Cancer associated fibroblast secreted miR-432-5p targets CHAC1 to inhibit ferroptosis and promote acquired chemoresistance in prostate cancer.

Prostate cancer (PCa) ranks as the sixth most serious male malignant disease globally. While docetaxel (DTX) chemotherapy is the standard treatment for advanced PCa patients with distant metastasis, some individuals exhibit insensitivity or resistance to DTX. Cancer-associated fibroblasts (CAFs) play a pivotal role as stromal cells within the tumor microenvironment, influencing tumor development, progression, and drug resistance through exosomes. Ferroptosis, a novel form of programmed cell death, is characterized by intracellular iron accumulation that triggers lipid peroxidation, ultimately leading to cell demise. To delve into the potential mechanisms of chemotherapy resistance in prostate cancer, our research delved into the impact of CAF-derived exosomes on ferroptosis. Our findings revealed that CAF exosomes hindered the buildup of lipid reactive oxygen species (ROS) in prostate cancer cells induced by erastin, as well as mitigated erastin-induced mitochondrial damage, thereby impeding iron-induced cell death in prostate cancer cells. Furthermore, miR-432-5p was identified to diminish glutathione (GSH) consumption by targeting CHAC1, consequently inhibiting ferroptosis in prostate cancer cells. Our study found that miR-432-5p, originating from cancer-associated fibroblast (CAF) exosomes, suppresses ferroptosis by targeting CHAC1, thereby increasing resistance to docetaxel (DTX) in PCa. This research introduces a novel approach to address resistance to DTX.

68Ga-PSMA PET/CT-targeted biopsy for the diagnosis of clinically significant prostate cancer in patients with serum PSA levels <20.0 ng/ml / 中华泌尿外科杂志

Objective:To evaluate the feasibility and efficacy of 68Ga-PSMA PET/CT-guided targeted prostate biopsy for the diagnosis of clinically significant prostate cancer(csPCa). Methods:This retrospective analysis allocated 89 patients with elevated PSA levels between 4.0-20.0 ng/ml to PET group(n=48) or TRUS group(n=41) between September 2017 and June 2019. Patients with PSMA-avid lesions (SUV max≥8.0) underwent PET-TB via a single-puncture percutaneous transgluteal approach (n=19), while patients with negative PSMA-PET underwent systematic TRUS-GB (n=29). Patients in the TRUS group who did not get 68Ga-PSMA PET/CT examination underwent TRUS-GB directly (n=41). The mean age, prostate volume, PSA value of PET group and TURS group were (71.2±9.1) years vs. (68.0±12.0) years, (62.9±29.1)ml vs. (65.4±38.9)ml , 8.8(6.6, 13.6) ng/ml vs. 9.8(7.1, 13.1)ng/ml, respectively (all P>0.05). The diagnostic efficacy and difference of PCa and csPCa between the two groups were compared. PET-TB adopts a new mode of percutaneous gluteus approach and carries out precise image fusion of PSMA-PET/CT and pelvic CT in the same machine and in the same position (prone position). Under the direct guidance of CT, the biopsy is performed with only one precise puncture. Results:PCa and csPCa were detected in 27/89(30.3%)and 20/89(22.5%)in all patients. PET group detected significantly more cases of PCa and csPCa than those of TRUS group [PCa: 41.7%(20/48) vs. 17.1%(7/41), χ2=6.328; csPCa: 33.3%(16/48) vs. 9.8%(4/41), χ2=7.055, P<0.01]. Of 19 patients with PSMA-PET positive, PET-TB detected 16 cases of PCa(84.2%) by a single needle puncture, and the proportions of cancer tissues were ≥80% in 2, 50%-79% in 8, and <50% in 6 cases. Among these, Gleason score was underestimated by biopsy histopathology in 2 patients. Of 3 patients with PET-TB negative, 1 case of low-risk PCa(Gleason 3+ 3) was detected by complementary TRUS-GB. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy of 68Ga-PSMA PET/CT(SUV max≥8.0) for the diagnosis of csPCa were 73.9%(14/19), 93.1%(27/29), 87.5%(14/16), 81.3%(26/32)and 85.4%(41/48), respectively. For PET-TB, only one patient had slight symptoms of haematuria after the puncture, no cases of hematochezia, hemospermia, urinary retention or pelvic infection were observed. Conclusions:68Ga-PSMA PET/CT is a feasible novel puncture technique that may serve as a triage tool for prostate biopsy, and PET-TB may improve the detection rate of csPCa compared with TURS-GB, especially in patients with serum PSA 4.0-20.0 ng/ml.

