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BACKGROUND: Obesity has become a prevalent issue worldwide, leading to various complications such as hyperlipidemia, diabetes, and cardiovascular problems. Statins, as FDA approved anti-hyperlipidemic drugs, still pose some concerns upon their administration. Recently, researchers have looked for natural products as an alternative to manage hyperlipidemia and obesity. AIM: This work aimed to study the hypolipidemic effect of Lepidium sativum garden cress (GC) from different preparations; orally administered seeds, and hydrogel, in comparison to atorvastatin. METHODS: GC hydrogel was prepared from the GC aqueous extract and pharmaceutically evaluated for its pH, spreadability, seeds content, homogeneity, rheology, and in vitro release. The rat's body weight, blood glucose levels, total lipid profile, and liver biomarkers were evaluated on obese rats for one month. In addition, the histopathology study was also performed. RESULTS: GC hydrogel had acceptable pharmaceutical properties and showed a sustained release performance over 24 h. Oral and topical GC significantly reduced the lipid profiles, blood sugar and ALT, AST levels more than the negative control group and comparable to atorvastatin. It was found that oral GC showed a significant effect on the percentage decrease in the rat's body weight than the applied hydrogel. Histopathology study revealed a better outcome in the histological structure of pancreas and liver compared with rats feed on high fat diet post-treatment for one month. CONCLUSION: GC orally administered, or topically applied hydrogel could be a promising, safe alternative formulation to atorvastatin in managing hyperlipidemia and normalizing body weight of obese rats.
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Since the first use of vaccine tell the last COVID-19 pandemic caused by spread of SARS-CoV-2 worldwide, the use of advanced biotechnological techniques has accelerated the development of different types and methods for immunization. The last pandemic showed that the nucleic acid-based vaccine, especially mRNA, has an advantage in terms of development time; however, it showed a very critical drawback namely, the higher costs when compared to other strategies, and its inability to protect against new variants. This showed the need of more improvement to reach a better delivery and efficacy. In this review we will describe different vaccine delivery systems including, the most used viral vector, and also variable strategies for delivering of nucleic acid-based vaccines especially lipid-based nanoparticles formulation, polymersomes, electroporation and also the new powerful tools for the delivery of mRNA, which is based on the use of cell-penetrating peptides (CPPs). Additionally, we will also discuss the main challenges associated with each system. Finlay, the efficacy and safety of the vaccines depends not only on the formulations and delivery systems, but also the dosage and route of administration are also important players, therefore we will see the different routes for the vaccine administration including traditionally routes (intramuscular, Transdermal, subcutaneous), oral inhalation or via nasal mucosa, and will describe the advantages and disadvantage of each administration route.
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Background: A fracture is considered a medical emergency leading to considerable complications. Aim: This study aimed to describe the accelerating action of Ag-NPs-FG on fracture healing in rabbits. Methods: Silver NPs (AgNPs) were reduced with fenugreek (FG), loaded into a starch gel base, and investigated for their morphology, size, and charge. Four equal groups were randomly formed of 40 adult male rabbits. A 3.5 mm diameter bone defect was created at the proximal metaphysis of the right tibia in each rabbit. Groups 1-4 were injected with placebo saline, AgNPs-FG, plain gel, and FG-gel at the bone defect zone, respectively. The healing was assessed for 8 weeks postoperatively based on the radiographic, bone turnover markers, and histopathological examinations. Results: The AgNPs-FG was obtained as a faint reddish color, spherical in shape, with an absorbance of 423 nm, a size of 118.0 ± 1.7 nm, and a surface charge of -7.8 ± 0.518 mV. The prepared AgNPs-FG hydrogel was clear, translucent, and homogenous. The pH values were 6.55-6.5 ± 0.2, the viscosity of 4,000 and 1,875 cPs, and spreadability of 1.6 ± 0.14 and 2.0 ± 0.15 for both FG and AgNPs-FG hydrogel, respectively. The radiographic union scale was significantly (p < 0.05) improved in group 2 with a significant (p < 0.05) increase in bone turnover markers was found in comparison to other treated groups. Histopathological examination revealed the formation of mature bone on the 28th postoperative day in groups 2 and 4. Conclusion: Colloidal nano-formulation of AgNPs-FG loaded hydrogel could be a promising formulation to accelerate rabbits' tibial bone healing process.
