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1.
Nanomedicine ; : 102480, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34748962

RESUMO

Proprotein convertase subtilisin/kexin type 9 is a protease enzyme secreted by liver that downregulates hepatic low-density lipoprotein receptor (LDLR) by binding and chaperoning LDLR to lysosomes for degradation, causing hypercholesteremia. The development of anti-PCSK9therapeutics attracted considerable attention for the management of cardiovascular disease risk. However, only subcutaneous injectable PCSK9 monoclonal antibodies have been FDA approved. Oral administration of small-molecule PCSK9 inhibitors has the potential to become a practical therapeutic option if achievable. In the present work, we used nanotechnological approaches to develop the first small oral molecule nano-hepatic targeted anti-PCSK9. Using high-throughput optimization and a series of evaluations, a stable water-dispersible 150-200nm nano-encapsulated drug (named P-4) conjugated with hepatic targeting moiety was synthesized and characterized (named P-21). Pharmacodynamic (PD), pharmacokinetic (PK) and bioavailability studies were conducted using a high fat diet nutritionally induced hypercholesterolemia mouse model to evaluate the efficacy of P-21 as an anti-PCSK9 LDL-cholesterol lowering hepatic targeted nanodrug. The PD results demonstrate that P-21 in a dose-dependent manner is highly effective in lowering LDL-C by 50-90%. PK results show the maximum plasma concentration (Cmax) of P-4 was observed after 30min of administration with 31% oral bioavailability and had a sustained longer half-life up to 24h. In vivo safety studies in rats showed no apparent adverse effects, normal chemical biomarkers and normal histopathological findings in all P-21 treated groups at different escalating doses. Compared to the FDA-approved monoclonal antibodies, P-21 offers a more efficient, and practical treatment protocol for targeting uncontrolled hypercholesterolemia in reducing the risk of cardiovascular diseases. The present study introduced a nano-targeted drug delivery approaches for PCSK9/LDLR antagonist.

2.
Biomedicines ; 9(11)2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34829942

RESUMO

Ischemic heart disease is the main cause of death globally. Cardioprotection is the process whereby mechanisms that reduce myocardial damage, and activate protective factors, contribute to the preservation of the heart. Targeting these processes could be a new strategy in the treatment of post-ischemic heart failure (HF). Triiodothyronine (T3) and thyroxine (T4), which have multiple effects on the heart, prevent myocardial damage. This study describes the formulation, and characterization, of chemically modified polymeric nanoparticles incorporating T3, to target the thyroid hormone receptors. Modified T3 was conjugated to polylactide-co-glycolide (PLGA) to facilitate T3 delivery and restrict its nuclear translocation. Modified T3 and PLGA-T3 was characterized with 1H-NMR. The protective role of synthesized phosphocreatine (PCr) encapsulated PLGA-T3 nanoparticles (PLGA-T3/PCr NPs) and PLGA-T3 nanoparticles (PLGA-T3 NPs) in hypoxia-mediated cardiac cell insults was investigated. The results showed that PLGA-T3/PCr NPs represent a potentially new therapeutic agent for the control of tissue damage in cardiac ischemia and resuscitation.

3.
Endocr Res ; : 1-6, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34775877

RESUMO

BACKGROUND: Integrin αvß3 is a cell membrane structural protein whose extracellular domain contains a receptor for L-thyroxine (T4). The integrin is expressed in rapidly dividing cells and its internalization is prompted by T4. The protein binds viruses and we have raised the possibility elsewhere that action of free T4 (FT4)-when he latter is increased in the nonthyroidal illness syndrome (NTIS) known to complicate COVID-19 infecction-may enhance cellular uptke of SARS-CoV-2 and its receptor. OBJECTIVE: Because T4 also acts nongenomically via the integrin to promote platelet aggregation and angiogenesis, we suggest here that T4 may contribute to the coagulopathy and endothelial abnormalities that can develop in COVID-19 infections, particularly when the lung is primary affected. DISCUSSION AND CONCLUSIONS: Elevated FT4 has been described in the NTIS of COVID-19 patients and may be associated with increased illness severity, but the finding of FT4 elevation is inconsistent in the NTIS literature. Circulating 3,5',3'-triiodo-L-thyronine (reverse T3, rT3) are frequently elevated in NTIS. Thought to be biologically inactive, rT3in fact stimulates cancer cell proliferation via avb3 and also may increase actin polymerization. We propose here that rT3 in the NTIS complicating systemic COVIF-19 infection may support coagulation and disordered blood vessel formation via actin polymerization.

