Research progress on HEG1 in cardiovascular generation and tumor development / 中华预防医学杂志

Heart development protein with EGF-like domains 1 (HEG1) is a novel mucin-like membrane protein with a long O-glycosylation region and EGF domain. HEG1 plays critical roles in embryo development and cardiogenesis, and is closely related to the occurrence and progression of malignant tumors. Here this article demonstrates the research progress on HEG1 in cardiovascular formation and tumor development in recent years, to inspire new ideas for the pathogenesis, diagnosis and treatment of related diseases.

Research progress on HEG1 in cardiovascular generation and tumor development / 中华预防医学杂志

Heart development protein with EGF-like domains 1 (HEG1) is a novel mucin-like membrane protein with a long O-glycosylation region and EGF domain. HEG1 plays critical roles in embryo development and cardiogenesis, and is closely related to the occurrence and progression of malignant tumors. Here this article demonstrates the research progress on HEG1 in cardiovascular formation and tumor development in recent years, to inspire new ideas for the pathogenesis, diagnosis and treatment of related diseases.

Research progress of the regulation of orphan nuclear receptors on chronic liver diseases / 生理学报

The development of chronic liver disease can be promoted by excessive fat accumulation, dysbiosis, viral infections and persistent inflammatory responses, which can lead to liver inflammation, fibrosis and carcinogenesis. An in-depth understanding of the etiology leading to chronic liver disease and the underlying mechanisms influencing its development can help identify potential therapeutic targets for targeted treatment. Orphan nuclear receptors (ONRs) are receptors that have no corresponding endogenous ligands to bind to them. The study of these ONRs and their biological properties has facilitated the development of synthetic ligands, which are important for investigating the effective targets for the treatment of a wide range of diseases. In recent years, it has been found that ONRs are essential for maintaining normal liver function and their dysfunction can affect a variety of liver diseases. ONRs can influence pathophysiological activities such as liver lipid metabolism, inflammatory response and cancer cell proliferation by regulating hormones/transcription factors and affecting the biological clock, oxidative stress, etc. This review focuses on the regulation of ONRs, mainly including retinoid related orphan nuclear receptors (RORs), pregnane X receptor (PXR), leukocyte cell derived chemotaxin 2 (LECT2), Nur77, and hepatocyte nuclear factor 4α (HNF4α), on the development of different types of chronic liver diseases in different ways, in order to provide useful references for the therapeutic strategies of chronic liver diseases based on the regulation of ONRs.

Study on mechanism of curcumol against liver fibrosis based on autophagy and apoptosis of hepatic stellate cells / 中国中药杂志

The present study clarified the molecular mechanism of curcumol against liver fibrosis based on its effects on the autopha-gy and apoptosis of hepatic stellate cells. The hepatic stellate cells were divided into a blank control group, a transforming growth factor-β1(TGF-β1)(10 ng·mL~(-1)) group, and low-(12.5 mg·L~(-1)), medium-(25 mg·L~(-1)), and high-dose(50 mg·L~(-1)) curcumol groups. The effect of curcumol on the viability of hepatic stellate cells induced by TGF-β1 was detected by the MTT assay kit. The apo-ptosis in each group was determined by flow cytometry. Real-time fluorescence-based quantitative PCR(RT-PCR) was employed for the detection of mRNA expression of α-smooth muscle actin(α-SMA), type Ⅰ collagen(collagen Ⅰ), and type Ⅲ collagen(collagen Ⅲ). Western blot was used to detect the protein expression of p62, microtubule-associated protein 1 light chain 3(LC3), beclin1, B cell lymphoma 2(Bcl-2), and Bcl-2-associated X protein(Bax). Transmission electron microscopy(TEM) was used to observe cell morphology and autophagosome formation in each group. The autophagic flux was observed after cell infection with adenovirus under double fluorescence labeling. The cell viability assay revealed that compared with the TGF-β1 group, the curcumol groups showed significantly decreased cell viability. The apoptosis assay showed that the apoptosis rates of the curcumol groups were significantly higher than that of the TGF-β1 group. RT-PCR indicated that the mRNA expression of α-SMA, collagenⅠ, and collagen Ⅲ in the curcumol groups was significantly lower than that of the TGF-β1 group. Western blot showed that the expression of p62, LC3, beclin1, Bcl-2, and Bax in the curcumol groups was significantly different from that in the TGF-β1 group. As demonstrated by TEM, compared with the TGF-β1 group, the curcumol groups showed significantly increased autophagosomes. The detection of autophagic flow by the adenovirus under double fluorescence labeling showed that autolysosomes in the curcumol groups were significantly increased compared with those in the TGF-β1 group. Curcumol can induce the autophagy and apoptosis of hepatic stellate cells, which may be one of its anti-liver fibrosis mechanisms.

