Icariin plus curcumol enhances autophagy through the mTOR pathway and promotes cathepsin B-mediated pyroptosis of prostate cancer cells

@#Objective: To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms. Methods: We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation. Autophagy expression was analyzed using monodansylcadaverine staining. Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy, pyroptosis, and the mTOR pathway. Cellular damage was examined using the lactate dehydrogenase assay. Moreover, cathepsin B and NLRP3 were detected by co-immunoprecipitation. Results: Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy. The levels of LC3- Ⅱ/LC3-Ⅰ and beclin-1 were increased, while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol. These changes were reversed upon overexpression of mTOR. Furthermore, 3-methyladenine resulted in a decrease in inflammatory cytokines, pyroptosis-related protein levels, and lactate dehydrogenase concentration, compared to the icariin plus curcumol group. Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol. Conclusions: Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B. These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.

Epidemiological characteristics of newly diagnosed HIV/AIDS cases aged50 years or over in Zhejiang Province from 2015 to 2019 / 预防医学

Objective@#To analyze the epidemiological characteristics of newly diagnosed HIV/AIDS cases aged 50 years or over in Zhejiang Province from 2015 to 2019, so as to provide reference for the development of prevention and control strategies.@*Methods @#The data of newly diagnosed HIV/AIDS cases in Zhejiang Province were collected through the China HIV/AIDS Comprehensive Response Information Management System, and the demographic characteristics, infection routes,regional distribution and time distribution of the cases were analyzed. @*Results@#A total of 6 726 HIV/AIDS patients were recruited in this study, and the number of new patients from 2015 to 2019 showed an increasing trend ( P <0.05 ) . The number of participants diagnosed at the age of 50-59, 60-69 and 70-91 years old were 3 433( 51.04% ), 2 242 ( 33.33% ) and 1 051 ( 15.63% ). The majority of them were males ( 5 180, 77.01% ) , married ( 4 286, 63.72% ) , Zhejiang residents ( 5 304, 78.86% ) , and lived in rural areas ( 4 095, 60.88% ) . In terms of exposure history,6 586 cases ( 97.92% ) were infected by sexual contact. Among the 5 083 males infected by sexual contact, 82.63% were through heterosexual contact, 94.79% had extramarital sex partners, among whom 76.61% were commercial sex partners. The married women patients who confirmed HIV positive accounted for 75.44%. There were increasing trends in the proportion of the cases living in rural areas, male cases infected through heterosexual contact and those with extramarital and commercial sex partners, and female cases with their husbands positive along with age ( P <0.05 ) . @*Conclusions@#The number of newly diagnosed HIV/AIDS cases aged ≥50 years is increasing in Zhejiang Province. Many of them live in rural areas. Commercial sexual contact is the main route of HIV transmission among males and further lead to HIV transmission within couples.

Melatonin Augments the Effects of Fluoxetine on Depression-Like Behavior and Hippocampal BDNF-TrkB Signaling / 神经科学通报·英文版

Depression is a debilitating psychiatric disorder with a huge socioeconomic burden, and its treatment relies on antidepressants including selective serotonin reuptake inhibitors (SSRIs). Recently, the melatonergic system that is closely associated with the serotonergic system has been implicated in the pathophysiology and treatment of depression. However, it remains unknown whether combined treatment with SSRI and melatonin has synergistic antidepressant effects. In this study, we applied a sub-chronic restraint stress paradigm, and evaluated the potential antidepressant effects of combined fluoxetine and melatonin in adult male mice. Sub-chronic restraint stress (6 h/day for 10 days) induced depression-like behavior as shown by deteriorated fur state, increased latency to groom in the splash test, and increased immobility time in the forced-swim test. Repeated administration of either fluoxetine or melatonin at 10 mg/kg during stress exposure failed to prevent depression-like phenotypes. However, combined treatment with fluoxetine and melatonin at the selected dose attenuated stress-induced behavioral abnormalities. Moreover, we found that the antidepressant effects of combined treatment were associated with the normalization of brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling in the hippocampus, but not in the prefrontal cortex. Our findings suggest that combined fluoxetine and melatonin treatment exerts synergistic antidepressant effects possibly by restoring hippocampal BDNF-TrkB signaling.

