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1.
Annu Rev Med ; 75: 145-157, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-37722709

RESUMEN

The treatment for COVID-19 has evolved rapidly since the start of the pandemic and now consists mainly of antiviral and immunomodulatory agents. Antivirals, such as remdesivir and nirmatrelvir-ritonavir, have proved to be most useful earlier in illness (e.g., as outpatient therapy) and for less severe disease. Immunomodulatory therapies, such as dexamethasone and interleukin-6 or Janus kinase inhibitors, are most useful in severe disease or critical illness. The role of anti-SARS-CoV-2 monoclonal antibodies has diminished because of the emergence of viral variants that are not anticipated to be susceptible to these treatments, and there still is not a consensus on the use of convalescent plasma. COVID-19 has been associated with increased rates of venous thromboembolism, but the role of antithrombotic therapy is limited. Multiple investigational agents continue to be studied, which will alter current treatment paradigms as new data are released.


Asunto(s)
COVID-19 , Inhibidores de las Cinasas Janus , Humanos , Sueroterapia para COVID-19 , Inmunomodulación , Interleucina-6 , Inhibidores de las Cinasas Janus/uso terapéutico
2.
Eur J Immunol ; 53(1): e2250010, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36239164

RESUMEN

Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with a dramatic increase in incidence since the beginning of the coronavirus disease 19 (COVID-19) pandemic. Neutrophils play a vital role in the immunopathology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by triggering the formation of neutrophil extracellular traps (NETs), producing cytokines including interleukin-8 (CXCL8), and mediating the recruitment of other immune cells to regulate processes such as acute and chronic inflammation, which can lead to ARDS. CXCL8 is involved in the recruitment, activation, and degranulation of neutrophils, and therefore contributes to inflammation amplification and severity of disease. Furthermore, activation of neutrophils also supports a prothrombotic phenotype, which may explain the development of immunothrombosis observed in COVID-19 ARDS. This review aims to describe hyperinflammatory ARDS due to SARS-CoV-2 infection. In addition, we address the critical role of polymorphonuclear neutrophils, inflammatory cytokines, and the potential targeting of CXCL8 in treating the hyperinflammatory ARDS population.


Asunto(s)
COVID-19 , Trampas Extracelulares , Síndrome de Dificultad Respiratoria , Humanos , COVID-19/patología , SARS-CoV-2 , Tromboinflamación , Activación Neutrófila , Neutrófilos , Inflamación/patología , Citocinas
3.
Trends Immunol ; 42(1): 31-44, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33281063

RESUMEN

The majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain paucisymptomatic, contrasting with a minority of infected individuals in danger of death. Here, we speculate that the robust disease resistance of most individuals is due to a swift production of type I interferon (IFNα/ß), presumably sufficient to lower the viremia. A minority of infected individuals with a preexisting chronic inflammatory state fail to mount this early efficient response, leading to a delayed harmful inflammatory response. To improve the epidemiological scenario, we propose combining: (i) the development of efficient antivirals administered early enough to assist in the production of endogenous IFNα/ß; (ii) potentiating early IFN responses; (iii) administering anti-inflammatory treatments when needed, but not too early to interfere with endogenous antiviral responses.


Asunto(s)
Antivirales/inmunología , COVID-19/inmunología , Factores Inmunológicos/inmunología , Interferón Tipo I/inmunología , SARS-CoV-2/inmunología , Enzima Convertidora de Angiotensina 2/inmunología , Enzima Convertidora de Angiotensina 2/metabolismo , Antivirales/metabolismo , Antivirales/uso terapéutico , COVID-19/virología , Citocinas/inmunología , Citocinas/metabolismo , Humanos , Factores Inmunológicos/metabolismo , Factores Inmunológicos/uso terapéutico , Interferón Tipo I/metabolismo , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/metabolismo , Serina Endopeptidasas/inmunología , Serina Endopeptidasas/metabolismo , Replicación Viral/efectos de los fármacos , Replicación Viral/inmunología , Tratamiento Farmacológico de COVID-19
4.
Pharmacol Res ; 199: 107032, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38061594

