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Microgels have been widely used for stabilizing emulsions due to their softness and stimulus responsiveness. Although ultrastable emulsions have been prepared by microgel nanoparticles, the role of electrostatic interactions on emulsion stability is still a controversial topic and further investigation of the effect of microgel deformability is required. In the present study, neutral poly(N-vinylcaprolactam) (PVCL) and charged poly(N-vinylcaprolactam)-co-methacrylic acid (P(VCL-co-MAA)) microgels were synthesized and further used as emulsifiers to stabilizing emulsion. The P(VCL-co-MAA) microgel has a swelling ratio larger than that of the PVCL microgel in water. The nanomechanical properties of the microgels in water were characterized by atomic force microscopy with using the tip of different radii. The result reveals that the P(VCL-co-MAA) microgel is more deformable than the PVCL counterpart. Stability tests of the emulsions showed that below the volume phase transition temperature (VPTT) of the microgels, both microgel types can stabilize the emulsions under various conditions. Unexpectedly, most of the emulsions still remain stable above the VPTT. Further increasing the temperature to 60 °C, P(VCL-co-MAA) microgel emulsions remained stable at a pH value above the pKa of MAA while the emulsion was unstable below the pKa. However, phase separation occurs in PVCL microgel-stabilized emulsions at 60 °C. These results demonstrate that electrostatic repulsion and deformability of the microgels can enhance the emulsion stability, providing insights into the rational design and preparation of ultrastable Pickering emulsions.
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Cardiovascular diseases (CVDs) are a major global health concern, and oxidative stress is known to play a central role in their pathogenesis. The identification of new agents capable of inhibiting oxidative stress presents a promising strategy for preventing and treating CVDs. Natural products and their derivatives offer a valuable source for drug discovery, and isosteviol, a readily available natural product, is known to exhibit cardioprotective effects. In this study, 22 new D-ring modified isosteviol derivatives were synthesized and evaluated for their cardioprotective effect inâ vivo using the zebrafish cardiomyopathy model. The findings revealed that derivative 4e exhibited the most potent cardioprotective effect, surpassing its parent compound isosteviol and the positive drug levosimendan. At 1â µM, derivative 4e significantly protected the cardiomyocytes from injury, while at 10â µM it effectively maintained normal heart phenotypes, preventing cardiac dysfunction in zebrafish. Further investigation demonstrated that 4e protected cardiomyocytes from oxidative stress-induced damage by inhibiting reactive oxygen species overaccumulation, activating superoxide dismutase 2 expression, and enhancing the endogenous antioxidant defense system. These results suggest that isosteviol derivatives, particularly 4e, have the potential to serve as a novel class of cardioprotective agents for the prevention and treatment of CVDs.
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Cardiotônicos , Diterpenos do Tipo Caurano , Estresse Oxidativo , Animais , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Diterpenos do Tipo Caurano/farmacologia , Diterpenos do Tipo Caurano/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Peixe-ZebraRESUMO
Steviol is an ent-kaurene diterpenoid with interesting pharmacological activity. Several steviol derivatives with an exo-methylene cyclopentanone unit were discovered as potent antitumor agents. However, their poor selectivity for tumor cells relative to normal cells reduces their prospects as potential anticancer drugs. In this study, based on previous work, 32 steviol derivatives, including 28 new analogues, were synthesized. Their cytotoxicity against tumor cells and normal cells was evaluated. Several new derivatives, such as 7a, 7h, and 8f, with improved cytotoxic selectivity and antiproliferative activity were obtained, and the structure-activity relationship correlations were investigated. The new compound 8f displayed potent antiproliferative activity against Huh7 cells (IC50 = 2.6 µM) and very weak cytotoxicity against the corresponding normal cells HHL5 (IC50 = 97.0 µM). Further investigation showed that 8f arrested the cell cycle at the G0/G1 phase and caused reactive oxygen species overproduction, decreased mitochondrial membrane potential, and induced apoptosis of Huh7 cells through inhibition of the PI3K/Akt/mTOR and NF-κB pathway as well as upregulation of Bax/Bcl-2 ratio. The present study suggested that 8f is a promising lead compound for new cancer therapies, and the results presented herein may encourage the further modification of steviol for additional derivatives with enhanced efficacy and selectivity.
