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Peroxisome proliferator-activated receptors γ (PPARγ) is a master regulator that controls energy metabolism and cell fate. PPARγ2, a PPARγ isoform, is highly expressed in the normal prostate but expressed at lower levels in prostate cancer tissues. In the present study, PC3 and LNCaP cells were used to examine the benefits of restoring PPARγ2 activity. PPARγ2 was overexpressed in PC3 and LNCaP cells, and cell proliferation and migration were detected. Hematoxylin and eosin (H&E) staining was used to detect pathological changes. The genes regulated by PPARγ2 overexpression were detected by microarray analysis. The restoration of PPARγ2 in PC3 and LNCaP cells inhibited cell proliferation and migration. PC3-PPARγ2 tissue recombinants showed necrosis in cancerous regions and leukocyte infiltration in the surrounding stroma by H&E staining. We found higher mixed lineage kinase domain-like (MLKL) and lower microtubule-associated protein 1 light chain 3 (LC3) expression in cancer tissues compared to controls by immunohistochemistry (IHC) staining. Microarray analysis showed that PPARγ2 gain of function in PC3 cells resulted in the reprogramming of lipid- and energy metabolism-associated signaling pathways. These data indicate that PPARγ2 exerts a crucial tumor-suppressive effect by triggering necrosis and an inflammatory reaction in human prostate cancer.
Subject(s)
Animals , Humans , Male , Mice , Cell Proliferation , PC-3 Cells , PPAR gamma/genetics , Prostatic Neoplasms/genetics , Signal Transduction , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND@#Acupuncture has been widely used to relieve migraine-related symptoms. However, the findings of previous systematic reviews (SRs) and meta-analyses (MAs) are still not completely consistent. Their quality is also unknown, so a comprehensive study is needed.@*OBJECTIVE@#To evaluate the reporting and methodological quality of these MAs concerning acupuncture for migraine, and summarize evidence about the efficacy and safety of acupuncture for migraine.@*SEARCH STRATEGY@#PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Databases, Wanfang Data, and VIP databases were searched from inception to September 2020, with a comprehensive search strategy.@*INCLUSION CRITERIA@#The pairwise MAs of randomized controlled trials (RCTs) concerning migraine treated by acupuncture or acupuncture-based therapies, with a control group that received sham acupuncture, medication, no treatment, or acupuncture at different acupoints were included.@*DATA EXTRACTION AND ANALYSIS@#Two independent investigators screened studies, extracted relevant data, and assessed reporting and methodological quality using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 and A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), then all results were cross-checked. Spearman correlation test was used to evaluate the correlation between reporting and methodological quality scores.@*RESULTS@#A total of 20 MAs were included in this study. The included MAs indicated that acupuncture was efficacious and safe in preventing and treating migraine when compared with control intervention. There was a high correlation between reporting and methodological quality scores (rs = 0.87, P < 0.001). The quality of the included SRs needs to be improved mainly with regard to protocol and prospective registration, using a comprehensive search strategy, summarizing the strength of evidence body for key outcomes, a full list of excluded studies with reasons for exclusion, reporting of RCTs' funding sources, and assessing the potential impact of risk of bias in RCTs on MA results.@*CONCLUSION@#Acupuncture is an effective and safe intervention for preventing and treating migraine, and could be considered as a good option for patients with migraine. However, the reporting and methodological quality of MAs included in this overview is suboptimal. In the future, AMSTAR 2 and PRISMA tools should be followed when making and reporting an SR with MA.