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Nanopartículas Metálicas , Prata , Tíbia , Trigonella , Animais , Coelhos , Trigonella/química , Prata/administração & dosagem , Prata/farmacologia , Prata/química , Masculino , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Tíbia/cirurgia , Tíbia/efeitos dos fármacos , Consolidação da Fratura/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/químicaRESUMO
Sechium edule, commonly known as chayote is known for its low glycemic index, high fiber content, and rich nutritional profile, which suggests it may be beneficial for individuals with diabetes. While research specifically examining the impact of chayote on diabetes is limited, this study screened its biological impacts by using different biomarkers on streptozotocin-induced diabetic (STZ-ID) rats. The ethanolic extract of the Sechium edule fruits was assessed for different phytochemical, biochemical, and anti-diabetic properties. In the results, chayote extract had high phenolic and flavonoid contents respectively (39.25 ± 0.65 mg/mL and 12.16 ± 0.50 mg/mL). These high phenolic and flavonoid contents showed high implications on STZ-ID rats. Altogether 200 and 400 mg/kg of the extract considerably reduced the blood sugar level and enhanced the lipid profile of the STZ-ID rats. Additionally, they have decreased blood urea and serum creatinine levels. Besides, the levels of SGOT, SGPT, LDH, sodium, and potassium ions were significantly lowered after the administration period. More importantly, the electrocardiogram (ECG) parameters such as QT, RR, and QTc which were prolonged in the diabetic rats were downregulated after 35 days of administration of S. edule extract (400 mg/kg). And, the histological examination of the pancreas and kidney showed marked improvement in structural features of 200 and 400 mg/kg groups when compared to the diabetic control group. Where the increase in the glucose levels was positively correlated with QT, RR, and QTc (r2 = 0.76, r2 = 0.76, and r2 = 0.43) which means that ECG could significantly reflect the diabetes glucose levels. In conclusion, our findings showed that the fruit extract exerts a high potential to reduce artifacts secondary to diabetes which can be strongly suggested for diabetic candidates. However, there is a need to study the molecular mechanisms of the extract in combating artifacts secondary to diabetes in experimental animals.
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Breast cancer is a wide-spread threat to the women's health. The drawbacks of conventional treatments necessitate the development of alternative strategies, where gene therapy has regained hope in achieving an efficient eradication of aggressive tumors. Monocarboxylate transporter 4 (MCT4) plays pivotal roles in the growth and survival of various tumors, which offers a promising target for treatment. In the present study, pH-responsive lipid nanoparticles (LNPs) based on the ionizable lipid,1,2-dioleoyl-3-dimethylammonium propane (DODAP), were designed for the delivery of siRNA targeting MCT4 gene to the breast cancer cells. Following multiple steps of characterization and optimization, the anticancer activities of the LNPs were assessed against an aggressive breast cancer cell line, 4T1, in comparison with a normal cell line, LX-2. The selection of the helper phospholipid to be incorporated into the LNPs had a dramatic impact on their gene delivery performance. The optimized LNPs enabled a powerful MCT4 silencing by â¼90â¯% at low siRNA concentrations, with a subsequent â¼80â¯% cytotoxicity to 4T1 cells. Meanwhile, the LNPs demonstrated a 5-fold higher affinity to the breast cancer cells versus the normal cells, in which they had a minimum effect. Moreover, the MCT4 knockdown by the treatment remodeled the cytokine profile in 4T1 cells, as evidenced by 90â¯% and â¼64â¯% reduction in the levels of TNF-α and IL-6; respectively. The findings of this study are promising for potential clinical applications. Furthermore, the simple and scalable delivery vector developed herein can serve as a breast cancer-targeting platform for the delivery of other RNA therapeutics.
