Association between gut microbiota and male infertility: a two-sample Mendelian randomization study.

Previous research has confirmed the significant association between gut microbiota (GM) and male infertility (MI), but the causality between them remains unclear. This study aims to investigate the causal relationship between GM and MI using Mendelian randomization (MR) and provide supplementary information for the optimization of future randomized controlled trials (RCTs). Instrumental variables for 211 GM taxa were obtained from genome-wide association studies (GWAS), and inverse variance weighted (IVW) method was used as the main analysis method for two-sample MR analysis to assess the impact of GM on the risk of MI. Four methods were used to test for horizontal pleiotropy and heterogeneity of MR results to ensure the reliability of the MR findings. A total of 50 single-nucleotide polymorphisms (SNPs) closely related to GM were included, and ultimately identified 1 family and 4 general are causally associated with MI. Among them, Anaerotruncus (OR = 1.96, 95% CI 1.31-3.40, P = 0.016) is significantly associated with increased MI risk. Furthermore, we used four MR methods to evaluate the causality, and the results supported these findings. The leave-one-out analysis showed stable results with no instrumental variables exerting strong influence on the results. The causal direction indicated a positive effect, and the effects of heterogeneity and horizontal pleiotropy on the estimation of causal effect were minimized. We confirmed a causal relationship between GM taxa and MI, providing new insights into the mechanisms underlying GM-mediated MI.

Tong Jing Yi Hao Formula Alleviates Ornidazole-Induced Oligoasthenospermia in Rats by Suppressing ROS/MAPK/HIF-1 Pathway.

BACKGROUND: Tong Jing Yi Hao Formula (TJYHF) is a Traditional Chinese medicine used for oligoasthenospermia (OAS) treatment. However, the role of TJYHF against OAS is unclear. This study was an initial attempt to solve this problem. METHODS: Rats were randomly allocated to normal, ornidazole (Orn), levocarnitine (450 mg/kg), low-dose TJYHF (6.5 g/kg) and high-dose TJYHF (26 g/kg) groups, each consisting of six rats. Oral administration of Orn (400 mg/kg) for 4 weeks was used to induce OAS, followed by oral doses of the respective drugs for an additional 4 weeks. Parameters, including the testicular index, epididymis index, testicular volume, sperm parameters, sex hormone levels, histological changes and markers of oxidative stress, were evaluated to assess the effects of treatment. The potential mechanism involved in the therapeutic effects of TJYHF was studied by evaluating the activity and expression levels of key molecules within the reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor 1 (HIF-1) pathway. RESULTS: Compared with healthy rats, the Orn-induced rats demonstrated decreases in testicular index, epididymis index, testicular volume, sperm concentration, total sperm count, percentage of forwarding sperm motility, total sperm motility, testosterone, spermatogenic epithelium, reproductive cell, glutathione peroxidase, superoxide dismutase and glutathione and increases in sperm deoxyribonucleic acid fragmentation index, follicle-stimulating hormone, luteinizing hormone and malondialdehyde. In the testicles, an enhancement in the ROS level and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) was observed after Orn challenge. Moreover, the protein expression levels and immunostaining intensity of p38 and HIF-1α increased, indicating the activation of the ROS/MAPK/HIF-1 pathway. All of the aforementioned changes exhibited statistical significance (p < 0.01). Compared with Orn-induced rats, TJYHF effectively rescued the Orn-induced aforementioned disorders. Mechanistically, TJYHF suppressed the ROS level and ERK1/2, JNK and p38 phosphorylation levels. Besides, it reduced the protein expression levels and immunostaining intensity of p38 and HIF-1α, demonstrating the inactivation of the ROS/MAPK/HIF-1 pathway. Notably, the aforementioned enhancements demonstrated statistical significance (p < 0.01). CONCLUSIONS: TJYHF exerted a beneficial effect on reproductive function in OAS rats through the inhibition of the ROS/MAPK/HIF-1 pathway.