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Antineoplásicos , Diterpenos do Tipo Caurano , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Diterpenos do Tipo Caurano/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Fosfatidilinositol 3-Quinases , Relação Estrutura-AtividadeRESUMO
Cardiovascular diseases (CVDs) remain the leading cause of death globally. Inhibiting ferroptosis and thus preventing cardiac cell death is a promising and effective strategy for cardiomyopathy prevention and therapy. Steviol, an ent-kaurene diterpenoid, possesses broad-spectrum bioactivity. In the present study, with the aim to discover new agents for CVDs treatment, 30 derivatives of steviol, including 22 new ones, were synthesized, and evaluated their protective activity in vivo using the doxorubicin (DOX) induced zebrafish cardiomyopathy model. Our results firstly demonstrated that steviol has promising cardioprotective activity and further modification of steviol can greatly improve the activity. Among the new derivatives, 16d and 16e show the most potent activity. Both 16d (1 µM) and 16e (0.1 µM) effectively maintain the normal heart shape and prevent the cardiac dysfunction impaired by DOX in zebrafish. Their therapeutic efficacy is much superior to the parent natural product, steviol, and positive drug, levosimendan. Further study demonstrated that 16d and 16e inhibit DOX-induced ferroptosis and thus protect cardiomyopathy, by suppressing the glutathione depletion, iron accumulation, and lipid peroxidation, decreasing reactive oxygen species overaccumulation, and restoring the mitochondrial membrane potential. Consequently, due to their unique structure and significant cardioprotective activity with ferroptosis inhibition, new steviol derivatives 16d and 16e merit further research for the development of new cardioprotective drug candidates.
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Cardiomiopatias , Diterpenos do Tipo Caurano , Ferroptose , Animais , Peixe-Zebra , Diterpenos do Tipo Caurano/farmacologia , Diterpenos do Tipo Caurano/uso terapêutico , Doxorrubicina/farmacologia , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/prevenção & controleRESUMO
Trimetazidine exhibits great therapeutic potential in cardiovascular diseases and mitochondria-mediated cardioprotection by trimetazidine has been widely reported. In this study, to enhance its cardioprotection, the triphenylphosphonium-based modification of trimetazidine was conducted to deliver it specifically to mitochondria. Fifteen triphenylphosphonium (TPP) conjugated trimetazidine analogs were designed and synthesized. Their protective effects were evaluated inâ vivo using a tert-butyl hydroperoxide (t-BHP) induced zebrafish injury model. Structure-activity relationship correlations revealed the best way to couple the TPP moiety to trimetazidine, and led to a new conjugate (18a) with enhanced therapeutic properties. Compared to trimetazidine, 18a effectively protects against heart injury in the zebrafish model at a much lower concentration. Further study in t-BHP treated zebrafish and H9c2 cells demonstrated that 18a protects against cardiomyocyte death and damage by inhibiting excessive production of ROS, maintaining mitochondrial morphology, and preventing mitochondrial dysfunction. Consequently, 18a can be regarded as a potential therapeutic agent for cardioprotection.
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Trimetazidina , Animais , Mitocôndrias , Miócitos Cardíacos , Trimetazidina/metabolismo , Trimetazidina/farmacologia , Trimetazidina/uso terapêutico , Peixe-Zebra , terc-Butil Hidroperóxido/farmacologiaRESUMO
We conducted a systematic review and meta-analysis to evaluate the effect of Berberine on glucose in patients with type 2 diabetes mellitus and identify potential factors may modifying the hypoglycemic effect. We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database to identify randomized controlled trials that investigated the effect of Berberine. We calculated weighted mean differences (WMD) and 95% confidence interval (CI) for fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and glycated haemoglobin (HbA1c) levels. Twenty-eight studies were identified for analysis, with a total of 2,313 type 2 diabetes mellitus (T2DM) patients. The pool data showed that Berberine treatment was associated with a better reduction on FPG (WMD = -0.54 mmol/L, 95% CI: -0.77 to -0.30), PPG (WMD = -0.94 mmol/L, 95% CI: -1.27 to -0.61), and HbA1c (WMD = -0.54 mmol/L, 95% CI: -0.93 to -0.15) than control groups. Subgroup-analyses indicated that effects of Berberine on blood glucose became unremarkable as the treatment lasted more than 90 days, the daily dosage more than 2 g/d and patients aged more than 60 years. The efficiency of Berberine combined with hypoglycaemics is better than either Berberine or hypoglycaemic alone. The dosage and treatment duration of Berberine and patients' age may modify the effect.
