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1.
ACS Appl Bio Mater ; 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040621

RESUMO

The emergence of CRISPR/Cas technology has enabled scientists to precisely edit genomic DNA sequences. This approach can be used to modulate gene expression for the treatment of genetic disorders and incurable diseases such as cancer. This potent genome-editing tool is based on a single guide RNA (sgRNA) strand that recognizes the targeted DNA, plus a Cas nuclease protein for binding and processing the target. CRISPR/Cas has great potential for editing many genes in different types of cells and organisms both in vitro and in vivo. Despite these remarkable advances, the risk of off-target effects has hindered the translation of CRISPR/Cas technology into clinical applications. To overcome this hurdle, researchers have devised gene regulatory systems that can be controlled in a spatiotemporal manner, by designing special sgRNA, Cas, and CRISPR/Cas delivery vehicles that are responsive to different stimuli, such as temperature, light, magnetic fields, ultrasound (US), pH, redox, and enzymatic activity. These systems can even respond to dual or multiple stimuli simultaneously, thereby providing superior spatial and temporal control over CRISPR/Cas gene editing. Herein, we summarize the latest advances on smart sgRNA, Cas, and CRISPR/Cas nanocarriers, categorized according to their stimulus type (physical, chemical, or biological).

2.
Crit Rev Food Sci Nutr ; : 1-18, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34978223

RESUMO

Although conventional drugs are widely used in the prevention and treatment of cardiovascular disease (CVD), they are being used less frequently due to concerns about possible side effects over the long term. There has been a renewed research interest in medicinal plant products, and their role in protecting the cardiovascular system and treating CVD, which are now being considered as potential alternatives to modern drugs. The most important mechanism causing damage to the myocardium after heart attack and reperfusion, is increased levels of free radicals and oxidative stress. Therefore, treatment approaches often focus on reducing free radicals or enhancing antioxidant defense mechanism. It has been previously reported that bioactive natural products can protect the heart muscle in myocardial infarction (MI). Since these compounds are readily available in fruits and vegetables, they could prevent the risk of MI if they are consumed daily. Although the benefits of a healthy diet are well known, many scientific studies have focused on whether pure natural compounds can prevent and treat MI. In this review we summarize the effects of curcumin, resveratrol, quercitin, berberine, and tanshinone on MI and CVD, and focus on their proposed molecular mechanisms of action.

3.
Biomed Pharmacother ; 146: 112517, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34902743

RESUMO

Rapid changes in the viral genome allow viruses to evade threats posed by the host immune response or antiviral drugs, and can lead to viral persistence in the host cells. RNA-dependent RNA polymerase (RdRp) is an essential enzyme in RNA viruses, which is involved in RNA synthesis through the formation of phosphodiester bonds. Therefore, in RNA viral infections such as SARS-CoV-2, RdRp could be a crucial therapeutic target. The present review discusses the promising application of RdRp inhibitors, previously approved or currently being tested in human clinical trials, in the treatment of RNA virus infections. Nucleoside inhibitors (NIs) bind to the active site of RdRp, while nonnucleoside inhibitors (NNIs) bind to allosteric sites. Given the absence of highly effective drugs for the treatment of COVID-19, the discovery of an efficient treatment for this pandemic is an urgent concern for researchers around the world. We review the evidence for molnupiravir (MK-4482, EIDD-2801), an antiviral drug originally designed for Alphavirus infections, as a potential preventive and therapeutic agent for the management of COVID-19. At the beginning of this pandemic, molnupiravir was in preclinical development for seasonal influenza. When COVID-19 spread dramatically, the timeline for development was accelerated to focus on the treatment of this pandemic. Real time consultation with regulators took place to expedite this program. We summarize the therapeutic potential of RdRp inhibitors, and highlight molnupiravir as a new small molecule drug for COVID-19 treatment.

4.
Lasers Med Sci ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34855034

RESUMO

This narrative review aimed to evaluate the effectiveness of PDT in early or advanced squamous cell carcinoma of the head and neck (SCCHN). Scopus, MEDLINE/PubMed, and Embase were searched electronically following the PRISMA protocol. Quality assessment was performed according to JBI, NIH, and AMSTAR protocols. The main outcomes evaluated were treatment response, recurrence, survival, and adverse effects. A total of 49 articles met the search criteria: 43 case series, two cohort studies, two prospective before-after clinical trials, one systematic review, and one meta-analysis. Data from 2121 SCCHN patients were included. The response to PDT was variable according to the type of photosensitizer, tumor location, and tumor stage. In general, higher complete responses rated were observed in T1/T2 SCCHN, mainly with mTHPC-mediated PDT. With regard to T3/T4 or advanced SCCHN tumors, there is no compelling evidence suggesting the effectiveness of PDT. Any adverse effects reported were well tolerated by patients. The present review suggests that PDT is a promising treatment modality for early-stage SCCHN. Although there are limitations due to the low level of evidence of the included studies, we believe that the present review could help to design robust clinical trials to determine the efficacy of PDT in SCCHN.

