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1.
Chem Biol Interact ; 371: 110334, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36610610

RESUMO

A key signaling channel for the signal transduction of several crucial cytokines implicated in sepsis is the JAK/STAT system. Once cytokines attach to the proper receptors, JAK kinases linked to them are activated and can selectively phosphorylate STATs. Activated STATs subsequently go to the nucleus, where they play a key role in the transcription of the target genes. Various biological activities use the JAK/STAT pathway, including hematopoiesis, immunological modulation, cell differentiation, and apoptosis. Inflammatory lung illnesses affect people worldwide and are a serious public health concern. Numerous common respiratory conditions, such as asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome, are strongly influenced by inflammation. Microorganism infections or the destruction or demise of host cells are the causes of inflammation and the factors that perpetuate it. This review discusses the main elements of severe lung inflammation and how the JAK/STAT signaling pathway is essential for lung inflammation.


Assuntos
Janus Quinases , Transdução de Sinais , Humanos , Janus Quinases/metabolismo , Transdução de Sinais/fisiologia , Fatores de Transcrição STAT/metabolismo , Citocinas/metabolismo , Pulmão/metabolismo , Inflamação
2.
Molecules ; 28(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36677532

RESUMO

The analytical quality by design (AQbD) approach is utilized for developing and validating the simple, sensitive, cost-effective reverse-phase high performance liquid chromatographic method for the estimation of xanthohumol (XH) in bulk and nanoformulations. The Box-Behnken design (BBD) is applied for method optimization. The mobile phase ratio, pH and flow rate were selected as independent variables, whereas retention time, peak area, peak height, tailing factor, and theoretical plates were selected as dependent variables. The chromatogram of XH obtained under optimized conditions has given optimum conditions such as retention time (5.392 min), peak area (1,226,737 mAU), peak height (90,121 AU), tailing factor (0.991) and theoretical plates (4446.667), which are contoured in the predicted values shown by BBD. Validation of the method has been performed according to ICH Q2(R1) recommendations, using optimized conditions for linearity, limit of detection (LOD) and limit of quantification (LOQ), accuracy, precision, robustness and system suitability. All the values of validation parameters lie within the acceptable limits prescribed by ICH. Therefore, the developed and validated method of XH by the AQbD approach can be applied for the estimation of XH in bulk and various nanoformulations.


Assuntos
Cromatografia de Fase Reversa , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Limite de Detecção
3.
Nanomedicine (Lond) ; 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36695306

RESUMO

Ductal carcinoma in situ describes the most commonly occurring, noninvasive malignant breast disease, which could be the leading factor in invasive breast cancer. Despite remarkable advancements in treatment options, poor specificity, low bioavailability and dose-induced toxicity of chemotherapy are the main constraint. A unique characteristic of nanocarriers may overcome these problems. Moreover, the intraductal route of administration serves as an alternative approach. The direct nanodrug delivery into mammary ducts results in the accumulation of anticancer agents at targeted tissue for a prolonged period with high permeability, significantly decreasing the tumor size and improving the survival rate. This review focuses mainly on the intraductal delivery of nanocarriers in treating ductal carcinoma in situ, together with potential clinical translational research.


Ductal carcinoma in situ (DCIS) describes the most commonly occurring, noninvasive malignant breast disease, in which it could be the leading factor to invasive breast cancer. Mammography screening is often the diagnosis method in DCIS. The conventional treatment of DCIS includes breast-conserving surgery, medical treatment, chemotherapy and hormonal therapy. Various approaches are now actively investigated to overcome a number of drawbacks presented in conventional drug-delivery systems. Incorporation of nanocarriers in the drug-delivery system has portrayed certain benefits over the conventional therapy in DCIS where it promotes targeting in tumor cells, in which provision of the maximum therapeutic effects with minimal adverse effects are eventually achieved. With direct intraductal delivery, the drug accumulates at the site of action. Discovery on the intraductal route of administration has also been greatly implemented in managing other diseases.

