CUDC-101 as a dual-target inhibitor of EGFR and HDAC enhances the anti-myeloma effects of bortezomib by regulating G2/M cell cycle arrest / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

CUDC-101, an effective and multi-target inhibitor of epidermal growth factor receptor (EGFR), histone deacetylase (HDAC), and human epidermal growth factor receptor 2 (HER2), has been reported to inhibit many kinds of cancers, such as acute promyelocytic leukemia and non-Hodgkin's lymphoma. However, no studies have yet investigated whether CUDC-101 is effective against myeloma. Herein, we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma (MM) cell lines and induces cell apoptosis in a time- and dose-dependent manner. Moreover, CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase (PI3K) and HDAC, and regulated the cell cycle G2/M arrest. Moreover, we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug. Bortezomib is one of the important drugs in MM treatment, and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib. The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment.

Mechanism of Sijunzi Decoction in treatment of Alzheimer's disease based on UPLC-Q-TOF-MS, network pharmacology, and experimental verification / 中国中药杂志

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.

Personalized surgical effect of labia minora hypertrophy / 中华医学美学美容杂志

Objective:To explore an optimal surgical approach for different types of labia minora hypertrophy and to design a better personalized surgical treatment plan for patients.Methods:From October 2017 to October 2020, 71 patients with labia minora hypertrophy were treated in the plastic surgery department of Sichuan Provincial People＇s Hospital, aged 18-38 years, with an average of 26 years. According to the type and degree of hypertrophy, the appropriate surgical method was selected. The wound healing and complications were observed after operation, and the shape of labia minora was followed up.Results:Among the 71 patients, 1 patient had postoperative hematoma and no flap necrosis after active treatment. 1 patient had poor healing of distal labia minora incision and improved after dressing change. The other patients had good blood supply of labia minora, no necrosis, no postoperative infection, hematoma and other complications. The patients were followed up for 1-6 months. The appearance of labia minora was natural, bilateral symmetry, and the incision scar was hidden. The improvement was significant compared with that before operation. The patients were satisfied with the shape and function.Conclusions:According to the degree of hypertrophy of the labia minora, the specific shape and the psychological expectation of patients, we can choose the appropriate operation method, which can achieve the aesthetic standard of symmetry and beautiful shape of the labia minora, and meet the normal physiological function and aesthetic requirements of patients.

Application of orbicularis oculi muscle shaping in lower blepharoplasty / 中华医学美学美容杂志

Objective:To investigate the clinical application and effect of orbicularis oculi muscle shaping in lower blepharoplasty.Methods:A retrospective analysis was performed on the clinical data of 32 cases of flabby blepharoplasty patients admitted to the Orthopedic Surgery Clinic of Sichuan people＇s Hospital from October 2018 to September 2019. At the same time of transcutaneous blepharoplasty, 32 patients were treated with orbicularis oculi muscle shaping to remove the relaxed orbicularis oculi muscle, to reconstruct the annular strength and shape of the orbicularis oculi muscle, to strengthen the supporting structure of the lower eyelid, to reset the relationship between the external canthus orbicularis muscle and the skin, and then to reconstruct the soft tissue filling degree of the lower eyelid margin. The safety, efficacy and stability of the operation were evaluated by Barton grading, postoperative complications and scoring before and after operation and satisfactory analysis based on patients＇ satisfaction scale after operation.Results:All the patients were free of postoperative infection and healed at stage I. There were 2 cases of ecchymosis, 3 cases of ocular foreign body sensation, and no cases of infection, lower eyelid retraction, lower eyelid ectropion, or retrobulbous hematoma. The mean Barton score of all patients before surgery was 1.88±0.49, and the mean Barton score after surgery was 0.53±0.51. The t-test showed that the difference was statistically significant ( t=15.75, P<0.05), and the postoperative lacrimal groove deformity was improved. According to the score of satisfaction scale, 7 people were basically satisfied (21.88%) and 25 people were very satisfied (78.12%). Conclusions:Forming in the orbicularis oculi muscle relaxation eyelid bag type of prosthesis, in addition to the part of the orbicularis oculi muscle relaxation, deformation, and widely shed canthus outside skin and orbicularis connection, make the next eyelid edge to reproduce the full shape, obviously the bulging under the eyelid relaxation, the shape of the degree of repair, lateral canthus wrinkles tail department have also improven, restoring the full eyelid platform. The operation has strong pertinence, simple procedures, less complications and better long-term effect.