5.
Front Bioeng Biotechnol ; 9: 732461, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858953

RESUMO

Antibiotic resistant microorganisms have become an enormous global challenge, and are predicted to cause hundreds of millions of deaths. Therefore, the search for novel/alternative antimicrobial agents is a grand global challenge. Cellulose is an abundant biopolymer with the advantages of low cost, biodegradability, and biocompatibility. With the recent growth of nanotechnology and nanomedicine, numerous researchers have investigated nanofibril cellulose to try to develop an anti-bacterial biomaterial. However, nanofibril cellulose has no inherent antibacterial activity, and therefore cannot be used on its own. To empower cellulose with anti-bacterial properties, new efficient nanomaterials have been designed based on cellulose-based nanofibrils as potential wound dressings, food packaging, and for other antibacterial applications. In this review we summarize reports concerning the therapeutic potential of cellulose-based nanofibrils against various bacterial infections.

6.
Bioorg Chem ; 119: 105550, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34920337

RESUMO

Infectious diseases caused by new or unknown bacteria and viruses, such as anthrax, cholera, tuberculosis and even COVID-19, are a major threat to humanity. Thus, the development of new synthetic compounds with efficient antimicrobial activity is a necessity. Herein, rationally designed novel multifunctional cationic alternating copolymers were directly synthesized through a step-growth polymerization reaction using a bivalent electrophilic cross-linker containing disulfide bonds and a diamine heterocyclic ring. To optimize the activity of these alternating copolymers, several different diamines and cross-linkers were explored to find the highest antibacterial effects. The synthesized nanopolymers not only displayed good to excellent antibacterial activity as judged by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli, but also reduced the number of biofilm cells even at low concentrations, without killing mammalian cells. Furthermore, in vivo experiments using infected burn wounds in mice demonstrated good antibacterial activity and stimulated wound healing, without causing systemic inflammation. These findings suggest that the multifunctional cationic nanopolymers have potential as a novel antibacterial agent for eradication of multidrug resistant bacterial infections.

7.
Lasers Med Sci ; 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34743255

RESUMO

Corticosteroid-resistant asthma (CRA) is a severe form of disease and clinically important, since patients do not respond to mainstay corticosteroid therapies. Thus, new therapies are needed. However, a big limiting factor in the understanding of CRA is the existence of different immunological and inflammatory phenotypes, a fact that makes it difficult to reproduce experimentally. Photobiomodulation (PBM) emerges as an alternative therapy based on earlier studies. This study aims to evaluate the effect of PBM using infrared light-emitting diode (ILED) on the development of corticosteroid-resistant asthma. Therefore, groups of rats were sensitized and challenged with ovalbumin plus Freund's adjuvant for the induction of CRA, and treated or not with ILED directly in the respiratory tract on the skin (wavelength 810 nm; power 100 mW; density energy 5 J/cm; total energy 15 J; time 150 s). Our experimental model was capable to induce neutrophilic asthma. Besides that, the corticosteroid treatment did not reverse the lung cell migration as well as the levels of leukotriene B4, and interleukins 17 and 6. The treatment with ILED reduced the lung cell migration; myeloperoxidase activity; mast cell degranulation; and the levels of leukotriene B4, thromboxane B2, prostaglandin E2, tumoral necrosis factor alpha, and interleukins 17 and 6. Still, ILED increased the level of interleukin 10. In conclusion, we showed promisor effects of ILED when irradiated directly in the respiratory tract as adjuvant treatment of corticosteroid-resistant asthma.

