TOR-mediated Ypt1 phosphorylation regulates autophagy initiation complex assembly.

The regulation of autophagy initiation is a key step in autophagosome biogenesis. However, our understanding of the molecular mechanisms underlying the stepwise assembly of ATG proteins during this process remains incomplete. The Rab GTPase Ypt1/Rab1 is recognized as an essential autophagy regulator. Here, we identify Atg23 and Atg17 as binding partners of Ypt1, with their direct interaction proving crucial for the stepwise assembly of autophagy initiation complexes. Disruption of Ypt1-Atg23 binding results in significantly reduced Atg9 interactions with Atg11, Atg13, and Atg17, thus preventing the recruitment of Atg9 vesicles to the phagophore assembly site (PAS). Likewise, Ypt1-Atg17 binding contributes to the PAS recruitment of Ypt1 and Atg1. Importantly, we found that Ypt1 is phosphorylated by TOR at the Ser174 residue. Converting this residue to alanine blocks Ypt1 phosphorylation by TOR and enhances autophagy. Conversely, the Ypt1S174D phosphorylation mimic impairs both PAS recruitment and activation of Atg1, thus inhibiting subsequent autophagy. Thus, we propose TOR-mediated Ypt1 as a multifunctional assembly factor that controls autophagy initiation via its regulation of the stepwise assembly of ATG proteins.

Two distinct regulatory pathways govern Cct2-Atg8 binding in the process of solid aggrephagy.

CCT2 serves as an aggrephagy receptor that plays a crucial role in the clearance of solid aggregates, yet the underlying molecular mechanisms by which CCT2 regulates solid aggrephagy are not fully understood. Here we report that the binding of Cct2 to Atg8 is governed by two distinct regulatory mechanisms: Atg1-mediated Cct2 phosphorylation and the interaction between Cct2 and Atg11. Atg1 phosphorylates Cct2 at Ser412 and Ser470, and disruption of these phosphorylation sites impairs solid aggrephagy by hindering Cct2-Atg8 binding. Additionally, we observe that Atg11, an adaptor protein involved in selective autophagy, directly associates with Cct2 through its CC4 domain. Deficiency in this interaction significantly weakens the association of Cct2 with Atg8. The requirement of Atg1-mediated Cct2 phosphorylation and of Atg11 for CCT2-LC3C binding and subsequent aggrephagy is conserved in mammalian cells. These findings provide insights into the crucial roles of Atg1-mediated Cct2 phosphorylation and Atg11-Cct2 binding as key mediators governing the interaction between Cct2 and Atg8 during the process of solid aggrephagy.

Homeobox B9 promotes the invasion and metastasis of hepatocellular carcinoma cells via the EZH2-MIR203A-SNAI2 axis.

BACKGROUND: Research has elucidated that homeobox B9 (HOXB9), an important transcriptional activator, plays a pivotal role in promoting the invasion and metastasis of hepatocellular carcinoma (HCC) cells. However, the mechanism by which HOXB9 promotes the invasion and metastasis of HCC cells is incompletely understood and needs further exploration. METHODS: HOXB9 and snail family transcriptional repressor 2 (SNAI2) expression were analyzed using qRT-PCR and western blotting. The invasion and metastasis of hepatocellular carcinoma (HCC) cells were investigated using in vitro and in vivo assays. The H3K27me3 enrichment and HOXB9 interaction with microRNA 203a (MIR203A) or SNAI2 were detected using ChIP-qPCR. Transcriptional activities of SNAI2 and MIR203A promoter were detected using dual-luciferase reporter assays. Co-IP and GST pull-down assays were performed to confirm the binding between HOXB9 and EZH2. RESULTS: HOXB9 and SNAI2 were highly expressed in HCC tissues and their expression was positively intercorrelated and associated with poor prognosis in patients with HCC. In vitro and in vivo experiments confirmed that HOXB9 can upregulate the expression of SNAI2 to promote the invasion and metastasis of HCC cells. Furthermore, HOXB9 elevated SNAI2 expression by inhibiting MIR203A expression, a tumor suppressor gene, in HCC cells. Mechanistically, HOXB9 recruited enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) through interaction with its WD-binding domain, which increased EZH2-mediated histone H3 lysine 27 trimethylation (H3K27me3) at the MIR203A promoter region, in turn repressing the transcriptional activity and expression of MIR203A and consequently increasing the SNAI2 level in HCC cells. Finally, empirical evidence from in vitro and in vivo studies confirmed that mitigation of the HOXB9-mediated enhancement of epigenetic silencing of MIR203A inhibited SNAI2 expression, impeding the invasion and metastasis of HCC cells. CONCLUSIONS: Our study reveals a novel mechanism by which HOXB9 promotes the invasion and metastasis of HCC cells and expands the understanding of the function of HOXB9 in tumor progression and provides a novel therapeutic strategy for curtailing HCC invasion and metastasis.

