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1.
Cureus ; 13(12): e20431, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35047268

RESUMO

The role of vitamin D receptor (VDR) has been well established and extensively studied in the hair cycle. Its deficiency is also closely linked to several types of alopecia, including alopecia areata, telogen effluvium, and androgenetic alopecia (AGA). Since there is limited research on the correlation between androgenetic alopecia and low serum vitamin D levels, our review aims to find relevant articles and comprehensively present them. A review of the literature was performed to gain insight into AGA. Specifically, PubMed and Google Scholar databases were searched to identify any relevant articles with a focus on androgenetic alopecia, male pattern baldness, and serum vitamin D levels. References within the included articles were also reviewed and taken into the study if found appropriate. All articles that met the inclusion criteria were analyzed for demographics, clinical, laboratory, radiographic, treatment, and outcomes data. We found 13 relevant studies that elucidated the relationship between low serum vitamin D levels and androgenetic alopecia and included them in the review. We concluded that serum vitamin D might be a possible parameter for diagnosing the onset and severity of AGA. Vitamin D supplementation has proven to be useful in the regrowth of hair in non-human subjects. Vitamin D could be a valid therapeutic approach, such as topical vitamin D (calcipotriol) seems to be a good treatment option to regrow hair follicles and prevent miniaturization of follicles due to androgenetic alopecia.

2.
J Clin Invest ; 130(11): 6093-6108, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32780722

RESUMO

Recent genome-wide association studies (GWAS) identified DUSP8, encoding a dual-specificity phosphatase targeting mitogen-activated protein kinases, as a type 2 diabetes (T2D) risk gene. Here, we reveal that Dusp8 is a gatekeeper in the hypothalamic control of glucose homeostasis in mice and humans. Male, but not female, Dusp8 loss-of-function mice, either with global or corticotropin-releasing hormone neuron-specific deletion, had impaired systemic glucose tolerance and insulin sensitivity when exposed to high-fat diet (HFD). Mechanistically, we found impaired hypothalamic-pituitary-adrenal axis feedback, blunted sympathetic responsiveness, and chronically elevated corticosterone levels driven by hypothalamic hyperactivation of Jnk signaling. Accordingly, global Jnk1 ablation, AAV-mediated Dusp8 overexpression in the mediobasal hypothalamus, or metyrapone-induced chemical adrenalectomy rescued the impaired glucose homeostasis of obese male Dusp8-KO mice, respectively. The sex-specific role of murine Dusp8 in governing hypothalamic Jnk signaling, insulin sensitivity, and systemic glucose tolerance was consistent with functional MRI data in human volunteers that revealed an association of the DUSP8 rs2334499 risk variant with hypothalamic insulin resistance in men. Further, expression of DUSP8 was increased in the infundibular nucleus of T2D humans. In summary, our findings suggest the GWAS-identified gene Dusp8 as a novel hypothalamic factor that plays a functional role in the etiology of T2D.


Assuntos
Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Tipo 2/enzimologia , Fosfatases de Especificidade Dupla/metabolismo , Hipotálamo/enzimologia , Resistência à Insulina , MAP Quinase Quinase 4/metabolismo , Transdução de Sinais , Animais , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Fosfatases de Especificidade Dupla/genética , MAP Quinase Quinase 4/genética , Camundongos , Camundongos Knockout
3.
PLoS One ; 6(8): e23360, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21858087

RESUMO

BACKGROUND: In spite of a consistent protection against tuberculosis (TB) in children, Mycobacterium bovis Bacille Calmette-Guerin (BCG) fails to provide adequate protection against the disease in adults as well as against reactivation of latent infections or exogenous reinfections. It has been speculated that failure to generate adequate memory T cell response, elicitation of inadequate immune response against latency-associated antigens and inability to impart long-term immunity against M. tuberculosis infections are some of the key factors responsible for the limited efficiency of BCG in controlling TB. METHODS/PRINCIPAL FINDINGS: In this study, we evaluated the ability of a DNA vaccine expressing α-crystallin--a key latency antigen of M. tuberculosis to boost the BCG induced immunity. 'BCG prime-DNA boost' regimen (B/D) confers robust protection in guinea pigs along with a reduced pathology in comparison to BCG vaccination (1.37 log(10) and 1.96 log(10) fewer bacilli in lungs and spleen, respectively; p<0.01). In addition, B/D regimen also confers enhanced protection in mice. Further, we show that B/D immunization in mice results in a heightened frequency of PPD and antigen specific multi-functional CD4 T cells (3(+)) simultaneously producing interferon (IFN)γ, tumor necrosis factor (TNF)α and interleukin (IL)2. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of α-crystallin based B/D regimen over BCG. Our study, also demonstrates that protection against TB is predictable by an increased frequency of 3(+) Th1 cells with superior effector functions. We anticipate that this study would significantly contribute towards the development of superior booster vaccines for BCG vaccinated individuals. In addition, this regimen can also be expected to reduce the risk of developing active TB due to reactivation of latent infection.