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Neoplasias da Mama , Citocinas , Transportadores de Ácidos Monocarboxílicos , Proteínas Musculares , Nanopartículas , RNA Interferente Pequeno , Microambiente Tumoral , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Nanopartículas/química , Humanos , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Feminino , Citocinas/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , RNA Interferente Pequeno/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Animais , Camundongos , Técnicas de Silenciamento de Genes , Tamanho da Partícula , Concentração de Íons de HidrogênioRESUMO
Due to tenoxicam (TX)'s poor aqueous solubility (0.072 mg/ml), it is poorly absorbable in the GIT, and the long-term oral administration of TX may cause severe GIT disturbances. Topical administration of TX can help in bypassing the GIT adverse effects. Therefore, in the present work, we constructed different pluronic/lecithin organogels (PLOs) for topical delivery of TX. PLO was constructed simply via direct mixing of an aqueous pluronic solution with lecithin solution. The prepared PLO formulations were characterized for their physicochemical properties including pH, drug content, visual inspection, viscosity, and spreadability. Also, the in vitro release and kinetic studies were carried out to investigate the mechanism of drug release. Moreover, the in vivo studies were carried out by investigating the anti-inflammatory and analgesic activities using albino male rats. The results showed that the modified PLOs have good physicochemical properties. The viscosity of the modified gels is a direct proportionality with both lecithin and pluronic concentrations. Also, subsequently, the drug release rate is directly proportional to gel viscosity. Moreover, the in vivo studies showed that the modified PLOs (F19) showed a significant ( < 0.05%) paw edema inhibition and pain analgesia compared with other investigated groups. Also, the results indicated that the increase in dose is accompanied by higher activity and a longer duration of action which extended to 12 h. Hence, the modified PLOs are promising safe candidates or vehicles for effective TX loading with sustained delivery behavior.
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Lecitinas , Piroxicam/análogos & derivados , Poloxâmero , Animais , Ratos , Cinética , Inflamação , DorRESUMO
Colorectal cancer (CRC) is a widespread cancer that starts in the digestive tract. It is the third most common cause of cancer deaths around the world. The World Health Organization (WHO) estimates an expected death toll of over 1 million cases annually. The limited therapeutic options as well as the drawbacks of the existing therapies necessitate the development of non-classic treatment approaches. Nanotechnology has led the evolution of valuable drug delivery systems thanks to their ability to control drug release and precisely target a wide variety of cancers. This has also been extended to the treatment of CRC. Herein, we shed light on the pertinent research that has been performed on the potential applications of nanoparticles in the treatment of CRC. The various types of nanoparticles in addition to their properties, applications, targeting approaches, merits, and demerits are discussed. Furthermore, innovative therapies for CRC, including gene therapies and immunotherapies, are also highlighted. Eventually, the research gaps, the clinical potential of such delivery systems, and a future outlook on their development are inspired.
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Neoplasias Colorretais , Nanopartículas , Humanos , Imunoterapia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Neoplasias Colorretais/tratamento farmacológicoRESUMO
BACKGROUND: Therapeutic resistance fails cancer treatment. Drug-nanoparticle combinations overcome resistance. Sanguinarine-conjugated nanoparticles may boost sanguinarine's anticancer effects. METHODS: Sanguinarine, HPMC-NPs, and doxorubicin were tested on Adriamycin-resistant MCF-7/ADR breast cancer cells, parent-sensitive MCF-7, and MCR-5 normal cells (DX). RESULTS: Regular distribution, 156 nm diameter, <1 µm average size, 100% intensity-SN is therapeutic. Furthermore, the obtained NPs showed PDI = 0.145, zeta-potential=-37.6, and EE%=90.5%. DX sensitized MCF-7 cells (IC50 = 1.4 µM) more than MCF-7/ADR cells (IC50 = 27 µM) with RR = 19.3. SA and SN were more toxic to MCF-7/ADR cells (overexpressed with P-gp) than their sensitive parent MCF-7 cells (IC50 = 4 µM, RR = 0.6 and 0.6 µM, RR = 0.7). MCR-5 normal lung cells were more resistant to SA (IC50 = 7.2 µM) and SN (IC50 = 1.6 µM) with a selection index > 2. Synergistic cytotoxic interactions reduced the IC50 from 27 µM to 1.6 (CI = 0.1) and 0.9 (CI = 0.4) after DX and nontoxic dosages (IC20) of SA and SN. DS and SN killed 27.1% and 39.4% more cells than DX (7.7%), SA (4.9%), SN (5.5%), or untreated control (0.3%). DS and DSN lowered CCND1 and survival in MCF-7/ADR cells while raising p21 and Casp3 gene and protein expression. CONCLUSIONS: Cellular and molecular studies suggested adjuvant chemosensitizers SA and SN to reverse MDR in breast cancer cells.
