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1.
BMC Public Health ; 24(1): 750, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38461259

RESUMEN

BACKGROUND: Women in their reproductive age have tremendous health implications that affect their health and well-being. Anaemia is an indicator of inadequate dietary intake and poor health. Maternal malnutrition significantly impacts maternal and child health outcomes, increasing the mother's risk of dying during delivery. High-risk fertility behaviour is a barrier to reducing mother and child mortality. This study aims to examine the level of high-risk fertility behaviour and anaemia among ever-married urban Indian women and also examine the linkages between the both. METHODS: Based on the National Family Health Survey's fifth round of data, the study analyzed 44,225 samples of ever-married urban women. Univariate and bivariate analysis and binary logistic regression have been used for the analysis. RESULTS: Findings suggested that more than half (55%) of the urban women were anaemic, and about one-fourth (24%) of women had any high-risk fertility behaviour. Furthermore, the results suggest that 20% of women were more vulnerable to anaemia due to high-risk fertility behaviour. For the specific category, 19% and 28% of women were more likely to be anaemic due to single and multiple high-risk fertility. However, after controlling for sociodemographic factors, the findings showed a statistically significant link between high-risk fertility behaviour and anaemia. As a result, 16% of the women were more likely to be anaemic due to high-risk fertility behaviour, and 16% and 24% were more likely to be anaemic due to single and multiple high-risk fertility behaviour, respectively. CONCLUSIONS: The findings exposed that maternal high-risk fertility behaviour is a significant factor in raising the chance of anaemia in ever-married urban women of reproductive age in forms of the short birth interval, advanced maternal age, and advanced maternal age & higher order. Policy and choice-based family planning techniques should be employed to minimize the high-risk fertility behaviour among Indian urban women. This might aid in the reduction of the malnutrition status of their children.


Asunto(s)
Anemia , Desnutrición , Niño , Femenino , Humanos , Fertilidad , Servicios de Planificación Familiar , Intervalo entre Nacimientos , Anemia/epidemiología
2.
Adv Mater ; 36(15): e2309843, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38302823

RESUMEN

Injectable scaffold delivery is a strategy to enhance the efficacy of cancer vaccine immunotherapy. The choice of scaffold biomaterial is crucial, impacting both vaccine release kinetics and immune stimulation via the host response. Extracellular matrix (ECM) scaffolds prepared from decellularized tissues facilitate a pro-healing inflammatory response that promotes local cancer immune surveillance. Here, an ECM scaffold-assisted therapeutic cancer vaccine that maintains an immune microenvironment consistent with tissue reconstruction is engineered. Several immune-stimulating adjuvants are screened to develop a cancer vaccine formulated with decellularized small intestinal submucosa (SIS) ECM scaffold co-delivery. It is found that the STING pathway agonist cyclic di-AMP most effectively induces cytotoxic immunity in an ECM scaffold vaccine, without compromising key interleukin 4 (IL-4) mediated immune pathways associated with healing. ECM scaffold delivery enhances therapeutic vaccine efficacy, curing 50-75% of established E.G-7OVA lymphoma tumors in mice, while none are cured with soluble vaccine. SIS-ECM scaffold-assisted vaccination prolonged antigen exposure is dependent on CD8+ cytotoxic T cells and generates long-term antigen-specific immune memory for at least 10 months post-vaccination. This study shows that an ECM scaffold is a promising delivery vehicle to enhance cancer vaccine efficacy while being orthogonal to characteristics of pro-healing immune hallmarks.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Animales , Ratones , Matriz Extracelular/metabolismo , Memoria Inmunológica , Neoplasias/metabolismo , Andamios del Tejido , Microambiente Tumoral , Interleucina-4/química , Interleucina-4/metabolismo
3.
Sci Rep ; 13(1): 19480, 2023 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-37945592