4.
Diagnostics (Basel) ; 11(11)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34829418

RESUMO

With almost 4 million deaths worldwide from the COVID-19 pandemic, the efficient and accurate diagnosis and identification of COVID-19-related complications are more important than ever. Scales such as the pneumonia severity index, or CURB-65, help doctors determine who should be admitted to the hospital or the intensive care unit. To properly treat and manage admitted patients, standardized sampling protocols and methods are required for COVID-19 patients. Using PubMed, relevant articles since March 2020 on COVID-19 diagnosis and its complications were analyzed. Patients with COVID-19 had elevated D-dimer, thrombomodulin, and initial factor V elevation followed by decreased factor V and factor VII and elevated IL-6, lactate dehydrogenase, and c-reactive protein, which indicated coagulopathy and possible cytokine storm. Patients with hypertension, newly diagnosed diabetes, obesity, or advanced age were at increased risk for mortality. Elevated BUN, AST, and ALT in severe COVID-19 patients was associated with acute kidney injury or other organ damage. The gold standard for screening COVID-19 is reverse transcriptase polymerase chain reaction (RT-PCR) using sputum, oropharyngeal, or nasopharyngeal routes. However, due to the low turnover rate and limited testing capacity of RT-PCR, alternative diagnostic tools such as CT-scan and serological testing (IgM and IgG) can be considered in conjunction with symptom monitoring. Advancements in CRISPR technology have also allowed the use of alternative COVID-19 testing, but unfortunately, these technologies are still under FDA review and cannot be used in patients. Nonetheless, increased turnover rates and testing capacity allow for a bright future in COVID-19 diagnosis.

5.
Clin Transl Sci ; 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34599865

RESUMO

Hyperphosphatemia is present in most patients with end-stage renal disease (ESRD) and has been associated with increased cardiovascular mortality. Phosphate binders (calcium-based and calcium free) are the mainstay pharmacologic treatment to lower phosphorus levels in patients with ESRD. We evaluated biochemical markers of vascular calcification, inflammation, and endothelial dysfunction in patients with chronic kidney disease (CKD) treated with sevelamer carbonate (SC) versus calcium acetate (CA). Fifty patients with CKD (stages 3 and 4) were enrolled and assigned to treatment with SC and CA for 12 weeks. At the end of the study the biomarkers of vascular calcification, inflammation, and endothelial dysfunction were analyzed. A significant increase in HDL-cholesterol was observed with SC but not with CA in patients with CKD. Treatment with SC reduced serum phosphate, calcium phosphate, and FGF-23 levels and there was no change with CA treatment. The inflammatory markers IL-8, IFN-γ, and TNFα decreased with response to both treatments. The levels of IL-6 significantly increased with CA treatment and no change was observed in the SC treatment group. SC showed favorable effects on anti-inflammatory and vascular calcification biomarkers compared to CA treatment in patients with CKD stages 3 and 4 with normal phosphorous values.

6.
Nanomedicine (Lond) ; 16(26): 2331-2342, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34651508

RESUMO

Aim: We previously synthesized a polyethylene glycol-based norepinephrine transporter-targeted agent, BG-P-TAT, which has a benzylguanidine and a triazolyl-tetrac group. This targeted conjugate showed suppression of neuroblastoma tumor progression. In this study we aimed to synthesize nanoparticles to encapsulate the chemotherapeutic agent paclitaxel for targeting neuroblastoma tumors by using benzylguanidine so that it can compete with norepinephrine for uptake by neuroendocrine cells. Methods: Biocompatible poly(lactide-co-glycolic acid)-polyethylene glycol was chosen to prepare targeted nanoparticles for safe delivery of the chemotherapy agent paclitaxel. Result: Paclitaxel concentration was 60% higher in neuroblastoma tumors of mice treated with paclitaxel encapsulated in targeted nanoparticles than with non-targeted nanoparticles. Conclusion: These findings support the targeted delivery of paclitaxel as a chemotherapeutic agent for neuroblastoma.


