At present, there is no cure for acquired immune deficiency syndrome (AIDS) due to HIV-1 latent reservoirs. Therefore, it urgently requires novel HIV-1 latency-regulating agents with high potency, low toxicity and favorable drug-like properties to achieve a functional cure for AIDS. Herein, we reviewed the advances in HIV-1 latency-regulating agents since 2019, including the drug discovery strategies, bioactivities, and mechanisms of these compounds. It is of great guiding significance in the development of latency-regulating agents with clinical value.

Body image disturbance (BID) in eating disorders (ED) has always been a focus of intense investigations and debates since its concept was brought out. Experimental studies conducted in clinical ED patients have not only provided insights into the components, mechanisms and roles of BID in ED psychopathology, but also brought changes to relevant theories and concepts. This article provided a review of theoretical and empirical literatures on BID in ED, as well as a summary and analysis of recent developments and future prospects in this field.

BACKGROUND:Bone marrow mesenchymal stem cells have low immunogenicity and immunomodulatory effect,but there are seldom reports concerning the immunomodulatory effect of Wharton's jelly-derived mesenchymal stem cells of human umbilical cord and its mechanims.OBJECTIVE:To investigate the immunomodulatory effects and mechanisms of Wharton's jelly-derived mesenchymal stem cells of human umbilical cord on varient peripheral blood T lymphocytes.METHODS:Mesenchymal stem cells were isolateded from Wharton's jelly of human umbilical cord by tissue culture.T lymphocytes from human peripheral blood were stimulated by phytohemagglutinin and co-cultured with umbilical cord Wharton's jelly-derived mesenchymal stem cells and umbilical cord Wharton's jelly-derived mesenchymal stem cells supernatant respectively to measure A value following 72 hours of coculture using multifunctional microplate reader.Expression of cytokines including transforming growth factor-beta 1(TGF-β1)and interferon-y(IFN-γ)was evaluated by enzyme-labeled immunosorbent assay.RESULTS AND CONCLUSION:Wharton's jelly-derived mesenchymal stem cells could inhibite the proliferation of T lymphocytes induced by phytohemagglutinin.The proliferation inhibition rate was 56%(P＜0.01).Wharton's jelly-derived mesenchymal stem cells supernatant also had inhibitory effects on proliferation of T lymphocytes induced by phytohemagglutinin,in a dose-dependent fashion.The proliferation inhibition rates were 8.3% and 27% respectively in the 50% Wharton's jelly-derived mesenchymal stem cells supernatant and 100% Wharton's jelly-derived mesenchymal stem cells supematant groups(P＜0.05).Wharton's jelly-derived mesenchymal stem cells significantly decreased γ-interferon secrted from T-lymphocytes(P＜0.05).The secretion of TGF-β1 was lower in the coculture of Wharton's jelly-derived mesenchymal stem cells and T lymphocytes group than Wharton's jelly-derived mesenchymal stem cells alone group(P＜0.05).These indicated that Wharton's jelly-derived mesenchymal stem cells and Wharton's jelly-derived mesenchymal stem cells supernatant have inhibitory effects on proliferation of T lymphocytes induced by phytohemagglutinin.The mechanims may be associated with cell contant and inhibition of v-interferon secrted from T-lymphocytes.

Adult ; Fatty Liver ; diagnosis ; diagnostic imaging ; Female ; Humans ; Male ; Pregnancy ; Pregnancy Complications ; diagnosis ; diagnostic imaging ; Ultrasonography ; Young Adult

OBJECTIVETo evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients.

METHODSPlasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated.

RESULTS(1) Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. (2) Median imatinib plasma trough levels was 1271 (109-4329). Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose < 400, 400 and > 400 mg were (969 ± 585), (1341 ± 595) and (1740 ± 748) µg/L (P < 0.01), respectively. (3) There was no statistic difference in imatinib plasma trough level with complete cytogenetic response [CCyR (1337 ± 571) µg/L vs no CCyR (1354 ± 689) µg/L, P = 0.255]. (4) Imatinib plasma trough level might be important for a good clinical response in some CML patients.