RESUMEN

Cancer is a leading cause of death worldwide. The burden of cancer incidence and mortality is increasing rapidly. New approaches to cancer prevention and treatment are urgently needed. Natural products are reliable and powerful sources for anticancer drug discovery. Baicalin and baicalein, two major flavones isolated from Scutellaria baicalensis Georgi, a multi-purpose traditional medicinal plant in China, exhibit anticancer activities against multiple cancers. Of note, these phytochemicals exhibit extremely low toxicity to normal cells. Besides their cytotoxic and cytostatic activities toward diverse tumor cells, recent studies demonstrated that baicalin and baicalein modulate a variety of tumor stromal cells and extracellular matrix (ECM) in the tumor microenvironment (TME), which is essential for tumorigenesis, cancer progression and metastasis. In this review, we summarize the therapeutic potential and the mechanism of action of baicalin and baicalein in the regulation of tumor microenvironmental immune cells, endothelial cells, fibroblasts, and ECM that reshape the TME and cancer signaling, leading to inhibition of tumor angiogenesis, progression, and metastasis. In addition, we discuss the biotransformation pathways of baicalin and baicalein, related therapeutic challenges and the future research directions to improve their bioavailability and clinical anticancer applications. Recent advances of baicalin and baicalein warrant their continued study as important natural ways for cancer interception and therapy.


Asunto(s)
Flavanonas , Neoplasias , Humanos , Microambiente Tumoral , Células Endoteliales/metabolismo , Flavonoides/farmacología , Flavonoides/uso terapéutico , Flavonoides/metabolismo , Flavanonas/farmacología , Flavanonas/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/patología
5.
Bioorg Med Chem Lett ; 99: 129599, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38185345

RESUMEN

Compared to small molecules and antibodies, cyclic peptides exhibit unique biochemical and therapeutic attributes in the realm of pharmaceutical applications. The interaction between the inducible costimulator (ICOS) and its ligand (ICOSL) plays a key role in T-cell differentiation and activation. ICOS/ICOSL inhibition results in a reduction in the promotion of immunosuppressive regulatory T cells (Tregs) in both hematologic malignancies and solid tumors. Herein, we implement the computational cPEPmatch approach to design the first examples of cyclic peptides that inhibit ICOS/ICOSL interaction. The top cyclic peptide from our approach possessed an IC50 value of 1.87 ± 0.15 µM as an ICOS/ICOSL inhibitor and exhibited excellent in vitro pharmacokinetic properties as a drug candidate. Our work will lay the groundwork for future endeavors in cancer drug discovery, with the goal of developing cyclic peptides that target the ICOS/ICOSL interaction.


Asunto(s)
Antineoplásicos , Linfocitos T Reguladores , Anticuerpos , Antineoplásicos/farmacología , Proteína Coestimuladora de Linfocitos T Inducibles , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología
6.
Support Care Cancer ; 32(7): 407, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38833106

RESUMEN

OBJECTIVE: Poor adherence to oral chemotherapy adversely impacts clinical outcomes and escalates overall healthcare costs. Despite barriers to medication adherence, a significant gap remains in assessing adherence to oral chemotherapy among multiple myeloma (MM) patients with lower socioeconomic status. Hence, our study aims to evaluate immunomodulator adherence in MM patients at a county hospital, primarily serving underrepresented and indigent individuals with low socioeconomic status across the greater Houston area. METHODS: Inclusion criteria composed of patients diagnosed with MM, aged at least 18 years, and treated with lenalidomide or pomalidomide-two widely used immunomodulators-for a minimum of 2 months or having two or more records of dispensation between May 2019 and May 2021. Adherence was gauged using an adjusted version of the medication possession ratio (MPR). RESULTS: Sixty-two patients were enrolled, yielding a mean MPR value of 88% (SD, ± 18.9). Of these, 43 patients (69.3%) demonstrated adherence with an MPR of ≥ 0.90. A significant difference was found in treatment duration between the adherent (mean 8.8 months; SD, ± 7.2) and non-adherent (mean 13.4 months; SD, ± 7.9) groups (p = 0.027). Notably, race/ethnicity demonstrated a significant difference (p = 0.048), driven by disparities in African American and Hispanic representation across adherence levels. CONCLUSION: In summary, our findings highlight race and treatment duration to be predictors of immunomodulator adherence among MM patients with lower socioeconomic status. Further research is imperative to devise and test innovative interventions aimed at enhancing medication adherence, thereby contributing to improved survival and healthcare quality in this population.