Value of 68Ga-PSMA-11 PET/CT SUVmax combined with MRI ADC in the diagnosis of prostate cancer / 中华核医学与分子影像杂志

Objective To evaluate the combined application of the maximum standardized uptake value (SUVmax) of 68Ga-N,N'-bis (2-hydroxy-5-(carboxyethyl) benzyl) ethylenediamine-N,N'-diacetic acid (HBED-CC)-(Ahx) Lys-CO-Glu (PSMA-11) PET/CT imaging and the apparent diffusion coefficient (ADC) value of MRI in the differential diagnosis of prostate cancer (PCa).Methods Seventy untreated patients (age:(68.3± 12.1) years) with suspected PCa between December 2016 and April 2018 were prospectively studied.All patients underwent PET/CT and MRI examinations.The SUVmax and average ADC value were measured as diagnostic parameters,and the SUVmax/ADC ratio was calculated.The sensitivity and specificity of the 3 parameters were calculated by receiver operating characteristic (ROC) curve analysis.Results Of the 70 patients,31 were pathologically diagnosed as benign diseases and 39 were as PCa.The diagnostic sensitivity and specificity of average ADC value for PCa were 81％ and 72％,respectively,with a threshold value of 1.08× 10-3 mm2/s (b=1 000 s/mm2).The diagnostic sensitivity and specificity of SUVmax were 82％ and 71％ for PCa with a critical value of 7.69,and those were 72％ and 93％ with SUVmax/ADC ratio of 11.87.Conclusion The combination of 68Ga-PSMA-11 PET/CT and MRI can improve the diagnostic specificity for PCa,and the SUVmax/ADC ratio is a valuable differential diagnostic index.

Synergistic antitumor activity of artesunate and HDAC inhibitors through elevating heme synthesis synergistic upregulation of ALAS1 expression

Artemisinin and its derivatives (ARTs) were reported to display heme-dependent antitumor activity. On the other hand, histone deacetylase inhibitors (HDACi) were known to be able to promote heme synthesis in erythroid cells. Nevertheless, the effect of HDACi on heme homeostasis in non-erythrocytes remains unknown. We envisioned that the combination of HDACi and artesunate (ARS) might have synergistic antitumor activity through modulating heme synthesis. studies revealed that combination of ARS and HDACi exerted synergistic tumor inhibition by inducing cell death. Moreover, this combination exhibited more effective antitumor activity than either ARS or HDACi monotherapy in xenograft models without apparent toxicity. Importantly, mechanistic studies revealed that HDACi coordinated with ARS to increase 5-aminolevulinate synthase (ALAS1) expression, and subsequent heme production, leading to enhanced cytotoxicity of ARS. Notably, knocking down significantly blunted the synergistic effect of ARS and HDACi on tumor inhibition, indicating a critical role of ALAS1 upregulation in mediating ARS cytotoxicity. Collectively, our study revealed the mechanism of synergistic antitumor action of ARS and HDACi. This finding indicates that modulation of heme synthesis pathway by the combination based on ARTs and other heme synthesis modulators represents a promising therapeutic approach to solid tumors.