Tong Jing Yi Hao Formula Alleviates Ornidazole-Induced Oligoasthenospermia in Rats by Suppressing ROS/MAPK/HIF-1 Pathway

Background: Tong Jing Yi Hao Formula (TJYHF) is a Traditional Chinese medicine used for oligoasthenospermia (OAS) treatment. However, the role of TJYHF against OAS is unclear. This study was an initial attempt to solve this problem. Methods: Rats were randomly allocated to normal, ornidazole (Orn), levocarnitine (450 mg/kg), low-dose TJYHF (6.5 g/kg) and high-dose TJYHF (26 g/kg) groups, each consisting of six rats. Oral administration of Orn (400 mg/kg) for 4 weeks was used to induce OAS, followed by oral doses of the respective drugs for an additional 4 weeks. Parameters, including the testicular index, epididymis index, testicular volume, sperm parameters, sex hormone levels, histological changes and markers of oxidative stress, were evaluated to assess the effects of treatment. The potential mechanism involved in the therapeutic effects of TJYHF was studied by evaluating the activity and expression levels of key molecules within the reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor 1 (HIF-1) pathway.Results: Compared with healthy rats, the Orn-induced rats demonstrated decreases in testicular index, epididymis index, testicular volume, sperm concentration, total sperm count, percentage of forwarding sperm motility, total sperm motility, testosterone, spermatogenic epithelium, reproductive cell, glutathione peroxidase, superoxide dismutase and glutathione and increases in sperm deoxyribonucleic acid fragmentation index, follicle-stimulating hormone, luteinizing hormone and malondialdehyde (AU)

Self-Catalysis Transformation of Metal-Organic Coordination Polymers.

Designing a multidimensional transformation of metal-organic coordination polymers (MOPs) is highly attractive yet very challenging. Herein, by combining the dynamicity of the coordination bond with the controllability of the chemical reaction, the concept of self-catalysis transformation of MOPs is first proposed. It uses the metal in MOPs as the catalyst to catalyze the chemical reaction of the ligand in the frameworks, simultaneously changing the coordination environment of the metal and the structure of the ligand, resulting in the controllable multidimensional transformation in the morphology and structure of MOPs. The self-catalysis transformation of MOPs can be triggered by heat or light, and crystals with various morphologies and structures can be obtained. Significantly, because the self-catalysis reaction is constraint in the framework, the products at different transformation processes are relatively stable. Monitoring and characterizing the transformation of MOPs give evidences for the exploration of the self-catalysis reaction, and a plausible transformation mechanism is proposed and proved. It can be foreseen that this novel self-catalysis transformation strategy might open up a new direction for the diverse development of MOPs and provide a powerful tool for the study of organic reaction mechanism.

Treatment progress of cryptozoospermia with Western Medicine and traditional Chinese medicine: A literature review.

Background and Aims: Cryptozoospermia is an extreme oligozoospermia with an unsatisfactory treatment effect, with an incidence rate of approximately 8.73% in male infertility, whose effective solution has become the call of the times. Western Medicine has achieved certain effects through drugs, surgery, and assisted reproductive therapy, but this is still not ideal. Traditional Chinese medicine (TCM) has made many achievements in other disciplines; however, there is still a lack of evidence-based medical evidence to improve sperm production. Methods: The relevant literatures from the China National Knowledge Internet (CNKI) and PubMed in the past 10 years were collected in this article, of which the mechanisms, advantages, or current controversies of various treatment methods of Western Medicine and TCM were analyzed, to find new treatment methods and research directions. Results: With the development of modern science and technology, medical treatments for cryptozoospermia have become increasingly abundant; however, there is still no universally recognized unified and effective guiding plan. Although TCM has not been fully verified by evidence-based medicine, most TCM combined with Western Medicine can achieve unexpected results. Conclusion: The combination of TCM and Western Medicine may become a bane for cryptozoospermia and bring good news to infertile men worldwide.

Prostatitis No.1 traditional chinese medicine significantly exhibited anti-inflammation role on prostatitis through miR-205-5p/YES1.