Assuntos
Nanopartículas , Neuroblastoma , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Guanidinas , Camundongos , Neuroblastoma/tratamento farmacológico , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Paclitaxel , Polietilenoglicóis
7.
Molecules ; 26(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34641577

RESUMO

Corchorus olitorius is a common, leafy vegetable locally known as "Saluyot" in the Philippines. Several studies have reported on its various pharmacological properties, such as antioxidant, anti-inflammatory, analgesic, and anticancer properties. However, little is known about its effects on angiogenesis. This study aimed to evaluate the anticancer properties, such as the antiproliferative, anti-angiogenic, and antitumor activities, of the C. olitorius aqueous extract (CO) and its bioactive compounds, chlorogenic acid (CGA) and isoquercetin (IQ), against human melanoma (A-375), gastric cancer (AGS), and pancreatic cancer (SUIT-2), using in vitro and in ovo biological assays. The detection and quantification of CGA and IQ in CO were achieved using LC-MS/MS analysis. The antiproliferative, anti-angiogenic, and antitumor activities of CO, CGA, and IQ against A-375, AGS, and SUIT-2 cancer cell lines were evaluated using MTT and CAM assays. CGA and IQ were confirmed to be present in CO. CO, CGA, and IQ significantly inhibited the proliferation of A-375, AGS, and SUIT-2 cancer cells in a dose-dependent manner after 48 h of treatment. Tumor angiogenesis (hemoglobin levels) of A-375 and AGS tumors was significantly inhibited by CO, CGA, IQ, and a CGA-IQ combination. The growth of implanted A-375 and AGS tumors was significantly reduced by CO, CGA, IQ, and a CGA-IQ combination, as measured in tumor weight. Our investigation provides new evidence to show that CO has promising anticancer effects on various types of human cancer cells. CO and its compounds are potential nutraceutical products that could be used for cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Extratos Vegetais/farmacologia , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Embrião de Galinha , Ácido Clorogênico/farmacologia , Cromatografia Líquida , Corchorus/química , Humanos , Extratos Vegetais/química , Folhas de Planta/química , Quercetina/análogos & derivados , Quercetina/farmacologia , Espectrometria de Massas em Tandem
8.
Front Pharmacol ; 12: 703761, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512336

RESUMO

Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes that mediate various cellular activities, including propagation, differentiation, motility, and survival. Abnormal activation of NF-κB is a common incidence in several cancers. Glioblastoma multiforme (GBM) is the most aggressive brain cancer described by high cellular heterogeneity and almost unavoidable relapse following surgery and resistance to traditional therapy. In GBM, NF-κB is abnormally activated by various stimuli. Its function has been associated with different processes, including regulation of cancer cells with stem-like phenotypes, invasion of cancer cells, and radiotherapy resistance identification of mesenchymal cells. Even though multimodal therapeutic approaches such as surgery, radiation therapy, and chemotherapeutic drugs are used for treating GBM, however; the estimated mortality rate for GBM patients is around 1 year. Therefore, it is necessary to find out new therapeutic approaches for treating GBM. Many studies are focusing on therapeutics having less adverse effects owing to the failure of conventional chemotherapy and targeted agents. Several studies of compounds suggested the involvement of NF-κB signaling pathways in the growth and development of a tumor and GBM cell apoptosis. In this review, we highlight the involvement of NF-κB signaling in the molecular understanding of GBM and natural compounds targeting NF-κB signaling.