RESUMEN

Wastewater malodour is the proverbial 'elephant in the room' notwithstanding its severe implications on sanitation, health, and hygiene. The predominant malodorous compounds associated with wastewater treatment plants and toilets are volatile organic compounds, such as hydrogen sulphide, ammonia, methanethiol, and organic acids. Among them, methanethiol warrants more attention owing to its relatively low olfactory threshold and associated cytotoxicity. This requires an efficient odour-abatement method since conventional techniques are either cost-prohibitive or leave recalcitrant byproducts. Bacteriophage-based methodology holds promise, and the described work explores the potential. In this study, a non-lysogenous Pseudomonas putida strain is used as a model organism that produces methanethiol in the presence of methionine. Two double-stranded DNA phages of genome sizes > 10 Kb were isolated from sewage. ɸPh_PP01 and ɸPh_PP02 were stable at suboptimal pH, temperature, and at 10% chloroform. Moreover, they showed adsorption efficiencies of 53% and 89% in 12 min and burst sizes of 507 ± 187 and 105 ± 7 virions per cell, respectively. In augmented synthetic wastewater, ɸPh_PP01 and ɸPh_PP02 reduced methanethiol production by 52% and 47%, respectively, with the concomitant reduction in P. putida by 3 logs in 6 h. On extension of the study in P. putida spiked-sewage sample, maximum reduction in methanethiol production was achieved in 3 h, with 49% and 48% for ɸPh_PP01 and ɸPh_PP02, respectively. But at 6 h, efficiency reduced to 36% with both the phages. The study clearly demonstrates the potential of phages as biocontrol agents in the reduction of malodour in wastewater.


Asunto(s)
Bacteriófagos , Pseudomonas putida , Bacteriófagos/genética , Aguas Residuales , Aguas del Alcantarillado/química , Compuestos de Sulfhidrilo
4.
Front Pharmacol ; 14: 1274076, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37745056

RESUMEN

[This corrects the article DOI: 10.3389/fphar.2023.1159409.].

5.
Front Pharmacol ; 14: 1159409, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37397502

RESUMEN

Programmed cell death (PCD) is the universal process that maintains cellular homeostasis and regulates all living systems' development, health and disease. Out of all, apoptosis is one of the major PCDs that was found to play a crucial role in many disease conditions, including cancer. The cancer cells acquire the ability to escape apoptotic cell death, thereby increasing their resistance towards current therapies. This issue has led to the need to search for alternate forms of programmed cell death mechanisms. Paraptosis is an alternative cell death pathway characterized by vacuolation and damage to the endoplasmic reticulum and mitochondria. Many natural compounds and metallic complexes have been reported to induce paraptosis in cancer cell lines. Since the morphological and biochemical features of paraptosis are much different from apoptosis and other alternate PCDs, it is crucial to understand the different modulators governing it. In this review, we have highlighted the factors that trigger paraptosis and the role of specific modulators in mediating this alternative cell death pathway. Recent findings include the role of paraptosis in inducing anti-tumour T-cell immunity and other immunogenic responses against cancer. A significant role played by paraptosis in cancer has also scaled its importance in knowing its mechanism. The study of paraptosis in xenograft mice, zebrafish model, 3D cultures, and novel paraptosis-based prognostic model for low-grade glioma patients have led to the broad aspect and its potential involvement in the field of cancer therapy. The co-occurrence of different modes of cell death with photodynamic therapy and other combinatorial treatments in the tumour microenvironment are also summarized here. Finally, the growth, challenges, and future perspectives of paraptosis research in cancer are discussed in this review. Understanding this unique PCD pathway would help to develop potential therapy and combat chemo-resistance in various cancer.

6.
Sci Adv ; 9(26): eadf2746, 2023 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-37390205

RESUMEN

Treatment of triple-negative breast cancer (TNBC) is challenging because of its "COLD" tumor immunosuppressive microenvironment (TIME). Here, we present a hydrogel-mediated localized delivery of a combination of docetaxel (DTX) and carboplatin (CPT) (called DTX-CPT-Gel therapy) that ensured enhanced anticancer effect and tumor regression on multiple murine syngeneic and xenograft tumor models. DTX-CPT-Gel therapy modulated the TIME by an increase of antitumorigenic M1 macrophages, attenuation of myeloid-derived suppressor cells, and increase of granzyme B+CD8+ T cells. DTX-CPT-Gel therapy elevated ceramide levels in tumor tissues that activated the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)-mediated unfolded protein response (UPR). This UPR-mediated activation of apoptotic cell death led to release of damage-associated molecular patterns, thereby activating the immunogenic cell death that could even clear the metastatic tumors. This study provides a promising hydrogel-mediated platform for DTX-CPT therapy that induces tumor regression and effective immune modulation and, therefore, can be explored further for treatment of TNBC.