Research progress on role of traditional Chinese medicine in hepatic fibrosis based on miRNA-mediated activation of NLRP3 inflammasome / 中国中药杂志

In recent years, liver fibrosis has become a hotspot in the field of liver diseases. MicroRNA(miRNA)-mediated Nod-like receptor pyrin domain containing 3(NLRP3) inflammasome activation is pivotal in the pathogenesis of liver fibrosis. The present study mainly discussed the role of miRNA-mediated NLRP3 inflammasome activation in the pathogenesis of liver fibrosis. Different miRNA molecules regulated liver fibrosis by mediating NLRP3 inflammasome activation, including miRNA-350-3 p(miR-350-3 p)/interleukin-6(IL-6)-mediated signal transducer and activator of transcription 3(STAT3)/c-myc signaling pathway, miR-148 a-induced autophagy and apoptosis of hepatic stellate cells via hedgehog signaling pathway, miR-155-mediated NLRP3 inflammasome by the negative feedback of the suppressor of cytokine signaling-1(SOCS-1), miR-181 a-mediated downstream NLRP3 inflammatory pathway activation through mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)/nuclear transcription factor κB(NF-κB) inflammatory pathway, miR-21-promoted expression of NF-κB and NLRP3 of RAW264.7 cells in mice by inhibiting tumor necrosis factor-α inducible protein 3(A20), and miR-20 b-promoted expression of IL-1β and IL-18 by activating NLRP3 signaling pathway. Additionally, the anti-liver fibrosis mechanism of different active components in Chinese medicines(such as Curcumae Rhizoma, Glycyrrhizae Radix et Rhizoma, Aurantii Fructus, Polygoni Cuspidati Rhizoma et Radix, Moutan Cortex, Paeoniae Radix Alba, Epimedii Folium, and Cinnamomi Cortex) was also explored based on the anti-liver fibrosis effect of miRNA-mediated NLRP3 inflammasome activation.

Advances in polydopamine-based drug delivery systems for tumor targeting / 药学学报

Polydopamine (PDA) is a novel type of polymer synthesized inspired by adhesion proteins in mussels. It has been widely used in tumor-targeting drug delivery systems due to its natural advantages such as good biocompatibility, excellent photothermal conversion performance, adhesion, high chemical reactivity and multiple drug release response mechanisms. This review summarizes the applications of PDA-based tumor-targeting drug delivery in recent years, hoping to provide references for designing a more reasonable and effective PDA-based multifunctional collaborative tumor therapy platform.

Research progress on pyroptosis and cardiovascular diseases / 生理学报

Pyroptosis is a form of programmed cell death which is closely related to the inflammatory response, mediated by Gasdermin protein and depends on the activity of cysteine aspartate specific protease (caspase). Pyroptosis is typically characterized by swelling and rupture of cell membrane, release of proinflammatory factors and cell contents from the plasma membrane to the extracellular environment, which aggravates inflammatory response. During the inflammatory response, NLRP3, caspase, Gasdermin D (GSDMD) and IL-1β play important roles in the occurrence and development of cardiovascular diseases. In this review, we focus on the role of pyroptosis in cardiovascular diseases including atherosclerosis, coronary heart disease, myocardial infarction, diabetic cardiomyopathy, pressure overload-induced ventricular remodeling and cardiac hypertrophy, myocarditis, arrhythmia and so on, and summarize the potential treatment targeting pyroptosis. It will provide the basis for prevention and treatment of clinical cardiovascular diseases.