Subject(s)
Humans , Acupuncture Points , Acupuncture Therapy/methods , China , Meta-Analysis as Topic , Migraine Disorders/therapy , Research ReportABSTRACT
Bexarotene is a synthetic analogue of retinoic acid and exerts protective effects on the nervous system. However, low bioavailability and poor solubility of the crystal type I form severely limits the application of bexarotene in the clinic. A co-amorphous sample of bexarotene-PVP-K30 was prepared and the structure was characterized by X-ray diffraction and infrared spectroscopy. To determine the pharmacokinetics and tissue distribution of bexarotene, an LC-MS method was established to profile and quantify bexarotene in plasma and tissues of SD rats. In vitro dissolution indicated that the co-amorphous form improved the dissolution of bexarotene in pure water 4.17-fold. After rats were orally administered bexarotene or bexarotene-PVP-K30 co-amorphous (equivalent to 30 mg·kg-1 bexarotene) the AUC of bexarotene was 7 034.89 and 10 174.03 μg·L-1·h respectively, the peak time was advanced from 7.33 h to 0.9 h with the amorphous form, and Cmax was enhanced from 627.76 to 3 011.88 μg·L-1. The co-amorphous form yielded higher concentrations of bexarotene in various tissues, especially brain, liver and kidney. Animal welfare and experimental procedures complied with the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. The results indicate that bexarotene-PVP-K30 co-amorphous improves the pharmacokinetic characteristics of bexarotene and provides preclinical data in support of bexarotene-PVP-K30 for the treatment of brain diseases.
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Objective:To investigate the clinical efficacy of sacral nerve root magnetic stimulation combined with Solifenacin in women with refractory overactive bladder (OAB). Methods:From January to December, 2017, 120 women with refractory OAB were randomly divided into sacral nerve root magnetic stimulation group (group A, n = 40), Solifenacin group (group B, n = 40), and combined treatment group (group C, n = 40). Before and after treatment, they were assessed with the urine diary (number of daily urination, number of nightly urination, single urine output, number of urgent urination), urodynamic index (initial urinary bladder capacity, maximum bladder capacity) and Overactive Bladder Symptom Score (OABSS). Results:Two patients from group A, one from group B and one from group C were dropped out. The number of daily urination, the number of nightly urination, the single urine output, the number of urgent urination, the initial urinary bladder capacity and maximum bladder capacity, and OABSS were better in group C than in groups A and B (P < 0.05). Conclusion:Sacral nerve root magnetic stimulation combined with Solifenacin is effective and better than anyone alone on women with refractory OAB.
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Objective To investigate the potential mechanisms of chronic stress-induced breast cancer progression. Methods Mouse breast cancer xenograft model was established by injecting 4T1 cells into 6-week-old BALB/c mice, followed by randomized into the control group (no induced stress or drug treatment), chronic stress group, Iso injection group [10 mg/(kg.d), served as positive control], chronic stress + DMSO group (served as control for drug treatment), and chronic stress +Rapa group [15 mg/(kg.d)]. The tumor size was monitored up to 21 days. The intratumor expression levels of Beclin1, LC3-II, and p62 were detected. The pulmonary metastatic nodules were visualized and counted using lung ink staining. The expression of autophagy-related molecules in 4T1 cells after NE treatment was also examined in vitro. Results Compared with the control group [(1359.7±173.9) mm3], chronic stress [(2119.7±130.0) mm3], and Iso [(1947.0±102.8) mm3] promoted the growth of breast cancer cells (Plt;0.05). Consistently, the lung nodules numbers were significantly increased in the chronic stress group (10.3±1.1) and the Iso group (8.8±0.5), compared to control group (4.3±0.3, Plt;0.05). In addition, compared to the control group, Beclin1 expression from samples of the stress group were decreased while p62 expression increased (Plt;0.05). Interestingly, the autophagy inducer Rapa reversed the pro-tumorigenic effect of chronic stress [(2275.477±187.397) mm3 vs. (1360.097±213.938) mm3, Plt;0.05]. We further confirmed that 4T1 cells treated with NE resulted in 60% decreased of Beclin1 expression in 4T1 (100% vs. 39.8%±2.0%, Plt;0.05) the fluorescence intensity of LC3 decreased as well (Plt;0.05). Bioinformatics analysis showed that breast cancer patients with high expression of Beclin1 had better survival prognosis, while those with high expression of p62 showed worse outcome (Plt;0.001). Conclusion Stress promotes the growth and metastasis of breast cancer through suppressing cell autophagy.