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Berberina/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Quimioterapia Combinada , Jejum/metabolismo , Humanos , Período Pós-PrandialRESUMO
The construction of state-of-the-art hole-transporting materials (HTMs) is challenging regarding the appropriate molecular configuration for simultaneously achieving high morphology uniformity and charge mobility, especially because of the lack of appropriate building blocks. Herein a semi-locked tetrathienylethene (TTE) serves as a promising building block for HTMs by fine-tuning molecular planarity. Upon incorporation of four triphenylamine groups, the resulting TTE represents the first hybrid orthogonal and planar conformation, thus leading to the desirable electronic and morphological properties in perovskite solar cells (PSCs). Owing to its high hole mobility, deep lying HOMO level, and excellent thin film quality, the dopant-free TTE-based PSCs exhibit a very promising efficiency of over 20 % with long-term stability, achieving to date the best performances among dopant-free HTM-based planar n-i-p structured PSCs.
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BACKGROUND: While vaccination remains the most effective method to control hepatitis B virus (HBV) infection, 5-10% of recipients exhibit non-responsiveness to the HB vaccine. Immunological analysis of strong, weak or absent protective antibody responses to the HB vaccine should provide insights into the mechanisms that contribute to non-responsiveness. RESULTS: We investigated the potential involvement of follicular helper T (Tfh) cells in the immune response to HB vaccine, and associations between the miR-17-92 cluster and Tfh cells. We recruited 12 adults who had completed the HB vaccination course during childhood. Following a booster dose of HB vaccine, hepatitis B surface antibody (HBsAb) titers, percentage of PD-1+ICOS+ circulating Tfh (cTfh) and plasma cells, and expression of miR-17-92 were assessed at baseline (before immunization) and after vaccination on days 7 and 14. Notably, the HBsAb level gradually increased after HB vaccination while the proportion of PD-1+ICOS+ cTfh cells was significantly increased on day 7 relative to baseline, so as plasma cells. Expression of miR-18a and miR-17 within the miR-17-92 cluster and HBsAb titers in CD4+ T cells were positively correlated with the PD-1+ICOS+ cTfh cells proportions after HB vaccination. CONCLUSIONS: The increase in HBsAb titers was positively associated with expression of all the components of the miR-17-92 cluster except miR-19a. Our findings indicate that the miR-17-92 cluster contributes to antibody production, and miR-18a and miR-17 are involved in Tfh cells differentiation after HB vaccination.
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Linfócitos T CD4-Positivos/imunologia , Vacinas contra Hepatite B/imunologia , Hepatite B/prevenção & controle , MicroRNAs/imunologia , Adulto , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , China , Estudos de Coortes , Feminino , Anticorpos Anti-Hepatite B/sangue , Humanos , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Masculino , Receptor de Morte Celular Programada 1/imunologia , VacinaçãoRESUMO
BACKGROUND: No previous study has evaluated disability in older persons according to the International Classification of Functioning, Disability and Health Framework guidelines. We conducted a more comprehensive investigation of disability and associated factors among older adults receiving home-based care in rural Dongguan, a city in the central Guangdong Province of Southern China. METHODS: A total of 819 individuals aged ≥60 years were recruited from Dongguan home-based care system of via a two-stage selection process. We interviewed participants and assessed their ability level using the Ability Assessment for Older Adults, which defined by a combination of activity of daily living, sensory perception, mental status and social involvement. Conditional probability and Logistic regression approaches were used to assess the strength of association between each pair of conditions. Factors significantly associated with disability were identified via χ2 tests and multinomial ordinal logistic regression. RESULTS: Of the 819 included participants (mean age 87 ±4.7 years), 75.5% were female, 76.7% had any disability, and 62.3% had a mild disability. The occurrence of any deficits significantly increased the likelihood of the co-occurrence of other deficits (odds ratio [OR] > 1, P < 0.05), with the lowest prevalence odds ratio observed among individuals with sensory and communication deficiency (OR: 2.99; 95% confidence interval [CI]: 2.21-4.05). Multivariable ordinal logistic regression analysis indicated that physical activity (OR: 0.96; 95% CI: 0.93-0.99), sedentary behavior (OR: 1.25; 95% CI: 1.13-1.38), not watching television (OR: 1.7; 95% CI: 1.07-2.72) and age (OR: 1.09; 95% CI: 1.02-1.17) were significantly associated with disability. CONCLUSIONS: Impairment of ADL, sensory perception, mental status or social involvement increased the likelihood of risk of the co-occurrence of other deficits. Comprehensive disability among older adults receiving home-based care is associated with age, sedentariness, physical activity and TV viewing.