Prostatitis is one common male disease with a high prevalence. Traditional Chinese medicine (TCM) has been used as an alternative method for the treatment. However, the molecular mechanism of Prostatitis No.1 Traditional Chinese Medicine (P1TCM) on prostatitis is still unclear. For this purpose, the rat models were constructed and treated with PITCM of control, model, low (10 g/kg/d), medium (20 g/kg/d), and high (40 g/kg/d), as well as the transfections of medium dosage+NC mimic, and medium dosage+miR-205-5p mimic, medium dosage+NC mimic+pc-NC, medium dosage+miR-205-5p mimic+pc-NC, and medium dosage+miR-205-5p mimic+pc-v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES1). Real-time quantitative PCR (qPCR) and western blotting analyses were carried out to evaluate the expression of miR-205-5p and YES1, respectively. The levels of interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay (ELISA). The targeting role of miR-205-5p on YES1 was predicted by StarBase and verified by a dual-luciferase reporter gene assay. Results showed that the optimal treatment of P1TCM relieved the damage of prostate tissue, decreased the immunity and inflammation factors, and reduced the expression level of miR-205-5p in prostate tissue and serum. miR-205-5p mimics significantly relieved tissue damage and reduced immunity and inflammatory functions. miR-205-5p targeted YES1. YES1 was significantly upregulated in medium dosage treatment compared with Control, while downregulated compared with the Model. YES1 was also upregulated in prostatitis patients. The pc-YES1 reversed the function of the miR-205-5p mimic. In conclusion, P1TCM significantly relieved the tissue damage and reduced prostate patients' inflammatory functions through miR-205-5p/YES1, which might be essential for clinical studies.

Scaling of Berry-curvature monopole dominated large linear positive magnetoresistance.

The linear positive magnetoresistance (LPMR) is a widely observed phenomenon in topological materials, which is promising for potential applications on topological spintronics. However, its mechanism remains ambiguous yet, and the effect is thus uncontrollable. Here, we report a quantitative scaling model that correlates the LPMR with the Berry curvature, based on a ferromagnetic Weyl semimetal CoS2 that bears the largest LPMR of over 500% at 2 K and 9 T, among known magnetic topological semimetals. In this system, masses of Weyl nodes existing near the Fermi level, revealed by theoretical calculations, serve as Berry-curvature monopoles and low-effective-mass carriers. Based on the Weyl picture, we propose a relation [Formula: see text], with B being the applied magnetic field and [Formula: see text] the average Berry curvature near the Fermi surface, and further introduce temperature factor to both MR/B slope (MR per unit field) and anomalous Hall conductivity, which establishes the connection between the model and experimental measurements. A clear picture of the linearly slowing down of carriers, i.e., the LPMR effect, is demonstrated under the cooperation of the k-space Berry curvature and real-space magnetic field. Our study not only provides experimental evidence of Berry curvature-induced LPMR but also promotes the common understanding and functional designing of the large Berry-curvature MR in topological Dirac/Weyl systems for magnetic sensing or information storage.

In situ fabrication of bendable epitaxial metal-organic framework films via spraying.

Epitaxial metal-organic framework (MOF) films have shown huge potential for use in separation applications. Herein, bendable epitaxial MOF films are fabricated via spraying. The synthesized MOF films show excellent oil-in-water emulsion separation performance even after being bent for multiple times at high curvatures.

Long Non-Coding RNA AC008972.1 as a Novel Therapeutic Target for Prostate Cancer.

Background: Prostate cancer is a common male malignancy and the leading cause of cancer death in men. Long non-coding RNAs (lncRNAs), microRNA (miRNAs) and mRNAs networks mediate prostate cancer progression. Here, we aim to investigate the functions of lncRNA AC008972.1 and its regulatory mechanism in prostate cancer. Materials and Methods: The expression levels of lncRNA AC008972.1, miR-143-3p, and TAOK2 were detected in prostate cancer tissues and cell lines by reverse transcription-quantitative polymerase chain reaction. PC3 and LNCaP cells were used to establish lncRNA AC008972.1-knockdown, miR-143-3p-overexpressing, and thousand-and-one-amino acid 2 kinase (TAOK2)-downregulated cells. Cell viability was examined by MTT assays and cell proliferation was detected by clone formation assay. Cell migration and invasion were detected by wound scratch assay and transwell chamber assay. The apoptosis rate was analyzed by flow cytometry. The protein expression was detected by Western blot assay. The RNA interaction was explored and validated by RNA binding protein immunoprecipitation (RIP) assay and dual luciferase activity assay. A mouse xenograft model was established to investigate the effect of lncRNA AC008972.1 on prostate cancer progression. Results: High expression of lncRNA AC008972.1 was associated with low overall survival in prostate cancer patients. Downregulation of lncRNA AC008972.1 suppressed prostate cancer progression by inhibiting cell viability, proliferation, migration, and invasion, in addition to the EMT process, whereas cell apoptosis was significantly promoted. LncRNA AC008972.1 bound with miR-143-3p and negatively regulated miR-143-3p expression. MiR-143-3p overexpression suppressed prostate cancer malignant behaviors in vitro. TAOK2 expression was decreased by miR-143-3p through the complementary targeting of TAOK2 mRNA. Downregulation of lncRNA AC008972.1 mitigated prostate cancer malignant behaviors in vitro based on miR-143-3p/TAOK2 node. Furthermore, the data of xenograft model experiment showed that inhibition of lncRNA AC008972.1 suppressed tumor growth in vivo. Conclusions: Knockdown of lncRNA AC008972.1 inhibits prostate cancer cell growth via downregulation of TAOK2 induced by miR-143-3p. LncRNA AC008972.1 acts as an oncogene in the progression of prostate cancer and may provide a novel therapeutic target for prostate cancer.