Asunto(s)
Hidrogeles , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Muerte Celular Inmunogénica , Linfocitos T CD8-positivos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Ceramidas , Modelos Animales de Enfermedad , Inmunosupresores , Respuesta de Proteína Desplegada , Microambiente Tumoral
7.
Front Nutr ; 10: 1200926, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37342549

RESUMEN

Introduction: Environmental enteropathy (EE), a chronic small intestine disease characterized by gut inflammation, is widely prevalent in low-income countries and is hypothesized to be caused by continuous exposure to fecal contamination. Targeted nutritional interventions using potential probiotic strains from fermented foods can be an effective strategy to inhibit enteric pathogens and prevent chronic gut inflammation. Methods: We isolated potential strains from fermented rice water and lemon pickle and investigated their cell surface properties, antagonistic properties, adhesion to HT-29 cells, and inhibition of pathogen adherence to HT-29 cells. Bacteriocin-like inhibitory substances (BLIS) were purified, and in vivo, survival studies in Caenorhabditis elegans infected with Salmonella enterica MW116733 were performed. We further checked the expression pattern of pro and anti-inflammatory cytokines (IL-6, IL8, and IL-10) in HT-29 cells supplemented with strains. Results: The strains isolated from rice water (RS) and lemon pickle (T1) were identified as Limosilactobacillus fermentum MN410703 and MN410702, respectively. Strains showed probiotic properties like tolerance to low pH (pH 3.0), bile salts up to 0.5%, simulated gastric juice at low pH, and binding to extracellular matrix molecules. Auto-aggregation of T1 was in the range of 85% and significantly co-aggregated with Klebsiella pneumoniae, S. enterica, and Escherichia coli at 48, 79, and 65%, respectively. Both strains had a higher binding affinity to gelatin and heparin compared to Bacillus clausii. Susceptibility to most aminoglycoside, cephalosporin, and macrolide classes of antibiotics was also observed. RS showed BLIS activity against K. pneumoniae, S. aureus, and S. enterica at 60, 48, and 30%, respectively, and the protective effects of BLIS from RS in the C. elegans infection model demonstrated a 70% survival rate of the worms infected with S. enterica. RS and T1 demonstrated binding efficiency to HT-29 cell lines in the 38-46% range, and both strains inhibited the adhesion of E. coli MDR and S. enterica. Upregulation of IL-6 and IL-10 and the downregulation of IL-8 were observed when HT-29 cells were treated with RS, indicating the immunomodulatory effects of the strain. Discussion: The potential strains identified could effectively inhibit enteric pathogens and prevent environmental enteropathy.

8.
J Med Chem ; 65(22): 15312-15326, 2022 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-36331380

RESUMEN

Emergence of vancomycin resistance in Gram-positive bacteria and the prevalence of vancomycin-resistant Enterococci (VRE) infections are highly alarming as very limited antibiotic options are available against VRE infections. Here, we present the synthesis of cholic acid-derived dimeric amphiphiles where two cholic acid moieties are tethered through carboxyl terminals using different alkylene spacers. Our investigations revealed that dimer 5 possessing a propylene spacer and glycine-valine peptides tethered on hydroxyl groups is the most effective antimicrobial against VRE. Dimer 5 can permeabilize bacterial membranes, generate reactive oxygen species, and clear preformed biofilms. We further demonstrate that dimer 5 downregulates vancomycin-mediated transcriptional activation of the vanHAX gene cluster and does not allow VSE to develop vancomycin resistance until 100 generations. Therefore, this study, for the first time, presents a bacterial membrane-targeting amphiphile that can mitigate VRE infections and inhibit the emergence of vancomycin resistance.