Effect of Pilates combined with pelvic floor muscle training on continence of post-prostatectomy incontinence in patients with different body mass index.

BACKGROUND: Urinary incontinence symptoms severely affect older people with different body mass index (BMI).To compare the efficacy of the pelvic floor muscle training (PFMT) in patients with post-prostatectomy incontinence with different BMI. METHODS: Thirty-seven patients with post-prostatectomy incontinence were included. They were divided into group A (BMI ≤ 25,12), group B (26 ≤ BMI ≤ 30,14), and group C (BMI ≥ 31,11) based on difference BMI. Three groups of patients underwent the same Pilates combined with kegel training. Participants were assessed with 1-hour pad test, the number of incontinence episodes, International Consultation on Incontinence Questionnaire and Oxford Grading Scale. RESULTS: In the 1-hour pad test, the differences before and after training were statistically significant in all three groups of participants. Group A decreased from 81.83 ± 8.79 to 31.08 ± 5.64 g (P < 0.01). Group B decreased from 80.57 ± 8.87 to 35.85 ± 5.66 g (P < 0.01). Group C decreased from 83.55 ± 10.24 to 40.18 ± 7.01 g (P < 0.01). The number of incontinent episodes in group A decreased from 9.33 ± 1.07 to 3.25 ± 0.62 (P < 0.01). Group B decreased from 8.86 ± 1.09 to 3.79 ± 0.80 (P < 0.01). Group C decreased from 9.27 ± 1.10 to 4.09 ± 0.70 (P < 0.01). The correlation between the three groups of participants and the 1-hour pad test, with an R2 of 0.51. The correlation between the three groups of participants and the number of urinary incontinence episodes with a R2 of 0.43. CONCLUSIONS: Pelvic floor muscle training can affect the recovery of urinary continence in patients with different BMI. Maintaining a lower BMI can be beneficial for improving urinary control. TRIAL REGISTRATION: Date of trial registration: November 27, 2023.

Postoperative subacute static progressive stretch does not increase the risk of distal lower limb venous thromboembolism.

PURPOSE: Static progressive stretch (SPS) can be applied to treat chronic joint stiffness. However, the impacts of subacute application of SPS to the distal lower limbs, where deep vein thrombosis (DVT) is common, on venous thromboembolism remain unclear. This study aims to explore the risk of venous thromboembolism events following subacute application of SPS. METHODS: A retrospective cohort study was conducted on patients diagnosed with DVT following a lower extremity orthopedic surgery before being transferred to the rehabilitation ward from May 2017 to May 2022. Patients with unilateral lower limb comminuted para-articular fractures, transferred to rehabilitation ward for further treatment within 3 weeks after operation, followed up more than 12 weeks since initial manual physiotherapy, and diagnosed DVT by ultrasound before rehabilitation course were included in the study. Patients with polytrauma, without evidence of previous peripheral vascular disease or incompetence, had medication for thrombosis treatment or prophylaxis before the operation, detected with paralysis due to nervous system impairment, infected after operation during the regime, or with acute progression of DVT were excluded. The included patients were randomized to the standard physiotherapy and the SPS integrated groups for observation. Associated DVT and pulmonary embolism data were collected during the physiotherapy course to compare the groups. SSPS 28.0 and GraphPad Prism 9 were used for data processing. A p < 0.05 was set significant difference. RESULTS: In total of 154 patients with DVT participating in this study, 75 of them were treated with additional SPS for postoperative rehabilitation. The participants in the SPS group showed improved range of motion (12.3° ± 6.7°). However, in the SPS group, there was no difference in thrombosis volume between the start and termination (p = 0.106, p = 0.787, respectively), although difference was seen intra-therapy (p < 0.001). Contingency analysis revealed the pulmonary embolism incidence (OR = 0.703) in the SPS group compared to the mean physiotherapy. CONCLUSION: The SPS technique is a safe and reliable option to prevent potential joint stiffness without aggravating the risk of distal DVT for postoperative patients suffering from relevant trauma.