Efficacy of tissue gradient difference principle in repairing over-wide eyelid fold after double eyelid plasty / 中华医学美学美容杂志

Objective:To explore the effect of the principle of tissue gradient difference in repairing the over wide eyelid fold after double eyelid operation by incision.Methods:From July 2019 to July 2020, we applied the principle of tissue gradient difference to 30 cases (a total of 60 eyes; age ranging 20-35 years with mean 30) of female patients with excessively wide eyelids after incision double eyelid surgery needing a repair. All cases were from the Plastic Surgery Department of Sichuan Provincial People＇s Hospital. The difference in tissue gradient was manifested as the difference in thickness, texture and tension of soft tissues such as the skin above and below the double eyelid line and the orbicularis oculi muscle.Results:Satisfactory evaluation results showed in a total of 30 patients with 60 eyes, 95.0% ( n=57) were satisfied, and 5.0% ( n=3) were dissatisfied. Two of the patients received the second repair due to the inconsistency of the double eyelid width after correction. One patient obtained satisfactory double eyelid morphology after the second repair, and the other patient obtained satisfactory double eyelid morphology after the third repair. Evaluation results of double eyelid morphology showed that it obeyed a normal distribution by analyzing the difference between preoperative and postoperative double eyelid morphology scores. The results of paired t test showed that the double eyelid morphology was significantly improved 6 months after operation compared with preoperative, and the difference was statistically significant ( t=15.86, P<0.01). Conclusions:The principle of tissue gradient difference guides the repair of double eyelid width that is simple and easy, the effect is good, and it is worth applying.

Current status and research progress of POCT-based detection technology for 2019-nCoV / 中华检验医学杂志

In view of the significant changes in the prevention and control of COVID-19 at home and abroad, "external prevention of importation and internal prevention of rebound" has become the focus of prevention and control of the epidemic in China. Due to the limitation of testing sites, equipment and reaction time, traditional detection methods cannot meet the needs of real-time and rapid detection of 2019-nCoV. Point-of-care testing (POCT) is rapid, portable and flexible. It plays an increasingly important role in the rapid detection and screening of 2019-nCoV. Here, we review the current status and research progress of POCT for 2019-nCoV in terms of antigens, specific antibodies and nucleic acids, in order to provide reference for epidemic prevention and control and clinical management.

Prediction of Q-markers of Citri Reticulatae Pericarpium volatile oil and GC-MS based quantitative analysis / 中国中药杂志

This study was designed to predict the Q-markers of Citri Reticulatae Pericarpium volatile oil and conduct quantitative analysis by GC-MS. The common components of Citri Reticulatae Pericarpium volatile oil were detected by GC-MS. The network pharmacology approaches were utilized for constructing the component-target network and protein-protein interaction(PPI) network, followed by the GO and KEGG pathway enrichment analysis to clarify the pharmacological effects of common components. Molecular docking was conducted to observe the biological activities of common components, thus identifying the Q-markers of Citri Reticulatae Pericarpium volatile oil. The obtained Q-markers were subjected to quantitative analysis by GC-MS. The GC-MS analysis of 19 batches of Citri Reticulatae Pericarpium volatile oil revealed three common components, namely, D-limonene, γ-terpinene, and myrcene. The common components were analyzed based on network pharmacology, and the results showed that Citri Reticulatae Pericarpium volatile oil mainly acted on the core targets GABRA1, GABRA6, GABRA5, GABRA3, and GABRA2 through D-limonene and γ-terpinene, with five important pathways such as nicotine addiction and GABAergic synapse involved. The core targets were mainly distributed in olfactory region, cerebral cortex, cerebellum, basal ganglia, hippocampus, and amygdala to exert the pharmacological effects. As revealed by molecular docking, D-limonene and γ-terpinene exhibited good biological activities, so they were identified as the Q-markers of Citri Reticulatae Pericarpium volatile oil. The results of quantitative analysis showed that the volume fraction of D-limonene was within the range of 0.77-1.03 μL·mL~(-1), and that of γ-terpinene within the range of 0.04-0.13 μL·mL~(-1). The prediction of D-limonene and γ-terpinene as the Q-markers of Citri Reticulatae Pericarpium volatile oil has laid an experimental foundation for the establishment of the quality evaluation standard for Citri Reticulatae Pericarpium volatile oil.