4.
Nanomedicine (Lond) ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36606499

RESUMO

The prevalence of lung diseases is increasing year by year and existing drug therapies only provide symptomatic relief rather than targeting the actual cause. Nucleic acids can be used as an alternative therapeutic approach owing to their potential to reform a homeostatic balance by upregulating protective genes or downregulating damaging genes. However, their inherent properties, such as poor stability, ineffective cellular uptake, negative charge and so on, hinder their clinical utility. Such limitations can be overcome by exploiting the functional chemistry of polymeric micelles (PMs) for site-specific delivery, transfection efficiency and improved stability. With this objective, the present work describes the advancements made in designing nucleic acid-based PMs for treating lung diseases followed by approaches requiring consideration for clinical applications.

5.
Interv Neuroradiol ; : 15910199221150471, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36617952

RESUMO

INTRODUCTION: Aneurysms of persistent primitive trigeminal artery (PPTAAs) are increasingly reported and commonly managed by endovascular (EN) techniques. There are no systematic reviews or meta-analyses which analyse outcomes and complications of treatment modalities for PPTAAs. We aim to highlight the change in trend of management of PPTAAs and to identify clinical and radiological parameters which may influence management paradigms. METHODOLOGY: A systematic search of literature was done in PubMed, Embase, Google Scholar, Cochrane library and Medline using keywords 'persistent primitive trigeminal artery', 'aneurysms', 'embolization', 'surgical clipping', etc. Only cases reporting aneurysms of PPTA were included. Three subgroups, such as conservative, open surgical (OS) and EN interventional, were studied for outcome evaluation. In the EN subgroup, relation of clinical and radiological parameters with outcome (complete/partial occlusion) was analysed using Microsoft Excel Data Analysis ToolPak. RESULTS: Of the 101 articles found eligible for assessment, 54 were analysed quantitatively. Mortality in the conservative group was 12.5% and OS group was 9.09%. After EN treatment, complete angiographic occlusion was seen in 88.89% PPTAAs and 5.5% warranted retreatment. In the EN subgroup, location (p=0.17), shape (p=0.69), Saltzman circulation (p=0.26) or status of rupture (p=0.08) did not significantly impact angiographic occlusion outcome. Multivariate regression analysis showed 6.6% influence of independent variables, that is, age, gender, aneurysm location, side, shape (saccular/fusiform), rupture status and type of Saltzman circulation on aneurysm occlusion outcome [F(7,27) =1.34] (p=0.27). Total mortality reported in the EN group was 8.57%. CONCLUSION: Clinical or radiological parameters do not influence angiographic occlusion outcome. Although EN techniques are successful, meticulous reporting of outcomes and complications is important.

6.
Curr Drug Metab ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627789

RESUMO

Cancer is characterized by disrupted molecular variables caused by cells that deviate from regular signal transduction. The uncontrolled segment of such cancerous cells annihilates most of the tissues that contact them. Gene therapy, immunotherapy, and nanotechnology advancements have resulted in novel strategies for anticancer drug delivery. Furthermore, diverse dispersion of nanoparticles in normal stroma cells adversely affects the healthy cells and disrupts the crosstalk of tumour stroma. It can contribute to cancer cell progression inhibition and, conversely, to acquired resistance, enabling cancer cell metastasis and proliferation. The tumour's microenvironment is critical in controlling the dispersion and physiological activities of nano-chemotherapeutics which is one of the targeted drug therapy. As it is one of the methods of treating cancer that involves the use of medications or other substances to specifically target and kill off certain subsets of malignant cells. A targeted therapy may be administered alone or in addition to more conventional methods of care like surgery, chemotherapy, or radiation treatment. The tumour microenvironment, stromatogenesis, barriers and advancement in the drug delivery system across tumour tissue are summarised in this review.