[Isolation and quantification of a 17-epi-dammarane triterpenoid rhuslactone from roots of Rhus chinensis and its preventive effects on coronary heart disease and thrombosis in zebrafish].

Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 µmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.

Relationship between family risk factors and adolescent mental health. / å®¶åº­é£Žé™©å› ç´ ä¸Žé’å°‘å¹´å¿ƒç†å¥åº·ä¹‹é—´çš„å ³ç³».

OBJECTIVES: Family risk factors are crucial to adolescent mental health. Few studies have investigated the complex relationship between family risk factors and adolescent mental health. This study aims to investigate the complex relationship between family cumulative risk (FCR) and adolescent mental health, and to clarify the factors contributing to adolescent mental health problems. METHODS: This study recruited 903 junior high school students and 991 senior high school students in Changsha, Hunan and was conducted through an offline computer-based questionnaire survey using the Middle School Student Mental Health Scale (MSSMHS) and the Family Cumulative Risk Questionnaire (FCRQ) to assess the mental health status and FCR factors, respectively. Statistical analyses were conducted to clarify the demographic factors influencing MSSMHS total and factor scores, and to analyze the relationship between FCRQ and MSSMHS total and factor scores. RESULTS: Females exhibited more mental health problems than males in various MSSMHS factors (all P<0.05); adolescents were prone to different mental health problems at different stages (junior high school first-grade vs. senior high school first-grade); senior high school first-grade students were more likely to experience academic pressure and maladjustment than junior high school first-grade students (P<0.01), and junior high school first-grade students were more likely to exhibit obsessive, paranoia, and hostility symptoms than senior high school first-grade students (all P<0.01); adolescents with low family intimacy and high family conflict reported more symptoms in every dimension of MSSMHS (all P<0.05); adolecents with poor parent-child separation reported higher obsessive-compulsive symptoms, interpersonal sensitivity, anxiety, academic pressure, maladjustment, emotional instability, and unbalanced mind than those with good parent-child separation (all P<0.05). CONCLUSIONS: Female, low family intimacy, high family conflict, and poor parent-child separation are risk factors of adolescent mental health problems. Higher-grade middle school students are prone to exhibit academic pressure and maladjustment, while lower-grade middle school students are prone to exhibit obsessive, paranoia, and hostility symptoms.

Leaf Photosynthesis and Its Temperature Response Are Different between Growth Stages and N Supplies in Rice Plants.

Leaf photosynthesis is highly correlated with CO2-diffusion capacities, which are determined by both leaf anatomical traits and environmental stimuli. In the present study, leaf photosynthetic rate (A), stomatal conductance (gs), mesophyll conductance (gm) and the related leaf anatomical traits were studied on rice plants at two growth stages and with two different N supplies, and the response of photosynthesis to temperature (T) was also studied. We found that gm was significantly higher at mid-tillering stage and at high N treatment. The larger gm was related to a larger chloroplast surface area facing intercellular air spaces and a thinner cell wall in comparison with booting stage and zero N treatment. At mid-tillering stage and at high N treatment, gm showed a stronger temperature response. The modelling of the gm-T relationships suggested that, in comparison with booting stage and zero N treatment, the stronger temperature response of gm was related to the higher activation energy of the membrane at mid-tillering stage and at high N treatment. The findings in the present study can enhance our knowledge on the physiological and environmental determinants of photosynthesis.

Production of ß-glucanase and protease from Bacillus velezensis strain isolated from the manure of piglets.

In this study, a strain producing ß-glucanase and protease, identified as Bacillus velezensis Y1, was isolated from the manure of piglet. We attempted to produce ß-glucanase and protease after optimization of various process parameters with the submerged fermentation. The effects of each factor on producing ß-glucanase and protease were as follows: temperature > time > pH > loaded liquid volume. The properties of the ß-glucanase showed that the most suitable reaction temperature was 65 °C and pH was 6.0. However for protease optimum reaction temperature was 50 °C, and pH was 6.0. The amplified PCR fragments of ß-glucanase and protease were 1434 bp containing an open reading frame of 1413 bp encoding a protein with 444 amino acids and 1752 bp containing an open reading frame of 1521 bp encoding a protein with 506 amino acids, respectively. So, the study demonstrated a viable approach of using newly identified B. velezensis Y1 strain for the maximum yield of two industrially important enzymes.

[Effect of total phenolic part of Rhus chinensis against myocardial ischemia in mice].