Effects and pathophysiological significance of intestinal flora on the enteric neuro-endocrine-immune system / 生理学报

Interactions among the nervous, the endocrine and the immune systems enable the gut to respond to the dietary products, pathogens and microbiota, which maintains the homeostasis of the body. However, dysbiosis may induce or aggravate the gastrointestinal (GI) and extra-GI diseases through changing the activities of enteric nervous system (ENS), enteroendocrine cells and enteric immune cells. Here we review recent advances in the understandings on how intestinal flora may impact the enteric neuro-endocrine-immune system in the gut, thereby contributing to the regulation of pathophysiological processes.

Circulating tumor cell detection approaching to clinical application / 中华检验医学杂志

As "seeds" of tumor metastasis, circulating tumor cell (CTC) has important clinical application value in early diagnosis, immunotherapy and prognosis evaluation of tumors. With a deep understanding of CTC, its applied research has switched from cell enumeration to the molecular typing and single-cell sequencing. However, the standardization of CTC detection is still at a primary stage, opportunities and challenges coexist. This paper will review the current status and challenges in clinical applications of CTC detection, and make some suggestions for future development.

Effect of Three Chinese Herbs Processed with Different Proportions of Glycyrrhizae Radix et Rhizoma on Pharmacokinetics of Dapsone in Rats / 中国实验方剂学杂志

Objective::To investigate the processing purpose of Morindae Officinalis Radix (MO), Euodiae Fructus (EF) and Polygalae Radix (PR) processed by Glycyrrhizae Radix et Rhizoma (Gly). Method::The content of dapsone in rat plasma was determined by high performance liquid chromatography (HPLC), the mobile phase was acetonitrile (A)-water (B) for gradient elution (0-5 min, 10%-25%A; 5-20 min, 25%A) and detection wavelength was set at 292 nm. PK Solution 2.0 software was used to simulate pharmacokinetic parameters. Result::Within 300 min after dapsone was administrated, compared with the control (CTL) group, the elimination of dapsone was slowed down and its plasma concentration was increased in the unprocessed product of MO (UMO) group. The elimination of dapsone was accelerated and its peak concentration (Cmax) was decreased in the processed products of MO with Gly (GMO) groups, and they had positive correlation with proportion of Gly in GMO. Compared with the CTL group, the elimination of dapsone was slowed down, and its plasma concentration was increased and its peak time (Tmax) was postponed in the unprocessed product of EF (UEF) group, while their Cmax and Tmax were changed in the processed products of EF with Gly (GEF) groups. Compared with the CTL group, the elimination of dapsone was slowed down and its plasma concentration was increased in the unprocessed product of PR (UPR) group, while the elimination was accelerated and its plasma concentration was decreased in the processed products of PR with Gly (GPR) groups. Conclusion::The elimination of dapsone is slowed down in rats administered with UMO, UEF and UPR, while its elimination is accelerated in rats administered with the processed products of these three herbs with different proportions of Gly. Among the proportions, effect of processed products of these three herbs with 100∶6 (ratio of unprocessed product-Gly) on pharmacokinetics of dapsone is not significant.

Circulating tumor cell detection approaching to clinical application / 中华检验医学杂志

As "seeds" of tumor metastasis, circulating tumor cell (CTC) has important clinical application value in early diagnosis, immunotherapy and prognosis evaluation of tumors. With a deep understanding of CTC, its applied research has switched from cell enumeration to the molecular typing and single-cell sequencing. However, the standardization of CTC detection is still at a primary stage, opportunities and challenges coexist. This paper will review the current status and challenges in clinical applications of CTC detection, and make some suggestions for future development.

How are MCPIP1 and cytokines mutually regulated in cancer-related immunity?

