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1.
Life Sci ; 346: 122629, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38631667

RESUMO

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs from other forms of cell death, such as apoptosis and necrosis. Molecular therapeutics have hard time playing the long-acting role of ferroptosis induction due to their limited water solubility, low cell targeting capacity, and quick metabolism in vivo. To this end, small molecule inducers based on biological factors have long been used as strategy to induce cell death. Research into ferroptosis and advancements in nanotechnology have led to the discovery that nanomaterials are superior to biological medications in triggering ferroptosis. Nanomaterials derived from iron can enhance ferroptosis induction by directly releasing large quantities of iron and increasing cell ROS levels. Moreover, utilizing nanomaterials to promote programmed cell death minimizes the probability of unfavorable effects induced by mutations in cancer-associated genes such as RAS and TP53. Taken together, this review summarizes the molecular mechanisms involved in ferroptosis along with the classification of ferroptosis induction. It also emphasized the importance of cell organelles in the control of ferroptosis in cancer therapy. The nanomaterials that trigger ferroptosis are categorized and explained. Iron-based and noniron-based nanomaterials with their characterization at the molecular and cellular levels have been explored, which will be useful for inducing ferroptosis that leads to reduced tumor growth. Within this framework, we offer a synopsis, which traverses the well-established mechanism of ferroptosis and offers practical suggestions for the design and therapeutic use of nanomaterials.


Assuntos
Ferroptose , Nanoestruturas , Neoplasias , Ferroptose/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Animais , Simulação de Dinâmica Molecular , Ferro/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
2.
Cell Biochem Biophys ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483755

RESUMO

Nucleoside analogs are a common form of chemotherapy that disrupts DNA replication and repair, leading to cell cycle arrest and apoptosis. Reactive oxygen species (ROS) production is a significant mechanism through which these drugs exert their anticancer effects. This study investigated a new nucleoside analog called FNC or Azvudine, and its impact on ROS production and cell viability in Dalton's lymphoma (DL) cells. The study found that FNC treatment resulted in a time- and dose-dependent increase in ROS levels in DL cells. After 15 and 30 min of treatment with 2 and 1 mg/ml of FNC, mitochondrial ROS production was observed in DL cells. Furthermore, prolonged exposure to FNC caused structural alterations and DNA damage in DL cells. The results suggest that FNC's ability to impair DL cell viability may be due to its induction of ROS production and indicate a need for further investigation.

3.
Discov Oncol ; 15(1): 16, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38252337

RESUMO

PURPOSE: T-cell lymphomas, refer to a diverse set of lymphomas that originate from T-cells, a type of white blood cell, with limited treatment options. This investigation aimed to assess the efficacy and mechanism of a novel fluorinated nucleoside analogue (FNA), 2'-deoxy-2'-ß-fluoro-4'-azidocytidine (FNC), against T-cell lymphoma using Dalton's lymphoma (DL)-bearing mice as a model. METHODS: Balb/c mice transplanted with the DL tumor model received FNC treatment to study therapeutic efficacy against T-cell lymphoma. Behavioral monitoring, physiological measurements, and various analyses were conducted to evaluate treatment effects for mechanistic investigations. RESULTS: The results of study indicated that FNC prevented DL-altered behavior parameters, weight gain and alteration in organ structure, hematological parameters, and liver enzyme levels. Moreover, FNC treatment restored organ structures, attenuated angiogenesis, reduced DL cell viability and proliferation through apoptosis. The mechanism investigation revealed FNC diminished MMP levels, induced apoptosis through ROS induction, and activated mitochondrial-mediated pathways leading to increase in mean survival time of DL mice. These findings suggest that FNC has potential therapeutic effects in mitigating DL-induced adverse effects. CONCLUSION: FNC represents an efficient and targeted treatment strategy against T-cell lymphoma. FNC's proficient ability to induce apoptosis through ROS generation and MMP reduction makes it a promising candidate for developing newer and more effective anticancer therapies. Continued research could unveil FNC's potential role in designing a better therapeutic approach against NHL.

