained release of the extract from the nanoemulsion formulation compared to the free extract solution. Furthermore, the developed nanoformulation exhibited enhanced anticancer properties against K562 cells while demonstrating low toxicity in normal cells (HEK293). The O. basilicum extract demonstrated antimicrobial activity against Pseudomonas aeruginosa, Candida albicans, and Staphylococcus epidermidis, with a potential synergistic effect observed when combined with the nanoemulsion. These findings contribute to the understanding of the constituents and potential applications of O. basilicum extract and its nanoemulsion formulation in various fields, including healthcare and pharmaceutical industries. Further optimization and research are necessary to maximize the efficacy and antimicrobial activity of the extract and its nanoformulation. RESEARCH HIGHLIGHTS: This study characterized the constituents of O. basilicum extract and assessed the physicochemical properties and stability of its nanoemulsion formulation. The O. basilicum extract contained 22 components, with Caryophyllene and Naringenin identified as the primary active constituents. The nanoemulsion formulation demonstrated excellent potential for biomedical applications, with sustained release of the extract, low toxicity, and enhanced anticancer and antimicrobial properties. The findings contribute to the understanding of the potential applications of O. basilicum extract and its nanoemulsion formulation in healthcare and pharmaceutical industries, highlighting the need for further optimization and research.


Assuntos
Anti-Infecciosos , Ocimum basilicum , Óleos Voláteis , Sesquiterpenos Policíclicos , Humanos , Ocimum basilicum/química , Preparações de Ação Retardada , Células HEK293 , Microfluídica , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química
16.
Crit Rev Anal Chem ; : 1-22, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829552

RESUMO

Field effect transistors (FETs)-based detection probes are powerful platforms for quantification in biological media due to their sensitivity, ease of miniaturization, and ability to function in biological media. Especially, FET-based platforms have been utilized as promising probes for label-free detections with the potential for use in real-time monitoring. The integration of new materials in the FET-based probe enhances the analytical performance of the developed probes by increasing the active surface area, rejecting interfering agents, and providing the possibility for surface modification. Furthermore, the use of new materials eliminates the need for traditional labeling techniques, providing rapid and cost-effective detection of biological analytes. This review discusses the application of materials in the development of FET-based label-free systems for point-of-care (POC) analysis of different biomedical analytes from 2018 to 2024. The mechanism of action of the reported probes is discussed, as well as their pros and cons were also investigated. Also, the possible challenges and potential for the fabrication of commercial devices or methods for use in clinics were discussed.

17.
Int J Biol Macromol ; 263(Pt 2): 130211, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423902

RESUMO

Nanocatalysts are vital in several domains, such as chemical processes, energy generation, energy preservation, and environmental pollution mitigation. An experimental study was conducted at room temperature to evaluate the catalytic activity of the new gelatin-chitosan hydrogel/CuO/Fe3O4 nanocomposite in the asymmetric Hantzsch reaction. All components of the nanocomposite exhibit a synergistic effect as a Lewis acid, promote the reaction. Dimedone, ammonium acetate, ethyl acetoacetate, and other substituted aldehydes were used to synthesize diverse polyhydroquinoline derivatives. The nanocomposite exhibited exceptional efficacy (over 90 %) and durability (retaining 80 % of its original capacity after 5 cycles) as a catalyst in the one-pot asymmetric synthesis of polyhydroquinoline derivatives. Also, turnover numbers (TON) and turnover frequency (TOF) have been checked for catalyst (TON and TOF = 50,261 and 100,524 h-1) and products. The experiment demonstrated several benefits, such as exceptional product efficacy, rapid reaction time, functioning at ambient temperature without specific requirements, and effortless separation by the use of an external magnet after the reaction is finished. The results suggest the development of a magnetic nanocatalyst with exceptional performance. The composition of the Ge-CS hydrogel/CuO/Fe3O4 nanocomposite was thoroughly analyzed using several methods including FT-IR, XRD, FE-SEM, EDX, VSM, BET, and TGA. These analyses yielded useful information into the composition and characteristics of the nanocomposite, hence further enhancing the knowledge of its possible uses.