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Avaliação da Deficiência , Serviços de Assistência Domiciliar , Serviços de Saúde Rural , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Exercício Físico , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Comportamento Sedentário , Fatores Socioeconômicos , TelevisãoRESUMO
As a two-dimensional (2D) material, palladium diselenide (PdSe2) has attracted extensive research attention due to its unique asymmetric crystal structure and extraordinary optoelectronic properties, showing great potential in electronic, optoelectronic, and other application fields. Thinner PdSe2 exhibits semiconductor properties, while the photoresponse of the photodetectors based on this film is weaker. Although increasing the thickness of the PdSe2 film can improve the photoresponse, thicker PdSe2 exhibits metallic-like properties, which is not conducive to the formation of the heterojunction. In this work, a PdSe2 2D material with a quantum island structure is prepared by a simple thermal-assisted conversion method. A new type of photodetector with a PdSe2/n--Si/n+-Si vertical PIN-like structure is innovatively proposed. Broad spectral absorption from 532 to 2200 nm and a high rectification ratio (106) of the device are achieved. The introduced n--Si layer concentrates the electric field in the depletion region, thereby shortening the transit time and accelerating the separation and collection of the carriers, resulting in the enhancement of the responsivity and 3 dB frequency compared to the traditional device with a PN structure. A recorded highest 3 dB frequency of â¼25 kHz is achieved for the PdSe2 2D-3D PIN-like device.
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ETHNOPHARMACOLOGICAL RELEVANCE: Tea (Camellia sinensis) is a favorite drink worldwide. Tea extracts and green tea main component (-)-epigallocatechin gallate (EGCG) are recommended for various vascular diseases. Anji white tea is a very popular green tea. Its vascular effect profile, the mechanisms, and the contribution of EGCG to its integrated effect need elucidation. AIM: To characterize the vasomotion effects of Anji white tea and EGCG, and to explore possible involvement of voltage-gated Ca2+ channels (VGCCs) and voltage-gated K+ (Kv) channels in their vasomotion effects. MATERIALS AND METHODS: Anji white tea water soaking solution (AJWT) was prepared as daily tea-making process and concentrated to a concentration amounting to 200 mg/ml of dry tea leaves. The tension of rat arteries including aorta, coronary artery (RCA), cerebral basilar artery (CBA), intrarenal artery (IRA), intrapulmonary artery (IPA) and mesenteric artery (MA) was recorded with myographs. In arterial smooth muscle cells (ASMCs) freshly isolated from RCA, the levels of intracellular Ca2+ were measured with Ca2+-sensitive fluorescent probe fluo 4-AM, and Kv currents were recorded with patch clamp. The expressions of VGCCs and Kv channels were assayed with RT-qPCR and immunofluorescence staining. RESULTS: At 0.4-12.8 mg/ml of dry tea leaves, AJWT profoundly relaxed all tested arteries precontracted with various vasoconstrictors about half with a small transient potentiation on the precontractions before the relaxation. KCl-induced precontraction was less sensitive than precontractions induced by phenylephrine (PE), U46619 and serotonin (5-HT). IPA was less sensitive to the relaxation compared with other arteries. AJWT pretreatment for 1 h, 24 h and 72 h time-dependently inhibited the contractile responses of RCAs. In sharp contrast, at equivalent concentrations according to its content in AJWT, EGCG intensified the precontractions in most small arteries, except that it induced relaxation in PE-precontracted aorta and MA, U46619-precontracted aorta and CBA. EGCG pretreatment for 1 h and 24 h did not significantly affect RCA contractile responses. In RCA ASMCs, AJWT reduced, while EGCG enhanced, intracellular Ca2+ elevation induced by depolarization which activates VGCCs. Patch clamp study showed that both AJWT and EGCG reduced Kv currents. RT-qPCR and immunofluorescence staining demonstrated that both AJWT and EGCG reduced the expressions of VGCCs and Kv channels. CONCLUSION: AJWT, but not EGCG, consistently induces vasorelaxation. The vasomotion effects of either AJWT or EGCG vary with arterial beds and vasoconstrictors. Modulation of VGCCs, but not Kv channels, contributes to AJWT-induced vasorelaxation. It is suggested that Anji white tea water extract instead of EGCG may be a promising food supplement for vasospastic diseases.