Jiawei Runjing Decoction Improves Spermatogenesis of Cryptozoospermia With Varicocele by Regulating the Testicular Microenvironment: Two-Center Prospective Cohort Study.

Objective: The aim of the study was to explore the evidence of JWRJD in the treatment of cryptozoospermia. Methods: A total of 162 cryptozoospermia patients with varicocele who refused to undergo surgery were included from January 2021 to December 2021. They were divided into the Jiawei Runjing Decoction group (group A), tamoxifen group (group B), and no treatment group (group C), and after the follow-up for 3 months, therapeutic effectiveness was compared. Network pharmacology was used to analyze and validate the effects and mechanisms of JWRJD. Results: Fifty-eight patients were treated with JWRJD, 55 with tamoxifen, and 49 without any treatment. After treatment, five patients were lost: one in group A, one in group B, and three in group C. The sperm count and the decrease of FSH in group A were significantly higher, but the degree of decline in the testicular volume and the degree of vein expansion have decreased significantly, which were closely related to the testicular volume (TV) [especially changes in the left testicular volume (ΔL-TV)], citric acid (CC) and its changes (ΔCC), and the vein width (VW) [especially left spermatic vein width (L-VW) and mean vein width (M-VW) and their changes (ΔL-VW and ΔM-VW)], as well as the sperm count before the treatment (bSC), which were the significant indexes to predict the therapeutic effect, especially for patients >35 years old and with grade III varicoceles. Network pharmacological analysis verifies that it can be regulated by fluid shear stress and the atherosclerosis pathway to improve the testicular microenvironment for spermatogenesis. Conclusion: JWRJD may promote spermatogenesis in cryptozoospermia patients with varicocele, which may be closely related to improving the testicular microenvironment, especially for >35 year olds and grade III varicocele patients.

Oriented self-assembly of metal-organic frameworks driven by photoinitiated monomer polymerization.

The self-assembly of metal-organic frameworks (MOFs) is crucial for the functional design of materials, including energy storage materials, catalysts, selective separation materials and optical crystals. However, oriented self-assembly of MOFs is still a challenge. Herein, we propose a novel strategy to drive oriented self-assembly of MOF polyhedral particles at the water-liquid interface by photoinitiated monomer polymerization. The MOF polyhedral particles self-assemble into ordered close-packed structures with obvious orientation in the polymer film, and the orientation is determined by the casting solvent on the water surface. The prepared large-area MOF polymer films show a Janus structure, containing a MOF monolayer and a polymer layer, and can be easily transferred to a variety of substrates. In addition, mixed MOF particles with different sizes and morphologies can also be assembled by this method. This novel method can be foreseen to provide a powerful driving force for the development of MOF self-assembly and to create more possibilities for utilizing the anisotropic properties of MOFs.

Risk Prediction of Ureaplasma urealyticum Affecting Sperm Quality Based on Mathematical Model and Cross-Sectional Study.