Asunto(s)
Lenalidomida , Cumplimiento de la Medicación , Mieloma Múltiple , Clase Social , Talidomida , Humanos , Mieloma Múltiple/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Cumplimiento de la Medicación/estadística & datos numéricos , Femenino , Persona de Mediana Edad , Anciano , Talidomida/uso terapéutico , Talidomida/análogos & derivados , Talidomida/administración & dosificación , Lenalidomida/administración & dosificación , Lenalidomida/uso terapéutico , Factores Inmunológicos/uso terapéutico , Factores Inmunológicos/administración & dosificación , Agentes Inmunomoduladores/uso terapéutico , Agentes Inmunomoduladores/administración & dosificación , Agentes Inmunomoduladores/farmacología , Texas , Anciano de 80 o más Años , Adulto
7.
Adv Exp Med Biol ; 1447: 139-149, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38724791

RESUMEN

Dupilumab and tralokinumab are currently the only FDA-approved biologic therapies for the treatment of moderate-to-severe atopic dermatitis. Tralokinumab is approved for patients greater than 18 years old, and dupilumab is approved for patients as young as 6 months old. Both medications are effective in clinical trials at improving atopic dermatitis. With a good safety profile and low-risk adverse events, dupilumab and tralokinumab are generally excellent treatment options for patients with severe or refractory atopic dermatitis.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales , Dermatitis Atópica , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Terapia Biológica/métodos , Resultado del Tratamiento
8.
Hepatobiliary Pancreat Dis Int ; 23(2): 195-209, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37806848

RESUMEN

BACKGROUND: As reported, γ-tubulin (TuBG1) is related to the occurrence and development of various types of malignant tumors. However, its role in hepatocellular cancer (HCC) is not clear. The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients. METHODS: The correlation between TuBG1 and clinical parameters and survival in HCC patients was explored by bioinformatics analysis. Immunohistochemistry was used for the verification. The molecular function of TuBG1 was measured using colony formation, scratch assay, trans-well assay and flow cytometry. Gene set enrichment analysis (GSEA) was used to pick up the enriched pathways, followed by investigating the target pathways using Western blotting. The tumor-immune system interactions and drug bank database (TISIDB) was used to evaluate TuBG1 and immunity. Based on the TuBG1-related immune genes, a prognostic model was constructed and was further validated internally and externally. RESULTS: The bioinformatic analysis found high expressed TuBG1 in HCC tissue, which was confirmed using immunohistochemistry and Western blotting. After silencing the TuBG1 in HCC cell lines, more G1 arrested cells were found, cell proliferation and invasion were inhibited, and apoptosis was promoted. Furthermore, the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3 (ATR), phospho-P38 mitogen-activated protein kinase (P-P38MAPK), phospho-P53 (P-P53), B-cell lymphoma-2 associated X protein (Bax), cleaved caspase 3 and P21; decreased the expressions of B-cell lymphoma-2 (Bcl-2), cyclin D1, cyclin E2, cyclin-dependent kinase 2 (CDK2) and CDK4. The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively correlated with the overall survival. The constructed immune prognosis model could effectively evaluate the prognosis. CONCLUSIONS: The increased expression of TuBG1 in HCC is associated with poor prognosis, which might be involved in the occurrence and development of HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/farmacología , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/farmacología , Apoptosis , Proliferación Celular , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/farmacología , Regulación Neoplásica de la Expresión Génica , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/farmacología
9.
J Allergy Clin Immunol ; 152(6): 1470-1492, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37678577

RESUMEN

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD systemic treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). RESULTS: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.