8.
Lasers Med Sci ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731332

RESUMO

Allergic rhinitis (AR) is an inflammatory disorder of the nasal mucosa, and is a worldwide health problem with a significant impact on the quality of life. The main goal of AR treatment is to relieve symptoms. However, standard treatments have considerable side effects or are not effective. Photobiomodulation (PBM) therapy has emerged as an alternative treatment. Here, we evaluated the effects of transcutaneous systemic (tail) or local (skin over nostrils) PBM using a 660-nm light-emitting diode (LED) array. Adult rats were assigned into 4 groups: basal, as non-manipulated animals; Sham, as rats sensitized with 7 intradermal injections of ovalbumin (OVA) plus alum followed by intranasal instillation with OVA (2%) daily for 7 days; and the LPBM and SPBM groups, in which the animals were treated with PBM (local or systemic) immediately after the last instillation of OVA (1%) daily for 3 days. Our results showed that local PBM treatment reduced mast cell degranulation in the nasopharynx and nostrils; levels of leukotriene B4, thromboxane A2, and interleukin 4 (IL-4) in the nasopharynx; and gene expression of IL-4. Moreover, we showed higher levels and gene expression of IL-10 after local PBM treatment. Systemic PBM treatment did not change any of the evaluated parameters. In conclusion, our data showed that local (but not systemic) treatment with PBM could improve parameters related to AR in an animal model, and should be tested clinically.

9.
Int Immunopharmacol ; 101(Pt B): 108282, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34737130

RESUMO

AIM: The effectiveness of nanofibers containing human placenta-derived mesenchymal stem cells (hPDMSCs) plus platelet-rich plasma (PRP) for healing of diabetic foot ulcers (DFUs) was investigated. METHODS: hPDMSCs were isolated from human donor placentas, and cultured in electrospun gelatin nanofibrous scaffolds (GNS). Twenty-eight patients with DFUs were randomized into three groups in a 12-week trial: (A) Treated with hPDMSCs; (B) Treated with hPDMSCs after coating the ulcer with PRP gel; (C) Control group received standard wound care. Wound area and pain freewalkingdistance were measured every 2 weeks. RESULTS: Flow cytometry showed the expression of mesenchymal markers. SEM images and DAPI staining indicated significantly higher levels of hPDMSC proliferation on GNS after 3 and 7 days of culture. The MTS assay showed a significant increase in proliferation on GNS, compared to controls. Wound size reduction was 66% in group A, 71% in group B, and 36% in control group C. A significant difference in wound closure and pain-free walking distance was observed between groups A and B, compared to control group C (p < 0.05), but no difference between groups A and B. Biopsy of the implanted tissue showed the development of new capillary formation in groups A and B. CONCLUSION: Implantation of hPDMSCs in GNS accelerated wound healing and improved clinical parameters in DFU patients.

10.
Nanotechnology ; 33(7)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34727527

RESUMO

An efficient and safe delivery system for the transfection of CRISPR plasmid (p/CRISPR) into target cells can open new avenues for the treatment of various diseases. Herein, we design a novel nonvehicle by integrating an arginine-disulfide linker with low-molecular-weight PEI (PEI1.8k) for the delivery of p/CRISPR. These PEI1.8k-Arg nanoparticles facilitate the plasmid release and improve both membrane permeability and nuclear localization, thereby exhibiting higher transfection efficiency compared to native PEI1.8kin the delivery of nanocomplexes composed of PEI1.8k-Arg and p/CRISPR into conventional cells (HEK 293T). This nanovehicle is also able to transfect p/CRISPR in a wide variety of cells, including hard-to-transfect primary cells (HUVECs), cancer cells (HeLa), and neuronal cells (PC-12) with nearly 5-10 times higher efficiency compared to the polymeric gold standard transfection agent. Furthermore, the PEI1.8k-Arg nanoparticles can edit the GFP gene in the HEK 293T-GFP reporter cell line by delivering all possible forms of CRISPR/Cas9 system (e.g. plasmid encoding Cas9 and sgRNA targeting GFP, and Cas9/sgRNA ribonucleoproteins (RNPs) as well as Cas9 expression plasmid andin vitro-prepared sgRNA) into HEK 293T-GFP cells. The successful delivery of p/CRISPR into local brain tissue is also another remarkable capability of these nanoparticles. In view of all the exceptional benefits of this safe nanocarrier, it is expected to break new ground in the field of gene editing, particularly for therapeutic purposes.