Identification of human serum protein targets of Qianggu Decoction () in primary type I osteoporosis based on tandem mass tag labeling and liquid chromatography-tandem mass spectrometry technology / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the serum protein targets of Qianggu Decoction (, QGD) on treating osteoporosis by the proteomics analysis using tandem mass tag (TMT) and liquid chromatographytandem mass spectrometry (LC-MS/MS).</p><p><b>METHODS</b>Twenty serum protein samples were recruited (10 patients with primary type I osteoporosis before and after QGD treatment) and the high abundance ratios protein was removed, two serum samples were extracted and labeled with TMT reagent. Then, mass spectrometric detection, identification of differentially expressed proteins and bioinformatics analysis of differentially expressed proteins were carried out.</p><p><b>RESULTS</b>A total of 60 proteins were identified, within a 99% confidence interval, to be differentially regulated of which, 34 proteins were up-regulated and 26 proteins were down-regulated. Differentially expressed proteins analyzed by Gene Ontology (GO) annotation mainly get involved in 12 different biological processes, 7 types of cellular components, and 6 kinds of molecular functions. Angiotensinogen (AGT), stromelysin-1 (MMP3), heparanase (HPSE) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were screened as candidate protein targets of QGD treatment, which were related to metabolic mechanism of bone remodeling and/or bone collagen of osteoporosis. By the utilization of the protein-protein interaction network analysis tool named STRING10.0, it showed that AGT, MMP3, HPSE and GAPDH were located in the key node of the protein-protein interactions network. Furthermore, AGT, MMP3, HPSE and GAPDH were found to be directly related to BMP, MAPK, Wnt, SMAD and tumor necrosis factor ligand superfamily member 11 (TNFSF11) families.</p><p><b>CONCLUSIONS</b>The proteomics analysis by using TMT combined with LC-MS/MS was a feasible method for screening the potential therapeutic targets associated with QGD treatment. It suggests that AGT, MMP3, HPSE and GAPDH may be candidate protein targets of QGD treatment which can be used as therapeutic effect monitor and early diagnosis of primary type I osteoporosis.</p>

Effects of the water channel aquaporin 4 deficiency on bleomycin-induced lung fibrosis in mice / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the effect of water channel aquaporin 4 (AQP4) on bleomycin-induced lung fibrosis in mice.</p><p><b>METHODS</b>In wild type and AQP4 gene knockout (AQP4-/-) mice, lung fibrosis was induced by injection of bleomycin (3 mg/kg) into the trachea and saline injection was used as a control. At d3, 7, 14, 28 after bleomycin-treatment, mice were randomly sacrificed in batch and the lung coefficient was determined. Serum levels of TGF-β1 and TNF-α were measured by ELISA and hydroxyproline contents in lung tissue were determined by Alkaline hydrolysis method. H-E staining and Masson's staining were performed to examine the pathological changes of lung tissues after bleomycin-treatment.</p><p><b>RESULTS</b>On d14 after bleomycin-treatment, the lung coefficients in wild type mice and AQP4-/- mice were 1.9-fold (12.69 ± 6.05 vs 6.80 ± 0.82, q=4.204, P<0.05) and 2.3-fold (14.05 ± 5.82 vs 6.05± 0.58, q=5.172, P<0.01) of that in control, respectively, but no significant difference was found between wild type and AQP4-/- mice in the lung coefficient value (P>0.05). The hydroxyproline contents in the lung increased after bleomycin-treatment; on d28, the lung hydroxyproline contents in wild type and in AQP4-/- mice were 1.55-fold (0.85 ± 0.22 g/mg vs 0.55 ± 0.14 μg/mg, q=4.313, P<0.05) and 1.4-fold (0.84 ± 0.13 μg/mg vs 0.60 ± 0.14μg/mg, q=4.595，P<0.05) of that in control, respectively, but no significant difference was noticed between wild type and AQP4-/- mice in lung hydroxyproline contents. There was a tendency that serum TGF-β1 and TNF-α levels increased in bleomycin-treated mice, but no significant difference was found between wild type and AQP4-/- mice. AQP4-knockout showed no effects on pathological changes of lung tissues with H-E staining and Masson's staining in mice with bleomycin-induced lung fibrosis.</p><p><b>CONCLUSION</b>AQP4 might not be involved in bleomycin-induced lung fibrosis in mice.</p>