Asunto(s)
Asma , Dermatitis Atópica , Eccema , Humanos , Dermatitis Atópica/tratamiento farmacológico , Metaanálisis en Red , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
10.
Molecules ; 29(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38731500

RESUMEN

A robust, well-functioning immune system is the cornerstone of good health. Various factors may influence the immune system's effectiveness, potentially leading to immune system failure. This review aims to provide an overview of the structure and action of immunomodulators isolated from African medicinal plants. The research was conducted according to PRISMA guidelines. Full-text access research articles published in English up to December 2023, including plant characteristics, isolated phytochemicals, and immuno-modulatory activities, were screened. The chemical structures of the isolated compounds were generated using ChemDraw® (version 12.0.1076), and convergent and distinctive signaling pathways were highlighted. These phytochemicals with demonstrated immunostimulatory activity include alkaloids (berberine, piperine, magnoflorine), polysaccharides (pectin, glucan, acemannan, CALB-4, GMP90-1), glycosides (syringin, cordifolioside, tinocordiside, aucubin), phenolic compounds (ferulic acid, vanillic acid, eupalitin), flavonoids (curcumin, centaurein, kaempferin, luteolin, guajaverin, etc.), terpenoids (oleanolic acid, ursolic acid, betulinic acid, boswellic acids, corosolic acid, nimbidin, andrographolides). These discussed compounds exert their effects through various mechanisms, targeting the modulation of MAPKs, PI3K-Akt, and NF-kB. These mechanisms can support the traditional use of medicinal plants to treat immune-related diseases. The outcomes of this overview are to provoke structural action optimization, to orient research on particular natural chemicals for managing inflammatory, infectious diseases and cancers, or to boost vaccine immunogenicity.


Asunto(s)
Fitoquímicos , Plantas Medicinales , Plantas Medicinales/química , Fitoquímicos/farmacología , Fitoquímicos/química , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación , África , Animales
11.
Inflammopharmacology ; 32(3): 1777-1789, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38581639

RESUMEN

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by itching and skin barrier dysfunction. Moderate to severe AD is often refractory to first-line topical treatments, and systemic immunosuppressants have been shown to be effective but have significant adverse effects. The paucity of basic treatments has contributed to the development of targeted topical and systemic immunotherapies based on the use of small molecules and biologic drugs which can directly interact with AD pathogenetic pathways. They represent a new era of therapeutic innovation. Additional new treatments are desirable since AD is a heterogeneous disease marked by different immunological phenotypes. This manuscript will review the mechanism of action, safety profile, and efficacy of promising new systemic immunological treatments for AD. Since moderate to severe AD can result in poor quality of life, the development of targeted and well-tolerated immunomodulators is a crucial purpose. The introduction of new pharmacological agents may offer new therapeutic options. However, there is the need to evaluate how "narrow-acting" agents, such as individual interleukin inhibitors, will perform under the safety and efficacy profiles compared with "broad-acting" agents, such as JAK inhibitors.


Asunto(s)
Dermatitis Atópica , Inmunoterapia , Humanos , Dermatitis Atópica/terapia , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Inmunoterapia/métodos , Animales , Calidad de Vida , Inmunosupresores/uso terapéutico , Factores Inmunológicos/uso terapéutico , Factores Inmunológicos/farmacología
12.
Molecules ; 29(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38611808

RESUMEN

An investigation was carried out on humic substances (HSs) isolated from the coal of the Kansk-Achinsk basin (Krasnoyarsk Territory, Russia). The coal HSs demonstrate the main parameters of molecular structure inherent to this class of natural compounds. An assessment was performed for the chemical, microbiological, and pharmacological safety parameters, as well as the biological efficacy. The HS sample meets the safety requirements in microbiological purity, toxic metals content (lead, cadmium, mercury, arsenic), and radionuclides. The presence of 11 essential elements was determined. The absence of general, systemic toxicity, cytotoxicity, and allergenic properties was demonstrated. The coal HS sample was classified as a Class V hazard (low danger substances). High antioxidant and antiradical activities and immunotropic and cytoprotective properties were identified. The ability of the HS to inhibit hydroxyl radicals and superoxide anion radicals was revealed. Pronounced actoprotective and nootropic activities were also demonstrated in vivo. Intragastric administration of the HS sample resulted in the improvement of physical parameters in mice as assessed by the "swim exhaustion" test. Furthermore, intragastric administration in mice with cholinergic dysfunction led to a higher ability of animals with scopolamine-induced amnesia to form conditioned reflexes. These findings suggest that the studied HS sample is a safe and effective natural substance, making it suitable for use as a dietary bioactive supplement.