11.
Comput Biol Med ; : 105043, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34839901

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the common subtypes of kidney cancer. Circular RNAs (circRNAs) act as competing endogenous RNAs (ceRNAs) to affect the expression of microRNAs (miRNAs), and hence the expression of genes involved in the development and progression of ccRCC. However, these interactions have not been sufficiently explored. METHODS: The differential expression of circRNAs (DEC) was extracted from the GEO database, and the expression of circRNAs was analyzed by the Limma R package. The interaction of miRNAs with circRNAs was predicted using (cancer-specific circRNA database) CSCD and circinteractome database. The genes affected by the miRNAs were predicted by miRwalk version 3, and the differential expression was retrieved using TCGA. Functional enrichment was assessed and a PPI network was created using DAVID and Cytoscape, respectively. The genes with significant interactions (hub-genes) were screened, and the total survival rate of ccRCC patients was extracted from the Gene Expression Profiling Interactive Analysis (GEPIA) database. To confirm the expression of OS genes we used the Immunohistochemistry (IHC) data and TCGA database. The correlation between gene expression and immune cell infiltration was investigated using TIMER2.0. Finally, potential drug candidates were predicted by the cMAP database. RESULTS: Four DECs (hsa_circ_0003340, hsa_circ_0007836, hsa_circ_0020303, and hsa_circ_0001873) were identified, along with 11 interacting miRNAs (miR-1224-3p, miR-1294, miR-1205, miR-1231, miR-615-5p, miR-940, miR-1283, and miR-1305). These miRNAs were predicted to affect 1282 target genes, and function enrichment was used to identify the genes involved in cancer biology. 18 hub-genes (CCR1, VCAM1, NCF2, LAPTM5, NCKAP1L, CTSS, BTK, LILRB2, CD53, MPEG1, C3AR1, GPR183, C1QA, C1QC, P2RY8, LY86, CYBB, and IKZF1) were identified from a PPI network. VCAM1, NCF2, CTSS, LILRB2, MPEG1, C3AR1, P2RY8, and CYBB could affect the survival of ccRCC patients. The hub-gene expression was correlated with tumor immune cell infiltration and patient prognosis. Two potantial drug candidates, naphazoline and lithocholic acid could play a role in ccRCC therapy, as well other cancers. CONCLUSION: This bioinformatics analysis brings a new insight into the role of circRNA/miRNA/mRNA interactions in ccRCC pathogenesis, prognosis, and possible drug treatment or immunotherapy.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34840055

RESUMO

Albumin is the most abundant serum protein that transports hormones, free fatty acids, bilirubin, various ions, and drugs. The current study investigated the potential application of laser-induced fluorescence (LIF) in clinical analysis of human serum albumin (HSA) as a biomarker of liver and kidney disease. The excitation wavelength and HSA concentrations were systematically varied, and the LIF spectrum was recorded, in order to construct a standard calibration curve. Over a wide range of excitation wavelengths, excitation at 350 nm showedthe maximum fluorescence emission centered at 500 nm. We compared the determination of certain concentrations of HSA using both LIF and conventional laboratory assays. The LIF technique proved to be highly accurate and efficient. It may be concluded that femtosecond LIF provides a new, easy, very sensitive, precise, and direct method of detecting albumin in various biological samples.

13.
Mol Ther Nucleic Acids ; 26: 892-926, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34760336

RESUMO

Gastrointestinal (GI) cancers, including colorectal, gastric, hepatic, esophageal, and pancreatic tumors, are responsible for large numbers of deaths around the world. Chemotherapy is the most common approach used to treat advanced GI cancer. However, chemoresistance has emerged as a critical challenge that prevents successful tumor elimination, leading to metastasis and recurrence. Chemoresistance mechanisms are complex, and many factors and pathways are involved. Among these factors, non-coding RNAs (ncRNAs) are critical regulators of GI tumor development and subsequently can induce resistance to chemotherapy. This occurs because ncRNAs can target multiple signaling pathways, affect downstream genes, and modulate proliferation, apoptosis, tumor cell migration, and autophagy. ncRNAs can also induce cancer stem cell features and affect the epithelial-mesenchymal transition. Thus, ncRNAs could possibly act as new targets in chemotherapy combinations to treat GI cancer and to predict treatment response.

16.
Crit Rev Oncol Hematol ; 169: 103545, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34838705

RESUMO

Cancer stem cells (CSCs) have been identified in various tumor types. CSCs are believed to contribute to tumor metastasis and resistance to conventional therapy. So targeting these cells could be an effective strategy to eliminate tumors and a promising new type of cancer treatment. Alterations in metabolism play an essential role in CSC biology and their resistance to treatment. The metabolic properties pathways in CSCs are different from normal cells, and to some extent, are different from regular tumor cells. Interestingly, CSCs can use other nutrients for their metabolism and growth. The different metabolism causes increased sensitivity of CSCs to agents that disrupt cellular homeostasis. Compounds that interfere with the central metabolic pathways are known as energy disruptors and can reduce CSC survival. This review highlights the differences between regular cancer cells and CSC metabolism and discusses the action mechanisms of energy disruptors at the cellular and molecular levels.