YTH Domain: A Family of N-methyladenosine (mA) Readers / 基因组蛋白质组与生物信息学报·英文版

Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many important biological functions. N-methyladenosine (mA) is the most abundant internal RNA modification found in a variety of eukaryotic RNAs, including but not limited to mRNAs, tRNAs, rRNAs, and long non-coding RNAs (lncRNAs). In mammalian cells, mA can be incorporated by a methyltransferase complex and removed by demethylases, which ensures that the mA modification is reversible and dynamic. Moreover, mA is recognized by the YT521-B homology (YTH) domain-containing proteins, which subsequently direct different complexes to regulate RNA signaling pathways, such as RNA metabolism, RNA splicing, RNA folding, and protein translation. Herein, we summarize the recent progresses made in understanding the molecular mechanisms underlying the mA recognition by YTH domain-containing proteins, which would shed new light on mA-specific recognition and provide clues to the future identification of reader proteins of many other RNA modifications.

Analysis of clinical effect of surgical treatment in patients with multiple tophi in extremities:A report of 23 cases / 吉林大学学报(医学版)

Objective:To explore the key points of preoperative preparation,the experience of operation and attentions of postoperative treatment of surgical treatment in multiple tophi in the extremities.Methods:A total of 23 cases of multiple tophi in extremities were selected,all were male;aged from 31 to 65 years old,average 48.7 years old;the course of the disease ranged from 4 to 20 years,with an average of 9.13 years;the blood uric acid before operation ranged from 380 to 665 μmol·L-1,the level of uric acid was controlled by physicians before operation and the patients were not in the attack period.The patients underwent gout stone resection.Some of the patients underwent functional reconstruction and were treated with standardized gout medicine after operation. Results:Twenty-one cases of incision were grade A healing 2 weeks after operation,and 2 cases of incision still had uric acid salt exudation and healed after debridement suture.Among 23 cases,18 patients were followed for 4-12 months,an average of 8 months;5 patients were lost to follow-up.Compared with before operation,the joint function was improved,the degrees of joint activity were increased,and the discomfort was relieved in 16 patients after operation;there was no improvement in postoperative joint function in 2 patients,and the pain symptom in 1 patient with carpal tunnel syndrome was reduced.Conclusion:When properly indicated,the comprehensive therapy is the best treatment for the patients with multiple tophi in extremities.It is reliable and can improve the quality of life of the patients.

Clinical value of 68Ga-PSMA-11 PET/CT in the diagnosis of castration-resistant prostate cancer / 中华核医学与分子影像杂志

Objective To assess the role of 68Ga-N,N'-bis (2-hydroxy-5-(carboxyethyl) benzyl) ethylenediamine-N,N'-diacetic acid(HBED-CC)-(Ahx) Lys-CO-Glu(PSMA-11) PET/CT on the detection of metastatic lesions from castration-resistant prostate cancer (CRPC).Methods Sixteen patients with CRPC who underwent 68Ga-PSMA-11 PET/CT between January 2015 and November 2015 were recruited in this study.Mean age of patients was (72±9) years.The PSA levels were 4-12 356 μg/L,Gleason score was 7-10.PET/CT was performed at 1 h postinjection of 68Ga-PSMA-11.Patient-based analysis and lesionbased analysis were performed.ROI analysis was used to calculate the tumor uptake (SUVmax).Final diagnosis was based on histopathology and results of other imaging examinations(99Tcm-MDP imaging,MRI).x2 test was used to compare the diagnostic efficiencies of PET and CT.Results No adverse effects were observed in patients.68Ga-PSMA-11 PET/CT showed moderate physiologic uptake in salivary glands and proximal small intestine,with predominant tracer clearance by the kidneys.All patients were positive on 68Ga-PSMA-11 PET/CT.Bone metastasis was found in 16 patients,liver metastasis in 2 patients (5 lesions),and lymph node metastasis in 4 patients (26 lesions).The SUVmax of liver,lymph node and bone metastases were 15.06±2.77,7.54±5.20,19.01± 16.96,respectively.The diagnostic sensitivity,specificity and accuracy on bone metastasis with 68Ga-PSMA-11 PET and CT were 96.30％(52/54) vs 61.11％(33/54),3/3 vs 1/3,96.49％ (55/57) vs 59.65％ (34/57).The sensitivities and accuracies of the two modalities were significantly different(x2=19.943,22.593,both P＜0.01).Conclusions 68Ga-PSMA-11 PET/CT could precisely detect both primary and metastatic lesions of CRPC,suggesting that it is of great value for the clinical management and treatment.