9.
Integr Cancer Ther ; 20: 15347354211035450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490824

RESUMO

Doxorubicin (Dox) induces senescence in numerous cancer cell types, but these senescent cancer cells relapse again if they are not eliminated. On this principle, we investigated the apoptotic effect of thymoquinone (TQ), the active ingredient of Nigella sativa seeds and costunolide (COS), the active ingredient of Costus speciosus, on the senescent colon (Sen-HCT116) and senescent breast (Sen-MCF7) cancer cell lines in reference to their corresponding proliferative cells to rapidly eliminate the senescent cancer cells. The senescence markers of Sen-HCT116 and Sen-MCF7 were determined by a significant decrease in bromodeoxyuridine (BrdU) incorporation and significant increases in SA-ß-gal, p53, and p21 levels. Then proliferative, Sen-HCT116, and Sen-MCF7 cells were subjected to either TQ (50 µM) or COS (30 µM), the Bcl2-associated X protein (Bax), B-cell lymphoma 2 (Bcl2), caspase 3 mRNA expression and its activity were established. Results revealed that TQ significantly increased the Bax/Bcl2 ratio in HCT116 + Dox5 + TQ, MCF7 + TQ, and MCF7 + Dox5 + TQ compared with their corresponding controls. COS significantly increased the Bax/Bcl2 ratio in HCT116 + Dox5 + TQ and MCF7 + Dox5 + TQ compared with their related controls. Also, TQ and COS were significantly increased caspase 3 activity and cell proliferation of Sen-HCT116 and Sen-MCF7. The data revealed a higher sensitivity of senescent cells to TQ or COS than their corresponding proliferative cells.


Assuntos
Apoptose , Recidiva Local de Neoplasia , Benzoquinonas , Colo , Doxorrubicina/farmacologia , Humanos , Sesquiterpenos
10.
Nutr Cancer ; : 1-22, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590505

RESUMO

Most current larynx cancer therapies are generally aimed at the global mass of tumor, targeting the non-tumorigenic cells, and unfortunately sparing the tumorigenic cancer stem cells (CSCs) that are responsible for sustained growth, metastasis, and chemo- and radioresistance. Phytochemicals and herbs have recently been introduced as therapeutic sources for eliminating CSCs. Therefore, we assessed the anti-tumor effects of two herbal ingredients, the green tea extract "Epigallocatechin-3-gallate (EGCG)" and Honokiol (HNK), on parental cells or CD44high CSCs of the human laryngeal squamous cell carcinoma cell line HEp-2. Results revealed that EGCG had a preeminent apoptotic potential on HEp-2 laryngeal CSCs. HNK conferred higher cytotoxic impacts on parental cells mostly by necrosis induction, especially with higher doses, but apoptosis induction with lower doses was also observed. The Notch signaling pathway genes were more potently suppressed by EGCG than HNK. However, HNK surpassed EGCG in downregulating the ß-catenin and the Sonic Hedgehog signaling pathways genes. On a genetic basis, both agents engaged the BCL-2 family-regulated and caspase-dependent intrinsic apoptotic pathway, but EGCG and HNK triggered apoptosis via p53-independent and p53-dependent pathways, respectively. Taken together, EGCG and HNK eradicated HEp-2 human larynx cancer cells through targeting multiple self-renewal pathways and activating diverse cell death modalities.

11.
Biomater Sci ; 9(19): 6609-6622, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582539

RESUMO

Mitochondria are reported to play a paramount role in tumorigenesis which positions them as an instrumental druggable target. However, selective drug delivery to cancer-localized mitochondria remains challenging. Herein, we report for the first time, the design, development and evaluation of a hepatic cancer-specific mitochondria-targeted dual ligated nanoscale metal-organic framework (NMOF) for cellular and mitochondrial sequential drug delivery. Surface functionalization was performed through covalent-linking of folic acid and triphenylphosphonium moieties to the aminated Zr-based MOF, NH2-UiO-66. The characterization of the dual-ligated NMOFs using XRD, FTIR, DSC and BET analysis proved the successful conjugation process. Assessment of the drug loading and release profiling of doxorubicin (DOX)-loaded NMOF confirmed the proper retention of the drug within the NMOF porous structure alongside enhanced release in the tumor acidic environment. Furthermore, biological evaluation of the anti-tumor activity of the DOX-loaded dual-ligated NMOF on hepatocellular carcinoma affirmed the superiority of the developed system in killing the cancerous cells via apoptosis induction and halting cell cycle progression. This study attempts to underscore the promising potential of surface functionalized NMOFs in developing anticancer drug delivery systems to achieve targeted therapy.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Estruturas Metalorgânicas , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Doxorrubicina/farmacologia , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Mitocôndrias
12.
Nanomedicine ; 39: 102466, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34587542