4.
Cell Biochem Biophys ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253918

RESUMO

Cytotoxic nucleoside analogs (NAs) hold great promise in cancer therapeutics by mimicking endogenous nucleosides and interfering with crucial cellular processes. Here, we investigate the potential of the novel cytidine analog, 4'-azido-2'-deoxy-2'-fluoro(arbino)cytidine (FNC), as a therapeutic agent for Non-Hodgkin lymphoma (NHL) using Dalton's lymphoma (DL) as a T-cell lymphoma model. FNC demonstrated dose- and time-dependent inhibition of DL cell growth and proliferation. IC-50 values of FNC were measured at 1 µM, 0.5 µM, and 0.1 µM after 24, 48, and 72 h, respectively. Further elucidation of FNC's mechanism of action uncovers its role in inducing apoptosis in DL cells. Notable DNA fragmentation and nuclear condensation point to activated apoptotic pathways. FNC-induced apoptosis was concomitant with changes in cellular membranes, characterized by membrane rupture and altered morphology. The robust anticancer effects of FNC are linked to its capacity to induce reactive oxygen species (ROS) production, prompting oxidative stress-mediated apoptosis. Additionally, FNC disrupted mitochondrial membrane potential (MMP), leading to mitochondrial dysfunction, further promoting apoptosis. Dysregulation of apoptotic genes, with upregulation of Bax and downregulation of Bcl-2 and Bcl-xl, implicates the mitochondrial-mediated apoptosis pathway. Furthermore, FNC-induced G2/M phase cell cycle arrest was mediated through modulation of the cell cycle inhibitor p21. Overall, this study highlights the potential of FNC as a promising therapeutic agent for NHL.

5.
Curr Drug Res Rev ; 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37605475

RESUMO

BACKGROUND: Nigella sativa (N. sativa), commonly known as black seed or black cumin, belongs to the family Ranunculaceae. It contains several phytoconstituents, thymoquinone (TQ), thymol, thymohydroquinone, carvacrol, and dithymoquinone. TQ is the main phytoconstituent present in N. sativa that is used as an herbal compound, and it is widely used as an antihypertensive, liver tonic, diuretic, digestive, anti-diarrheal, appetite stimulant, analgesic, and antibacterial agent, and in skin disorders. OBJECTIVE: The study focused on collecting data on the therapeutic or pharmacological activities of TQ present in N. sativa seed. METHODS: Antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, antiinflammatory, hepato-protective, renal protective, and antioxidant properties of TQ have been studied by various scientists. CONCLUSION: TQ seems to have a variety of consequences on how infected cells behave at the cellular level.

6.
Asian Pac J Cancer Prev ; 24(6): 2157-2170, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37378948

RESUMO

OBJECTIVES: The present study aimed to provide an insight into the acute toxicity of a novel fluorinated nucleoside analogue (FNA), FNC (Azvudine or2'-deoxy-2'-ß-fluoro-4'-azidocytidine). FNC showed potent anti-viral and anti-cancer activities and approved drug for high-load HIV patients, despite, its acute toxicity study being lacking. MATERIALS AND METHODS: OECD-423 guidelines were followed during this study and the parameters were divided into four categories - behavioral parameters, physiological parameters, histopathological parameters, and supplementary tests. The behavioral parameters included feeding, body weight, belly size, organ weight and size, and mice behavior. The physiological parameters consisted of blood, liver, and kidney indicators. In histopathological parameters hematoxylin and eosin staining was performed to analyse the histological changes in the mice organs after FNC exposure. In addition, supplementary tests were conducted to assess cellular viability, DNA fragmentation and cytokine levels (IL-6 and TNF-α) in response to FNC. RESULTS: In the behavioral parameters FNC induced changes in the mice-to-mice interaction and activities. Mice's body weight, belly size, organ weight, and size remained unchanged. Physiological parameters of blood showed that FNC increased the level of WBC, RBC, Hb, and neutrophils and decreased the % count of lymphocytes. Liver enzymes SGOT (AST), and ALP was increased. In the renal function test (RFT) cholesterol level was significantly decreased. Histopathological analysis of the liver, kidney, brain, heart, lungs, and spleen showed no sign of tissue damage at the highest FNC dose of 25 mg/kg b.wt. Supplementary tests for cell viability showed no change in viability footprint, through our recently developed dilution cum-trypan (DCT) assay, and Annexin/PI. No DNA damage or apoptosis was observed in DAPI or AO/EtBr studies. Pro-inflammatory cytokines IL-6 and TNF-α increased in a dose-dependent manner. CONCLUSION: This study concluded that FNC is safe to use though higher concentration shows slight toxicity.