Cytokines are secreted by various cell types and act as critical mediators in many physiological processes, including immune response and tumor progression. Cytokines production is precisely and timely regulated by multiple mechanisms at different levels, ranging from transcriptional to post-transcriptional and posttranslational processes. Monocyte chemoattractant protein-1 induced protein 1 (MCPIP1), a potent immunosuppressive protein, was first described as a transcription factor in monocytes treated with monocyte chemoattractant protein-1 (MCP-1) and subsequently found to possess intrinsic RNase and deubiquitinase activities. MCPIP1 tightly regulates cytokines expression via various functions. Furthermore, cytokines such as interleukin 1 beta (IL-1B) and MCP-1 and inflammatory cytokines inducer lipopolysaccharide (LPS) strongly induce MCPIP1 expression. Mutually regulated MCPIP1 and cytokines form a complicated network in the tumor environment. In this review, we summarize how MCPIP1 and cytokines reciprocally interact and elucidate the effect of the network formed by these components in cancer-related immunity with aim of exploring potential clinical benefits of their mutual regulation.

Analysis of independent risk factors for early castrate-resistant after endocrine therapy in elderly patients with prostate cancer / 解放军医学杂志

[Abstract] Objective To analyze the independent risk factors for castrate-resistant prostate cancer (CRPC) after conservative endocrine therapy in elderly prostate cancer patients. Methods Totally 90 elderly prostate cancer patients undergoing endocrine therapy from July 2013 to July 2015 were included into this study as research objects. The basic data and pathological, and laboratory indexes were collected from them. The incidence of CRPC in 2 years after discharge was recorded by follow-up, the Cox risk regression model was used to analyze the high-risk factors of CRPC. The application value of the risk factors to predict CRPC were analyzed by receiver operating characteristic curve and the exponential equation was established to predict the occurrence of CRPC in elderly patients with prostate cancer for 2 years. Results Totally 90 patients were followed up for 24 months in average, of whom 2 cases were lost to follow-up, 26 developed CRPC, the incidence of CRPC was 29.55%. The Cox risk regression model showed that T stage (OR=3.823, 95%CI 2.137-6.839, P<0.001), Gleason score (OR=8.045, 95%CI 3.501-18.487, P<0.001), prostatic specific antigen (PSA) (OR=2.983, 95%CI 1.407-6.324, P=0.004) and prostate cancer gene 3 (PCA3) (OR=1.998, 95%CI 1.263-3.161, P=0.003) were the independent risk factors for prostate cancer progressing to early CRPC in elderly prostate cancer patients. The exponential equation for predicting CRPC model was 0.367X1+0.642X2+0.409X3 +0.815X4 according to the results of multivariate analysis (X1: T stage, X2: Gleason score, X3: PSA value, X4: PCA3 value), the AUC was 0.855 (β=0.056, 95%CI 0.745-0.965, P<0.001). The sensitivity was 0.919, the specificity 0.857, the Youden index 0.776, and the corresponding index of prognosis 1.325. Conclusion The T stage, Gleason score, PSA and PCA3 are independent risk factors for prostate cancer progressing to CRPC after endocrine therapy in elderly prostate cancer patients, can be used comprehensively to establish a model of predicting CRPC for improving the accuracy of judgments.

Effect of Wuzi Yanzong Fang in Promoting Spermatogonial Stem Cells Proliferation in Aging Rats by Regulating miR-let-7-Imp Axis / 中国实验方剂学杂志

Objective: To explore the effect and mechanism of Wuzi Yanzong Fang (WZ) on proliferation of spermatogonial stem cells in aging rats by regulating miR-let-7-Imp axis.Method: A total of 40 18-month-old male SD rats were randomly divided into aging model group, and low, middle and high-dose WZ groups, with 10 rats in each group. Ten 2-month old rats were used as young control group. Low, middle and high-dose WZ groups were given by gastric WZ 0.4, 0.8, 1.6 g·kg-1 respectively. Young control group and aging model group were given normal saline for 4 months, which was suspended for 2 days every week. Rats were put to death after the final treatment with WZ, and then the testes were quickly removed from rats. The relative mRNA expression levels of miR-let-7 and Imp were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expressions and localization of p-JAK2/JAK2, phosphate(p)-signal transduction and transcriptional activators3 (STAT3)/STAT3 signaling pathway proteins were detected by Western blot and immunofluorescence. The numbers of spermatogonial stem cells and the expression levels of proliferating cell nuclear antigen (PCNA) were detected by immunofluorescence. The testicular tissue morphology was observed using htoxylin eosin (HE) staining.Result: Compared with young control group, the expression levels of miR-let-7 mRNA were significantly increased, while the expression levels of Imp mRNA were decreased in the aging model group(PPPPPPPConclusion: WZ effectively promote the proliferation of spermatogonial stem cells by regulating miR-let-7-imp axis in testis.

The effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation in acute leukemia / 中华血液学杂志

Objective@#To study the effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia (AL) and its significance as molecular marker to dynamically monitor minimal residual disease (MRD) .@*Methods@#Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017, a total number of 314 cases, 163 males and 151 females, median age was 30 (9-64) years old. Comparing the difference of WT1 expression at diagnosed, pre-HSCT and after HSCT. Using the receiver operating characteristic (ROC) curve to determine the WT1 threshold at different time so as to predict relapse. The threshold of WT1 expression before transplantation was 1.010%, within 3 months after HSCT was 0.079% and 6 months after HSCT was 0.375%. According to these thresholds, WT1 positive patients were divided into low expression groups and high expression groups. Analyzed the relationship between overall survival (OS) , disease-free survival (DFS) , cumulative incidence of relapse (CIR) and WT1 expression.@*Results@#The OS and DFS of high expression group pre-HSCT were lower than low expression group [69.2% (9/13) vs 89.1% (57/64) , χ2=4.086, P=0.043; 53.8% (7/13) vs 87.5% (56/64) , χ2=9.766, P=0.002], CIR was higher than low expression group [30.8% (4/13) vs 7.8% (5/64) , P=0.017]. There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT (P=0.558, P=0.269) . The OS and DFS of high expression group of 6 months after transplantation were both lower than low expression group (P=0.049, P=0.035) . Multivariate analysis showed that WT1>0.375% when 6 months after transplantation was the only independent prognostic factor for shorter DFS (P=0.022) . There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6 months after transplantation (P=0.114, P=0.306) .@*Conclusion@#High expression of WT1 before and after HSCT was an adverse prognosis factor. It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.

Clinical study on the treatment of prominent ear by personalized horizontal mattress suture combined with cartilage tube method / 中华整形外科杂志

Objective@#To study the effect of individualized treatment of prominent ears using mattress suture combined tubed cartilage method.@*Methods@#A total of 21 patients (28 ears) with prominent ear deformity were retrospectively analyzed from January 2013 to December 2015. Horizontal mattress suture and tubed cartilage were used to correct the deformed ears. The patients were followed up for 6 months to 1 year (mean: 9 months).@*Results@#Hematoma occurred in 3 cases after operation, but the wounds were healed after removal of hematoma. No infection, flap necrosis, cartilage absorption or deformation, or other complications occurred. 28 ears were corrected. The shape of the antihelix was smooth and the auriculocephalic angle and scapha-conchal angle were significantly reduced, compared with preoperative. No obvious scar hypertrophy was left on incision.@*Conclusions@#The method of horizontal mattress suture combined with tubed cartilage is simple to use for prominent ear, result in satisfactory and stable outcomes.

Detail repair technique for alar deformity after the first stage reconstruction of alar defect / 中华整形外科杂志

Objective@#To sum up the repair techniques of secondary alar deformity after the first phase reconstruction of alar defect.@*Methods@#From January 2010 to December 2017, 17 patients with secondary alar deformity were included. Secondary alar deformities after the first stage reconstruction of alar defect included the abnormalities of alar groove line, absence of alar-cheek groove and the notch of alar rim. Z-plasty, V-Y advanced flaps, local skin flap and other technologies were introduced to repair details.@*Results@#Infection was found in one case of the reconstruction of the alar-cheek groove and the wound was healed by treatment. There was no necrosis occurred in other flap. The shape of the alar was satisfactory and the anterior nostril was not narrow. Patients were followed up for 1 month to 1 year. The average follow-up time was 5 months. No recurrence of nasal alar tumor was found. The patients were satisfied with the appearance.@*Conclusions@#The symmetrical and satisfactory nasal shape can be obtained with local flaps such as Z-plasty, V-Y advancement of flaps for secondary alar deformities.