7.
Curr Drug Deliv ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627785

RESUMO

Amongst different routes of drug delivery systems, ophthalmic drug delivery still requires a careful investigation and strict parameter measurements because the eyes are one of the most sensitive parts of the body and require special attention. The conventional systems for eyes lead to rapid elimination of formulation and hence very small contact time on the ocular epithelium. The current review article covers various types of polymers used in ocular drug delivery along with their applications/limitations. Polymers are widely used by researchers in prodrug techniques and as a penetration enhancer in ocular delivery. This article covers the role and use of different polymeric systems which makes the final formulation a promising candidate for ophthalmic drug delivery. The researchers are still facing multiple challenges in order to maintain the therapeutic concentration of the drug in the eyes because of its complex structure. There are several barriers that further restrict the intraocular entry of the drug. In order to remove/reduce such challenges, these days various types of polymers are used for ocular delivery in order to develop different drug carrier systems for better efficacy and stability. The polymers used are highly helpful in increasing residence time by increasing the viscosity at the ocular epithelium layer. Such preparations also get easily permeated in ocular cells. The combination of different polymeric properties makes the final formulation stable with prolonged retention, high viscosity, high permeability, and better bioavailability, making the final formulation a promising candidate for ocular drug delivery.

8.
ACS Omega ; 8(1): 10-41, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36643475

RESUMO

Carcinoma of the lungs is among the most menacing forms of malignancy and has a poor prognosis, with a low overall survival rate due to delayed detection and ineffectiveness of conventional therapy. Therefore, drug delivery strategies that may overcome undesired damage to healthy cells, boost therapeutic efficacy, and act as imaging tools are currently gaining much attention. Advances in material science have resulted in unique nanoscale-based theranostic agents, which provide renewed hope for patients suffering from lung cancer. Nanotechnology has vastly modified and upgraded the existing techniques, focusing primarily on increasing bioavailability and stability of anti-cancer drugs. Nanocarrier-based imaging systems as theranostic tools in the treatment of lung carcinoma have proven to possess considerable benefits, such as early detection and targeted therapeutic delivery for effectively treating lung cancer. Several variants of nano-drug delivery agents have been successfully studied for therapeutic applications, such as liposomes, dendrimers, polymeric nanoparticles, nanoemulsions, carbon nanotubes, gold nanoparticles, magnetic nanoparticles, solid lipid nanoparticles, hydrogels, and micelles. In this Review, we present a comprehensive outline on the various types of overexpressed receptors in lung cancer, as well as the various targeting approaches of nanoparticles.

9.
Drug Deliv Transl Res ; 13(1): 292-307, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35831776

RESUMO

Thymoquinone (TQ) is an antioxidant, anti-inflammatory, and hepatoprotective compound obtained from the black seed oil of Nigella sativa. However, high hydrophobicity, instability at higher pH levels, photosensitivity, and low oral bioavailability hinder its delivery to the target tissues. A self-nanoemulsifying drug delivery system (SNEDDS) was fabricated using the microemulsification technique to address these issues. Its physicochemical properties, thermodynamic stability studies, drug release kinetics, in vivo pharmacokinetics, and hepatoprotective activity were evaluated. The droplet size was in the nano-range (< 90 nm). Zeta potential was measured to be -11.35 mV, signifying the high stability of the oil droplets. In vivo pharmacokinetic evaluation showed a fourfold increase in the bioavailability of TQ-SNEDDS over pure TQ. Furthermore, in a PCM-induced animal model, TQ-SNEDDS demonstrated significant (p < 0.05) hepatoprotective activity compared to pure TQ and silymarin. Reduction in liver biomarker enzymes and histopathological examinations of liver sections further supported the results. In this study, SNEDDS was demonstrated to be an improved oral delivery method for TQ, since it potentiates hepatotoxicity and enhances bioavailability.