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BACKGROUND: Lepidium sativum, Garden Cress (GC), seeds have a lot of natural molecules with a pronounced activity against different disorders. It was reported that GC seeds have the ability to lower the blood glucose level. AIM: The aim of this work was to formulate GC seeds into oral tablets containing a fixed dose of the grounded seeds. Furthermore, the anti-diabetic performance of the prepared tablets was studied in the streptozotocin rats' model in comparison with positive control metformin. METHODS: Micrometrics of GC grounded seeds with different excipients were investigated. Then, GC tablets were prepared via direct compression technique. GC tablets were characterized for their uniformity of dosage unit, friability, hardness, disintegration time, and in vitro release. The antidiabetic effect was studied in rats for a period of 28 days. Glycosylated hemoglobin, liver performance, and lipid levels include total cholesterol (TC), triglycerides (TGs), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were also estimated. In addition, histopathological study of liver and pancreas was also performed. RESULTS: Prosolv®EasyTab produced tablets with higher hardness, lower disintegration time, and fast release. GC tablets significantly lower the elevated blood glucose level. In addition, they have antihyperlipidemic activity, hepatocellular protective role and restore the histology of the liver and pancreas. CONCLUSION: GC tablets could be a promising alternative formulation to control the high blood glucose level in diabetic rats rather than chemically derivatized drugs.
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Diabetes Mellitus Experimental , Lepidium , Metformina , Ratos , Animais , Hipoglicemiantes/farmacologia , Glicemia , Diabetes Mellitus Experimental/tratamento farmacológico , Comprimidos/químicaRESUMO
INTRODUCTION: Bacterial infections caused by different strains of bacteria still one of the most important disorders affecting humans worldwide. Polymers nanocomposite systems could be considered as an alternative to conventional antibiotics to eradicate bacterial infections. SIGNIFICANCE: In an attempt to enhance the antibacterial performance of silver and iron oxide nanoparticles, decrease their aggregation and toxicity, a polymeric hybrid nanocomposite system combining both nanoparticles is produced. METHODS: Magnetic Ag-Fe3O4@polymer hybrid nanocomposites prepared using different polymers, namely polyethylene glycol 4000, ethyl cellulose, and chitosan were synthesized via wet impregnation and ball-milling techniques. The produced nanocomposites were tested for their physical properties and antibacterial activities. RESULTS: XRD, FT-IR, VSM, and TEM results confirmed the successful preparation of hybrid nanocomposites. Hybrid nanocomposites have average crystallite sizes in the following order Ag-Fe3O4@CS (8.9 nm) < Ag-Fe3O4@EC (9.0 nm) < Ag-Fe3O4@PEG4000 (9.4 nm) and active surface area of this trend Ag-Fe3O4@CS (130.4 m2g-1) > Ag-Fe3O4@EC (128.9 m2g-1) > Ag-Fe3O4@PEG4000 (123.4 m2g-1). In addition, they have a saturation magnetization in this order: Ag-Fe3O4@PEG4000 (44.82 emu/g) > Ag-Fe3O4@EC (40.14 emu/g) > Ag-Fe3O4@CS (22.90 emu/g). Hybrid nanocomposites have a pronounced antibacterial action against Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus intermedius compared to iron oxide nanoparticles and positive antibacterial drug. In addition, both Ag-Fe3O4@EC and Ag-Fe3O4@CS have a lower MIC values compared to Ag-Fe3O4@PEG and positive control. CONCLUSION: Magnetic Ag-Fe3O4 hybrid nanocomposites could be promising antibacterial nanomaterials and could pave the way for the development of new materials with even more unique properties and applications.
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Infecções Bacterianas , Nanopartículas Metálicas , Nanocompostos , Humanos , Polímeros , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos/farmacologia , Fenômenos MagnéticosRESUMO
BACKGROUND: Chemotherapeutic agents have numerous side effects. There is a major interest in using natural and safe plants as food or drink to prevent from cancer. Origanum marjoram (OMAE) is a medicinal plant that can be used as a tea, food, and additive in traditional medicine. OBJECTIVE: This study aimed to evaluate the potential anticancer effects of OMAE as a soft drink for daily use against a model cancer, prevention and treatment. METHOD: MCF-7 cells were chosen as model cancer cells. The MTT assay was used to assess the in vitro inhibitory effects of OMAE on cell growth. Moreover, quantitative real-time PCR (qRT-PCR) was used to detect specific genes associated with cancer, such as ESR1, Bax, Bcl-2, and p53. Furthermore, the DNA damage was evaluated using the comet assay. RESULTS: OMAE has IC50 of 53.1 and IC90 of 97.5 µg/ml dependent inhibition of cell proliferation after 48 h of treatment toward MCF-7. Also, a significant decrease in the expression level of the ESR1 gene in the MCF-7 cell line. Furthermore, there was a significant increase in the comet length and comet-positive cells after treatment with OMAE (88.7%) compared with those in the untreated control cells (9.5%), suggesting a high induction of DNA damage by OMAE. Also, OMAE showed a modification in bcl-2, tumor suppressor gene (p53), and Bax levels and influenced the BAX/BCL-2 ratio via releasing the cytochrome C. CONCLUSION: The results of the study were promising, suggesting that the reduced apoptotic rate of MCF-7 breast cancer cells in this work was correlated to the potential anticancer effect of OMAE which would be a suitable preventable drink against cancer. However, further studies are needed to fully understand the potential of OMAE as a cancer treatment.