CONCLUSIONThere was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Benzamides ; blood ; therapeutic use ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; blood ; therapeutic use ; Pyrimidines ; blood ; therapeutic use ; Treatment Outcome ; Young Adult

iASPP can prompt the cell proliferation and inhibit the apoptosis of many cells. There are putative binding sites of transcription factor GATA-2 upstream of iASPP transcription start site. GATA-2 plays an important role in the proliferation and differentiation of hematopoietic stem cells (HSC) and progenitors. This study was aimed to explore the role of GATA-2 protein in iASPP gene transcription. Firstly, the expression of iASPP and GATA-2 protein in some leukemia cell lines was detected by Western blot. Second, The expressive vector of pCMV5-GATA2 and the luciferase reporter vectors containing possible binding sites of GATA-2 were constructed and co-transfected into HEK293 and CV-1 cells. Then the luciferase activity was assayed by luminometer. Also, ChIP assays were performed to further confirm the specific binding of GATA-2 to iASPP promoter. The results showed that GATA-2 was overexpressed in most cell lines with high level of iASPP. GATA-2 exhibited a significant effect on luciferase activity of reporter gene iASPP and in a dose-dependant manner. The relative luciferase activity was up-regulated to about two-fold of the empty vector control when the transfection dose of pCMV5-GATA2 plasmid was increased to 100 ng. While the effect was more significant in CV-1 cells and showed a 6.7-fold increase. The ChIP assay demonstrated the in vivo specific binding of GATA-2 to iASPP. The binding sites of GATA2 were located between nt -361 ∼ -334 in upstream of iASPP gene transcription start site. It is concluded that transcription factor GATA-2 can bind with the cis-regulatory region of the iASPP promoter and up-regulate iASPP expression.
Animals ; Cell Line ; Cercopithecus aethiops ; GATA2 Transcription Factor ; genetics ; Gene Expression Regulation, Leukemic ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; K562 Cells ; Repressor Proteins ; genetics ; Transcription, Genetic ; Transcriptional Activation ; Transfection

[To explore the effect of Humifuse Euphorbia Herb ( HEH) on alleviating insulin resistance in type 2 diabetic KK-Ay mice. Totally 40 KK-Ay mice fed with high-fat diet were divided into four groups: the metformin group, the model group, the HEH low-dose group and the HEH high-dose group, and orally administrated with metformin hydrochloride (250 mg x kg(-1)), distilled water, humifuse euphorbia herb 1 g x kg(-1) and 2 g x kg(-1). Besides, C57BL/6J mice with ordinary feed were taken as the normal control group and orally administrated with equal distilled water. The oral administration for the five groups lasted for eight weeks. Before and after the experiment, weight, fasting glucose and insulin tolerance were determined. The morphological changes in pancreas were observed through hematoxylin-eosin (HE) staining on pancreatic tissue sections. The serum insulin, TNF-α, IL-6, adiponectin (ADPN) and leptin (LEP) were detected by ELISA. The results showed that HEH could reduce weight and fasting glucose in KK-Ay mice, alleviate hyperinsulinemia, reduce blood glucose-time AUC, increase 30-min blood glucose decline rate, relieve insulin resistance, significantly ameliorate the pathomorphological changes in pancreas in each group, decrease serum TNF-α, IL-6 and leptin levels in KK-Ay mice and rise serum ADPN level. This study proved that humifuse euphorbia herb can ameliorate the insulin resistance in KK-Ay mice, and its mechanism may be related to the effect on inflammatory factors and adipocytokines.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Euphorbia ; chemistry ; Humans ; Insulin ; metabolism ; Insulin Resistance ; Interleukin-6 ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

OBJECTIVETo evaluate the CD4+CD25+ regulatory T cells (Treg) and other lymphocyte subsets in the peripheral blood of patients with advanced lung adenocarcinoma.

METHODSPeripheral blood samples were obtained from 64 patients with advanced lung adenocarcinoma (case group) and analyzed by flow cytometry. The ratios of CD4+CD25+Treg T cells and other T lymphocyte subsets in peripheral blood were compared with those from 33 healthy controls (control group).