Asunto(s)
Arsénico , Sustancias Húmicas , Animales , Ratones , Amnesia , Antioxidantes/farmacología , Carbón Mineral
13.
Acta Neurol Taiwan ; 33(4): 175-184, 2024 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-38073167

RESUMEN

PURPOSE: With the extensive presence of Covid-19, it is imperative to find compounds that can obstruct the virus's inflammatory activity and perhaps even stop the inflammatory phase from occurring. Several neuropeptides act as immune system regulators, which nerve terminals release as co-transmitters. It has been suggested that Neuropeptide Y (NPY) may be involved in inflammatory diseases through its ability to regulate the function of inflammatory cells. Consequently, the present study was designed to examine the changes in this neuropeptide in the serum of patients with Covid-19 disease, particularly following anti-inflammatory treatment, and its relationship with other inflammatory factors such as TNF-α. METHODS: The demographic information, vital and clinical signs (blood oxygen saturation level, blood pressure, heart rate, and body temperature), laboratory factors such as blood factors, inflammation, and blood electrolytes, as well as the use of steroids, were collected before and after steroid treatment the patient files. As part of the study, serum samples from patients were used to measure levels of NPY and TNF-α inflammatory factors using an ELISA kit. Additionally, the correlation between NPY values, other inflammatory factors, and other variables was examined before and after treatment. RESULTS: NPY, TNF-α, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels were significantly reduced after steroid treatment. But the blood urea nitrogen (BUN) factor level increased after treatment compared to the initial evaluation. Lymphocytes and neutrophils also changed after drug treatment. Results indicated a high correlation between NPY and TNF-α. In addition to TNF-α, NPY, creatinine, and BUN presented a direct and significant relationship. ESR and BUN factors showed a positive and significant correlation regarding the length of hospitalization. However, the correlation between NPY and TNF-α with hospitalization length was insignificant. CONCLUSION: Since the current study had a significant association between NPY and TNF-α, the regulating function of this peptide in Covid-19 inflammatory processes may be validated. Enough that it is crucial to consider NPY as a marker and its antagonist as a potential Covid-19 therapy. Also, the considerable reduction in NPY levels after steroid therapy to lower inflammatory variables supports the regulatory function of this peptide in inflammatory processes.


Asunto(s)
COVID-19 , Neuropéptido Y , Humanos , Neuropéptido Y/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Hospitales , Esteroides
14.
Int Ophthalmol ; 44(1): 157, 2024 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-38522059

RESUMEN

PURPOSE: This meta-analysis aimed to review the safety and efficacy of topical cyclosporine A (CsA) and topical tacrolimus in allergic eye disease. METHODS: A systematic search identified thirteen studies and a total of 445 patients for inclusion, making this the largest meta-analysis published on the subject. The current review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Thirteen randomized control trials were included in the meta-analysis. Eleven studies used CsA as the treatment, and two used Tacrolimus. In total, 445 participants were included, of whom 76.6% were male. The mean age of participants across the included studies was 14 years. All studies reported clinical signs as evaluated by an examining clinician. Signs were usually assessed by anatomical region, with the most common regions being the conjunctiva and the cornea, and the most common signs assessed were hyperemia and papillae. Three studies accounted for more than 50% of the meta-analysis's weight. Effect size (d) ranged from - 2.37 to - 0.03, negative values favoring immunomodulators. Fixed Effect Meta-Analysis returned an SMD of - 0.81 (95% CI [- 0.98, - 0.65]). However, there was significant heterogeneity (I2 = 61%, Qw = 30.76) in the outcome measure (P = 0.0021); therefore, a random-effect meta-analysis was also completed in which the pooled SMD was - 0.98 (95% CI [- 1.26, - 0.69], τ2 = 0.16). CONCLUSIONS: This study affirms the current scientific community's stance that immunomodulators effectively treat clinical signs, including blepharitis, conjunctival hyperemia, edema, papillae, and corneal damage in severe ocular allergic disease.