Mechanism of detoxification of Chebulae Fructus against Aconiti kusnezoffii radix toxicity based on network pharmacology / 药学学报

The mechanism of detoxification of Chebulae Fructus against Aconiti kusnezoffii radix toxicity, which was known as Mongolian medical theory, was studied by establishing network of active components-targets-pathways of detoxification and enrichment analysis of targets and pathways based on network pharmacology. Firstly, the targets of active components collected from TCMSP and TCM Database@Taiwan were obtained through SwissTargetPrediction compared with disease targets from OMIM, TTD, DiGSeE. Then, the target enrichment analysis of GO functional annotations and KEGG pathways and protein function were analyzed by Metascape, furthermore, the action between main active ingredients and targets was assessed by SystemsDock Web Site. At last, the Cytoscape was used to construct the network of active components-targets-pathways. In conclusion, there were 15 components and 40 targets related to the cardiotoxicity caused by Aconiti kusnezoffii radix. Furthermore, Chebulae Fructus could regulate cardiac function to detoxify the toxicity by Aconiti kusnezoffii radix through the biological process of negative regulation of blood vessel diameter, regulation of ion transport circulatory system process, muscle contraction inorganic ion homeostasis and the pathways of neuroactive ligand-receptor interaction, calcium signaling pathway, adrenergic signaling in cardiomyocytes, etc.

Protective effect of Wuzi Yanzong recipe on testicular DNA damage and apoptosis in natural ageing rats / 中国中药杂志

To study the protective effect of Wuzi Yanzong recipe on testicular DNA damage and apoptosis in natural ageing rats, SPF grade 16-month-old SD male rats were randomly divided into three groups: ageing model group, low and high dose Wuzi Yanzong recipe groups (WZ, 1， 4 g·kg⁻¹). In addition, 2-month-old SD rats were used as adult control group (10 rats in each group). The ageing model group and the adult control group were fed with normal diet for 4 months. Wuzi Yanzong groups received medicated feed for 4 months. After fasting for 12 hours, the rats were sacrificed. Then testis tissues were taken and weighed to calculate the testis index. The change of testicular tissue morphology was observed by HE staining. Expression and localization of DNA damage-associated protein ATR were observed by immunofluorescence. The expressions of DNA damage-related proteins γ-H2AX, Chk1, p-p53 and apoptosis-related proteins Bcl-2 and Bax in testes were detected by Western blot. The apoptosis of testis tissue in rats was detected by using TUNEL. The results showed that as compared with the youth control group, the protein expression levels of γ-H2AX, Chk1, p-p53 and Bax were significantly increased while Bcl-2 protein expression level was significantly decreased intestis tissues of ageing model group. Wuzi Yanzong recipe significantly decreased protein expression levels of γ-H2AX, Chk1, p-p53 and Bax and increased Bcl-2 protein expression level as well as Bcl-2/Bax ratio. Immunofluorescence results showed that Wuzi Yanzong recipe could significantly decrease the ageing-induced ATR, increase in testis tissues. TUNEL results showed that Wuzi Yanzong recipe could significantly attenuate the germ cell apoptosis in testicular tissues. All the above results suggest that Wuzi Yanzong recipe could protect the germ cell in testicular tissues of natural ageing rates from DNA damage and apoptosis, and the mechanism may be associated with regulating p53 signaling pathway.

Pirh2 mediates the sensitivity of myeloma cells to bortezomib via canonical NF-κB signaling pathway

Clinical success of the proteasome inhibitor established bortezomib as one of the most effective drugs in treatment of multiple myeloma (MM). While survival benefit of bortezomib generated new treatment strategies, the primary and secondary resistance of MM cells to bortezomib remains a clinical concern. This study aimed to highlight the role of p53-induced RING-H2 (Pirh2) in the acquisition of bortezomib resistance in MM and to clarify the function and mechanism of action of Pirh2 in MM cell growth and resistance, thereby providing the basis for new therapeutic targets for MM. The proteasome inhibitor bortezomib has been established as one of the most effective drugs for treating MM. We demonstrated that bortezomib resistance in MM cells resulted from a reduction in Pirh2 protein levels. Pirh2 overexpression overcame bortezomib resistance and restored the sensitivity of myeloma cells to bortezomib, while a reduction in Pirh2 levels was correlated with bortezomib resistance. The levels of nuclear factor-kappaB (NF-κB) p65, pp65, pIKBa, and IKKa were higher in bortezomib-resistant cells than those in parental cells. Pirh2 overexpression reduced the levels of pIKBa and IKKa, while the knockdown of Pirh2 via short hairpin RNAs increased the expression of NF-κB p65, pIKBa, and IKKa. Therefore, Pirh2 suppressed the canonical NF-κB signaling pathway by inhibiting the phosphorylation and subsequent degradation of IKBa to overcome acquired bortezomib resistance in MM cells.