Objective: To explore the risk of Ureaplasma urealyticum (UU) affecting sperm quality. Methods: Prospective cross-sectional study was conducted. In total, 340 semen samples were collected. According to whether they were infected with UU, the samples were divided into the UU-positive group (observation group) and UU-negative group (control group). The patients with UU-positive were followed up to obtain treatment and collected the semen again after treatment. The semen characteristics and sperm parameters were detected and compared, and the relationship of UU and the sperm quality was analyzed by mathematical models. Results: There were 104 UU-positive semen samples in all, with an overall infection rate of 30.6%, which was highest in 31 to 40-year-old men, and over 40-year-old men were the lowest. The pH, PR, VCL, VSL, and STR in the observation group were significantly lower than those in the control group (allP < 0.001), while SV, NP, and WOB were significantly higher (allP < 0.001). After treatment, the pH, VSL, LIN, WOB, and STR in the observation group were significantly higher than before (allP < 0.001), while SV and VCL were significantly lower (allP < 0.001). UU infection was closely correlated with pH, PR, NP, VCL, VSL, WOB, and STR. During the treatment, pH, PR, VSL, WOB, and STR increased, but NP and VCL decreased. 7 major factors that would affect SQ were extracted, of which VAP, LIN, and UU were the first three main factors. The risk of SQ declining after UU infection increased nearly twice with the change of PR and VCL and increased 0.08 times with STR. Conclusion: UU may approximately double the risk of altering the sperm's curvilinear movement rate and straightness to affect the sperm quality.

Ureaplasma urealyticum induces polymorphonuclear elastase to change semen properties and reduce sperm motility: a prospective observational study.

OBJECTIVE: To elucidate the mechanism underlying how Ureaplasma urealyticum (UU) affects sperm quality and identify a therapeutic target. METHODS: In this prospective observational study, the differences in and relationships among semen volume, pH, viscosity, liquefaction time, sperm concentration, sperm motility [progressive motility (PR)], and seminal polymorphonuclear (PMN) elastase were analyzed in 198 normal semen samples (control group) and 198 UU-infected semen samples (observation group). The UU-infected samples were treated and the above parameters were compared between the two groups. RESULTS: The semen volume, viscosity, liquefaction time, and seminal PMN elastase were significantly higher in the observation than control group, but the pH and PR were significantly lower. In the observation group, the pH and PR were significantly higher after than before treatment, whereas the semen volume, PMN elastase, viscosity, and liquefaction time were lower. UU was closely related to semen volume, pH, viscosity, liquefaction time, sperm motility (PR), and PMN elastase. PMN elastase had significant negative effects on semen pH and sperm motility (PR) but positive effects on viscosity and liquefaction time. CONCLUSION: UU might induce PMN elastase to increase the liquefaction time and viscosity of semen, eventually decreasing PR. PMN elastase might be a therapeutic target of UU.

Runjing extract promotes spermatogenesis in rats with ornidazole-induced oligoasthenoteratozoospermia through extracellular signal-regulated kinase signalling, and regulating vimentin expression.

OBJECTIVE: To investigate the efficacy of Runjing (RJ) extract on oligoasthenoteratozoospermia (OAT) induced by ornidazole (ORN) in rats, and to study the underlying mechanism. METHODS: Twenty-four adult male Sprague-Dawley rats were treated with normal saline (control), ORN (OAT model), ORN + 4.725 g·kg－1·d－1 RJ extract (low-dose) and ORN+ 18.9 g·kg－1·d－1 RJ extract (high-dose) for 4 weeks. The rats were then euthanized and sperm and testis samples were collected for analysis. Sperm count, motility and morphology were calculated by sperm suspension from cauda epididymis. Testicular histopathological changes were analyzed by hematoxylin and eosin staining and TdT mediated dUTP nick end labelling. Moreover, the expression of vimentin and extracellular signal-regulated kinase (ERK) were examined through Western blot, and the distribution of vimentin was detected via immunohistochemistry. RESULTS: ORN successfully induces seminiferous epithelium injury, cellular apoptosis, and finally OAT (P < 0.05). However, both low-dose and highdose RJ extract partially rescues the phenotypes (P < 0.05). Moreover, the expressions of vimentin and ERK were significantly altered in ORN testes (all P < 0.001), while RJ extract partially reversed these effects (P < 0.01 or P < 0.001). CONCLUSION: RJ extract can help maintain spermatogenesis through ERK signalling, and regulating vimentin expression.