Asunto(s)
Conjuntivitis Alérgica , Hiperemia , Queratoconjuntivitis , Humanos , Masculino , Adolescente , Femenino , Conjuntivitis Alérgica/diagnóstico , Conjuntivitis Alérgica/tratamiento farmacológico , Tacrolimus , Factores Inmunológicos , Queratoconjuntivitis/diagnóstico , Queratoconjuntivitis/tratamiento farmacológico , Conjuntiva , Ciclosporina
15.
Int Ophthalmol ; 44(1): 49, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38337030

RESUMEN

PURPOSE: Dry eye disease (DED) is a prevalent ocular surface disease that is conventionally characterized by tear film hyperosmolarity and instability. This review presents a summarized classification of DED, followed by a comprehensive discussion of the most recent topical and systemic medications and clinical recommendations for selecting the most appropriate option for each patient. METHODS: An extensive literature search was conducted on electronic databases, such as PubMed, Scopus, and Web of Science, using keywords including "dry eye syndrome," "ocular surface disease," "medical management," "artificial tears," "topical immunomodulators," and "meibomian gland dysfunction." RESULTS: The underlying reasons for DED can range from insufficient aqueous tear production to increased tear evaporation. Recent literature has provided a more in-depth understanding of the pathophysiology of DED by examining the tear film's lipid, aqueous, and mucin layers. However, despite these advancements, medical management of patients with symptomatic DED has not fully reflected this modernized knowledge of its pathophysiology. CONCLUSION: To develop a rationalized strategy for treating DED, it is crucial to have updated knowledge of therapeutic options, their mechanisms of actions, and indications based on the DED type and underlying causes.


Asunto(s)
Síndromes de Ojo Seco , Disfunción de la Glándula de Meibomio , Humanos , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/etiología , Lágrimas/fisiología , Disfunción de la Glándula de Meibomio/complicaciones
16.
Mol Cancer ; 22(1): 40, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36810079

RESUMEN

Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are gaining ground in the treatment of lung cancer. Recent advances in adoptive cell therapy (CAR T, TCR, TIL), the associated clinical trials on lung cancer, and associated hurdles are discussed in this review. Recent trials on lung cancer patients (without a targetable oncogenic driver alteration) reveal significant and sustained responses when treated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint blockade immunotherapies. Accumulating evidence indicates that a loss of effective anti-tumor immunity is associated with lung tumor evolution. Therapeutic cancer vaccines combined with immune checkpoint inhibitors (ICI) can achieve better therapeutic effects. To this end, the present article encompasses a detailed overview of the recent developments in the immunotherapeutic landscape in targeting small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Additionally, the review also explores the implication of nanomedicine in lung cancer immunotherapy as well as the combinatorial application of traditional therapy along with immunotherapy regimens. Finally, ongoing clinical trials, significant obstacles, and the future outlook of this treatment strategy are also highlighted to boost further research in the field.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Recurrencia Local de Neoplasia , Carcinoma Pulmonar de Células Pequeñas/terapia
17.
FASEB J ; 36(1): e22090, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34907595

RESUMEN

Despite many advances in infection control practices, including prophylactic antibiotics, surgical site infections (SSIs) remain a significant cause of morbidity, prolonged hospitalization, and death worldwide. Our innate immune system possesses a multitude of powerful antimicrobial strategies which make it highly effective in combating bacterial, fungal, and viral infections. However, pathogens use various stealth mechanisms to avoid the innate immune system, which in turn buy them time to colonize wounds and damage tissues at surgical sites. We hypothesized that immunomodulators that can jumpstart and activate innate immune responses at surgical sites, would likely reduce infection at surgical sites. We used three immunomodulators; fMLP (formyl-Methionine-Lysine-Proline), CCL3 (MIP-1α), and LPS (Lipopolysaccharide), based on their documented ability to elicit strong inflammatory responses; in a surgical wound infection model with Pseudomonas aeruginosa to evaluate our hypothesis. Our data indicate that one-time topical treatment with these immunomodulators at low doses significantly increased proinflammatory responses in infected and uninfected surgical wounds and were as effective, (or even better), than a potent prophylactic antibiotic (Tobramycin) in reducing P. aeruginosa infection in wounds. Our data further show that immunomodulators did not have adverse effects on tissue repair and wound healing processes. Rather, they enhanced healing in both infected and uninfected wounds. Collectively, our data demonstrate that harnessing the power of the innate immune system by immunomodulators can significantly boost infection control and potentially stimulate healing. We propose that topical treatment with these immunomodulators at the time of surgery may have therapeutic potential in combating SSI, alone or in combination with prophylactic antibiotics.