17.
Phytother Res ; 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697839

RESUMO

Curcumin is a phytochemical isolated from Curcuma longa with potent tumor-suppressor activity, which has shown significant efficacy in pre-clinical and clinical studies. Curcumin stimulates cell death, triggers cycle arrest, and suppresses oncogenic pathways, thereby suppressing cancer progression. Cisplatin (CP) stimulates DNA damage and apoptosis in cancer chemotherapy. However, CP has adverse effects on several organs of the body, and drug resistance is frequently observed. The purpose of the present review is to show the function of curcumin in decreasing CP's adverse impacts and improving its antitumor activity. Curcumin administration reduces ROS levels to prevent apoptosis in normal cells. Furthermore, curcumin can inhibit inflammation via down-regulation of NF-κB to maintain the normal function of organs. Curcumin and its nanoformulations can reduce the hepatoxicity, neurotoxicity, renal toxicity, ototoxicity, and cardiotoxicity caused by CP. Notably, curcumin potentiates CP cytotoxicity via mediating cell death and cycle arrest. Besides, curcumin suppresses the STAT3 and NF-ĸB as tumor-promoting pathways, to enhance CP sensitivity and prevent drug resistance. The targeted delivery of curcumin and CP to tumor cells can be mediated nanostructures. In addition, curcumin derivatives are also able to reduce CP-mediated side effects, and increase CP cytotoxicity against various cancer types.

18.
Hum Genet ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34713317

RESUMO

Tumor heterogeneity is a major challenge for breast cancer researchers who have struggled to find effective treatments despite recent advances in oncology. Although the use of 2D cell culture methods in breast cancer research has been effective, it cannot model the heterogeneity of breast cancer as found within the body. The development of 3D culture of tumor cells and breast cancer organoids has provided a new approach in breast cancer research, allowing the identification of biomarkers, study of the interaction of tumor cells with the microenvironment, and for drug screening and discovery. In addition, the possibility of gene editing in organoids, especially using the CRISPR/Cas9 system, is convenient, and has allowed a more detailed study of tumor behavior in models closer to the physiological condition. The present review covers the application of organoids in breast cancer research. The recent use of gene-editing systems to provide insights into therapeutic approaches for breast cancer, is highlighted. The study of organoids and the possibility of gene manipulation may be a step towards the personalized treatment of breast cancer, which has so far remained unattainable due to the high heterogeneity of breast cancer.

19.
Rev Environ Contam Toxicol ; 257: 93-119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34622369

RESUMO

Despite the increasing use of silver nanoparticles in medical sciences, published studies on their interaction with nerve cells and evaluation of risks are dispersed. This systematic review and meta-analysis could be used to devise safety guidelines for the use of silver nanoparticles in industry and medicine to reduce adverse effects on the CNS.After extensive searches, the full text of 30 related studies was reviewed and data mining completed. Data were analyzed by calculating the mean of different ratios between treated and untreated groups. Linear regression between variables was evaluated by meta-regression. Subgroup analysis was also performed due to heterogeneity.Treatment with silver nanoparticles significantly reduced cell viability (SMD = -1.79%; 95% CI: -2.17 to -1.40; p < 0.0001). Concentration > 0.1 µg/mL could kill neurons, while lower concentration would not (SMD -0.258; 95% CI: -0.821 to 0.305; p = 369). In addition to the concentration, the coating, size of the nanoparticles, and cell type are also factors that influence SNP nerve cell toxicity. Measurement of apoptosis (SMD = 2.21; 95% CI: 1.62 to 2.80; p=0.001) and lactate dehydrogenase release rate (SMD = 0.9; 95% CI: 0.33 to 1.47; p < 0.0001) also confirmed the destructive effect of silver nanoparticles on nerve cells.


Assuntos
Nanopartículas Metálicas , Prata , Apoptose , Sobrevivência Celular , Nanopartículas Metálicas/toxicidade , Neurônios , Prata/toxicidade
20.
Trends Analyt Chem ; 143: 116342, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34602681

RESUMO

There have been many efforts to synthesize advanced materials that are capable of real-time specific recognition of a molecular target, and allow the quantification of a variety of biomolecules. Scaffold materials have a porous structure, with a high surface area and their intrinsic nanocavities can accommodate cells and macromolecules. The three-dimensional structure (3D) of scaffolds serves not only as a fibrous structure for cell adhesion and growth in tissue engineering, but can also provide the controlled release of drugs and other molecules for biomedical applications. There has been a limited number of reports on the use of scaffold materials in biomedical sensing applications. This review highlights the potential of scaffold materials in the improvement of sensing platforms and summarizes the progress in the application of novel scaffold-based materials as sensor, and discusses their advantages and limitations. Furthermore, the influence of the scaffold materials on the monitoring of infectious diseases such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and bacterial infections, was reviewed.

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