Assuntos
Infecções por HIV , Humanos , Camundongos , Animais , Camundongos Endogâmicos BALB C , Interleucina-6 , Fator de Necrose Tumoral alfa , Desoxicitidina , Peso Corporal
7.
Pharm Nanotechnol ; 11(1): 44-55, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36121090

RESUMO

BACKGROUND: Herbal preparations with low oral bioavailability have a fast first-pass metabolism in the gut and liver. To offset these effects, a method to improve absorption and, as a result, bioavailability must be devised. OBJECTIVE: The goal of this study was to design, develop, and assess the in vivo toxicity of polyherbal phytosomes for ovarian cyst therapy. METHODS: Using antisolvent and rotational evaporation procedures, phytosomes containing phosphatidylcholine and a combination of herbal extracts (Saraca asoca, Bauhinia variegata, and Commiphora mukul) were synthesized. For a blend of Saraca asoca, Bauhinia variegata, and Commiphora mukul, Fourier-transform infrared spectroscopy (FTIR), preformulation investigations, qualitative phytochemical screening, and UV spectrophotometric tests were conducted. Scanning electron microscopy (SEM), zeta potential, ex vivo release, and in vivo toxicological investigations were used to examine phytosomes. RESULTS: FTIR studies suggested no changes in descriptive peaks in raw and extracted herbs, although the intensity of peaks was slightly reduced. Zeta potential values between -20.4 mV to - 29.6 mV suggested stable phytosomes with an accepted particle size range. Percentage yield and entrapment efficiency were directly correlated to the amount of phospholipid used. Ex vivo studies suggested that the phytosomes with low content of phospholipids showed good permeation profiles. There was no difference in clinical indications between the extract-loaded phytosomes group and the free extract group in in vivo toxicological or histopathological examinations. CONCLUSION: The findings of current research work suggested that the optimized phytosomes based drug delivery containing herbal extracts as bioenhancers has the potential to improve the bioavailability of hydrophobic extracts.


Assuntos
Fosfolipídeos , Síndrome do Ovário Policístico , Feminino , Humanos , Fosfolipídeos/química , Fitossomas , Sistemas de Liberação de Medicamentos/métodos , Fosfatidilcolinas
8.
Curr Drug Res Rev ; 14(3): 225-238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35579127

RESUMO

BACKGROUND: Biochanin-A (5,7 dihydroxy 4 methoxy isoflavone) is a phytochemical phytoestrogen that is highly effective against various diseases. Biochanin-A is a nutritional and dietary isoflavonoid naturally present in red clover, chickpea, soybeans and other herbs. Biochanin- A possesses numerous biological activities. OBJECTIVE: The study focused on collective data of therapeutic activities of Biochanin-A. METHODS: According to the literature, biochanin-A revealed a range of activities starting from chemoprevention, by hindering cell growth, activation of tumor cell death, hampering metastasis, angiogenic action, cell cycle regulation, neuroprotection, by controlling microglial activation, balancing antioxidants, elevating the neurochemicals, suppressing BACE-1, NADPH oxidase hindrance to inflammation, by mitigating the MAPK and NF- κB, discharge of inflammatory markers, upregulating the PPAR-γ, improving the function of heme oxygenase-1, erythroid 2 nuclear factors, detoxifying the oxygen radicals and stimulating the superoxide dismutase action, and controlling its production of transcription factors. Against pathogens, biochanin-A acts by dephosphorylating tyrosine kinase proteins, obstructing gram-negative bacteria, suppressing the development of cytokines from viruses, and improving the action of a neuraminidase cleavage of caspase-3, and acts as an efflux pump inhibitor. In metabolic disorders, biochanin-A acts by encouraging transcriptional initiation and inhibition, activating estrogen receptors, and increasing the activity of differentiation, autophagy, inflammation, and blood glucose metabolism. CONCLUSION: Therefore, biochanin-A could be used as a therapeutic drug for various pathological conditions and treatments in human beings.