Diagnosis of ileocecal valve syndrome by ultrasound / 中华医学超声杂志（电子版）

Objective To discuss the clinical value of transabdominal sonography after bowl preparation in diagnosis of ileocecal valve syndrome ( IVS) .Methods The ultrasonic features of IVS in 37 cases were summerized and correlated with the follow-up findings after conservative treatment or the pathologic results after operation .Twenty-eight cases were confirmed by follow-up and 9 cases by operative pathology.Results Among the 37 cases of IVS,28 were idiopathic IVS (75.7%,28/37) and 9 were secondary IVS (24.3%, 9/37%).For the secondary cases, the primary diseases included 5 acute appendicitis,2 Meckel diverticulum,1 terminal ileitis and 1 carcinoma of ascending colon .The diagnostic accuracy rate of ultrasound was 89.2%(33/37).Misdiagnosis rate was 10.8%(4/37),including 1 case of idiopathic and 3 cases of secondary IVS .The IVS ultrasonic images coulde be displayed clearly using 7.0-10.0 MHz probes.In fasting examination,three ultrasonic characteristic signss were found in interminal ileum region at the right lower abdomen .And these features were bagel-shaped sign [91.9%(34/37),average size (1.9 ±1.6) cm ×(0.8 ±0.3) cm],short sleevelet-shaped sign [91.9% (34/37,average size (2.1 ± 0.4)cm ×(1.3 ±0.2) cm],and rose-shaped sign [83.8% (31/37),average size (1.4 ±0.2) cm × (1.0 ±0.2) cm].The shapes of some signs were changeable when the probe compressed .In the case of idiopathic IVS ,several pathologic changes could be seen on sonography after intestinal tract filling of oral 20%mannitol,including slight thickened mucosa and submucosa of erminalileum ,enlarged ieocecal valve and the crocodile-mouth sign.Conclusions Transabdominal ultrasonic examination with high frequency probe after bowl preparation plays an important role in diagnosis of IVS .The method is simple and accurate and should be recommended and applied clinically .

Relationship between polymorphism of interleukin-8 and silicosis susceptibility / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the relationship between the polymorphisms of interleukin-8 (IL-8) and the silicosis susceptibility.</p><p><b>METHODS</b>The case group consisted of 101 male patients with stage I silicosis diagnosed by the Pneumoconiosis Diagnosis Expert Panel according to the Chinese National Diagnosis Criteria of Pneumoconiosis (GBZ 70-2009). The control group consisted of 121 workers without silicosis exposed to same dusts. The cases and the controls had the same dust exposure history. The peripheral venous blood was drawn from each subject. DNA was extracted from leucocytes by the salting method. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) techniques and PCR were used to examine polymorphism of IL-8 (Met31Arg, 781C/T, -251A/T and RA+860).</p><p><b>RESULTS</b>There were no the differences of age, cumulative exposure time and smoking between the cases and the controls (P > 0.05). The frequencies of IL-8 (Met31Arg) GT genotypes in cases and controls were 12.87% and 2.48%, respectively, there was significant difference (P < 0.05). The frequencies of allele G in cases and controls were 6.44% and 2.07%, respectively, there was significant difference (P < 0.05). The frequencies of IL-8 (-251A/T) AA genotypes in cases and controls were 9.90% and 25.64%, respectively, there was significant difference (P < 0.05). The frequencies of IL-8 (781C/T) CC, CT, TT genotypes in cases and controls were 38.61%, 40.59%, 20.79% and 46.28%, 40.50%, 13.22%, respectively, there was no significant difference (P > 0.05). The frequencies of IL-8 (RA+860) GG, GC and CC genotypes in cases and controls were 75.25%, 21.78%, 2.97%, 80.17%, 14.88%, 4.96%, respectively, there was no significant difference (P > 0.05).</p><p><b>CONCLUSIONS</b>IL-8 (Met31Arg and -251A/T) genetic polymorphisms might play a role in the development of silicosis. The risk of pneumoconiosis in workers carrying (Met31Arg) genotype GT is likely to increase. The risk of pneumoconiosis in workers carrying IL-8 (-251A/T) AA genotype is likely to decrease. The relationship between IL-8 781C/T and RA+860 genes polymorphisms and silicosis is not found.</p>