Rhus chinensis is an important resource plant. The aqueous extract of R. chinensis roots or stems was to produce Shuguantong Syrup, which is mainly used for the treatment of coronary heart disease and angina pectoris with definite curative effect. On this basis, the crude phenolic part of R. chinensis prepared by macroporous resin was evaluated for the cardio protective effect against myocardial ischemia in mice. The results showed that the phenolic part group with oral administration at the dosages of 190.8-381.6 mg·kg~(-1), compared with the model group, reduced the values of left ventricular end systolic diameter(LVEDs) and the left ventricular end diastolic diameter(LVEDd), and increased the cardiac ejection fraction(EF) and left ventricular fractional shortening(FS) rate, which could effectively improve cardiac function and exert its anti-myocardial ischemia effect, and reduce the rising levels of creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH) in serum. HE staining showed that the phenolic part group reduced the infiltration of myocardial inflammatory cells and alleviated the degree of myocardial fibrosis and collagen deposition. TUNEL staining showed that the blue-green fluorescence of the phenolic part group decreased successively, and the degree of myocardial cell apoptosis was reduced. Immunohistochemical staining suggested that it could reduce the number of positive cells for p53 protein expression and significantly improve myocardial cell damage. All above data suggested that the phenolic part group had an anti-mycardial ischemis effect. Related mechanism studies revealed that the crude phenolic part could regulate the expressions of the p53 gene(p53), Bcl-2-associated X protein(Bax), B lymphoma-2 gene(Bcl-2), and caspase-3 protein(caspase-3) in myocardial tissue, suggesting that it could reduce cardiac remodeling and myocardial ischemic damage, and improve cardiac function by inhibiting myocardial apoptosis.This research laid a foundation for the elucidation of the pharmacological ingredients R. chinensis.

Effects of inner muscle resistance exercise on stress urinary incontinence: a randomized clinical controlled trial.

[Purpose] This study investigated the effects of co-contraction resistance exercises of the transverse abdominal and pelvic floor muscles in middle-aged females with stress urinary incontinence. [Participants and Methods] We included 32 females with stress urinary incontinence and divided them into two groups: the inner muscle training group and the pelvic floor muscle group. The thickness of the transverse abdominal muscle was measured during four tasks: (1) rest, (2) maximum contraction of the transverse abdominal muscle, (3) maximum contraction of the pelvic floor muscle, and (4) maximum co-contraction of the transverse abdominal and pelvic floor muscles. In the latter three tasks, measurements were obtained while the participants performed resistance movements using a Thera-band®. A home program was conducted in both groups, and the intervention lasted for 8 weeks. [Results] The cure rates for SUI were 87.5% and 68.8% in the inner muscle training and pelvic floor muscle groups, respectively. After the intervention, the thickness of the transverse abdominal muscle significantly increased in the inner muscle training groups performing maximum co-contraction of the transverse abdominal and pelvic floor muscles and maximum contraction of the transverse abdominal muscle. [Conclusion] Inner muscle training exercises are more effective than pelvic floor muscle exercises in improving inner muscle function and urinary incontinence in middle-aged females.

A General Model for Seed and Seedling Respiratory Metabolism.

The ontogeny of seed plants usually involves a dormant dehydrated state and the breaking of dormancy and germination, which distinguishes it from that of most organisms. Seed germination and seedling establishment are critical ontogenetic stages in the plant life cycle, and both are fueled by respiratory metabolism. However, the scaling of metabolic rate with respect to individual traits remains poorly understood. Here, we tested metabolic scaling theory during seed germination and early establishment growth using a recently developed model and empirical data collected from 41 species. The results show that (i) the mass-specific respiration rate (Rm) was weakly correlated with body mass, mass-specific N content, and mass-specific C content; (ii) Rm conformed to a single Michaelis-Menten curve as a function of tissue water content; and (iii) the central parameters in the model were highly correlated with DNA content and critical enzyme activities. The model offers new insights and a more integrative scaling theory that quantifies the combined effects of tissue water content and body mass on respiratory metabolism during early plant ontogeny.

A 3D screening approach identifies the compound epitajixanthone hydrate as a new inhibitor of cancer cell growth and invasion.