Assuntos
Quitosana , Nanocompostos , Nanopartículas , Quitosana/química , Cobre/química , Gelatina , Espectroscopia de Infravermelho com Transformada de Fourier , Hidrogéis , Fenômenos Magnéticos , Óxidos , Nanocompostos/química
18.
Pathol Res Pract ; 254: 155072, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38228039

RESUMO

MicroRNAs (miRNAs) are short, non-coding RNA molecules that regulate gene expression. They are involved in a wide range of biological processes, including development, differentiation, cell cycle regulation, and response to stress. Numerous studies have demonstrated that miRNAs are present in different bodily fluids, which could serve as an important biomarker. The advancement of techniques and strategies for the identification of cancer-associated miRNAs in human specimens offers a novel opportunity to diagnose cancer in early stages, predict patient prognosis and evaluate response to treatment. Isothermal techniques including loop-mediated isothermal amplification (LAMP), rolling circle amplification (RCA), or recombinase polymerase amplification (RPA) offer simplicity, efficiency, and rapidity in miRNA detection processes. In contrast to traditional PCR (polymerase chain reaction), these techniques analysis and quantify miRNA molecules in specimens using a single constant temperature. In this comprehensive review, we summarized the recent advances in cancer-related miRNA detection via highly sensitive isothermal amplification methods by more focusing on the involved mechanism.


Assuntos
MicroRNAs , Neoplasias , Humanos , MicroRNAs/metabolismo , Neoplasias/diagnóstico , Neoplasias/genética
19.
Pathol Res Pract ; 253: 154996, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38118214

RESUMO

Since cancer is one of the world's top causes of death, early diagnosis is critical to improving patient outcomes. Artificial intelligence (AI) has become a viable technique for cancer diagnosis by using machine learning algorithms to examine large volumes of data for accurate and efficient diagnosis. AI has the potential to alter the way cancer is detected fundamentally. Still, it has several disadvantages, such as requiring a large amount of data, technological limitations, and ethical concerns. This overview looks at the possibilities and restrictions of AI in cancer detection, as well as current applications and possible future developments. We can better understand how to use AI to improve patient outcomes and reduce cancer mortality rates by looking at its potential for cancer detection.


Assuntos
Inteligência Artificial , Neoplasias , Humanos , Neoplasias/diagnóstico , Algoritmos
20.
Crit Rev Anal Chem ; : 1-14, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38165810

RESUMO

The selective and sensitive diagnosis of diseases is a significant matter in the early stages of the cure of illnesses. To elaborate, although several types of probes have been broadly applied in clinics, magnetic nanomaterials-aptamers, as new-generation probes, are becoming more and more attractive. The presence of magnetic nanomaterials brings about quantification, purification, and quantitative analysis of biomedical, especially in complex samples. Elaborately, the superparamagnetic properties and numerous functionalized groups of magnetic nanomaterials are considered two main matters for providing separation ability and immobilization substrate, respectively. In addition, the selectivity and stability of aptamer can present a high potential recognition element. Importantly, the integration of aptamer and magnetic nanomaterials benefits can boost the performance of biosensors for biomedical analysis by introducing efficient and compact probes that need low patient samples and fast diagnosis, user-friendly application, and high repeatability in the quantification of biomolecules. The primary aim of this review is to suggest a summary of the effect of the employed other types of nanomaterials in the fabrication of novel aptasensors-based magnetic nanomaterials and to carefully explore various applications of these probes in the quantification of bioagents. Furthermore, the application of these versatile and high-potential probes in terms of the detection of cancer cells and biomarkers, proteins, drugs, bacteria, and nucleoside were discussed. Besides, research gaps and restrictions in the field of biomedical analysis by magnetic nanomaterials-aptamers will be discussed.

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