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Objective Higher expression of B-cell activating factor (BAFF) in patients with Graves' disease can activate B cells and increase proportion of plasma cells. However, the mechanism is still unclear. This study aims to investigate the effects of T3 on the BAFF level and plasma cell ratio in bone marrow, spleen and peripheral blood of mice, and to explore the mechanism of T3 in affecting the mature and differentiation of B cells. Methods 80 C57BL/6J mice were randomly divided into control group and T3 group, and were given isotonic saline or T3 5/10μg once a day for 6 weeks, respectively. The levels of T3 in peripheral blood of each group were measured with ELISA. Flow cytometry was used to detect the proportion of B220+CD138+ plasma cells and IgM, IgG and IgD expression of B cells in the spleen, bone marrow and peripheral blood. Immunohistochemistry, Western blot and PCR were performed to determine the expression of BAFF in spleen and thyroid. ELISA was used to determine the expression of BAFF in peripheral blood. Results Compared with control group, the levels of T3 in peripheral blood, diet and drinking water in the T3 group were significantly increased after 6 weeks T3 intervention. The mRNA and protein expression of BAFF in spleen mononuclear cells of T3 group (2.03±0.52, 0.50±0.03) were higher than those in control group (1.06±0.19, 0.05±0.01) (P<0.01). HE staining showed that the white medulla in the spleen of the T3 group increased and merged. Flow cytometry indicated that the proportion of spleen plasma cells and antibody expression of B cells in T3 group [(3.92±1.55)%, (75.76±8.88)%] increased compared with control group [(2.43±1.18)%, (65.26±8.38)%] (P<0.05); Proportion of bone marrow plasma cells [(8.48±3.62)%] and antibody expression [(40.63±18.96)%] in T3 group were significantly increased compared with control group [(4.96±3.11)%, (22.89±7.32)%](P<0.05); Peripheral plasma cell ratio [(8.56±4.27)%] and antibody expression [(76.15±9.44)%] were lower than those in control group [(14.70±4.76)%, (84.20±3.98)%](P<0.05); Compared with control group [(5.98±0.78) pg/mL], the BAFF level in peripheral blood increased [(7.61±1.72) pg/mL] (P<0.01). Immunohistochemistry showed that the expression of BAFF increased in mononuclear cells of thyroid of the T3 group. Conclusion T3 could activate BAFF expression in bone marrow, spleen, peripheral blood and thyroid mononuclear cells, and induce differentiation of bone marrow and spleen B cells, thus causing pathological changes in thyroid tissue. Such mechanisms might play an important role in the pathogenesis of thyroid autoimmune diseases.
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Objective High levels of triiodothyronine (T3) can lead to hyperthyroid heart disease, but its mechanism is unclear. This study aims to investigate the effects of T3 on the expression of B-cell activating factor (BAFF) in cardiomyocytes and to explore its possible role in the pathogenesis of hyperthyroid heart disease. Methods Sixty healthy C57BL/6J mice were selected and randomly divided into two groups: the experimental group and the control group. The experimental group received intraperitoneal injection of T3 at 5 μg/ml, one time/d, for 42 consecutive days. The concentrations of serum T3 and tetraiodothyronine (T4) were detected by radioimmunoassay; ELISA was used to determine BAFF expression in peripheral blood, and the cardiac index and the transverse diameter of myocardial cells in each group were determined. Immunohistochemistry and Western blot were used to detect the expression of BAFF protein in myocardium and of myocardial tumor necrosis factor-α (TNF-α) protein; the expression of BAFF mRNA in myocardium was detected by Real-Time PCR; flow cytometry (FCM) was used to detect changes in the proportion of B-cells in the heart. Results Compared with the control group, the serum T3 concentration, cardiac index, BAFF and myocardial cell transverse diameter of the experimental group significantly increased (P<0.05), and the T4 concentration decreased (P<0.05). Under the light microscope, the cardiomyocytes of the control group were normal, while those of the experimental group were hypertrophied and disordered in structure. Compared with the control group (0.765±0.164), BAFF protein expression significantly increased in the experimental group (1.865±0.290) (P<0.05). Compared with the control group (0.537±0.089), the expression of TNF-α protein significantly increased in the experimental group (0.737±0.065) (P<0.05). Correlation analysis of T3 with BAFF gene expression in cardiomyocytes and BAFF level in peripheral blood showed that T3 was positively correlated with both the former with a correlation coefficient of 0.637 (P<0.01) and the latter with 0.778 (P<0.01). For FCM, compared with the control group [(12.40±1.09)%], the proportion of myocardial B-cells increased in the experimental group [(16.12±0.631)%] (P<0.05). Conclusion High concentration of T3 can promote the expression of BAFF in myocardial cells and lead to the activation of B-cells, thus increasing the inflammatory response and leading to myocardial hypertrophy.