RESUMO

The purpose of this work was to incorporate an optimized pomegranate extract loaded solid lipid nanoparticles (PE-SLNs) formula in a transdermal emulgel to evaluate its anticancer effect. The prepared emulgel formulae were evaluated for their physicochemical properties. An ex vivo permeation study was done through mouse skin and the kinetic parameters were determined. Kinetic data showed that the ex vivo permeation of PE from SLNs transdermal emulgel through mouse skin followed non-Fickian diffusion transport. Further, in vivo study was done by applying the optimized PE-SLNs transdermal emulgel on mice skin bearing a solid form of Ehrlich ascites carcinoma (EAC) as well as free PE, control, placebo, and standard groups for comparison. In addition, histopathological examinations of the samples obtained from the EAC mice model were performed. The results proved that application of the selected PE-SLNs emulgel formulation on the mice skin bearing solid tumor revealed statistically significant anticancer effects.

13.
Cancers (Basel) ; 13(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34439224

RESUMO

(1) Background: Acute myeloid leukemia (AML) accounts for up to one-third of more than 60,000 leukemia cases diagnosed annually in the U.S. Primary AML cells express membrane αvß3 integrin, which is associated with adverse prognosis and resistance to chemotherapies. A novel anticancer compound Polyethylene glycol-conjugated bi-TriAzole Tetraiodothyroacetic acid (P-bi-TAT) interacts with high affinity (Ki 0.3 nM) and specificity with the thyrointegrin αvß3. We evaluated P-bi-TAT activities in two different AML models representing monocytic and myelocytic forms of acute leukemia. (2) Methods and Results: The in vivo AML models were established prior to initiation of treatment protocols by grafting human leukemia cells in immunocompromised mice. IVIS imaging scans revealed that leukemic colonies were extensively established throughout the bone marrow, liver, and lung of the untreated animals. In animals treated with P-bi-TAT at daily doses ranging from 1-10 mg/kg, subcutaneously for 2-3 weeks, IVIS imaging scans revealed 95% reduction in bone marrow colonies and leukemic colonies in liver and lung. Also, the leukemic cells were not detected in bone marrow samples of P-bi-TAT-treated animals. The anti-neoplastic effect of P-bi-TAT administration on leukemic cells was associated with marked inhibition of NF-κB activity. We conclude that experimental P-bi-TAT therapy in vivo appears extraordinarily effective against the two forms of human AML models in mice. Because the P-bi-TAT molecular target, thyrointegrin αvß3, is consistently expressed in many, if not all, clinical AML samples, P-bi-TAT-based therapy seems to have significant clinical potential in treating most AML sub-types. Hence, P-bi-TAT represents a promising targeted therapeutic agent for AML patients.

14.
Biomedicines ; 9(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34440193

RESUMO

Costunolide (COS) is a sesquiterpene lactone with anticancer properties. The present study investigated the anticancer effects of COS against the human colon (HCT116) and breast (MDA-MB-231-Luc) cancer cell lines. Inhibition of cell lines viability and IC50 of COS were assessed via an MTT assay. Furthermore, the apoptotic rate was detected by assessment of Bcl2-associated X (Bax) and B-cell lymphoma 2 (Bcl2) protein levels by flow cytometry. Xenograft mice model of HCT116 and MDA-MB-231-Luc were carried out to determine the effect of COS and its nanoparticles (COS-NPs). The results demonstrated that COS inhibited the viability of HCT116 and MDA-MB-231-Luc cells, with a half maximal inhibitory concentration value (IC50) of 39.92 µM and 100.57 µM, respectively. COS significantly increased Bax and decreased Bcl2 levels in treated cells. COS and COS-NPs, in combination with doxorubicin (DOX), significantly decreased the tumor growth of HCT116 and MDA-MB-231-Luc implants in mice. Furthermore, oral administration of COS and COS-NPs significantly decreased the viable cells and increased necrotic/apoptotic cells of HCT116 and MDA-MB-231-Luc implants. Interestingly, both COS and COS-NPs protected the cardiac muscles against DOX's cardiotoxicity. The current results indicated the promising anticancer and cardiac muscles protection of COS and COS-NPs when administered with chemotherapy.