Assuntos
Produtos Biológicos , Isoflavonas , Humanos , Heme Oxigenase-1 , Caspase 3 , Antioxidantes/farmacologia , Fitoestrógenos/farmacologia , Espécies Reativas de Oxigênio , Receptores de Estrogênio , Neuraminidase , NF-kappa B/metabolismo , Inflamação , PPAR gama/metabolismo , Citocinas , Proteínas Tirosina Quinases , NADPH Oxidases , Superóxido Dismutase , Glucose
9.
J Control Release ; 346: 71-97, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35439581

RESUMO

The idea of employing natural cell membranes as a coating medium for nanoparticles (NPs) endows man-made vectors with natural capabilities and benefits. In addition to retaining the physicochemical characteristics of the NPs, the biomimetic NPs also have the functionality of source cell membranes. It has emerged as a promising approach to enhancing the properties of NPs for drug delivery, immune evasion, imaging, cancer-targeting, and phototherapy sensitivity. Several studies have been reported with a multitude of approaches to reengineering the surface of NPs using biological membranes. Owing to their low immunogenicity and intriguing biomimetic properties, cell-membrane-based biohybrid delivery systems have recently gained a lot of interest as therapeutic delivery systems. This review summarises different kinds of biomimetic NPs reported so far, their fabrication aspects, and their application in the biomedical field. Finally, it briefs on the latest advances available in this biohybrid concept.


Assuntos
Nanopartículas , Neoplasias , Membrana Celular/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fototerapia
10.
Planta ; 255(4): 88, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35304667

RESUMO

MAIN CONCLUSION: The review summarizes our advanced understanding of the heterotrimeric G-protein research from model plants and their emerging roles in modulating various plant architecture and agronomical traits in crop species. Heterotrimeric G-proteins (hereafter G-proteins), consisting of G-alpha (Gα), G-beta (Gß) and G-gamma (Gγ) subunits, are key signal transducers conserved across different forms of life. The discovery of plant lineage-specific G-protein components (extra-large G-proteins and type-C Gγ subunits), inherent polyploidy in angiosperms, and unique modes of G-protein cycle regulation in plants pointed out to a few fundamental differences of plant G-protein signaling from its animal counterpart. Over the last 2 decades, extensive studies in the model plant Arabidopsis thaliana have confirmed the involvement of G-proteins in a wide range of plant growth and development, and stress adaptation processes. The G-protein research in crop species, however, is still in its infancy, and a handful of studies suggest important roles of G-proteins in regulating plant architectural and key agronomical traits including plant's response to abiotic and biotic factors. We propose that the advancement made in plant G-proteins research will facilitate the development of novel approaches to manage plant yield and fitness in changing environments.


Assuntos
Arabidopsis , Proteínas Heterotriméricas de Ligação ao GTP , Animais , Arabidopsis/genética , Arabidopsis/metabolismo , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Proteínas Heterotriméricas de Ligação ao GTP/genética , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Desenvolvimento Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
11.
Drug Res (Stuttg) ; 72(1): 5-17, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34412126

RESUMO

Resveratrol (RSV), the most effective stilbene phytoalexin synthesized naturally or induced in plants as part of their defense mechanism, is a key component of natural phenolic compounds and is being considered as a treatment option for a variety of diseases. RSV was discovered in the skin of red grapes, mulberries, peanuts, pines, and Polygonum cuspidatum weed root extracts. It was first extracted from white hellebore (Veratrum grandiflorum O. Loes) roots in 1940, then from Polygonum cuspidatum roots in 1963. However, RSV's use as a drug is limited due to its initial conformational strength and poor stability. The research focused on a set of RSV biological activity data. RSV has been the subject of growing concern, despite its wide range of biological and therapeutic applications. According to the literature, RSV has antioxidant, anti-cancer, cardioprotective, neuroprotective, anti- inflammatory, anti-microbial, immunomodulatory, and radioprotective properties. The current analysis summarized biological applications of RSV, their mechanisms of action, and recent scientific development in the area of their delivery. It is possible to infer that RSV has many effects on infected cells' cellular functions.