Pathogenesis and clinical features of cerebral small vessel disease / 国际脑血管病杂志

Cerebral small vessel disease (SVD) is an important subtype of cerebrovascular disease. It is also one of the major reasons for resulting in vascular cognitive impairment or dementia in the elderly. SVD is a small arteriovenous lesion in subcortex caused by a variety of causes, mainly causing subcortical lacunar infarction, white matter damage, microblecds and other pathological changes. There is evidence that vascular endothelial function and blood-brain barrier damage may result in small vessel structures and perivascular changes, which may be the initial factors.of causing SVD. Genetic susceptibility is also one of the risk factors that can not be ignored.

Partial endothelium-dependent vasorelaxation of crocetin and its mechanism / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the vasorelaxation effect of crocetin (CCT) and its mechanism.</p><p><b>METHODS</b>Isolated aortic rings from Sprague-Dawley rats were mounted in the organ bath system. The tension of the aorta was recorded.</p><p><b>RESULT</b>CCT significantly provoked concentration-dependent relaxation in both endothelium-intact and-denuded aortic rings pre-constricted by phenylephrine (10⁻⁵ mol/L), and the vasorelaxation in endothelium-intact aortic rings was stronger than that in endothelium-denuded ones. CCT had no significant effects on aortic rings pre-constricted with KCl (6 × 10⁻² mol/L). Pretreatment with eith L-NAME (10⁻⁴ mol/L), an inhibitor of nitric oxide synthase (NOS), or indomethacin (10⁻⁵ mol/L), an inhibitor of cyclooxygenase, for 30 min significantly attenuated the relaxation of endothelium-intact aortic rings induced by CCT. Besides, both tetraethylammonium (a Ca²(+)-activated K(+) channel inhibitor, 5 × 10⁻³ mol/L) and 4-aminopyridine (a voltage-sensitive K(+) channel inhibitor, 10⁻³ mol/L), but not the ATP-sensitive K(+) channel inhibitor glibenclamide (3 × 10⁻⁶ mol/L), significantly attenuated CCT-induced relaxation in endothelium-denuded aortic rings.</p><p><b>CONCLUSION</b>CCT had partial endothelium-dependent relaxation in rat aortas, which may be mediated by activating the endothelial NOS-NO and cyclooxygenase-prostacyclin pathways. The endothelium-independent relaxation in rat aortas induced by CCT may be mediated by Ca²(+)-activated K(+) channels and voltage-sensitive K(+) channels.</p>

The impact of diabetes mellitus and insulin interference on cortical SCF/KIT of mice / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of cortical SCF/KIT system at different blood glucose level in mice.</p><p><b>METHODS</b>27 male C57 mice were randomly divided into control group, diabetes group, and diabetes plus insulin group. The diabetic mice were induced by streptozotocin. Western-blot and double-immunofluorescence histochemistry were used to detect the expression of SCF and KIT.</p><p><b>RESULTS</b>Both methods indicate that the level of S-SCF and M-SCF were decreased significantly in the diabetes group, and this trend can be reversed effectively when the insulin was utilized.</p><p><b>CONCLUSION</b>The decline of SCF might be one of underlying mechanisms of diabetic encephalopathy.</p>