Clinical value of 68Ga-PSMA-11 PET/CT in the diagnosis of castration-resistant prostate cancer / 中华核医学与分子影像杂志

Objective To assess the role of 68Ga-N,N′-bis(2-hydroxy-5-(carboxyethyl)benzyl) ethylenediamine-N,N′-diacetic acid(HBED-CC)-(Ahx)Lys-CO-Glu(PSMA-11) PET/CT on the detection of metastatic lesions from castration-resistant prostate cancer (CRPC).Methods Sixteen patients with CRPC who underwent 68Ga-PSMA-11 PET/CT between January 2015 and November 2015 were recruited in this study.Mean age of patients was (72±9) years.The PSA levels were 4-12 356 μg/L, Gleason score was 7-10.PET/CT was performed at 1 h postinjection of 68Ga-PSMA-11.Patient-based analysis and lesion-based analysis were performed.ROI analysis was used to calculate the tumor uptake (SUVmax).Final diagnosis was based on histopathology and results of other imaging examinations(99Tcm-MDP imaging, MRI).χ2 test was used to compare the diagnostic efficiencies of PET and CT.Results No adverse effects were observed in patients.68Ga-PSMA-11 PET/CT showed moderate physiologic uptake in salivary glands and proximal small intestine, with predominant tracer clearance by the kidneys.All patients were positive on 68Ga-PSMA-11 PET/CT.Bone metastasis was found in 16 patients, liver metastasis in 2 patients (5 lesions), and lymph node metastasis in 4 patients (26 lesions).The SUVmax of liver, lymph node and bone metastases were 15.06±2.77, 7.54±5.20, 19.01±16.96, respectively.The diagnostic sensitivity, specificity and accuracy on bone metastasis with 68Ga-PSMA-11 PET and CT were 96.30%(52/54) vs 61.11%(33/54), 3/3 vs 1/3, 96.49%(55/57) vs 59.65%(34/57).The sensitivities and accuracies of the two modalities were significantly different(χ2=19.943, 22.593, both P<0.01).Conclusions 68Ga-PSMA-11 PET/CT could precisely detect both primary and metastatic lesions of CRPC, suggesting that it is of great value for the clinical management and treatment.

Research Progress in Preparation of Antimicrobial Peptides and Their Mechanisms of Action / 生物医学工程学杂志

Currently, all the conventional antibiotics have developed corresponding drug-resistant pathogenic strains, which have increasingly become a serious threat to people's health. Development of completely new types of antibiotics is one of effective ways to solve the drug resistance issue. Antimicrobial peptides with broad-spectrum antibacterial and antimicrobial activity and wild variety become the ideal alternative to traditional antibiotics. Antimicrobial peptides are derived from wide range of sources, such as plants, animals, and microorganisms. Mechanism of function of the antimicrobial peptides and the investigation approaches of different antimicrobial peptides also vary dramatically. In this paper, we give an overview of preparation, antibacterial mechanisms, and research methodology of antimicrobial peptides.

Lipopolysaccharide--a Target for the Development of Novel Drugs Being Aimed at Gram-Negative Bacteria / 生物医学工程学杂志

Lipopolysaccharide (LPS), the important component of the outer membrane of Gram-negative bacteria, contributes to the integrity of the outer membrane, and protects the cell against bactericidal agents. LPS, also called endotoxin synonymously, is well known as a potent inducer of the innate immune system that often causes septic shock in the intensive cares. Chemically, the amphiphilic LPS is made up of three parts, i.e., hydrophobic lipid A, hydrophilic core oligosaccharide chain, and hydrophilic O-antigenic polysaccharide side chain. Specially, the lipid A is known to be responsible for a variety of biological effects during Gram-negative sepsis. LPS can elicit a strong response from innate immune system and result in local or systemic adverse reactions. LPS can trigger massive inflammatory responses and may result in immunopathology, for which the molecular basis is mediated by the signal path- way of LPS. In recent years, a tremendous progress has been made in determining the associated proteins and receptors in the LPS signaling that leads to the disease. This review gives a summary of recent progresses of research on LPS and LPS receptors.