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Origanum , Humanos , Origanum/metabolismo , Apoptose , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Células MCF-7 , Proliferação de CélulasRESUMO
[This corrects the article DOI: 10.1016/j.heliyon.2023.e13876.].
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Lung cancer is one of the most aggressive and deadliest health threats. There has been an increasing interest in non-coding RNA (ncRNA) recently, especially in the areas of carcinogenesis and tumour progression. However, ncRNA-directed therapies are still encountering obstacles on their way to the clinic. In the present article, we provide an overview on the potential of targeting ncRNA in the treatment of lung cancer. Then, we discuss the delivery challenges and recent approaches enabling the delivery of ncRNA-directed therapies to the lung cancer cells, where we illuminate some advanced technologies including chemically-modified oligonucleotides, nuclear targeting, and three-dimensional in vitro models. Furthermore, advanced non-viral delivery systems recruiting nanoparticles, biomimetic delivery systems, and extracellular vesicles are also highlighted. Lastly, the challenges limiting the clinical trials on the therapeutic targeting of ncRNAs in lung cancer and future directions to tackle them are explored.
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Neoplasias Pulmonares , RNA não Traduzido , Humanos , RNA não Traduzido/genética , RNA não Traduzido/uso terapêutico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Carcinogênese , Terapia de Alvo Molecular/métodosRESUMO
The real problem in pharmaceutical preparation is drugs' poor aqueous solubility, low permeability through biological membranes, and short biological t1/2. Conventional drug delivery systems are not able to overcome these problems. However, cyclodextrins (CDs) and their derivatives can solve these challenges. This article aims to summarize and review the history, properties, and different applications of cyclodextrins, especially the ability of inclusion complex formation. It also refers to the effects of cyclodextrin on drug solubility, bioavailability, and stability. Moreover, it focuses on preparing and applying gold nanoparticles (AuNPs) as novel drug delivery systems. It also studies the uses and effects of cyclodextrins in this field as novel drug carriers and targeting devices. The system formulated from AuNPs linked with CD molecules combines the advantages of both CD and AuNPs. Cyclodextrins benefit in increasing aqueous drug solubility, loading capacity, stability, and size control of gold NPs. Also, AuNPs are applied as diagnostic and therapeutic agents because of their unique chemical properties. Plus, AuNPs possess several advantages such as ease of detection, targeted and selective drug delivery, greater surface area, high loading efficiency, and higher stability than microparticles. In the present article, we tried to present the potential pharmaceutical applications of CD-derived AuNPs in biomedical applications including antibacterial, anticancer, gene-drug delivery, and various targeted drug delivery applications. Also, the article highlighted the role of CDs in the preparation and improvement of catalytic enzymes, the formation of self-assembling molecular print boards, the fabrication of supramolecular functionalized electrodes, and biosensors formation.