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@# 【Objective】To summarize current situation of multiple sclerosis in South China and provide reference for MS diagnosis and treatment.【Methods】We selected patients of whom the first diagnosis was MS from 2011 to March 2019，and divided them into Adults group and Pediatrics group according to onset age above or below 14. We analyzed them from epidemiology，symptomatology，accessory examinations and treatment situation.【Results】296 patients were admitted into this research. The ratio of male to female was 1∶1.67. Median onset age was 26. Relapsing-remitting MS accounted for 63.2% of all patients. For initial episode，130 patients had motor symptoms（43.9%），118 patients showed sensory symptoms（39.9%），and 55 patients were accompanied with visual symptoms（18.6%）. Statistical difference exists in sensory symptoms（114 vs. 4，Z = -2.155，P = 0.031）and paroxysmal symptoms（4 vs. 3，Z = -3.610，P = 0.000） of Adults group and Pediatrics group. For following episodes，the total relapsing time was 712，with motor symptoms relapsing 380 times（53.4%），sensory symptoms 265 times（37.2%）and visual symptoms 134 times（18.8%）. Statistical difference existed in motor，sensory，visual，other ocular symptoms and paroxysmal symptoms. Positive rate of Oligoclonal bond was 45.5%. Positive rate of MOG-Ab was 16.7%. For brain MRI，periventricular lesions ≥ 9 accounted for 57.4% of all patients，with cortical & juxtacortical lesions 28.1% and infratentorial lesions 0.3%. Patients who had optic nerve lesions accounted for 63.2%. No statistical difference existed in them. For treatment，drugs they had used previously were glucocorticoid（79.7%），beta Interferon（15.9%）and azathioprine（13.9%）.During the study，drugs they were using were glucocorticoid（15.5%），rituximab（9.1%），azathioprine（8.1%）and teriflunomide（8.1%）.【Conclusions】For gender， age，symptomatology and accessory examinations，results of this research are similar to previous papers about multiple sclerosis in Asian. For treatment，the trend indicates that usage of new disease-modifying drugs goes up.
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OBJECTIVE@#To compare the therapeutic effects on the relevant symtoms in the patients with dry eye syndrome treated with the acupoint thread-embedding therapy versus topical artificial tears eye drops.@*METHODS@#A total of 88 patients with dry eye syndrome of deficiency lacrima production were randomized into an acupoint thread-embedding therapy group (thread-embedding group) and a control group with topical artificial tears eye drops (medication group), 44 cases in each one. In the thread-embedding group, 3 cases were dropped out. In the thread-embedding group, Ganshu (BL 18), Pishu (BL 20) and Shenshu (BL 23) etc. were selected and the acupoint thread-embedding therapy was operated once every 30 days, totally for two treatments. In the medication group, the topical artificial tears eye drops was used, 4 to 6 times a day, one drop each time, for 8 weeks totally. Separately, before treatment, after 4-week treatment and 8-week treatment as well as in 8 weeks and 12 weeks of the follow-up, the levels of lactoferrin in tears were determined and the scores of the relevant symptoms of ocular surface such as eye dryness, foreign body sensation in the eyes and eye fatigue were evaluated.@*RESULTS@#In the thread-embedding group, after 4-week and 8-week of treatment as well as in 8-week and 12-week follow-up, the scores of eye dryness, foreign body sensation, burning sensation of eye, phengophobia and eye fatigue were reduced significantly as compared with those before treatment (all 0.05). The levels of lactoferrin in tears at each time point after treatment in the thread-embedding group were higher than the medication group (<0.05).@*CONCLUSION@#The acupoint thread-embedding therapy effectively improves in the relevant symptoms of ocular surface, such as eye dryness, foreign body sensation, burning sensation of eye, phengophobia and eye fatigue, and increases the level of lactoferrin in tears in the patients with dry eye syndrome of deficiency aqueous production. In the follow-up, the therapeutic effects of the acupoint thread-embedding therapy are significantly better than artificial tears eye drops.