Current developments in pharmacological therapeutics for chronic constipation

Chronic constipation is a common gastrointestinal disease severely affecting the patient׳s quality of life. The traditional treatment of constipation is the use of laxatives. Recently, several new drugs including lubiprostone, linaclotide and prucalopride have been approved for treatment of chronic constipation. However, a significant unmet medical need still remains, particularly among those patients achieving poor results by current therapies. The 5-HT4 receptor modulators velusetrag and naronapride, the guanylate cyclase C agonist plecanatide and the ileal bile acid transporter inhibitor elobixibat are recognized as the most promising drugs under investigation. Herein, we give a comprehensive review on the pharmacological therapeutics for the treatment of chronic constipation, with the purpose of reflecting the drug development trends in this field.

Advances in inhibitors of MDM2 and MDM4 / 中国药科大学学报

@#The protein p53 plays an important role in the regulation of DNA repair, cell cycle arrest, apoptosis, senescence, autophagy and metabolism. MDM2 and MDM4 are the key negative regulatory proteins of p53. Inhibition of MDM2 and MDM4 has become a research hotspot in cancer therapy. Currently, seven MDM2 inhibitors(RG7112, MI-77301, RG7388, AMG232, CGM097, MK-8242, DS-3032b)and one MDM2/MDM4 dual inhibitor(ALRN-6924)have entered clinical trials. This paper highlights small molecule discovery, pharmacological activities and clinical research advances of MDM2 inhibitors in clinical trials, in addition, this review introduces research advances of MDM2/MDM4 dual inhibitors.

Feasibility of Low Tube Voltage Combined with Low Contrast Dose in 64-slice Spiral CT Cerebral and Carotid Arteriography / 中国医学影像学杂志

PurposeTo evaluate the feasibility of a low-dose contrast medium protocol for 64-slice spiral CT angiography (CTA) of cerebral and carotid using a low-tube-voltage setting, and to compare the display effect of cerebral and carotid arteries by low-tube-voltage low-dose contrast medium and routine-tube-voltage routine-dose contrast medium scanning, and to assess the effect on radiation dose.Materials and MethodsEighty consecutive patients were prospectively selected to perform cerebral and carotid CTA inspection. The patients were randomly divided into control group and low dose group with 40 people in each group. The voltage in control group was 120 kV and the contrast agent was 80 ml; those in low dose group were 80 kV and 50 ml, respectively. The artery image quality was evaluated and venous interference was scored. The CT value, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and radiation dose in both groups were statistically analyzed.Results The consistency of uniform in artery image quality score and venous interference score was rather high according to the assessment of two physicians (Kappa=0.782 and 0.867). There was no statistical difference in artery image quality score, venous interference score, SNR and CNR between the two groups (Z=-0.864--0.032,P>0.05). The CT value in low dose group was higher than that in control group (differences with statistical significance,t=-8.789-1.715,P<0.05). The CT dose index of volume, dose-length product and effective dose in low dose group were all signiifcantly lower than those in control group (Z=-8.888,t=78.092 and 78.350, respectively,P<0.05).Conclusion The use of low tube voltage and low contrast dose in cerebral and carotid CTA examination can result in high quality images which meets the diagnostic needs and obviously reduce radiation dosage.

Progress of antimicrobial peptides research and application / 中国生化药物杂志

Antimicrobial peptides ( AMPs) are critical component of the innate immune system of organisms, and have been demonstrated with the activity against a variety of microorganisms including bacteria, yeast, fungi, viruses and even tumor cells.Broad-spectrum activity and low propensity for resistance development make the AMPs as a kind of great potential for development of new anti-infective agents.In this paper, the origins, the action, the mechanism, the application prospects are reviewed.