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Catequina/análogos & derivados , Miócitos de Músculo Liso , Chá , Ratos , Animais , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/metabolismo , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Vasodilatação , Vasos Coronários , Artérias Mesentéricas , Vasoconstritores/farmacologia , Água/farmacologiaRESUMO
Few research discuss whether the body measurement indexs of obesity in general populations is applicable to patients with type 2 diabetes. We explore the optimal cutoffs of visceral fat area (VFA) and subcutaneous fat area (SFA) in the diagnosis of central obesity and the cutoffs of corresponding waist circumference (WC) and body mass index (BMI) in patients with Type 2 Diabetes (T2D). Cross-sectional cohort study. 1057 patients with T2D (550 males and 507 females) aged 18 or above that satisfied the criteria were included. The definition and diagnostic criteria of Metabolic syndrome (Mets) were analyzed according to the 2020 Chinese Diabetes Society (CDS) Guideline. The VFA and SFA were measured by bioelectrical impedance analysis (BIA). The optimal VFA and SFA cutoffs and corresponding WC and BMI when two or more nonadipose components of MetS (without central obesity) were met were analyzed by ROC curve. Among all of the T2D patients, the optimal VFA cutoff for identifying two or more nonadipose components of MetS was 73.30 cm2 for females and 69.20 cm2 for males, while the optimal SFA cutoff was 186.70 cm2 for females and 123.30 cm2 for males. The ROC area under curve (AUC) of VFA for identifying two or more nonadipose components of MetS was higher than that of SFA (Female: 0.65 vs. 0.58, P = 0.01). The VFA cutoff of newly diagnosed T2D patients (females = 86.10 cm2, males = 69.00 cm2) was higher than that of non-newly diagnosed T2D patients (females = 73.30 cm2, males = 65.40 cm2). A stratification analysis of gender and whether newly diagnosed with T2D or not showed that the WCs corresponding to VFA were 85.00 cm and BMI was about 24.00 kg/m2. VFA measured by BIA can be a non-invasive method to detect central obesity in patients with T2D, the corresponding WC were 85.00 cm and BMI was 24.00 kg/m2.
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Diabetes Mellitus Tipo 2 , Síndrome Metabólica , Masculino , Humanos , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/metabolismo , Estudos Transversais , Obesidade/metabolismo , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/metabolismo , Índice de Massa Corporal , Gordura Intra-Abdominal/metabolismo , Circunferência da Cintura , Fatores de RiscoRESUMO
Fourier transform infrared (FTIR) microspectroscopy technology is the combination of the FTIR spectrometer and the microscope. This technology is of simple preparation of the samples, can be used in micro-area analysis and micro-samples, and reflect the nature of the samples spectra. Panax ginseng include mountain cultivated ginseng (MCG), garden cultivated ginseng (GCG) and mountain wild ginseng (MWG), but the excavation of MWG is prohibited in China. So, only MCG and GCG were collected and recorded in Chinese pharmacopoeia. In this study, we developed a discriminant analysis (DA) method for recognition of MCG and GCG using FTIR microspectroscopy technology. Twenty MCG samples and twenty four GCG samples were obtained, and their spectra of IR microspectroscopy were collected. Then 33 samples were randomly selected into calibration set and the remaining 11 of the samples were selected into validation set. The authors optimized the pretreatment method, the principal components, the modeling region and the scanning parts when developing the models. The optimized model of discriminant analysis was developed using the pretreatment multiplicative scatter correction (MSC) + Savitzky-Golay filter (SG) smoothing, the region 3 932.14-669.18 cm(-1), 4 principal components and the rhizome part. The accuracy of the optimized model got up to 100%. The result demonstrated that infrared microspectroscopy technology combined with DA is of simple operation, rapid, nondestructive and effective, and can be applied to recognize MCG and GCG.