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Ciclodextrinas , Nanopartículas Metálicas , Preparações Farmacêuticas , Ciclodextrinas/química , Ouro , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/químicaRESUMO
BACKGROUND: Ginkgo biloba (GB) leaves extract is known to possess potent antioxidants and other bioactivities such as improved skin conditions and rejuvenation. OBJECTIVE: This study aimed to develop a cosmeceutical preparation to utilize the strong antioxidant potential of GB leaves as part of the skincare formulation. METHODS: Cream incorporated GB (GBC) was prepared by mixing the obtained extract with stearic acid-sodium hydroxide components in an emulsion format. The obtained GBC was characterized for GB contents, uniformity, pH, compatibility, stability, and skin's human application. RESULTS: A homogeneous, physically, and chemically stable, with pH near the skin pH and shiny cream, was obtained. The prepared cream was easy to rub and pearly in appearance. It was effective and safe during the two-week trial conducted on human volunteers according to clinical trial registry protocols. The cream scavenged free radicals in DPPH assay tests. The cream incorporated GB made the skin more spirited and tauter. Furthermore, the wrinkles were reduced and the skin was renewed vigor. CONCLUSION: The GBC worked at the topical level and provided benefits when applied daily for the trial duration. The formulation also provided visually observable anti-wrinkle effects on the skin, with visible improvements in the skin's shape and texture. The prepared cream can be used to rejuvenate the skin.
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Cosmecêuticos , Envelhecimento da Pele , Humanos , Cosmecêuticos/farmacologia , Ginkgo biloba , Rejuvenescimento , Voluntários Saudáveis , Creme para a Pele , Extratos Vegetais/farmacologia , Antioxidantes/farmacologiaRESUMO
Graft versus host disease (GVHD) remains the major cause of morbidity and mortality after allogeneic stem cell transplantation, especially for intestinal GVHD, as steroid resistant GVHD results in high mortality. For this reason, new treatments of GVHD are needed. One approach is the reduction of pathogenic bacteria using anti-E. coli Immunoglobulin Yolk (IgY). In a haploidentical murine model, B6D2F1 mice conditioned with total body irradiation (TBI), received bone marrow cells (BM) and splenocytes (SC) from either syngeneic (Syn = B6D2F1) or allogeneic (Allo = C57BL/6) donors. Following this, animals received from day -2 until day +28 chow contained IgY or control chow. Thereafter the incidence and severity of aGVHD, the cytokines, chemokines, IDO1 and different pathogen-recognition receptors (PRR) were analyzed and compared to control animals (received chow without IgY). We found that animals receiving chow with IgY antibody showed reduced GVHD severity compared to control animals. On day28 after alloBMT, IDO, NOD2, TLR2, TLR4 and the inflammatory chemokine CCL3, were reduced in the colon and correlated with a significant decrease in E. coli bacteria. In summary chow containing chicken antibodies (IgY) improved GVHD via decrease in bacterial load of E coli conducting to reduction of pathogen receptors (NOD2, TLR2 and 4), IDO, chemokines and cytokines.
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Medicinal plants are being used from time immemorial for their therapeutic benefits and have immense value in the therapy of neurodegenerative disorders. One of the most important neurological disorders is Alzheimer's disease (AD) which is a major contributor to dementia and is accompanied by abundant oxidative stress in the brain tissue. A critical pathway to target the increased oxidative stress is to administer agents with antioxidant potential. Despite currently available clinical treatments to treat AD such as cholinesterase inhibitors or NMDA antagonists which address only the symptoms and cannot hamper disease progression, no efficient available clinical treatment can break the vicious cycle of oxidative stress and neurodegeneration till date. The main objective of presenting this review is that traditional Chinese medicine (TCM) acts as a promising candidate in breaking this vicious cycle and improves the quality of life of the debilitating patients. The active constituents of various herbs in TCM including Angelica sinensis, Radix polygalae, Polygala tenuifolia, and members of the Lamiaceae family have acquired experience of managing oxidative stress as indicated in the review for more than a thousand years now, and the preclinical and clinical evidence of their therapeutic potential has been highlighted in the review. Most importantly, Chinese herbs provide a multiple-target approach rather than a single-target approach and thus can target multiple pathways involved in AD at once. The Chinese herbs can definitely untangle the issues in the current therapy regimen of AD.
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Doença de Alzheimer , Medicamentos de Ervas Chinesas , Humanos , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Doença de Alzheimer/tratamento farmacológico , Neuroproteção , Qualidade de Vida , Estresse OxidativoRESUMO
Throughout decades, the intrinsic power of the immune system to fight pathogens has inspired researchers to develop techniques that enable the prevention or treatment of infections via boosting the immune response against the target pathogens, which has led to the evolution of vaccines. The recruitment of Lipid nanoparticles (LNPs) as either vaccine delivery platforms or immunogenic modalities has witnessed a breakthrough recently, which has been crowned with the development of effective LNPs-based vaccines against COVID-19. In the current article, we discuss some principles of such a technology, with a special focus on the technical aspects from a translational perspective. Representative examples of LNPs-based vaccines against cancer, COVID-19, as well as other infectious diseases, autoimmune diseases, and allergies are highlighted, considering the challenges and promises. Lastly, the key features that can improve the clinical translation of this area of endeavor are inspired.