Assuntos
Vacina BCG/imunologia , Proteínas de Bactérias/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Vacinas de DNA/imunologia , alfa-Cristalinas/imunologia , Adulto , Animais , Vacina BCG/administração & dosagem , Proteínas de Bactérias/genética , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Feminino , Citometria de Fluxo , Granuloma/imunologia , Granuloma/patologia , Granuloma/prevenção & controle , Cobaias , Humanos , Imunização Secundária/métodos , Interferon gama/imunologia , Interferon gama/metabolismo , Rim/efeitos dos fármacos , Rim/imunologia , Rim/patologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Pneumopatias/imunologia , Pneumopatias/patologia , Pneumopatias/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium bovis/imunologia , Mycobacterium tuberculosis/genética , Tuberculose/prevenção & controle , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Vacinas de DNA/administração & dosagem , alfa-Cristalinas/genética
4.
Nat Prod Res ; 24(6): 534-41, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20182947

RESUMO

The aim of the present study was to assess the wound-healing activity of ethanolic extracts of Acorus calamus leaves. A wound was induced by an excision- and incision-based wound model in rats of either sex. The mature green leaves of A. calamus were collected and authenticated. Extractions of dried leaves were carried out with 80% ethanol in a soxhlet apparatus. For wound-healing activity, the extracts were applied topically once daily in conc. of 40% w/w and 20% w/w in the form of ointment and compared with a standard drug (povidion-iodine). The healing of the wound was assessed by the rate of wound closure, period of epithelialisation, tensile strength and weight of the granulation tissue, hydroxyproline content and histopathology of the granulation tissue. The ethanolic extract of A. calamus promoted wound-healing activity significantly in both the wound models studied. The histological study of the granulation tissue with 20% A. calamus extract ointment-treated animals showed a larger number of inflammatory cells and lesser collagen when compared with the 40% A. calamus extract ointment-treated animals. However, this was better than the control group of animals. Enhanced wound contraction, decreased epithelialisation time, increased hydroxyproline content and histological characteristics suggest that A. calamus extract may have therapeutic benefits in wound healing.


Assuntos
Acoraceae , Fitoterapia , Extratos Vegetais/uso terapêutico , Cicatrização/efeitos dos fármacos , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Masculino , Extratos Vegetais/farmacologia , Folhas de Planta , Povidona-Iodo/uso terapêutico , Ratos , Ratos Wistar
6.
Int J Parasitol ; 38(2): 137-41, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17991467

RESUMO

The protozoan parasite Entamoeba histolytica is the etiologic agent of amebiasis, a major global public health problem, particularly in developing countries. There is an effective anti-amoebic drug available, however its long term use produces undesirable side effects. As E. histolytica is a micro-aerophilic organism, it is sensitive to high levels of oxygen and the enzymes that are involved in protecting against oxygen-stress are crucial for its survival. Therefore serine acetyltransferase, an enzyme involved in cysteine biosynthesis, was used as a target for identifying potential inhibitors. Virtual screening with Escherichia coli serine acetyltransferase was carried out against the National Cancer Institute chemical database utilizing molecular docking tools such as GOLD and FlexX. The initial analysis yielded 11 molecules of which three compounds were procured and tested for biological activity. The results showed that these compounds partially block activity of the E. coli enzyme and the growth of E. histolytica trophozoites but not mammalian cells.


Assuntos
Antiprotozoários/uso terapêutico , Entamoeba histolytica/fisiologia , Escherichia coli/enzimologia , Serina O-Acetiltransferase/antagonistas & inibidores , Animais , Bases de Dados de Proteínas , Entamebíase/prevenção & controle , Engenharia Genética , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Serina O-Acetiltransferase/genética , Trofozoítos/efeitos dos fármacos
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