Effects of ziprasidone and chlorpromazine on the ECG and cognitive function of patients with first episode of schizophrenia / 中国基层医药

Objective To investigate the effects of ziprasidone and chlorpromazine on the ECG and cognitive function of patients with first episode of schizophrenia .Methods According to the digital table ,90 patients with first-episode schizophrenia were divided into two groups ,45 cases in each group .The control group was given chlorproma-zine,while the observation group received oral ziprasidone .Clinical efficacy,cognitive function and ECG results were compared before and after treatment .Results The PANSS scores of the study group and the control group were (57.78 ±4.16) points and (58.43 ±4.33) points after treatment,which were significantly lower than (72.62 ± 4.66)points and (72.39 ±4.87)points before treatment (t=7.15,7.46,all P0.05).The total number of tests of WCST ,continuous errors and CT error rate in study group after treatment were (73.32 ±5.08),(40.35 ±4.15) and (12.72 ±2.00)%,which were signif-icantly lower than (86.43 ±5.58),(67.72 ±4.26) and (21.02 ±2.33)%before treatmemt and (84.32 ±5.16), (65.82 ±4.25) and (20.05 ±2.20)%in the control group(t=6.84,7.21,7.85,7.52,8.21,8.12,all P<0.05). WCST categories completed and the number of CT net scores were (5.32 ±0.40) and (125.83 ±11.65) points, which were significantly higher than (3.41 ±0.38) and (102.82 ±10.72) points before treatment and (3.52 ± 0.39) and (108.37 ±10.24)points in the control group,the differences were statistically significant (t=6.72,7.11, 7.01,7.53,all P<0.05).The incidence rate of abnormal ECG in study group was 22.22% after treatment,which was significantly lower than 55.56% in the control group(χ2 =11.02,P<0.05).Conclusion Ziprasidone and chlorpromazine have a equivalent efficacy in the treatment of first-episode schizophrenia ,but ziprasidone can signifi-cantly improve cognitive function and has little effect on ECG ,it is safe.

Effect of valproic acid on Ca2+ and cell apoptosis in spinal cord motor neurons after brachial plexus injury in rats / 中华显微外科杂志

Objective To examine the effect of valproic acid (VPA) on concentration of Intracellular Ca2+ and on cell apoptosis in spinal cord motor neurons after brachial plexus injury in rats. Methods Totally 210 adult male Wistar rats were randomly divided into Sham operation group (disposed the brachial plexus nerve root, but not cutted it off), control group (rats with brachial plexus nerve root amputating wound)and VPA group(rats with brachial plexus nerve root amputating wound and fed by VPA water),with 70 rats in each group.The specimens were taken at 12,24,48,72 h,1,2 and 4 weeks after operation.Whole-cell patch-clamp recording techniques were used to assayed the L-type calcium channel of motoneuron and monitored the changes in intracellular concentration of Ca2+ with spectrofluorometer. The motoneruron apoptosis was detected by TUNEL. Results The set of indicators did not change in the sham group.From 12h to 1 weeks after the operation, the electrical current of L-type calcium channel and the intra-cellular Ca2+ concentration of the neuron were obviously more in control group than in sham operation group (P ＜0.05). From 12 h to 4 weeks after the injury, there were more apoptosis neurons in control group than in sham operation group (P ＜ 0.05). There was no obviously difference in electrical current of L-type calcium channel between the VPA group and the control group at each time point(P ＞ 0.05).Compared to the control group,the intra-cellular Ca2+ concentration was lower in VPA group from 48 h to 1 week after nerve injury (P ＜ 0.05) ; the number of apoptosis neurons were less in VPA group from 24 h to 2 weeks after the injury (P ＜ 0.05). Conclusions Brachial plexus nerve root amputating wound in rats can increase the intra-cellular Ca2+ concentration and apoptosis of the motor neuron.VPA can reduce the intra-cellular Ca2+ concentration and apoptosis,but has no effect on the L-type calcium channel of the motor neuron.