Asunto(s)
Infecciones por Bacterias Grampositivas , Enterococos Resistentes a la Vancomicina , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ácido Cólico/farmacología , Infecciones por Bacterias Grampositivas/microbiología , Pruebas de Sensibilidad Microbiana , Operón , Vancomicina/farmacología , Resistencia a la Vancomicina/genética , Enterococos Resistentes a la Vancomicina/genética , Farmacorresistencia Bacteriana/genética
9.
Appl Microbiol Biotechnol ; 106(24): 8273-8284, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36380193

RESUMEN

Bacterial pathogens are fostered in and transmitted through wastewater. Hence, monitoring their impact on sanitation and hygiene is imperative. As part of the monitoring process, culture-based methodologies are primarily used, which centre on the use of selective and differential media. Media available today are, at best, difficult to formulate and, at worst, prohibitively expensive. To address this lacuna, the study proposes a selective and differential medium for Klebsiella spp. Klebsiella blue agar (KBA) is completely selective against selected gram-positive bacteria (Bacillus spp., Staphylococcus aureus) and a few gram-negative bacteria (Acinetobacter baumanii, Serratia marcescens). On the other hand, it supports the growth of the chosen members of the Klebsiella pneumoniae species-complex with a characteristic green colouration. Methylene blue, tryptophan, and bile salt make up the selective components of KBA. Moreover, methylene blue, 0.6% NaCl, and glycerol render it differential. KBA was more selective than HiCrome™ Klebsiella Selective Agar Base (KSA) in replica plating experiments. KBA promoted only 157 CFUs against 209 CFUs in KSA when stamped with 253 CFUs grown on LB. The colonies so isolated were predominantly Klebsiella spp., on identification through colony polymerase chain reaction. Moreover, the differential nature of KBA distinguished Klebsiella aerogenes from other species. On the contrary, KSA lodged colonies indistinguishable from each other and Klebsiella spp. Due to its ease of formulation, high selectivity, differential nature, and cost-effective composition, KBA is a viable option for the routine culture of Klebsiella spp. in environmental and clinical settings. KEY POINTS: • Formulated a novel selective and differential media for Klebsiella spp., named Klebsiella Blue agar • Facile formulation methodology • Can be employed to isolate Klebsiella spp. from complex sources such as wastewater.


Asunto(s)
Klebsiella , Azul de Metileno
10.
Sci Rep ; 12(1): 19406, 2022 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-36371482

RESUMEN

Bacteriophages are generally specific, and a cocktail of phages is needed to combat different bacterial targets. Their production usually requires pathogenic isolation hosts. We identified a novel strain, Escherichia coli ST155, that could serve as a production host for three different polyvalent phages (ϕPh_SE03, ϕPh_SD01, and ϕPh_EC01), thus superseding the use of individual isolation hosts. Upon propagation in E. coli ST155, the phages demonstrated differential intergeneric infectivity against Salmonella enterica, E. coli OP50, Shigella dysenteriae, E. coli MDR, and Acinetobacter baumannii. Phages were characterised based on morphology, latent period, burst size, the efficiency of plating, and restriction enzyme profile. Survival assay on Caenorhabditis elegans, the absence of Shiga toxin, and enterotoxigenic E. coli virulence genes indicated that E. coli ST155 could be non-pathogenic. Lack of antibiotic resistance and absence of functional prophages rendered the host suitable for environmental applications. As a proof-of-concept, phage ϕPh_SE03 was produced in ST155 by employing a unique Bacteriophage Amplification Reactor-Lytics Broadcasting System and was simultaneously disseminated into S. enterica augmented wastewater, which resulted in a 3-log reduction in 24 h. The study establishes the potential of E. coli ST155 as a phage production host thereby minimising the possibility of accidental release of pathogenic hosts into wastewater.


Asunto(s)
Bacteriófagos , Infecciones por Escherichia coli , Humanos , Bacteriófagos/genética , Escherichia coli , Aguas Residuales , Clonidina , Desinfección
11.
Results Eng ; 13: None, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35372823

RESUMEN

Owing to their selective nature, bacteriophages are prospective in targeted wastewater disinfection. Other potential applications include the removal of biogenic malodour and the mitigation of corrosion in sewerage pipelines. Nevertheless, its applications are ridden with challenges, the most prominent of which is scaling up. Towards that end, effective methodologies are required for dispersing phages into wastewater. The study describes a device arbitrarily named Lytics Broadcasting System. In principle, the device contains phages that can be continuously dispersed into wastewater. The modified version is called Bacteriophage Amplification Reactor, which operates with both phages and their respective hosts, ensuring continual production and dissemination of phages. Both prototypes utilize 0.22 µm cellulose membranes as an interface through which phage diffuse passively and selectively owing to its smaller size and established through membrane-overlay method. In the study, previously reported bacteriophage φPh_Se01 and Salmonella enterica were used. A reduction of 3-4 log was achieved with both the prototypes after 48 h of operation in 1 L of augmented synthetic sewage. Subsequently, the biogenic H2S produced by Salmonella enterica was reduced by 64-74% indicating its utility for targeted disinfection and malodour mitigation of wastewater. This study aims to provide a framework for the development of scalable prototypes of Lytic Broadcasting Systems for real-world wastewater applications.