With unique advantages, the small-molecule anticancer drugs have recently gained growing attention. Particular strategies, exemplified by high-throughput screening, fragment-based drug discovery, virtual screening and knowledge-based design, have been developed to identify active compounds. However, such screens generally rely on sophisticated and expensive instrumentations. Herein, we developed a simple spheroids 3D culture system to enable direct screening of small molecules with reliable results. Using this system, we screened 27 fungal natural products and three fungal crude extracts for their inhibitory effects on cancer cell growth, and invasion. We identified that the compound M23 (epitajixanthone hydrate, a derivative of prenylxanthone) and the crude extracts (MPT-191) from the fungi Taxus chinensis showed potential anticancer activity. The effect of epitajixanthone hydrate on cancer cell growth and invasion were further confirmed by the assays of cells viability, trans-well migration and invasion, colony formation and cells reattachment. Overall, Epitajixanthone hydrate was identified as an effective inhibitor of cancer cell growth and invasion by our simple and fast screening platform.

Protective effects of dihydromyricetin on primary hippocampal astrocytes from cytotoxicity induced by comorbid diabetic neuropathic pain and depression.

Activated astrocytes play a key role in diabetic neuropathic pain and depression. We aimed to assess the protective effects of dihydromyricetin (DHM) on primary hippocampal astrocytes cultured with high glucose (HG), substance P (SP), and corticosterone (CORT). Culturing with HG + SP + CORT resulted in damage to primary hippocampal astrocytes, which simulates the clinical damage caused by comorbidity of diabetic neuropathic pain and depression. Western blot, qPCR, and immunofluorescence analyses revealed that HG + SP + CORT increased P2X7 receptor expression in primary hippocampal astrocytes, which was reversed by DHM treatment. Further, HG + SP + CORT elevated TNF-α, IL-1ß, free Ca2+, and ERK1/2 phosphorylation levels, which was inhibited by DHM or P2X7 shRNA treatment. Moreover, DHM significantly reduced the P2X7 agonist-activated currents in HEK293 cells transfected with the P2X7 receptor. These findings suggest that DHM can protect primary hippocampal astrocytes cultured with HG + SP + CORT from P2X7 receptor-mediated damage. Culturing cells with HG + SP + CORT might be a viable cell model for cellular injury exploration of diabetic comorbid pain and depression.

Dammarane-Type Triterpenoids from the Roots of Rhus chinensis and Their Preventive Effects on Zebrafish Heart Failure and Thrombosis.

Eight new dammarane-type triterpenoids (1-8), together with a related known analogue (9), were isolated from the roots of Rhus chinensis, a traditional Chinese medicine for treating coronary artery heart disease, guided by LC-MS analysis. Their structures were elucidated based on extensive spectroscopic analysis and quantum chemical calculations. Notably, compounds 1-7 and 9 possess an unusual 17α-side chain, and 1-4, 6, and 9 contain an uncommon 3-methyl-5,6-dihydro-2H-pyran-2-one moiety in the side chain. Compounds 1-5 and 9 have a 3,19-hemiketal bridge in the A ring. In an in vivo bioassay, 1, 2, and 4-6 exhibited significant preventive effects on zebrafish heart failure at 0.5 µg/mL, improving heart dilatation, venous congestion, cardiac output, blood flow velocity, and heart rate. Compound 5, displaying the most promising heart failure preventive activities, showed even better effects on increasing cardiac output (72%) and blood flow velocity (83%) than six first-line heart failure therapeutic drugs. Moreover, 1, 2, and 6 prevented the formation of thrombosis in zebrafish at 0.5 µg/mL. The present investigation suggests that the new dammarane triterpenoids might be partially responsible for the utility of R. chinensis in treating coronary artery heart disease.

Effect of Bacillus velezensis to substitute in-feed antibiotics on the production, blood biochemistry and egg quality indices of laying hens.

BACKGROUND: The excessive use of antibiotics in the livestock feed industry caused inevitable side effects of microbial resistance. Besides this residual antibiotics in animal-derived foodstuff imposed serious health problems for humans. So this study aimed to investigate the potential use of Bacillus velezensis to substitute antibiotics for poultry production. A total of 468, 49-week-old Hy-Line Brown chickens, were randomly divided into four groups the control group (regular diet), experiment group I (0.1% B. veleznesis), experiment group II (0.2% B. veleznesis), and antibiotic group (50 mg/kg flavomycin), with three replicates per group and trial period consisted on 42 days. RESULTS: The results showed that, compared with the control group, the average egg production rate and daily feed intake of experimental groups I and II increased significantly (P < 0.05), while the average egg weight was increased in experimental group II as compared to (I) (P < 0.01). The feed conversion ratio was decreased (P > 0.05) in group (II) Egg quality parameters such as yolk weight of the experimental group II was increased, but that of the antibiotic group and experiment group I was decreased, neither significant (P > 0.05). Moreover, the eggshell strength, yolk color, albumen height, and Haugh unit were significantly increased (P < 0.05). Compared with the control group, probiotic groups can increase the progesterone and motilin (P > 0.05) but decrease the secretin and cholecystokinin in the blood plasma (P > 0.05). CONCLUSIONS: This study suggested that B. velezensis can substitute in-feed-antibiotics and improved most of the study parameters significantly. Which suggested that B. velezensis has potential future application value to replace the feed antibiotics.