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Panax/classificação , Espectroscopia de Infravermelho com Transformada de Fourier , China , Análise DiscriminanteRESUMO
In this paper, betaine (Bet) was used as a hydrogen bond acceptor (HBA), and acrylic acid (AA) and acrylamide (AM) were used as hydrogen bond donors (HBD) and mixed to form a deep eutectic solvent (DES). Different concentrations of ß-cyclodextrin (ß-CD) were dispersed in the DES, and a novel ß-CD/P(AA-co-AM) hydrogel was prepared by frontal polymerization (FP). The characteristic structure and morphology of the hydrogels were analyzed using Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM), and the properties of the hydrogels were investigated. The results show that the mechanical properties of the hydrogel were improved by ß-CD acting as a second cross-linking agent in the polymerization process, thus increasing the cross-link density of the hydrogel. Because the carboxyl groups contained in the acrylic acid dissociate under alkaline conditions, the composite hydrogel shows excellent pH responsiveness under alkaline conditions. Tetracycline hydrochloride was used as a drug model to test the drug loading and drug release performance of the hydrogels. With the increase of ß-CD content, the loading capacity of the hydrogels for tetracycline hydrochloride gradually increased. The data of drug release indicated that the hydrogel has good drug delivery performance and has promising applications in drug delivery systems and other areas.
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Glutamate-induced oxidative stress is well-known to play a crucial role in the development of neurodegenerative diseases, such as stroke. Genipin, a natural iridoid compound, has demonstrated potential neuroprotective properties but is unstable in physiological conditions. The present study aimed to develop new derivatives of genipin that exhibit improved stability and activity for the treatment of stroke. Nineteen new derivatives were thus designed and synthesized. Their neuroprotective effect against glutamate-induced injury was evaluated in HT22 cells. Among the newly synthesized derivatives, 3e demonstrated significantly greater neuroprotection and improved stability compared to genipin. Specifically, 0.01 µM of 3e was found to effectively attenuate glutamate-induced oxidative damage by inhibiting ROS over-accumulation, reducing MDA content, and restoring the endogenous antioxidative system. Further investigation revealed that 3e inhibited oxidative stress by downregulating the phosphorylation levels of p38 MAPK and activating Nrf2 and HO-1 proteins. These results suggested that 3e has the potential to serve as a promising candidate for the treatment of stroke by protecting against glutamate-induced oxidative stress.
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Ácido Glutâmico , Fármacos Neuroprotetores , Ácido Glutâmico/toxicidade , Ácido Glutâmico/metabolismo , Fármacos Neuroprotetores/farmacologia , Linhagem Celular , Estrutura Molecular , Estresse Oxidativo , Iridoides/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismoRESUMO
As modern medicine began to emerge at the turn of the 20th century, glycan-based therapies advanced. DNA- and protein-centered therapies became widely available. The research and development of structurally defined carbohydrates have led to new tools and methods that have sparked interest in the therapeutic applications of glycans. One of the latest omics disciplines to emerge in the contemporary post-genomics age is glycomics. In addition, to providing hope for patients and people with different health conditions through a deeper understanding of the mechanisms of common complex diseases, this new specialty in system sciences has much to offer to communities involved in the development of diagnostics and therapeutics in medicine and life sciences.This review focuses on recent developments that have pushed glycan-based therapies into the spotlight in medicine and the technologies powering these initiatives, which we can take as the most significant success of the 21st century.
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Carboidratos , Glicômica , Humanos , Polissacarídeos , Genômica , ProteínasRESUMO
Deep eutectic solvent (DES) was prepared by using acrylic acid (AA) and acrylamide (AM) as hydrogen bonding donors (HBD) and choline chloride (ChCl) as hydrogen bonding receptors (HBA). Nitrogen-doped carbon nanotubes (N-CNTs) were dispersed in DES as fillers, and N-CNTs/P(AA-co-AM) composite hydrogels were prepared by FP. The interaction mode between the hydrogel and N-CNTs was characterized by Fourier infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The mechanical properties, pH response and electrical conductivity of the composite hydrogels were studied. The results showed that the mechanical properties of the hydrogel were significantly enhanced with the increase of N-CNT content. The tensile strength and compressive strength of the FP4 composite hydrogel reached 5.42 MPa and 4.29 MPa, respectively. Due to the dissociation of carboxyl groups in AA in an alkaline environment the composite hydrogel showed excellent pH response performance. The conductivity of the hydrogel was also found to be improved with the content of N-CNTs. When the content of N-CNTs is 1.0 wt%, the conductivity of the hydrogel was 4.2 times higher than that of the hydrogel without N-CNTs, and connecting it to a circuit can make an LED lamp emit bright light. In this study, a simple and green method was proposed to prepare composite hydrogels with excellent mechanical properties and electrical conductivity by FP of DES in less than 5 min.