Assuntos
Sistemas de Liberação de Medicamentos , Disponibilidade Biológica
10.
Chem Biol Interact ; 369: 110296, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36496108

RESUMO

As the second-oldest atypical antipsychotic, risperidone has a long history of off-label usage for treating behavioural and psychological signs and symptoms of dementia (BPSD), such as agitation, aggressiveness, and psychosis. Risperidone has been shown in several trials to have a statistically significant benefit when used in a therapeutic context. Several lines of evidence suggest a possible role of risperidone via the antagonistic effect of Dopamine D2 and 5HT-receptor in different neurological diseases like cognitive dysfunction of schizophrenia, neuroinflammation, Huntington's disease, and sleep cycle management. Therefore, the pharmacological interactions of risperidone in all these diseases were investigated. Some reports on the use of risperidone in the treatment of dopaminergic psychosis have been slightly conflicting. However, more research is needed to evaluate the role of risperidone in the treatment of these neurological diseases.


Assuntos
Antipsicóticos , Doença de Huntington , Transtornos Psicóticos , Esquizofrenia , Humanos , Risperidona/farmacologia , Risperidona/uso terapêutico , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Doença de Huntington/tratamento farmacológico
11.
Indian J Ophthalmol ; 70(12): 4295-4299, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36453332

RESUMO

Purpose: This study was conducted to evaluate the accuracy of intraoperative aberrometry (IA) in intraocular lens (IOL) power calculation and compare it with conventional IOL formulas. Methods: This was a prospective case series. Eyes with visually significant cataract and axial hyperopia (AL <22.0 mm) underwent IA-assisted phacoemulsification with posterior chamber IOL (Alcon AcrySof IQ). Postoperative spherical equivalent (SE) was compared with predicted SE to calculate the outcomes with different formulas (SRK/T, Hoffer Q, Haigis, Holladay 2, Barrett Universal Ⅱ and Hill-RBF). Accuracy of intraoperative aberrometer was compared with other formulas in terms of mean absolute prediction error (MAE), percentage of patients within 0.5 D and 1 D of their target, and percentage of patients going into hyperopic shift. Results: Sixty-five eyes (57 patients) were included. In terms of MAE, both Hoffer Q (MAE = 0.30) and IA (MAE = 0.32) were significantly better than Haigis, SRK/T, and Barrett Universal Ⅱ (P < 0.05). Outcomes within ±0.5 D of the target were maximum with Hoffer Q (80%), superior to IA (Hoffer Q > IA > Holladay 2 > Hill-RBF > Haigis > SRK/T > Barrett Universal Ⅱ). Hoffer Q resulted in minimum hyperopic shift (30.76%) followed by Hill-RBF (38.46%), Holladay 2 (38.46%), Haigis (43.07%), and then IA (46.15%), SRK/T (50.76%) and Barrett Universal Ⅱ (53.84%). Conclusion: IA was more effective (statistically significant) in predicting IOL power than Haigis, SRK/T, and Barrett Universal Ⅱ although it was equivalent to Hoffer Q. Hoffer Q was superior to all formulas in terms of percentage of patients within 0.5 D of their target refractions and percentage of patients going into hyperopic shift.


Assuntos
Hiperopia , Lentes Intraoculares , Humanos , Aberrometria , Hiperopia/diagnóstico , Hiperopia/cirurgia , Biometria , Refração Ocular
13.
Cancer Cell Int ; 22(1): 386, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36482329

RESUMO

Therapeutic effect of phytochemicals has been emphasized in the traditional medicine owing to the presence of bioactive molecules, such as polyphenols. Luteolin is a flavone belonging to the flavonoid class of polyphenolic phytochemicals with healing effect on hypertension, inflammatory disorders, and cancer due to its action as pro-oxidants and antioxidants. The anticancer profile of luteolin is of interest due to the toxic effect of contemporary chemotherapy paradigm, leading to the pressing need for the development and identification of physiologically benevolent anticancer agents and molecules. Luteolin exerts anticancer activity by downregulation of key regulatory pathways associated with oncogenesis, in addition to the induction of oxidative stress, cell cycle arrest, upregulation of apoptotic genes, and inhibition of cell proliferation and angiogenesis in cancer cells. In this review, we discuss about the anticancer profile of luteolin.