Effect of heart rate variability on image quality of 3D free-breathing whole-heart coronary MR angiography with 3.0T scanner / 中国医学影像技术

Objective To observe the effect of the average heart rate (HR) and the variability of HR on image quality of 3D free-breathing whole-heart coronary MR angiography (MRCA). Methods A total of 65 healthy volunteers underwent retrospectively electrocardiography-gated 3D free-breathing whole-heart coronary MRA with ECG-gated 3D segmented-k-space gradient echo sequence. Two observers evaluated image quality of each coronary segment. Visualization of the proximal coronary arteries (CA) with coronary MRA was qualitatively evaluated using a four point grading scale (1: excellent; 2: good; 3: moderate; 4: non-diagnostic). Pearson correlation analysis was performed to analyze the correlation between image quality of each coronary artery and the average HR and heart rate variability. Results Average HR was 64.5±13.3 beats per minute (bpm) (range 40-86 bpm) with a variability of (6.1%±2.6)%. No significant correlation presented between mean HR and image quality of all segments of the left circumflex and left anterior descending artery except the right coronary artery (P<0.05). heart rate variability significantly correlated with overall image quality (P<0.001) and image quality of each coronary artery. Conclusion heart rate variability influences the image quality of 3D free-breathing coronary MRA more obvious than HR does.

Synthesis and phosphodiesterase type-5 inhibitory activity of sildenafil analogues possessing a guanidine group in the phenyl ring / 中国药科大学学报

In this study,a series of new sildenafil analogues 11-27 possessing a guanidine group were synthesized to investigate their PDE5 inhibitory activity and selectivity using[~3H]cGMP SPA kit in vitro and efficacy in the rat model of erection.Most of the compounds showed potent activity against PDE5,and more importantly,several compounds exhibited higher PDE5 selectivity over PDE6 than that of sildenafil.Structure-activity relationship of these sildenafil analogues was also discussed.Within this series of compounds,compound 15(IC_(50) =1.7 nmol/L)not only exhibited more potent PDE5 inhibitory activity than that of sildenafil (IC_(50) = 6.5 nmol/L),but also showed functional efficacy in the rat model of erection.

Synthesis and in vitro antitumor activities of novel soladulcidine derivatives / 中国药科大学学报

Soladulcidine is a steroidal alkaloid abundant in Solanum dulcamara L. with antitumor and other biological activities. In this study, ten soladulcidine derivatives were synthesized through esterification at C-3-hydroxy group, modification at NH group of F ring of esterification of E ring-opening products. The in vitro antiproliferative activity of these synthesized derivatives against prostate cancer (PC-3) cell line was assessed. Within this series of compounds, compound 19 exhibited the most potent inhibitory effect against the proliferation of PC-3 cell line (IC50=4.80±.9μmol/L).

Expression of growth associated protein 43 at the corresponding dorsal root ganglia following sciatic nerve transplantation in rats / 中国组织工程研究

BACKGROUND: Following peripheral nerve transplantation, the time phases and law of growth associated protein 43 (GAP-43) expression in sensory neuron soma of the corresponding dorsal root ganglia remain unclear.OBJECTIVE: To investigate the expression of GAP-43 at the corresponding dorsal root ganglia following sciatic nerve transplantation in rats.METHODS: Adult male Wistar rats were randomly divided into 2 groups: control group (sham-operated group) and experimental group (nerve transplantation group). The rats were killed at 3 days, 1, 2, 4, 6, and 8 weeks after operation and the dorsal root ganglia U-s of every rat was taken for observation. The expression of GAP-43 mRNA and protein in the corresponding segments of spinal cord were detected by RT-PCR and Western-blot techniques.RESULTS AND CONCLUSION: GAP-43 mRNA showed a low level of expression in the control group, which had no obvious changes in different phases. In the experimental group, GAP-43 mRNA expression was observed remarkably in the dorsal root ganglia at the first week, reached a peak at the second week and gradually descended from the sixth week. The GAP-43 protein expression showed the same laws as that of GAP-43 mRNA. The results demonstrated that there exists damage reactivity change in the regeneration ability of neurons.