15.
Int J Nanomedicine ; 16: 5117-5131, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349511

RESUMO

As a crucial organ, the lung is exposed to various harmful agents that may induce inflammation and oxidative stress, which may cause chronic or acute lung injury. Nigella sativa, also known as black seed, has been widely used to treat various diseases and is one of the most extensively researched medicinal plants. Thymoquinone (TQ) is the main component of black seed volatile oil and has been proven to have antioxidant, anti-inflammatory, and antineoplastic properties. The potential therapeutic properties of TQ against various pulmonary disorders have been studied in both in vitro and in vivo studies. Furthermore, the application of nanotechnology may increase drug solubility, cellular absorption, drug release (sustained or control), and drug delivery to lung tissue target sites. As a result, fabricating TQ as nanoparticles (NPs) is a potential therapeutic approach against a variety of lung diseases. In this current review, we summarize recent findings on the efficacy of TQ and its nanotypes in lung disorders caused by immunocompromised conditions such as cancer, diabetes, gastric ulcers, and other neurodegenerative diseases. It is concluded that TQ nanoparticles with anti-inflammatory, antioxidant, antiasthma, and antitumor activity may be safely applied to treat lung disorders. However, more research is required before TQ nanoparticles can be used as pharmaceutical preparations in human studies.


Assuntos
Lesão Pulmonar , Nanopartículas , Benzoquinonas , Humanos , Nigella sativa
16.
J Neurosci Methods ; 363: 109340, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34461154

RESUMO

BACKGROUND: Neurogenic differentiation of human marrow stromal stem cells (hMSCs) into neural precursor cells (NPCs) offers new hope in many neurological diseases. Stromal cells can be differentiated into NPCs using small molecules acting as chemical inducers. The aim of this study is to formulate an efficient, direct, fast and safe protocol to differentiate hMSCs into NPCs using different inducers: b-mercaptoethanol (BME), triiodothyronine (T3), and curcumin (CUR). NEW METHOD: hMSCs were subjected to either 1 mM BME, 0.5 µM T3, or 5 µM CUR. Neurogenic differentiation was determined by assessing the protein expression of PAX6, SOX2, DLX2, and GAP-43 with flow cytometry and immunofluorescence, along with Nissl staining of differentiated cells. RESULTS AND COMPARISON WITH EXISTING METHOD: It was revealed that T3 and CUR are 70-80% better than BME in terms of efficiency and safety, and surprisingly BME was a good promoting factor for cell preconditioning with limited effects on neural trans-differentiation related to its toxic effects on cell viability. CONCLUSION: Reprogramming of bone marrow stromal cells into neural cells gives hope for treating different neurological disorders. Our study shows that T3 and CUR were effective in generation of NPCs from hMSCs with preservation of cell viability. BME was a good promoting factor for cell preconditioning with limited effects on neural transdifferentiation related to its toxic effects on cell viability.


Assuntos
Células-Tronco Mesenquimais , Células-Tronco Neurais , Células da Medula Óssea , Diferenciação Celular , Humanos , Neurônios
17.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202112

RESUMO

D-galactose (D-gal) administration causes oxidative disorder and is widely utilized in aging animal models. Therefore, we subcutaneously injected D-gal at 200 mg/kg BW dose to assess the potential preventive effect of thymoquinone (TQ) and curcumin (Cur) against the oxidative alterations induced by D-gal. Other than the control, vehicle, and D-gal groups, the TQ and Cur treated groups were orally supplemented at 20 mg/kg BW of each alone or combined. TQ and Cur effectively suppressed the oxidative alterations induced by D-gal in brain and heart tissues. The TQ and Cur combination significantly decreased the elevated necrosis in the brain and heart by D-gal. It significantly reduced brain caspase 3, calbindin, and calcium-binding adapter molecule 1 (IBA1), heart caspase 3, and BCL2. Expression of mRNA of the brain and heart TP53, p21, Bax, and CASP-3 were significantly downregulated in the TQ and Cur combination group along with upregulation of BCL2 in comparison with the D-gal group. Data suggested that the TQ and Cur combination is a promising approach in aging prevention.


