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Signal Transduct Target Ther ; 6(1): 405, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795208


Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Front Immunol ; 11: 583274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072131


Background: A complex interplay between different cell types in the epithelium leads to activation of the luminal acidifying capacity of the epididymis, a process that is crucial for sperm maturation and storage. Basal cells sense the luminal angiotensin II (ANG II) and stimulate proton secretion in clear cells through nitric oxide (NO). Our previous study has shown the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) was expressed in the F4/80 positive macrophages of human epididymis. The objective of this study was to explore the involvement of RANTES in regulating the luminal acidification in the rat epididymis. Methods: The role of RANTES was investigated by in vivo perfusion with recombinant RANTES, Met-RANTES, and PBS of different pH values. Furthermore, rats vasectomy was performed to alter the epididymal luminal pH. RIA was used to measure the tissue homogenate ANG II concentration. Real time-PCR and western blot were employed to examine the expression levels of AGTR2, RANTES, CCR1, CCR5, and iNOS in epididymis. Results: RANTES was restricted to the basal macrophages of epididymal ducts and co-localized with its receptors CCR1 and CCR5. Both V-ATPase and iNOS were up-regulated in the cauda epididymis after perfused with recombinant RANTES, while the antagonist Met-RANTES perfusion led to a complete abrogation of the increased expression of V-ATPase in the apical membrane of clear cells and iNOS in macrophages. Upon alkaline perfusion, RANTES expression was significantly increased and the apical accumulation of V-ATPase in the clear cells was induced in the cauda epididymis. The luminal pH in the cauda epididymis increased after vasectomy. The concentration of the ANG II and the expression levels of AGTR2, RANTES, CCR1, CCR5, and iNOS dropped in the cauda epididymis following vasectomy. Conclusion: Upon the activation of basal cells, RANTES might induce the NO release from macrophages by interacting with its receptors, which increases proton secretion by adjacent clear cells. Thus, RANTES is possible to participate in the crosstalk among basal cells, macrophages and clear cells for the fine control of an optimum acidic luminal environment that is critical for male fertility.

Quimiocina CCL5/metabolismo , Epididimo/metabolismo , Maturação do Esperma/fisiologia , Animais , Quimiocina CCL5/imunologia , Epididimo/imunologia , Concentração de Íons de Hidrogênio , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
Hemoglobin ; 42(5-6): 342-343, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30626226


Hb A2 (α2δ2) is one of the key components looked for in hemoglobinopathies screening programs. Therefore, quantitative and accurate method for Hb A2 value determination is essential for routine screening. Here, we report a case of Hb A2 and Hb Constant Spring (Hb CS, HBA2: c.427T>C) with Hb H-Hb CS disease that was not detected by high performance liquid chromatography (HPLC), while Hb A2 and Hb CS were clearly quantified by capillary electrophoresis (CE).

Hemoglobina A2/análise , Hemoglobinopatias/diagnóstico , Hemoglobinas Anormais/análise , Eletroforese Capilar/métodos , Humanos
Reprod Fertil Dev ; 2015 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-25786351


Our previous study showed that the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) originating from the mouse epididymis bound to the midpiece of luminal spermatozoa. The present study was undertaken to investigate the association between RANTES and epididymal spermatozoa and to determine whether the association is mediated by the RANTES receptors CCR1, CCR3 or CCR5. The use of reverse transcription polymerase chain reaction (RT-PCR), immunohistochemical staining and immunofluorescent staining demonstrated that RANTES secreted by apical and narrow cells of mouse epididymal ducts was associated with luminal spermatozoa. Flow cytometric analysis and immunofluorescent labelling revealed that the association between RANTES and spermatozoa of different regions weakened gradually as the spermatozoa moved along the epididymis. Moreover, CCR1, CCR3 and CCR5 were expressed in epididymal spermatozoa and located on the head of epididymal spermatozoa, while RANTES was generally located at the midpiece. In conclusion, RANTES and its receptors were not in the same sperm location, suggesting that RANTES binding to mouse epididymal spermatozoa is independent of CCR1, CCR3 and CCR5.

Sheng Li Ke Xue Jin Zhan ; 45(6): 410-5, 2014 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-25872345


Estrogen receptors (ERs), including two sub-types ERα and ERß, belong to the steroid hormone superfamily of nuclear receptors. ERα distributes in the male reproductive system and plays a crucial role in the regulation of male reproduction through estrogen-dependent and -independent ways. In this article, we mainly reviewed the molecular structure, mode of action and location of ERα in the male reproductive system, and explored the mechanism of ERα in regulating the male reproductive system by analyzing different animal models of disrupted ERα.

Reprodução , Animais , Receptor alfa de Estrogênio , Genitália Masculina , Masculino