Asunto(s)
Factores Inmunológicos/farmacología , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/inmunología , Infección de la Herida Quirúrgica/tratamiento farmacológico , Animales , Evaluación de Medicamentos , Ratones , Ratones Noqueados , Infecciones por Pseudomonas/inmunología , Infección de la Herida Quirúrgica/inmunología , Infección de la Herida Quirúrgica/microbiología
18.
Expert Opin Emerg Drugs ; 28(4): 311-332, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38100555

RESUMEN

INTRODUCTION: Despite the recent full FDA approval of lecanemab, there is currently no disease modifying therapy (DMT) that can efficiently slow down the progression of Alzheimer's disease (AD) in the general population. This statement emphasizes the need to identify novel DMTs in the shortest time possible to prevent a global epidemic of AD cases as the world population experiences an increase in lifespan. AREAS COVERED: Here, we review several classes of anti-cancer drugs that have been or are being investigated in Phase II/III clinical trials for AD, including immunomodulatory drugs, RXR agonists, sex hormone therapies, tyrosine kinase inhibitors, and monoclonal antibodies. EXPERT OPINION: Given the overall course of brain pathologies during the progression of AD, we express a great enthusiasm for the repositioning of anti-cancer drugs as possible AD DMTs. We anticipate an increasing number of combinatorial therapy strategies to tackle AD symptoms and their underlying pathologies. However, we strongly encourage improvements in clinical trial study designs to better assess target engagement and possible efficacy over sufficient periods of drug exposure.


Asunto(s)
Enfermedad de Alzheimer , Antineoplásicos , Reposicionamiento de Medicamentos , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico
19.
J Am Acad Dermatol ; 89(2): 338-344, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37156337

RESUMEN

Atopic dermatitis is a chronic inflammatory skin condition with a high prevalence that is increasing. The most universal symptom in patients with atopic dermatitis is pruritus; it is often the most troublesome symptom. New insights on the mechanism of itch in patients with eczema have been elucidated, involving cross-talk between neural and immune systems, which have advanced our treatments significantly. In the last few years, there are emerging treatments currently undergoing investigation that yield a promising outlook in treating this symptom. In this review, we aimed to provide an updated overview of future treatments undergoing phase II and III clinical trials that may be used to treat pruritus of atopic dermatitis.


Asunto(s)
Dermatitis Atópica , Humanos , Dermatitis Atópica/complicaciones , Dermatitis Atópica/tratamiento farmacológico , Prurito/tratamiento farmacológico , Prurito/etiología
20.
Support Care Cancer ; 32(1): 35, 2023 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-38103099

RESUMEN

PURPOSE: The use of immunomodulators in the treatment of multiple myeloma (MM) patients has been associated with venous thromboembolism (VTE). Due to the increase in mortality of cancer patients, venous thromboembolism is an important concern for newly diagnosed multiple myeloma (NDMM) patients. The aim of this study was to determine the incidence of thromboembolic events and evaluate associated risk factors among Brazilian NDMM patients using immunomodulators. METHODS: Real-life retrospective cohort study in two Brazilian institutions with newly diagnosed multiple myeloma (NDMM) patients treated with immunomodulators from January 2009 to December 2019. Data was collected from patients' medical records for the period of 1 year, and Cox regression was performed to identify risk factors on the development of VTE. RESULTS: We included 131 patients of which there was a mean age of 61.5 years (SD 11.3), 51.9% female, and predominantly using thalidomide (97.7%) as immunomodulator. We found 9 VTE episodes among our patients, with a 12-month cumulative incidence of 6.97% (95% CI 3.41-12.24). Associated factors after multivariate analysis were recent sepsis, recent traumatic injury, previous VTE, and thromboprophylaxis. CONCLUSION: Our real-life retrospective cohort presented a low incidence of VTE among Brazilian NDMM patients treated with immunomodulators.


Asunto(s)
Mieloma Múltiple , Tromboembolia Venosa , Humanos , Femenino , Persona de Mediana Edad , Masculino , Mieloma Múltiple/complicaciones , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Estudios Retrospectivos , Incidencia , Brasil/epidemiología , Anticoagulantes/uso terapéutico , Agentes Inmunomoduladores , Factores Inmunológicos/uso terapéutico , Factores de Riesgo , Adyuvantes Inmunológicos/uso terapéutico
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