Assuntos
Benzoquinonas/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Curcumina/farmacologia , Galactose/farmacologia , Miocárdio/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Benzoquinonas/química , Curcumina/química , Imuno-Histoquímica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Especificidade de Órgãos , Ratos , Relação Estrutura-Atividade
18.
Drug Des Devel Ther ; 15: 3151-3162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34321865

RESUMO

Introduction: Skin aging is a normal process that might be accelerated or delayed by altering the balance between antioxidants and free radicals due to increase in the exposure to reactive oxygen species (ROS) into skin cells via UV radiation. Antioxidants can neutralize the harmful effects of ROS, and secondary plant metabolites might help protect against UV radiation. Methods: In this study, punicalagin was extracted from pomegranate, and concentrations of total polyphenolics and flavonoids were determined, and antioxidant activities were measured. Punicalagin was loaded onto niosomes, and its morphology and release were studied. An in vitro study was performed on human fibroblast cell line HFB4 cells with aging induced by H2O2 and UV radiation. Cell cycle arrest was studied, and different genes (MMP3, Col1A1, Timp3, and TERT) involved in the skin aging process were selected to measure punicalagin's effect. Results: Punicalagin succeeded in reducing the growth arrest of HFB4 cells, activated production of the Col1A1 and Timp3 genes, maintained collagen level, and lowered MMP3. Punicalagin increased human TERT concentration in skin cells. Discussion: Punicalagin is promising as a natural antioxidant to protect human skin from aging.

19.
Front Endocrinol (Lausanne) ; 12: 691736, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234745

RESUMO

L-Thyroxine (T4) is the principal ligand of the thyroid hormone analogue receptor on the extracellular domain of integrin αvß3. The integrin is overexpressed and activated in cancer cells, rapidly dividing endothelial cells, and platelets. The biologic result is that T4 at physiological concentration and without conversion to 3,3',5-triiodo-L-thyronine (T3) may stimulate cancer cell proliferation and cancer-relevant angiogenesis and platelet coagulation. Pro-thrombotic activity of T4 on platelets is postulated to support cancer-linked blood clotting and to contribute to tumor cell metastasis. We examine some of these findings as they may relate to cancers of the thyroid. Differentiated thyroid cancer cells respond to physiological levels of T4 with increased proliferation. Thus, the possibility exists that in patients with differentiated thyroid carcinomas in whom T4 administration and consequent endogenous thyrotropin suppression have failed to arrest the disease, T4 treatment may be stimulating tumor cell proliferation. In vitro studies have shown that tetraiodothyroacetic acid (tetrac), a derivative of T4, acts via the integrin to block T4 support of thyroid cancer and other solid tumor cells. Actions of T4 and tetrac or chemically modified tetrac modulate gene expression in thyroid cancer cells. T4 induces radioresistance via induction of a conformational change in the integrin in various cancer cells, although not yet established in thyroid cancer cells. The thyroid hormone receptor on integrin αvß3 mediates a number of actions of T4 on differentiated thyroid cancer cells that support the biology of the cancer. Additional studies are required to determine whether T4 acts on thyroid cancer cells.

20.
Nutr Res Rev ; : 1-13, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34253265

RESUMO

Aspirin (acetylsalicylic acid, ASA) is inexpensive and is established in preventing cardiovascular disease (CVD) and colorectal adenomas. Omega-3 (n3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have also shown benefit in preventing CVD. The combination could be an effective preventative measure in patients with such diseases. ASA and n3 PUFA reduced the risk of CVD in ASA-resistant or diabetic patients. EPA- and DHA-deficient patients also benefited the most from n3 PUFA supplementation. Synergistic effects between ASA and EPA and DHA are 'V-shaped' such that optimal ASA efficacy is dependent on EPA and DHA concentrations in blood. In colorectal adenomas, ASA (300 mg/d) and EPA reduced adenoma burden in a location- and subtype-specific manner. Low doses of ASA (75-100 mg/d) were used in CVD prevention; however, ultra-low doses (30 mg/d) can also reduce thrombosis. EPA-to-DHA ratio is also important with regard to efficacy. DHA is more effective in reducing blood pressure and modulating systemic inflammation; however, high-dose EPA can lower CVD events in high-risk individuals. Although current literature has yet to examine ASA and DHA in preventing CVD, such combination warrants further investigation. To increase adherence to ASA and n3 PUFA supplementation, combination dosage form may be required to improve outcomes.

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