Prenylated Indole Diterpene Alkaloids from a Mine-Soil-Derived Tolypocladium sp.

Ten new prenylated indole diterpene alkaloids, tolypocladin A-J (1-10), including four chlorinated metabolites, have been isolated from a culture of a mine-soil-derived fungus, Tolypocladium sp. XL115. The structures and absolute configurations of 1-10 were determined by spectroscopic analysis, ECD calculations, and comparison with known compounds. Compounds 1 and 8 displayed significant antimicrobial activities. In addition, compound 1 also showed weak cytotoxic activity against all tested human cancer cell lines and suppressed the growth and viability of the patient-derived HCC cells T1224.

Three new α-pyrone derivatives from the plant endophytic fungus Penicillium ochrochloronthe and their antibacterial, antifungal, and cytotoxic activities.

Three new 3,4,6-trisubstituted α-pyrone derivatives, namely 6-(2'R-hydroxy-3'E,5'E-diene-1'-heptyl)-4-hydroxy-3-methyl-2H-pyran-2-one (1), 6-(2'S-hydroxy-5'E-ene-1'-heptyl)-4-hydroxy-3-methyl-2H-pyran-2-one (2), and 6-(2'S-hydroxy-1'-heptyl)-4 -hydroxy-3-methyl-2H-pyran-2-one (3), together with one known compound trichodermic acid (4), were isolated from the solid-substrate fermentation culture of Penicillium ochrochloronthe associated the roots of Taxus media. Compounds 1-4 displayed the antimicrobial activity selectively against tested fungal and bacterial strains with minimum inhibitory concentration (MIC) values ranging from 12.5 to 100 µg/ml. Furthermore, we found that only compound 4 exhibited moderate cytotoxicity against five human cancer cells (A549, LN229, MGC, LOVO, and MDA231) with IC50 values of 51.45, 23.43, 39.16, 46.97, and 42.85 µg/ml, respectively.

[Sonic hedgehog signaling pathway and erectile dysfunction: Advances in studies].

Sonic hedgehog (Shh) is an important regulator of penile erectile function in adult males, and abnormal Shh signals may be involved in the mechanisms of ED. Current studies on the relationship of the Shh signaling pathway with ED are mainly concentrated on neurogenic ED caused by bilateral cavernous nerve injury, diabetes-induced endocrinological ED, and senile ED. This review focuses on the changes of the Shh signaling pathway in different types of ED and clarifies the mechanisms of the Shh signaling pathway regulating ED, hoping to give some inspiration to further related studies.

[Inhibitory effect of salidroside on H2O2-induced down-regulation of Cx43 expression in corpus cavernosum smooth muscle cells in rats].

OBJECTIVE: To explore the regulatory effect of salidroside on H2O2-induced decrease in the expression of the connexin43 (Cx43) protein in corpus cavernosum smooth muscle cells (CCSMC). METHODS: Rat CCSMCs were isolated, primarily cultured in vitro and identified by immunocytochemical assay. The optimum concentration of H2O2 for intervention was determined by detecting its effect on the viability of the CCSMCs and used in the treatment of the CCSMCs for different lengths of time, and meanwhile salidroside was applied at 16 µg/ml (low dose) or 64 µg/ml (high dose) for intervention. Finally, the expressions of the Cx43 protein in the CCSMCs of different groups of rats were determined by Western blot. RESULTS: The CCSMCs grew normally, with a positive rate of over 90%. At 1, 2 and 4 hours of treatment with H2O2 at the optimum concentration of 200 µmol/L, the expression of Cx43 in the CCSMCs was significantly decreased as compared with that in the blank control group (P < 0.01), even more significantly at 4 hours than at 1 and 2 (P < 0.01). Intervention with high-dose salidroside, however, markedly inhibited the down-regulation of the Cx43 expression (P < 0.05), which showed no statistically significant difference from that in the normal control group (P = 0.322 2). CONCLUSIONS: Salidroside can suppress H2O2-induced decrease in the expression of the Cx43 protein in rat CCSMCs.