Intranasal administration of low dosage recombinant human erythropoietin inhibits seizure in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of intranasal administration of low dosage recombinant human erythropoietin (r-HuEPO) on seizure in rats.</p><p><b>METHODS</b>After intranasal or intraperitoneal administration of r-HuEPO, the behavioral and electroencephalographic changes were observed in pentylenetetrazol (PTZ) and maximal electroshock (MES) induced seizure or electrical amygdaloid-kindled seizure of rats.</p><p><b>RESULT</b>Intranasal administration of low dosage r-HuEPO increased the seizure latency, and decreased the seizure grade and duration, and the number of convulsive episodes in PTZ induced seizure, with the most potential dosage of 2.4 IU. Intraperitoneal administration of r-HuEPO (3 000, 4 000 IU/kg) only decreased the seizure duration and number of convulsive episodes. The seizure grade, forelimb or hindlimb extension duration were decreased in MES-induced seizure by intranasal administration of 2.4 IU r-HuEPO. In addition, intranasal administration of 2.4 IU r-HuEPO decreased the seizure grade, generalized seizure duration and afterdischarge in electrical amygdaloid-kindled rats stimulated with generalized seizure threshold.</p><p><b>CONCLUSION</b>Intranasal administration of low dosage r-HuEPO can inhibit the seizure in rats.</p>

Effect of cinobufacini on vascular contractile of rat thoracic aorta / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To examine the effect of cinobufacini on rat thoracic aorta and its mechanism.</p><p><b>METHODS</b>Isolated rat thoracic aorta was perfused and isometric tension was recorded by organ bath technique before and after cinobufacini treatment.</p><p><b>RESULT</b>Cinobufacini induced contraction of isolated thoracic aorta with or without endothelium in a concentration-dependent manner (at concentration of 2.5,5.0,7.5,10.0 g/L). The vasoconstriction effect of cinobufacini was more potent in endothelium-denuded aorta ring [(16.3+/-3.39)%, (52.5+/-7.70)%, (60.9+/-8.84)%, (69.2+/-11.34)%] than in endothelium-intact aorta ring [(6.2+/-2.07)%, (14.7+/-4.91), (17.6+/-5.86)%, (20.3+/-6.78)% (P<0.01)]. Its contractile effect was attenuated in Ca(2+)-free solution (about 1/10 of that in buffer with 1.25 mmol/L CaCl(2)) or by the treatment with verapamil (10(-7)mol/L), an L-type calcium channel antagonist. Cinobufacini induced contraction on the endothelium-intact rat aorta was augmented by pretreatment with L-NAME (10(-4)mol/L), a nitric oxide synthase inhibitor.</p><p><b>CONCLUSION</b>Cinobufacini contracts rat thoracic aorta by opening the voltage-dependent Ca(2+) channel and increasing Ca(2+) influx into vascular smooth muscle. Cinobufacini can also stimulate the release of vascular relaxant factor, nitric oxide, from the endothelium and thus antagonize cinobufacini-induced contraction.</p>

Preliminary Study on the Activation of TRAFs Mediated by Epstein-Barr Virus Encoded LMP1 in Nasopharyngeal Carcinoma / 中国病毒学

The present is aimed at identifying the activation of TRAFs in n asopharyngeal carcinoma (NPC) in vitro. The differential expression of TRAF2\,TRAF3 was not detected in RN A and protein level, whereas the expression of TRAF1 in HNE2-LMP1 cell lines wa s much more abundant than that in HNE2 cell lines, suggesting that TRAF1 may be an inducible molecule; More importantly, TRAF1, TRAF2 or TRAF3 were activated in the HNE2-LMP1 cells, whereas TRAF1, TRAF2 or TRAF3 were not activated in HNE2 cells as detected by the immunoprecipitation-Western blotting assay. These data provide an experimental basis for our study beginning from the signal transduca tion pathway for the eluccidation of the mechanism of LMP1 carcinogenesis in NP C.

The effects of compressive stress on TGF-?1 expression in condylar cartilage in vitro / 实用口腔医学杂志

Objective:To investigate the expression of transforming growth factor-?1 (TGF-?1) in mandibular condylar chondrocytes after the condylar cartilage was stimulated by compressive stress.Methods:20 condylar cartilage samples were obtained from 10 new borne SD rats and cultured for 24 h.Then,10 samples were treated by a static compressive stress with a magnitude of 10 kPa for 1 h.Another 10 samples without stress treatment were used as the controls. At end of stress stimulation, the expression of TGF-?1 in the samples of both groups was examined by immunohistochemistry and image pattern analysis.Results:The grayscale values of TGF-?1 in perichondrium lay of stress treated and control samples were 159.21?19.84 and 174.20?14.47(P