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A deep eutectic solvent (DES) was synthesized from urea (U), acrylamide (AM), and choline chloride (ChCl). ZnO was dispersed in the DES as a filler, and nanocomposite hydrogels (ZnO/P(U-AM-ChCl)) were successfully prepared by frontal polymerization (FP). The hydrogels were verified by Fourier infrared spectroscopy to contain ZnO nanoparticles (ZnO-NPs). The swelling behaviour, conductivity, and antibacterial properties of the ZnO nanocomposite hydrogels were investigated. The results showed that the ZnO/P(U-AM-ChCl) hydrogels had excellent antibacterial properties and exhibited super high inhibition rates of 81.87% and 88.42% against two basic colonies of Gram-negative and Gram-positive bacteria, respectively. The equilibrium swelling of the hydrogels was found to increase significantly from 9.30 to 12.29 with the addition of ZnO, while the ZnO/P(U-AM-ChCl) hydrogel conductivity exhibited good UV sensitivity. This study provides a rapid and low-energy method for the preparation of nanocomposite hydrogels with excellent antibacterial properties.
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A series of mitochondria-targeted triphenylphosphonium conjugated C-3 modified betulin were synthesized and evaluated against tumor cells. As a result, a new derivative 13 i, the conjugate of 3-O-(3'-acetylphenylacetate)-betulin with triphenylphosphonium, was identified as the one with the best anti-tumor effect. Conjugate 13 i significantly inhibited HCT116 cells with IC50 at 0.66â µM. While betulin, C-3 modified betulin, and the triphenylphosphonium moiety showed no inhibition of HCT116â cell proliferation at 20â µM. More importantly, 13 i exhibited a more cytotoxic effect against the tumor cell HCT116 than normal cell NCM460. Mode of action studies demonstrated that 13 i induced the G2/M phase cell cycle arrest and apoptosis in HCT116 cells through the mitochondrial pathway. Structure-activity relationship analysis revealed that integration of triphenylphosphonium moiety into the C-28 of betulin can greatly improve cytotoxicity. Appropriate modification on C-3 of the conjugate would improve the selectivity.
Assuntos
Antineoplásicos/farmacologia , Mitocôndrias/efeitos dos fármacos , Compostos Organofosforados/farmacologia , Triterpenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Mitocôndrias/metabolismo , Estrutura Molecular , Compostos Organofosforados/química , Relação Estrutura-Atividade , Triterpenos/químicaRESUMO
BACKGROUND: Severe acidosis deteriorates cardiac injury. Rat coronary arteries (RCAs) are unusually hypercontractive to extracellular (o) acidosis (EA). TMEM16A-encoded anoctamin 1 (ANO1), a Ca2+-activated chloride channel (CaCC), plays an important role in regulating coronary arterial tension. PURPOSE: We tested the possibility that the activation of CaCCs in the arterial smooth muscle cell (ASMC) contributes to EA-induced RCA constriction. METHODS: ANO1 expression was detected with immunofluorescence staining and Western blot. TMEM16A mRNA was assessed with quantitative Real-Time PCR. Cl- currents and membrane potentials were quantified with a patch clamp. The vascular tension was recorded with a myograph. Intracellular (i) level of Cl- and Ca2+ was measured with fluorescent molecular probes. RESULTS: ANO1 was expressed in all tested arterial myocytes, but was much more abundant in RCA ASMCs as compared with ASMCs isolated from rat cerebral basilar, intrarenal and mesenteric arteries. EA reduced [Cl-]i levels, augmented CaCC currents exclusively in RCA ASMCs and depolarized RCA ASMCs to a greater extent. Cl- deprivation, which depleted [Cl-]i by incubating the arteries or their ASMCs in Cl--free bath solution, decreased EA-induced [Cl-]i reduction, diminished EA-induced CaCC augmentation and time-dependently depressed EA-induced RCA constriction. Inhibitor studies showed that these EA-induced effects including RCA constriction, CaCC current augmentation, [Cl-]i reduction and/or [Ca2+]i elevation were depressed by various Cl- channel blockers, [Ca2+]i release inhibitors and L-type voltage-gated Ca2+ channel inhibitor nifedipine. ANO1 antibody attenuated all observed changes induced by EA in RCA ASMCs. CONCLUSION: The greater activity of RCA ASMC CaCCs complicated with an enhanced Ca2+ mobilization from both [Ca2+]i release and [Ca2+]o influx plays a pivotal role in the distinctive hypercontractility of RCAs to acidosis. Translation of these findings to human beings may lead to a new conception in our understanding and treating cardiac complications in severe acidosis.