12.
Foods ; 10(11)2021 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-34828830

RESUMEN

Value-added phytochemicals from food by-products and waste materials have gained much interest and among them, dietary polyphenolic compounds with potential biological properties extend a promising sustainable approach. Oxyresveratrol (Oxy), a stilbenoid polyphenol, possesses great therapeutic potential, though its pharmacokinetic issues need attention. A good source of oxyresveratrol was found in underutilized coconut shells and the synbiotic applications of the compound in combination with a potential probiotic isolate Limosilactobacillus fermentum ASBT-2 was investigated. The compound showed lower inhibitory effects on the strain with minimum inhibitory concentration (MIC) of 1000 µg/mL. Oxyresveratrol at sub-MIC concentrations (500 µg/mL and 250 µg/mL) enhanced the probiotic properties without exerting any inhibitory effects on the strain. The combination at sub- MIC concentration of the compound inhibited Salmonella enterica and in silico approaches were employed to elucidate the possible mode of action of oxy on the pathogen. Thus, the combination could target pathogens in the gut without exerting negative impacts on growth of beneficial strains. This approach could be a novel perspective to address the poor pharmacokinetic properties of the compound.

13.
ACS Appl Mater Interfaces ; 13(37): 44041-44053, 2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-34491724

RESUMEN

Treatment of chronic wound infections caused by Gram-positive bacteria such as Staphylococcus aureus is highly challenging due to the low efficacy of existing formulations, thereby leading to drug resistance. Herein, we present the synthesis of a nonimmunogenic cholic acid-glycine-glycine conjugate (A6) that self-assembles into a supramolecular viscoelastic hydrogel (A6 gel) suitable for topical applications. The A6 hydrogel can entrap different antibiotics with high efficacy without compromising its viscoelastic behavior. Activities against different bacterial species using a disc diffusion assay demonstrated the antimicrobial effect of the ciprofloxacin-loaded A6 hydrogel (CPF-Gel). Immune profiling and gene expression studies after the application of the A6 gel to mice confirmed its nonimmunogenic nature to host tissues. We further demonstrated that topical application of CPF-Gel clears S. aureus-mediated wound infections more effectively than clinically used formulations. Therefore, cholic acid-derived hydrogels are an efficacious matrix for topical delivery of antibiotics and should be explored further.


Asunto(s)
Antibacterianos/uso terapéutico , Ciprofloxacina/uso terapéutico , Portadores de Fármacos/química , Hidrogeles/química , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infección de Heridas/tratamiento farmacológico , Animales , Antibacterianos/química , Ácidos Cólicos/síntesis química , Ácidos Cólicos/química , Ciprofloxacina/química , Dipéptidos/síntesis química , Dipéptidos/química , Portadores de Fármacos/síntesis química , Liberación de Fármacos , Hidrogeles/síntesis química , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Staphylococcus aureus/efectos de los fármacos
14.
Nanoscale ; 13(31): 13225-13230, 2021 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-34477730

RESUMEN

We present a non-immunogenic, injectable, low molecular weight, amphiphilic hydrogel-based drug delivery system (TB-Gel) that can entrap a cocktail of four front-line antitubercular drugs, isoniazid, rifampicin, pyrazinamide, and ethambutol. We showed that TB-Gel is more effective than oral delivery of the combination of four drugs in reducing the mycobacterial infection in mice. Results show that half the dose of chemotherapeutic drugs is sufficient to achieve a comparable therapeutic effect to that of oral delivery.