Robust anomalous Hall effect and temperature-driven Lifshitz transition in Weyl semimetal Mn3Ge.

Topological Weyl semimetals have attracted considerable interest because they manifest underlying physics and device potential in spintronics. Large anomalous Hall effect (AHE) in non-collinear antiferromagnets (AFMs) represents a striking Weyl phase, which is associated with Bloch-band topological features. In this work, we report robust AHE and Lifshitz transition in high-quality Weyl semimetal Mn3Ge thin film, comprising stacked Kagome lattice and chiral antiferromagnetism. We successfully achieved giant AHE in our Mn3Ge film, with a strong Berry curvature enhanced by the Weyl phase. The enormous coercive field HC in our AHE curve at 5 K reached an unprecedented 5.3 T among hexagonal Mn3X systems. Our results provide direct experimental evidence of an electronic topological transition in the chiral AFMs. The temperature was demonstrated to play an efficient role in tuning the carrier concentration, which could be quantitatively determined by the two-band model. The electronic band structure crosses the Fermi energy level and leads to the reversal of carrier type around 50 K. The results not only offer new functionality for effectively modulating the Fermi level location in topological Weyl semimetals but also present a promising route of manipulating the carrier concentration in antiferromagnetic spintronic devices.

Local Disorder-Induced Elevation of Intrinsic Anomalous Hall Conductance in an Electron-Doped Magnetic Weyl Semimetal.

Topological materials are expected to show distinct transport signatures owing to their unique band-inversion characteristic and band-crossing points. However, the intentional modulation of such topological responses through experimentally feasible means has yet to be explored in depth. Here, an unusual elevation of the anomalous Hall effect (AHE) is obtained in electron (Ni)-doped magnetic Weyl semimetals Co_{3-x}Ni_{x}Sn_{2}S_{2}, showing peak values in the anomalous Hall-conductivity, Hall-angle, and Hall-factor at a relatively low doping level of x=0.11. The separation of intrinsic and extrinsic contributions using the TYJ scaling model indicates that such a significant enhancement is dominated by the intrinsic mechanism of the electronic Berry curvature. Theoretical calculations reveal that compared with the Fermi-level shifting from electron filling, a usually overlooked effect of doping, that is, local disorder, imposes a striking effect on broadening of the bands and narrowing of the inverted gap, thus resulting in an elevation of the integrated Berry curvature. Our results not only realize an enhancement of the AHE in a magnetic Weyl semimetal, but also provide a practical design principle for modulating the bands and transport properties in topological materials by exploiting the local disorder effect from doping.

Electronic behaviors during martensitic transformations in all-d-metal Heusler alloys.

For solid-state phase transitions, the alterations of electronic structure driven by the band Jahn-Teller effect would play an essential role in the structural phase transitions and in switching the resistivity or magnetization states for potential applications. However, this evolution of the electronic structure and electronic transport during the martensitic transformations (MT) still lacks comprehensive investigations, especially in magnetic martensitic materials studied in recent years. In this work, we report a study on the electronic behaviors during the MT in a kind of all-d-metal Ni50-x Fe x Mn35Ti15 Heusler magnetic shape memory alloys, by combining x-ray diffraction, calorimetric, magnetic, transport measurements and calculations. Based on the magnetic MTs, the system shows large magnetocaloric effect and magnetoresistance. In the whole temperature range, the system is dominated by hole carriers in both parent and martensite phases. A sharp increase in carrier concentration is observed across the transformations. Meanwhile, the mobility of holes is depressed due to the lattice distortion. A picture of the characteristics of MTs has been proposed for general understanding and clues of the potential spintronic applications based on the magnetostructural phase transitions.

The chromatin remodeling protein BRG1 links ELOVL3 trans-activation to prostate cancer metastasis.