Effect of microRNA-125b on proliferation, apoptosis and collagen expression of hepatic stellate cells / 中国药理学通报

Aim To investigate the effect of miR-125b on HSC proliferation, apoptosis and collagen expression. Methods HSCs were transfected with miR- 125b mimics and inhibitors, and then molecular biology methods were used to detect the expression of Collagen I and HI in HSCs; MIT method was employed to detect HSC proliferation, and flow cytometry to detect HSC apoptotic rate. Results Molecular biological testing found that miR-125b mimics inhibited the expression of Collagen I and HI, and miR-125b inhibitors promoted the expression of Collagen I and HI mRNA; miR-125b mimics inhibited the proliferation of HSC, and miR-125b inhibitors promoted HSC proliferation; miR-125b mimics promoted HSC cell apoptosis, miR- 125b inhibitor inhibited HSC apoptosis, the above experimental results were statistically significant compared with its negative control group ( P < 0. 05 ). Conclusions miR-125b has anti-liver fibrosis effects, which may be related to the regulation of the phenotype of hepatic stellate cells.

Chemical Constituents from Mycelia and Spores of Fungus Cordyceps cicadae / 中草药·英文版

Objective To isolate and identify the chemical constituents from mycelia and spores of the fungus Cordyceps cicadae, respectively. Methods The chemical constituents were isolated and purified by repeated silica gel, Sephadex LH-20, and reversed phase HPLC. The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR. Results Nine known sterols such as ergosterol (1), ergosterol peroxide (2), 9,11-dehydroergosterol peroxide (3), 3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (4), 3β,5α,9α,14α-tetrahydroxy-(22E, 24R)-ergosta-7,22-dien-6-one (5), 5α,6α-epoxy-(22E,24R)-ergosta-8(14),22-diene-3β,7α-diol (6), 3β,5α,6β-(22E,24R)-ergosta-7,22-dien-3,5,6-triol (7), 3β,5α,6α-6-methoxyergosta-(22E,24R)-7,22-diene-3,5-diol (8), 4-hydroxy-17R-methylincisterol (9), together with a resorcinol derivative, 5-n-nonadecylresorcinol (10), a cyclodesipeptide, beauvericin (11), and a nucleoside, N6-(2-hydroxyethyl)adenosine (12) were successively isolated from the cultivated C. cicadae mycelia and spores. Conclusion Compounds 3–10 are reported for the first time from the title sample, beauvericin exhibits significant cytotoxicity against human leukemia cell line and human lung cancer cell line.

Bushen Daozhuo Granules for type Ⅲ prostatitis: A multicenter randomized controlled clinical trial / 中华男科学杂志

Objective@#To study the safety and efficacy of Bushen Daozhuo Granules (BDG) in the treatment of type Ⅲ prostatitis.@*METHODS@#This multicenter randomized controlled clinical trial included 478 patients with type Ⅲ prostatitis, 290 in the trial group and 188 as controls, the former treated with BDG at 200 ml bid and the latter with tamsulosin hydrochloride sustainedrelease capsules at 0.2 mg qd, both for 4 weeks. Before treatment, after 4 weeks of medication, and at 4 weeks after drug withdrawal, we obtained the NIH Chronic Prostatitis Symptom Index (NIHCPSI) scores and compared the safety and effectiveness rate between the two groups of patients.@*RESULTS@#Compared with the baseline, the NIHCPSI score was markedly decreased in the control group after 4 weeks of medication (21.42 ± 4.02 vs 15.67 ± 3.65, P 0.05), while the NIHCPSI score in the trial group was remarkably lower than the baseline both after 4 weeks of medication and at 4 weeks after drug withdrawal (10.92 ± 2.06 and 12.91 ± 2.64 vs 21.58 ± 3.67, P < 0.05). The trial group exhibited both a higher rate of total effectiveness and safety than the control (P < 0.05).@*CONCLUSIONS@#BDG is safe and effective for the treatment of type Ⅲ prostatitis.