Asunto(s)
Antituberculosos , Hidrogeles , Animales , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Etambutol , Isoniazida , Ratones , Pirazinamida
15.
Biomater Sci ; 9(16): 5626-5639, 2021 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-34254078

RESUMEN

Herein, we present the engineering of a supramolecular nanomicellar system that is composed of self-assembled units of the PEGylated lithocholic acid (LCA)-docetaxel (DTX) conjugate (LCA-DTX-PEG). We tethered a short polyethylene glycol unit to LCA and used an esterase-sensitive ester linkage between DTX and LCA. The LCA-DTX-PEG conjugate formed nanomicelles (LCA-DTX-PEG NMs) with ∼160 nm hydrodynamic diameter that are sensitive to cellular esterases and maximized the release of DTX under high esterase exposure. LCA-DTX-PEG NMs were found to be effective as the parent drug in breast cancer cells by stabilizing tubulin and arresting the cells in the G2/M phase. We determined the maximum tolerated dose (MTD) and systemic and vital organ toxicity of LCA-DTX-PEG NMs in mice, rats, and rabbits. LCA-DTX-PEG NMs showed a MTD of >160 mg kg-1 and are found to be safe in comparison with their parent FDA-approved drug formulation (Taxotere® or DTX-TS) that is highly toxic. LCA-DTX-PEG NMs effectively reduced the tumor volume and increased the survival of 4T1 tumor-bearing mice with improved blood circulation time of the drug and its higher accumulation in tumor tissues. Therefore, this study highlights the potential of PEGylated bile acid-drug conjugate based nanomicelles for the development of next generation cancer therapeutics.


Asunto(s)
Antineoplásicos , Micelas , Animales , Antineoplásicos/uso terapéutico , Ácidos y Sales Biliares , Línea Celular Tumoral , Docetaxel , Portadores de Fármacos , Ratones , Conejos , Ratas
16.
Biomed Mater ; 16(2): 024102, 2021 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-33461186

RESUMEN

Chemotherapy is the primary option for the treatment of cancer, inflammation, and infectious diseases. Conventional drug delivery poses solubility and bioavailability challenges, systemic toxicity, non-specific targeting, and poor accumulation of chemotherapeutic drugs at the desired site. Nanotechnology has led to the development of various nanomaterials that have decreased the toxicity and increased the accumulation of drugs at the target site. Systemic administration of nanomaterials causes burst release and non-specific targeting of chemotherapeutics, leading to off-target organ toxicity. Drug delivery based on low molecular weight hydrogels (LMWHs) provides a suitable alternative for drug delivery due to their ability to entrap chemotherapeutic drugs. Injectable and biodegradable LMWHs allow the administration of chemotherapeutics with minimal invasion, allow the sustained release of chemotherapeutic drugs for long periods, and reduce the challenges of immunogenicity and low drug entrapment efficiency. Herein, we summarize the advances in the engineering of LMWHs for controlled and prolonged delivery of chemotherapeutics for cancer, infectious diseases, and inflammatory disorders.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Hidrogeles/química , Neoplasias/tratamiento farmacológico , Ingeniería de Proteínas/métodos , Ingeniería de Tejidos/métodos , Animales , Química Farmacéutica/métodos , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Inflamación , Ensayo de Materiales , Ratones , Peso Molecular , Neoplasias/metabolismo
17.
ACS Appl Bio Mater ; 4(9): 7332-7341, 2021 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-35006962

RESUMEN

Infections caused by fungal species via their existence as biofilms on medical devices can cause organ damage via candidiasis and candidemia. Different Candida species like Candida albicans can pose a serious threat by resisting host's immune system and by developing drug resistance against existing antimycotic agents. Therefore, targeting of fungal membranes can be used as an alternative strategy to combat the fungal infections. Here, we present screening of different amphiphiles based on cholic acid against different Candida strains as these amphiphiles can act as potent membrane-targeting antimycotic agents. Structure-activity correlations, biochemical assays and electron microscopy studies showed that amphiphiles having 4 and 6 carbon chains are most potent, safe and can act on the fungal membranes. Candida albicans did not show emergence of drug resistance on repeated usage of these amphiphiles unlike fluconazole. We show that these amphiphiles can prevent the formation of biofilms and also have the ability to degrade preformed biofilms on different substrates including acrylic teeth. We further demonstrate that amphiphiles 4 and 6 can clear the Candida albicans wound infections and prevent the biofilm formation on indwelling devices in murine models. Therefore, amphiphiles derived from cholic acid and their coatings provide suitable alternatives for inhibiting the fungal infections.