Assuntos
Neoplasias , Estilbenos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos , Resveratrol/farmacologia , Estilbenos/farmacologia , Estilbenos/uso terapêutico
12.
Mol Plant Pathol ; 22(10): 1180-1194, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34374201

RESUMO

Heterotrimeric G-proteins are one of the highly conserved signal transducers across phyla. Despite the obvious importance of G-proteins in controlling various plant growth and environmental responses, there is no information describing the regulatory complexity of G-protein networks during pathogen response in a polyploid crop. Here, we investigated the role of extra-large G-proteins (XLGs) in the oilseed crop Brassica juncea, which has inherent susceptibility to the necrotrophic fungal pathogen Sclerotinia sclerotiorum. The allotetraploid B. juncea genome contains multiple homologs of three XLG genes (two BjuXLG1, five BjuXLG2, and three BjuXLG3), sharing a high level of sequence identity, gene structure organization, and phylogenetic relationship with the progenitors' orthologs. Quantitative reverse transcription PCR analysis revealed that BjuXLGs have retained distinct expression patterns across plant developmental stages and on S. sclerotiorum infection. To determine the role of BjuXLG genes in the B. juncea defence response against S. sclerotiorum, RNAi-based suppression was performed. Disease progression analysis showed more rapid lesion expansion and fungal accumulation in BjuXLG-RNAi lines compared to the vector control plants, wherein suppression of BjuXLG3 homologs displayed more compromised defence response at the later time point. Knocking down BjuXLGs caused impairment of the host resistance mechanism to S. sclerotiorum, as indicated by reduced expression of defence marker genes PDF1.2 and WRKY33 on pathogen infection. Furthermore, BjuXLG-RNAi lines showed reduced accumulation of leaf glucosinolates on S. sclerotiorum infection, wherein aliphatic glucosinolates were significantly compromised. Overall, our data suggest that B. juncea XLG genes are important signalling nodes modulating the host defence pathways in response to this necrotrophic pathogen.


Assuntos
Ascomicetos/patogenicidade , Proteínas de Ligação ao GTP/metabolismo , Glucosinolatos , Mostardeira , Doenças das Plantas , Glucosinolatos/metabolismo , Mostardeira/metabolismo , Mostardeira/microbiologia , Filogenia , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo
13.
Plant Mol Biol ; 106(6): 505-520, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34176052

RESUMO

KEY MESSAGE: Gene expression analysis coupled with in-planta studies showed that specific Gßγ combination regulates plant growth and defence traits in the allotetraploid Brassica juncea. Plant heterotrimeric G-proteins regulate a wide range of responses despite their limited repertoire of core components. The roles and functional interactions between different G-protein subunits are quite perplexing, which get further complicated with polyploidy. Here, we show that the allotetraploid Brassica juncea comprises multiple homologs of G-protein genes, encoding six BjuGß and ten highly divergent BjuGγ subunit proteins, later being classified into type-A1, type-A2 and type-C Gγ proteins. The encoded BjuGß and BjuGγ proteins shared close evolutionary relationship and have retained distinct spatio-temporal expression patterns during plant developmental stages and in response to the necrotrophic pathogen, Sclerotinia sclerotiorum. RNAi based suppression of BjuGß and BjuGγ genes suggested functional overlap and selectivity of BjuGßs with three distinct BjuGγ type subunits, to regulate plant height (BjuGßγA2 and BjuGßγC), seed weight (BjuGßGγA1 and BjuGßGγC), silique size (BjuGßGγC) and pathogen response (BjuGßGγA1 and BjuGßGγC). Further, the triplicated BjuGß genes, formed due to Brassica specific whole-genome-triplication event, showed differential involvement during pathogen response, wherein overexpression of BjuGß2 displayed higher resistance to Sclerotinia infection. Taken together, our study demonstrates that multiple BjuGß and BjuGγ proteins have retained distinct spatio-temporal expression and functional selectivity to regulate specific plant growth and defence traits in the oilseed B. juncea.