Subject(s)
Humans , Acupuncture Points , Asthenopia , Dry Eye Syndromes , TherapeuticsABSTRACT
<p><b>BACKGROUND</b>Active tuberculosis (TB) with negative results of sputum smear is difficult to be identified. Till now, there is no effective and noninvasive diagnostic method. This study evaluated the diagnostic power of Mycobacterium tuberculosis T-cell (T.SPOT®.TB) assays for active TB.</p><p><b>METHODS</b>We retrospectively screened 450 suspected TB patients that were hospitalized in the Respiratory Department of Henan Province People's Hospital from June 2015 to June 2016. The patients were divided into the active, previous, and non-TB groups according to their final diagnosis. We evaluated the diagnostic value of the T-SPOT®.TB assay by constructing receiver operating characteristic (ROC) curves and calculating the optimal diagnostic cutoff value. In addition, we compared the levels of A antigen (ESAT-6) and B antigen (CFP-10) in active TB.</p><p><b>RESULTS</b>The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of T-SPOT®.TB for active TB were 89.78%, 63.16%, 0.56, 0.92, 2.47, and 0.16, respectively. For active TB, the area under the ROC curve (AUC) of the A antigen (0.89) was higher than that of the B antigen (0.86). The AUC of the A antigen for active TB was largest at a cutoff value of 13.5 spot-forming cells (SFCs) per 2.5 × 105 peripheral blood mononuclear cells (PBMCs). The AUC of the A and B antigens was 0.60 and 0.58 for previous TB. The levels of A and B antigen in the active TB group were significantly different from those in the previous- and non-TB groups (A antigen: χ2 = 105.41, P< 0.01 and B antigen: χ2 = 91.03, P< 0.01; A antigen: χ2 = 12.99, P< 0.01 and B antigen: χ2 = 8.56, P< 0.01, respectively). There were no significant differences in the levels of A and B antigens between the non-TB group and previous TB group (A antigen: χ2 = 1.07, P> 0.05 and B antigen: χ2 = 0.77, P> 0.05).</p><p><b>CONCLUSIONS</b>T-SPOT®.TB has high sensitivity and specificity for the diagnosis of active TB at a cutoff value of 13.5 SFCs per 2.5 × 105 PBMCs and is not influenced by previous TB.</p>
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The aim of the present study was to study the effect of β-estradiol (β-E(2)) on the large-conductance Ca(2+)-activated potassium (BK(Ca)) channel in mesenteric artery smooth muscle cells (SMCs). The mesenteric arteries were obtained from post-menopause female patients with abdominal surgery, and the SMCs were isolated from the arteries using an enzymatic disassociation. According to the sources, the SMCs were divided into non-hypertension (NH) and essential hypertension (EH) groups. Single channel patch clamp technique was used to investigate the effect of β-E(2) and ICI 182780 (a specific blocker of estrogen receptor) on BK(Ca) in the SMCs. The results showed the opening of BK(Ca) in the SMCs was voltage and calcium dependent, and could be blocked by IbTX. β-E(2) (100 μmol/L) significantly increased open probability (Po) of BK(Ca) in both NH and EH groups. After β-E(2) treatment, NH group showed higher Po of BK(Ca) compared with EH group. ICI 182780 could inhibit the activating effect of β-E(2) on BK(Ca) in no matter NH or EH groups. These results suggest β-E(2) activates BK(Ca) in mesenteric artery SMCs from post-menopause women via estrogen receptor, but hypertension may decline the activating effect of β-E(2) on BK(Ca).