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COVID-19 , Nanopartículas , Vacinas , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , TecnologiaRESUMO
The present study is aimed to investigate the antioxidative potential and ameliorative effects of Lens culinaris Medikus sprouts hydroalcoholic extract (LSHE) on CCl4-induced oxidative stress in rats. The research has been carried out in two successive stages. Firstly, the highest phenolic content and antioxidant activity of L. culinaris sprouts were assessed at 20 ± 1°C and 90-93% RH during sprouting. Total phenolic content (TPC), total carotenoids (TC), total flavonoids (TF), total flavonols (TFL), DPPH-RSA, and vitamin C contents of L. culinaris seeds and 6-days sprouts were determined. Subsequently, phenolics by HPLC analysis of L. culinaris seeds, 3rd and 6th-day sprouts were identified and quantified. Results indicated that 6th-day sprouts contained considerable phenolics with superior antioxidant capacity, thus selected to be examined for biological activity in a rat's module consisting of five groups. G1, normal rats orally received distilled water. G2 received 1.0 mL kg-1 of CCl4 and olive oil (1:1) intraperitoneally (i.p.) twice a week. G3 received CCl4 (i.p.) and 50 mg GAE kg-1 of LSHE daily/orally. G4 received CCl4 (i.p.) 100 mg kg-1 of LSHE orally/daily. G5 (reference group) treated by intramuscular injection (i.m.) of vit. E+Selenium (Vit. E+Se, 50 mg kg-1 twice a week). The weight gain, relative weight of organs, hypoglycemic and hypolipidemic efficiencies, liver's and kidneys' functions, and antioxidant biomarkers were examined. LSHE enhanced the weight gain recovery % and significantly reduced fasting blood glucose. The hypolipidemic effect of LSHE was dramatically reduced triglycerides (TG), total cholesterol (CHO), high- and low-density lipoproteins (HDL-c and LDL-c), and very-low-density lipoproteins (VLDL-c). Administration of 50 and 100 LSHE mg kg-1 ameliorated liver and kidney function in dose-dependent manure. Intriguingly, LSHE considerably reduced malondialdehyde (MDA) while significantly raising reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in a dose-dependent manner. In conclusion, biochemical examinations confirmed the therapeutic efficacy of LSHE as a functional product. It encouraged us to recommend L. culinaris sprout production for attenuating hepatotoxicity and nephrotoxicity, as well as being beneficial and profitable for controlling oxidative stress complications.
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Tumor necrosis factor (TNF-α) and inflammatory cytokine (IL-6) play a vital role in various cellular incidents such as the proliferation and death of cells during carcinogenesis. Hence, regulation of these biomarkers could be a promising tool for controlling tumor progression using nanoformulations. Silver nanoparticles-poly (vinyl pyrrolidone) (AgNPs-PVP) were prepared using the reduction of silver nitrate and stabilized with PVP. They are characterized through yield percentage, UV-VIS, FT-IR, size, charge, and morphology. The obtained AgNPs were tested for anticancer activity against prostate cancer (PC 3) and human skin fibroblast (HFS) cell lines. Moreover, biomarker-based confirmations like TNF-α and IL-6 were estimated. The synthesized AgNPs-PVP were stable, spherical in shape, with particle sizes of 122.33 ± 17.61 nm, a polydispersity index of 0.49 ± 0.07, and a negative surface charge of -19.23 ± 0.61 mV. In vitro cytotoxicity testing showed the AgNPs-PVP exhibited antiproliferation properties in PC3 in a dose-dependent manner. In addition, when compared to control cells, AgNPs-PVP has lower TNF-α with a significant value ( ∗ p < 0.05); the value reached 16.84 ± 0.71 pg/ml versus 20.81 ± 0.44 pg/ml, respectively. In addition, HSF cells showed a high level of reduction ( ∗∗∗ p < 0.001) in IL-6 production. This study suggested that AgNPs-PVP could be a possible therapeutic agent for human prostate cancer and anti-IL-6 in cancerous and noncancerous cells. Further studies will be performed to investigate the effect of AgNPs-PVP in different types of cancer.