RESULTSThe percentages of CD3+ and CD3+CD4+ were (66.5±11.0)% and (37.7±10.6)% respectively in the peripheral blood of the case group, which were significantly lower than those [(72.0±6.0)% and (42.0±6.4)%] in the control group (t=-3.2,-2.4; P=0.020, 0.015, respectively). The ratio of CD4+ CD25+ Treg cells in case group (10.5±4.0)% was significantly higher than that [(8.4±3.5)%] in the control group (t=-2.2, P=0.013). CD4+/CD8+ value of case group (1.4±0.8) was significantly lower than that (1.8±0.7) in control group(t=-2.2, P=0.029). CD3+CD8+, CD8+CD28-, and CD8+CD28+ showed no significant differences (all P>0.05). Smoking, differentiation grade, and size of the tumor showed no association with the function damage of T lymphocyte subsets, while the carcino-embryonic antigen level did.

CONCLUSIONSIn patients with advanced lung adenocarcinoma, Treg increases and CD4+/CD8+ decreases, suggesting remarkably suppressed immune functions. However, more research is warranted to validate the association of T cells subset dysfunction with smoking, differentiation grade, and size of tumor.

Adenocarcinoma ; immunology ; Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Lung Neoplasms ; immunology ; Male ; Middle Aged ; Risk Factors ; T-Lymphocyte Subsets ; immunology

Objective To investigate the change of 14-3-3 protein in cerebrospinal fluid (CSF) in different types of meningoencephalitis in children and its value in judging brain injury.Methods CSF 14-3-3 protein bands were detected by means of Western blot in 22 patients with viral meningoencephalitis and 20 cases of purulent meningoencephalitis and with 15 cases of febrile seizures as the control group from Jul.2009 to Jun.2010,and in addition,the quantitative detection of 14-3-3 protein was done by way of ELISA.Correlation was analyzed between the clinical manifestations,prognosis,EEG,head CT or MRI and the changes of 14-3-3 protein.Results The positive rate of 14-3-3 protein in cases of purulent meningitis was 65.0(13/22 cases),higher than viral meningoencephalitis group(27.3％,6/22 cases),and the difference was significant.In the quantitative detection,14-3-3 protein was increased in both the purulent meningitis [(5.6 + 0.2) μg/L] and viral encephalitis groups[(3.2 + 0.3) μg/L] compared with the control group [(0.9 + 0.1) μg/L].After treatment,14-3-3 proteins were less than before in the purulent meningitis and viral meningoencephalitis groups.In the cases with severe clinical manifestations and severe injury brain suggested by imaging and EEG,the 14-3-3 protein in cerebrospinal fluid was elevated;and the prognosis of the cases with increased 14-3-3 protein was poor,as a result of epilepsy,death and so on.Conclusions 14-3-3 protein in the CSF increases with disease severity,so to a certain extent,it can be used to identify viral meningitis and purulent meningitis.

BACKGROUNDFood composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The aim of this study was to explore the fast response of C-peptide, glucagon-like peptide-1 (GLP-1), ghrelin and endomorphin-1 (EM-1) to the eastern and western style meals in patients with type 2 diabetes mellitus.

METHODSThe study enrolled 57 patients with type 2 diabetes (20 men and 37 women, mean age (67.05 ± 8.26) years). Eastern style meal (meal A) and western style meal (meal B) were designed to produce the fullness effect. C-peptide, GLP-1, ghrelin and EM-1 were assessed before (0 hour) and after (2 hours) each diet.

RESULTSThe delta (2h - 0h) of C- peptide in meal A was significantly lower than that in meal B (P = 0.0004). C-peptide, GLP-1, ghrelin and EM-1 were obviously higher before meal B than those before meal A (P < 0.0001, < 0.0001, = 0.001, = 0.0004 respectively). Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A (P = 0.0005, 0.0079 respectively). Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B (r(A0h) = 0.7836, r(B0h) = 0.9368, r(A2h) = 0.7615, r(B2h) = 0.9409, r(A(2h-0h)) = 0.7531, r((2h-0h))B = 0.9980, respectively, P < 0.0001).

CONCLUSIONWestern style meal (high fat and protein food) could make more response of C-peptide than eastern style meal, and could stimulate more gut hormones (GLP-1, ghrelin) and brain peptide (EM-1) at the first phase of digestion.

Aged ; C-Peptide ; blood ; Diabetes Mellitus, Type 2 ; blood ; Diet ; Fasting ; blood ; Female ; Ghrelin ; blood ; Glucagon-Like Peptide 1 ; blood ; Humans ; Male ; Middle Aged ; Oligopeptides ; blood ; Postprandial Period