Asunto(s)
Antifúngicos , Candidiasis , Animales , Antifúngicos/farmacología , Biopelículas , Candida , Candida albicans , Candidiasis/tratamiento farmacológico , Ácido Cólico/farmacología , Ratones
18.
Angew Chem Int Ed Engl ; 60(10): 5394-5399, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33258265

RESUMEN

In this study, we describe the engineering of sub-100 nm nanomicelles (DTX-PC NMs) derived from phosphocholine derivative of docetaxel (DTX)-conjugated lithocholic acid (DTX-PC) and poly(ethylene glycol)-tethered lithocholic acid. Administration of DTX-PC NMs decelerate tumor progression and increase the mice survivability compared to Taxotere (DTX-TS), the FDA-approved formulation of DTX. Unlike DTX-TS, DTX-PC NMs do not cause any systemic toxicity and slow the decay rate of plasma DTX concentration in rodents and non-rodent species including non-human primates. We further demonstrate that DTX-PC NMs target demethylation of CpG islands of Sparcl1 (a tumor suppressor gene) by suppressing DNA methyltransferase activity and increase the expression of Sparcl1 that leads to tumor regression. Therefore, this unique system has the potential to improve the quality of life in cancer patients and can be translated as a next-generation chemotherapeutic.


Asunto(s)
Antineoplásicos/uso terapéutico , Docetaxel/uso terapéutico , Epigénesis Genética/efectos de los fármacos , Ácido Litocólico/análogos & derivados , Ácido Litocólico/uso terapéutico , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/síntesis química , Antineoplásicos/farmacocinética , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Línea Celular Tumoral , Islas de CpG , Desmetilación , Progresión de la Enfermedad , Docetaxel/síntesis química , Docetaxel/farmacocinética , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Ácido Litocólico/farmacocinética , Ratones Endogámicos BALB C , Micelas , Neoplasias/fisiopatología , Tensoactivos/síntesis química , Tensoactivos/farmacocinética , Tensoactivos/uso terapéutico
19.
Nanoscale ; 12(35): 18463-18475, 2020 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-32941570

RESUMEN

The release of anticancer drugs in systemic circulation and their associated toxicity are responsible for the poor efficacy of chemotherapy. Therefore, the identification of new chemotherapeutic combinations designed to be released near the tumor site in a sustained manner has the potential to enhance the efficacy and reduce the toxicity associated with chemotherapy. Here, we present the identification of a combination of doxorubicin, a DNA-binding topoisomerase inhibitor, with a naturally occurring triterpenoid, celastrol, that induces a synergistic effect on the apoptosis of colon cancer cells. Hydrogel-mediated sustained release of a combination of doxorubicin and celastrol in a murine tumor model abrogates tumor proliferation, and increases the median survival with enhanced apoptosis and concurrent reduction in proliferation. Sphingolipid profiling (LC-MS/MS) of treated tumors showed that the combination of celastrol and doxorubicin induces global changes in the expression of sphingolipids with an increase in levels of ceramides. We further demonstrate that this dual drug combination induces a significant increase in the expression of ceramide synthase 1, 4, and 6, thereby increasing the level of ceramides that contribute to the synergistic apoptotic effect. Therefore, hydrogel-mediated localized delivery of a combination of celastrol and doxorubicin provides a new therapeutic combination that induces a sphingolipid-mediated synergistic effect against colon cancer.


Asunto(s)
Neoplasias , Triterpenos , Animales , Ceramidas , Cromatografía Liquida , Doxorrubicina/farmacología , Hidrogeles , Ratones , Triterpenos Pentacíclicos , Espectrometría de Masas en Tándem , Triterpenos/farmacología , Regulación hacia Arriba
20.
Microbiol Resour Announc ; 9(29)2020 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-32675192

RESUMEN

We report the draft genome sequence of a putative probiotic strain, Lactobacillus fermentum ASBT-2, isolated from domestic sewage in Kerala, India. The strain showed probiotic properties (tolerance to low pH and bile salts, binding to host matrix) and reduced the coliform count by 90% in a biofilter used to treat wastewater.

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