14.
Transplantation ; 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36575574

RESUMO

BACKGROUND: We studied the variation in molecular T cell-mediated rejection (TCMR) activity in kidney transplant indication biopsies and its relationship with histologic lesions (particularly tubulitis and atrophy-fibrosis) and time posttransplant. METHODS: We examined 175 kidney transplant biopsies with molecular TCMR as defined by archetypal analysis in the INTERCOMEX study (ClinicalTrials.gov #NCT01299168). TCMR activity was defined by a molecular classifier. RESULTS: Archetypal analysis identified 2 TCMR classes, TCMR1 and TCMR2: TCMR1 had higher TCMR activity and more antibody-mediated rejection ("mixed") activity and arteritis but little hyalinosis, whereas TCMR2 had less TCMR activity but more atrophy-fibrosis. TCMR1 and TCMR2 had similar levels of molecular injury and tubulitis. Both TCMR1 and TCMR2 biopsies were uncommon after 2 y posttransplant and were rare after 10 y, particularly TCMR1. Within late TCMR biopsies, TCMR classifier activity and activity molecules such as IFNG fell progressively with time, but tubulitis and molecular injury were sustained. Atrophy-fibrosis was increased in TCMR biopsies, even in the first year posttransplant, and rose with time posttransplant. TCMR1 and TCMR2 both reduced graft survival, but in random forests, the strongest determinant of survival after biopsies with TCMR was molecular injury, not TCMR activity. CONCLUSIONS: TCMR varies in intensity but is always strongly related to molecular injury and atrophy-fibrosis, which ultimately explains its effect on survival. We hypothesize, based on the reciprocal relationship with hyalinosis, that the TCMR1-TCMR2 gradient reflects calcineurin inhibitor drug underexposure, whereas the time-dependent decline in TCMR activity and frequency after the first year reflects T-cell exhaustion.

15.
Pharmaceutics ; 14(12)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36559215

RESUMO

Biologic-based medicines are used to treat a variety of diseases and account for around one-quarter of the worldwide pharmaceutical market. The use of biologic medications among cancer patients has resulted in substantial advancements in cancer treatment and supportive care. Biosimilar medications (or biosimilars) are very similar to the reference biologic drugs, although they are not identical. As patent protection for some of the most extensively used biologics begins to expire, biosimilars have the potential to enhance access and provide lower-cost options for cancer treatment. Initially, regulatory guidelines were set up in Europe in 2003, and the first biosimilar was approved in 2006 in Europe. Many countries, including the United States of America (USA), Canada, and Japan, have adopted Europe's worldwide regulatory framework. The use of numerous biosimilars in the treatment and supportive care of cancer has been approved and, indeed, the count is set to climb in the future around the world. However, there are many challenges associated with biosimilars, such as cost, immunogenicity, lack of awareness, extrapolation of indications, and interchangeability. The purpose of this review is to provide an insight into biosimilars, which include various options available for oncology, and the associated adverse events. We compare the regulatory guidelines for biosimilars across the world, and also present the latest trends and challenges in medical oncology both now and in the future, which will assist healthcare professionals, payers, and patients in making informed decisions, increasing the acceptance of biosimilars in clinical practice, increasing accessibility, and speeding up the health and economic benefits associated with biosimilars.