Assuntos
Subunidades beta da Proteína de Ligação ao GTP/genética , Subunidades gama da Proteína de Ligação ao GTP/genética , Mostardeira/genética , Doenças das Plantas/genética , Proteínas de Plantas/genética , Poliploidia , Ascomicetos/fisiologia , Resistência à Doença/genética , Subunidades beta da Proteína de Ligação ao GTP/classificação , Subunidades beta da Proteína de Ligação ao GTP/metabolismo , Subunidades gama da Proteína de Ligação ao GTP/classificação , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas , Interações Hospedeiro-Patógeno , Modelos Genéticos , Mostardeira/crescimento & desenvolvimento , Mostardeira/microbiologia , Filogenia , Doenças das Plantas/microbiologia , Proteínas de Plantas/classificação , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Ligação Proteica , Interferência de RNA
14.
Ann Med Surg (Lond) ; 66: 102419, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34094531

RESUMO

Coronavirus disease 2019 (COVID-19) has already affected millions of people worldwide. There are reports of SARS-CoV-2 transmission as a consequence of environmental contamination. The SARS-CoV-2 laden infective droplets can actively persist on the surface of different materials for several hours to days. Sunlight can affect the stability of SARS-CoV-2 in these aerosols and thereby have an impact on the decay rate of the virus. Solar radiation might play an important role in inactivating SARS-CoV-2 that persists in different surfaces and the environment. Among the different climatological factors, ultraviolet radiation was found to have an important role in determining the spread of SARS-CoV-2. Although ultraviolet radiation C (UVC), UVB, UVA, visible light, and infrared radiation possess germicidal properties, human CoVs including the recently emerged SARS-CoV-2 are inherently sensitive to UVC. However, the successful decontamination using other wavebands requires higher dosages and longer administration times. Furthermore, studies have also identified association between COVID-19 fatalities and the latitude. The intensity of sunlight is highest near the equator, and therefore populations in these regions with more regular exposure to sunlight are less susceptible to vitamin D deficiency. This article has analyzed the potential impact of sunlight in reducing SARS-CoV-2 transmissibility, morbidity, and mortality. It is evident that there exists an interesting link between sunlight exposure, latitude, and vitamin D status with COVID-19 incidence, fatality and recovery rates that requires further investigation.

15.
J Med Virol ; 93(9): 5295-5309, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33990972

RESUMO

The human immune system is not adequately equipped to eliminate new microbes and could result in serious damage on first exposure. This is primarily attributed to the exaggerated immune response (inflammatory disease), which may prove detrimental to the host, as evidenced by SARS-CoV-2 infection. From the experiences of Novel Coronavirus Disease-19 to date, male patients are likely to suffer from high-intensity inflammation and disease severity than the female population. Hormones are considered the significant pillars of sex differences responsible for the discrepancy in immune response exhibited by males and females. Females appear to be better equipped to counter invading respiratory viral pathogens, including the novel SARS-CoV-2, than males. It can be hypothesized that females are more shielded from disease severity, probably owing to the diverse action/influence of estrogen and other sex hormones on both cellular (thymus-derived T lymphocytes) and humoral immunity (antibodies).


Assuntos
Enzima de Conversão de Angiotensina 2/imunologia , COVID-19 , Estrogênios/imunologia , Fatores Sexuais , COVID-19/epidemiologia , COVID-19/imunologia , Feminino , Humanos , Imunidade Humoral , Masculino , Linfócitos T/citologia , Linfócitos T/imunologia
16.
Ann Med Surg (Lond) ; 61: 122-125, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33456770

RESUMO

The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important therapeutic target as it plays a major role in the processing and maturation of the viral polyprotein. GC376 is a pre-clinical dipeptide-based protease inhibitor that has been previously used for managing feline infectious peritonitis virus (FIPV). Since both GC373 and GC376 have already been successfully used in treating animal coronavirus infection, they can be considered as strong drug candidates for COVID-19 in humans. GC376 is a broad-spectrum antiviral drug that inhibits Mpro of several viruses, including the coronaviruses like feline coronavirus, porcine epidemic diarrhoea virus, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, ferret, and mink coronavirus. However, further studies should be conducted to evaluate the potency, efficacy, and safety of these broad-spectrum Mpro inhibitors in patients with COVID-19. The lessons learned from the successful use of drug candidates for treating animal coronavirus infections will help us to develop framework for their use in human trials.