Effect of Yijing Recipe on apoptosis of testis spermatogenic cells and the expression of Bcl-2 and Bax protein in infertility rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Yijing Recipe (YR) on the apoptosis of testis spermatogenic cells and the protein expression of Bcl-2/Bax in rats with adenine induced infertility.</p><p><b>METHODS</b>Totally 75 Wistar rats were randomly divided into 5 groups, i.e., the blank control group, the model group, the high dose YR group, the middle dose YR group, and the low dose YR group, 15 in each group. Except those in the blank control group, rats in the rest groups were intragastrically administered with adenine for 10 successive days. From the 11th day, rats in the blank control group and the model group were fed with equal volume of normal saline. Rats in the YR groups were intragastrically administered with YR at different doses (3.38 g/100 g; 1.69 g/100 g; 0.85 g/100 g), once daily for 20 consecutive days. All rats were killed by the end of the experiment and their testes extracted. The apoptosis of spermatogenic cells and the expression of Bcl-2/Bax proteins were detected by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) and SABC method.</p><p><b>RESULTS</b>Compared with the blank control group, the Bcl-2 protein expression decreased, the Bax protein expression increased, and the apoptosis index increased in the model group, showing statistical difference (P <0.01). Compared with the model group, the Bcl-2 protein expression increased in the three YR treated groups (P <0.01, P <0.05). The Bax protein expression level decreased in the high and middle dose YR groups (P <0. 01, P <0. 05). The apoptosis index decreased in the middle dose YR group (P <0.01).</p><p><b>CONCLUSION</b>YR could inhibit the apoptosis of spermatogenic cells through regulating the expression of Bcl-2 and Bax protein in the testis.</p>

Regulatory effect of yijing fang on adenine-induced infertility in rat models: a pharmacodynamic study / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the regulatory effect of Yijing Fang (YJF) on adenine-induced infertility in rats with kidney deficiency.</p><p><b>METHODS</b>Sixty healthy Wistar male rats, aged 1.5 mo and weighing (180 +/- 10) g, were normally fed for a week, and then divided into five groups of equal number (blank control, infertile model, high-dose YJF, mid-dose YJF, and low-dose YJF) according to the body weight of the rats. The models were made by intragastric administration of 500 mg/ml adenine in gum arabic solution in the ratio of 1:10 at the dose of 1 ml per 100 g body weight per day for 10 days. YJF was given at 3.38 g, 1.69 g and 0.85 g per 100 g body weight per day to the rats in the high-, mid- and low-dose groups, respectively. After 48 days of treatment, we observed kidney deficiency-related changes in sperm concentration and motility, the levels of testosterone (T) and other hormones and the volumes of the testis, epididymis, seminal vesicle and prostate, and compared the indexes among different groups.</p><p><b>RESULTS</b>YJF exhibited a significant regulatory effect on sperm concentration and motility, the T level and the indexes of the gonad and other accessory glands in the model rats (P < 0.05). After 48 days of treatment, sperm concentrations were (87.85 +/- 28.44), (7.11 +/- 2.15), (35.98 +/- 14.04), (32.65 +/- 11.80) and (33.51 +/- 13.26) x 10(6)/ml in the blank control, infertile model, high-dose YJF, mid-dose YJF, and low-dose YJF groups, respectively; sperm motilities were (52.79 +/- 16.43), (31.14 +/- 3.07), (45.88 +/- 16.97), (51.56 +/- 13.35) and (49.53 +/- 10.16)%; the T levels were (194.07 +/- 40.29), (61.27 +/- 13.70), (121.87 +/- 24.35), (127.44 +/- 19.38) and (127.81 +/- 20.28) nmol/L; the luteinizing hormone (LH) levels were (7.017 +/- 0.269), (6.117 +/- 0.894), (7.060 +/- 0.871), (7.156 +/- 0.937) and (6.967 +/- 0.778) IU/L; the testis volumes were (3.775 +/- 0.183), (2.865 +/- 0.258), (3.236 +/- 0.058), (3.457 +/- 0.066) and (3.398 +/- 0.091) g; the epididymis volumes were (1.119 +/- 0.116), (0.833 +/- 0.226), (1.124 +/- 0.104), (1.132 +/- 0.107) and (1.114 +/- 0.106) g; the prostate volumes were (176.75 +/- 427.09), (131.67 +/- 39.45), (178.70 +/- 37.97), (180.11 +/- 37.39) and (179.00 +/- 35.42) mg; and the body weights were (188.50 +/- 7.12), (189.92 +/- 6.67), (187.42 +/- 5.47), (189.17 +/- 6.19) and (188.75 +/- 6.12) g. Testis histopathology showed obvious injuries in the infertile models and different degrees of improvement in the three YJF groups, most evidently in the mid-dose group.</p><p><b>CONCLUSION</b>Yifing Fang had an evident therapeutic effect on kidney deficiency-related infertility in adenine-induced rat models.</p>