16.
Kidney Int ; 2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36572246

RESUMO

Machine learning (ML) models have recently shown potential for predicting kidney allograft outcomes. However, their ability to outperform traditional approaches remains poorly investigated. Therefore, using large cohorts of kidney transplant recipients from 14 centers worldwide, we developed ML-based prediction models for kidney allograft survival and compared their prediction performances to those achieved by a validated Cox-Based Prognostication System (CBPS). In a French derivation cohort of 4000 patients, candidate determinants of allograft failure including donor, recipient and transplant-related parameters were used as predictors to develop tree-based models (RSF, RSF-ERT, CIF), Support Vector Machine models (LK-SVM, AK-SVM) and a gradient boosting model (XGBoost). Models were externally validated with cohorts of 2214 patients from Europe, 1537 from North America, and 671 from South America. Among these 8422 kidney transplant recipients, 1081 (12.84%) lost their grafts after a median post-transplant follow-up time of 6.25 years (Inter Quartile Range 4.33-8.73). At seven years post-risk evaluation, the ML models achieved a C-index of 0.788 (95% bootstrap percentile confidence interval 0.736-0.833), 0.779 (0.724-0.825), 0.786 (0.735-0.832), 0.527 (0.456-0.602), 0.704 (0.648-0.759) and 0.767 (0.711-0.815) for RSF, RSF-ERT, CIF, LK-SVM, AK-SVM and XGBoost respectively, compared with 0.808 (0.792-0.829) for the CBPS. In validation cohorts, ML models' discrimination performances were in a similar range of those of the CBPS. Calibrations of the ML models were similar or less accurate than those of the CBPS. Thus, when using a transparent methodological pipeline in validated international cohorts, ML models, despite overall good performances, do not outperform a traditional CBPS in predicting kidney allograft failure. Hence, our current study supports the continued use of traditional statistical approaches for kidney graft prognostication.

17.
Pharmaceutics ; 14(12)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36559281

RESUMO

A primary illness that accounts for a significant portion of fatalities worldwide is cancer. Among the main malignancies, lung cancer is recognised as the most chronic kind of cancer around the globe. Radiation treatment, surgery, and chemotherapy are some medical procedures used in the traditional care of lung cancer. However, these methods lack selectivity and damage nearby healthy cells. Several polysaccharide-based nanomaterials have been created to transport chemotherapeutics to reduce harmful and adverse side effects and improve response during anti-tumour reactions. To address these drawbacks, a class of naturally occurring polymers called polysaccharides have special physical, chemical, and biological characteristics. They can interact with the immune system to induce a better immunological response. Furthermore, because of the flexibility of their structures, it is possible to create multifunctional nanocomposites with excellent stability and bioavailability for the delivery of medicines to tumour tissues. This study seeks to present new views on the use of polysaccharide-based chemotherapeutics and to highlight current developments in polysaccharide-based nanomedicines for lung cancer.

19.
Ecancermedicalscience ; 16: 1459, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405939

RESUMO

Sarcoma pathology discrepancy is well known owing to the extremely heterogenous and rare nature of this tumour. Through this case, we want to highlight the difficulty that a patient has to undergo in a case of misdiagnosis. A 20-year-old male presented with swelling in the right foot for 4 months, which was initially diagnosed as alveolar rhabdomyosarcoma, subsequently as synovial sarcoma and finally as Ewing's sarcoma (based upon positive Ewing Sarcoma Breakpoint Region 1 (EWSR1) by fluorescence in situ hybridisation and he underwent neoadjuvant chemotherapy and surgical excision with grafting before he presented to our institute, where the pathologists reviewed the biopsy slides, which were positive for HMB45 and negative for Melan-A suggestive of clear cell sarcoma. The next-generation sequencing suggested EWSR1-ATF1 fusion, which again reinforced the diagnosis. This case throws light on the importance of expert pathology and interpreting molecular results in the right context.

20.
Curr Drug Deliv ; 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36380413

RESUMO

Molecular pharmaceutics play a critical role in the drug delivery system, representing the direct interconnection of drug bioavailability with its molecular form. There is a diversity in the molecular structures by which it affects its properties, such as amorphous form, crystalline form, partialamorphous molecular dispersion, and disordered state. The active pharmaceutical ingredient (API) and the excipients utilized in the formulation process contain various divergent modes used in the formulation process. They include better formulations of any type to obtain good quality pharmaceutical products. This review reveals how the molecular states affect the API and are important in maintaining the quality of dosage forms. Furthermore, the physio-chemical properties of the components and various pharmaceutical approaches employed in the formulation of dosage forms are studied from the point of view of molecular pharmaceutics.

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