17.
19.
J Cosmet Dermatol ; 19(8): 2093-2104, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31829513

RESUMO

BACKGROUND: Clinically, melatonin (MLT) has variable oral absorption and extensive first-pass effect, making its oral mode less preferable. Ethosomes are able to permeate intact through the human skin due to its high deformability. AIM: Present study assessed topical potential of ethosomes loaded with MLT for the prevention of UV radiation. METHODS: Melatonin was encapsulated using different ratios of ethanol, soya lecithin, and cholesterol. Prepared ethosomes were characterized for scanning electron microscopy (SEM), zeta potential, % entrapment efficiency (%EE), in vitro drug release kinetics. Then, optimized formulation was incorporated in gel and evaluated for viscosity, pH, extrudability, homogeneity, skin irritation study, spreadability, in vitro skin permeation study, flux, and stability. RESULTS: Ethosomes were spherical in structure as confirmed by SEM, and zeta potential was in range of -12.4 mV to -27.4 mV. %EE of the vesicles was in the range of 49.61%-78.047%. Cumulative percentage drug release from various ethosomal formulations was ranged from 64.82%-81.01%. F3 was selected as optimized formulation on the basis of highest %EE, zeta potential, and in vitro drug release. An ethosomal gel of optimized formulation F3 was prepared by using carbopol 934 and compared with plain gel formulation. G3 formulation showed pseudoplastic rheological behavior, optimum pH, spreadability and also showed maximum % in vitro drug permeation with flux 13.85 µg/cm2 /hr and followed zero-order release kinetics which was good for topical drug delivery system. CONCLUSION: This research suggested that MLT loaded ethosomes can be potentially used as a topically drug delivery system.


Assuntos
Melatonina , Administração Cutânea , Sistemas de Liberação de Medicamentos , Géis/metabolismo , Humanos , Lipossomos/metabolismo , Pele/metabolismo , Absorção Cutânea , Raios Ultravioleta
20.
J Anim Physiol Anim Nutr (Berl) ; 104(1): 245-256, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31595607

RESUMO

Green tea (Camellia sinensis) is a popular herbal plant with abundant health benefits, and thus, it has been used as a potent antioxidant for a long time. Based on the available literature, the diversity and the availability of multifunctional compounds in green tea offer its noteworthy potential against many diseases such as liver and heart diseases, inflammatory conditions and different metabolic syndromes. Owing to its bioactive constituents including caffeine, amino acids, l-theanine, polyphenols/flavonoids and carbohydrates among other potent molecules, green tea has many pharmacological and physiological effects. The effects of green tea include anti-oxidative, anti-inflammatory, anti-arthritic, anti-stress, hypolipidaemic, hypocholesterolaemic, skin/collagen protective, hepatoprotective, anti-diabetic, anti-microbial, anti-infective, anti-parasitic, anti-cancerous, inhibition of tumorigenesis and angiogenesis, anti-mutagenic, and memory and bone health-improving activities. Apart from its utilization in humans, green tea has also played a significant role in livestock production such as in dairy, piggery, goatry and poultry industries. Supplementation of animal feeds with green tea and its products is in line with the modern concepts of organic livestock production. Hence, incorporating green tea or green tea by-products into the diet of poultry and other livestock can enhance the value of the products obtained from these animals. Herein, an effort is made to extend the knowledge on the importance and useful applications of green tea and its important constituents in animal production including poultry. This review will be a guideline for researchers and entrepreneurs who want to explore the utilization of feeds supplemented with green tea and green tea by-products for the enhancement of livestock production.


Assuntos
Ração Animal/análise , Glutamatos/farmacologia , Gado , Chá , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária
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