Longbixiao capsule reduces expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells cultured in vitro / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of the Chinese herbal medicine of Longbixiao (LBX) Capsule on the expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells cultured in vitro.</p><p><b>METHODS</b>Blood serum medicated with LBX was incubated with the stromal cells isolated from men with benign prostatic hyperplasia (BPH) and cultured in vitro. The mRNA expression levels of TGF-beta1 and Smoothelin were detected by real-time RT-PCR and other relevant techniques.</p><p><b>RESULTS</b>In the high and low concentration groups, the gene relative expressions of TGF-beta1 were (0.158 +/- 0.020) and (0.169 +/- 0.020) , while those of Smoothelin were (0.035 +/- 0.007) and (0.036 +/- 0.007) respectively, both significantly decreased in comparison with the control group(P < 0.01).</p><p><b>CONCLUSION</b>LBX reduces the mRNA expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells and can be used in the treatment of BPH.</p>

Construction of the male rat model of adenine-induced infertility with kidney-yang deficiency / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the time- and dose-related reproductive toxicity of adenine in male Wistar rats.</p><p><b>METHODS</b>Adenine was dissolved with Arabian sol at the proportion of 1:10 and different adenine solutions were prepared at the concentration of 0, 50, 100, 150 and 200 mg/ml. Seventy-five male Wistar rats were equally assigned to 5 dose groups and received intragastric administration of the adenine solution at 1 ml/(100 g x d). Five from each group were sacrificed every 10, 20 and 30 days, their sperm quality and body and genital weight measured, pathological examinations conducted, sex hormone changes detected by radioimmunoassay, and analyses made on the time- and dose-related reproductive toxicity of adenine.</p><p><b>RESULTS</b>With the increase in the time and dose of adenine administration, signs of kidney-yang deficiency gradually appeared in all the dose groups on the third day; and statistically significant changes were observed in sperm concentration and motility, and serum testosterone and luteinizing hormone levels in the 100 mg/(100 g x d) group (P < 0.05 or P < 0.01) by the 10th day. The same changes were observed in 50 mg/(100 g x d) group by the 20th day. Different degrees of pathological changes were noted in a time and dose-dependent manner in all the dose groups, suggestive of a progressive reduction of the reproductive function with the increase of time and dose of adenine administration.</p><p><b>CONCLUSION</b>For the construction of the male rat model of adenine-induced infertility with kidney-yang deficiency, the best dose is 50-100 mg/(100 g x d) and the best administration time is 10-20 consecutive days intragastrically.</p>