Prostate cancer malignancies are intimately correlated with deregulated fatty acid metabolism. The underlying epigenetic mechanism is not fully understood. In the present study we investigated the mechanism whereby the chromatin remodeling protein BRG1 regulates the transcription of long-chain fatty acid elongase 3 (Elovl3) in prostate cancer cells. We report that in response to pro-metastatic cues (androgen and TGF-ß) BRG1 expression was up-regulated along with Elvol3 in prostate cancer cells. BRG1 over-expression potentiated whereas BRG1 knockdown attenuated prostate cancer cell migration and invasion. Coincidently, Elovl3 was up-regulated following BRG1 over-expression and down-regulated after BRG1 knockdown in prostate cancer cells. Further analysis revealed that BRG1 interacted with and was recruited by retinoic acid receptor-related orphan receptor (RORγ) to the Elovl3 promoter to activate transcription. Chromatin immunoprecipitation (ChIP) profiling demonstrated that BRG1 interacted with histone acetyltransferase p300 to activate Elovl3 transcription. Depletion of p300 by siRNA or inhibition of p300 by curcumin attenuated Elovl3 trans-activation in prostate cancer cells. Together, our data identify a novel epigenetic pathway that links Elovl3 transcription to prostate cancer cell migration and invasion.

The effect of naringenin on the pharmacokinetics of ibrutinib in rat: A drug-drug interaction study.

The aim of this study was to investigate the effect of naringenin on the pharmacokinetics of ibrutinib in rats. A simple and sensitive quantitation method based on ultra-high-performance liquid chromatography-Q-Exactive Orbitrap tandem mass spectrometry was developed and validated for the determination of ibrutinib in rat plasma. The samples were extracted using ethyl acetate containing 1% triethylamine and separated on a Waters Acquity UPLC BEH C18 column with acetonitrile and water containing 0.1% formic acid as mobile phase. The assay showed good linearity over the concentration range of 1-1000 ng/mL with coefficient of correlation >0.995. The LLOQ was 1 ng/mL. The assay showed acceptable precision (RSD < 8.65%), accuracy (RE within ±15%), extraction recovery (>78.25%) and negligible matrix effects. The validated method has been successfully applied to the pharmacokinetic study of ibrutinib in rats after oral administration of ibrutinib with or without coadministration of naringenin. Our results demonstrated that naringenin could significantly affect the pharmacokinetics of ibrutinib, including prolonging its half-life, increase the area under the concentration-time curve and reducing its clearance time. This study indicated that there is potential for drug-drug interactions between naringenin and ibrutinib, and coadministration of ibrutinib with naringenin or naringenin-containing herbal medicines should be avoided in the clinic.

[Efficacy and safety of № I Empirical Prescription for Chronic Prostatitis in the treatment of type ⠢ refractory chronic prostatitis].

OBJECTIVE: To evaluate the efficiency and safety of № I Empirical Prescription for Chronic Prostatitis (№ I EPCP) in the treatment of type Ⅲ refractory chronic prostatitis. METHODS: We randomly assigned 53 cases of type Ⅲ refractory chronic prostatitis with damp-heat and blood stasis to an experimental and a control group to receive № I EPCP at 1 dose per day and saw palmetto extract at 160 mg bid), respectively, all for 8 weeks. Before and after 4 and 8 weeks of treatment, we obtained The National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores, Traditional Chinese Medicine Syndrome Scores (TCMSS), maximum urinary flow rate (Qmax), average urinary flow rate (Qavg), Hamilton Depression Rating Scale (HAMD) scores and Hamilton Anxiety Rating Scale (HAMA) scores, and compared them between the two groups of patients. RESULTS: Totally 48 of the patients completed the medication and follow-up, 25 in the experimental and 23 in the control group. Compared with the baseline, the NIH-CPSI scores after 8 weeks of treatment were significantly decreased in the experimental (27.82 ± 7.25 vs 15.46 ± 4.77, P <0.05) and the control group (25.98 ± 6.47 vs 21.06 ± 5.74, P <0.05), and so were the TCMSSs (24.64 ± 9.82 vs 16.42 ± 6.33 and 9.15 ± 3.74, P <0.05, and 23.67 ± 8.73 vs 18.55 ± 5.92 and 13.48 ± 4.45, P <0.05); the Qmax at 8 weeks were dramatically increased in the experimental group (ï¼»18.45 ± 7.81ï¼½ vs ï¼»23.44 ± 8.73ï¼½ ml/s, P <0.05) and the control (ï¼»17.58 ± 6.92ï¼½ vs ï¼»21.26 ± 8.32ï¼½ ml/s, P <0.05), and so was the Qavg (ï¼»11.27 ± 5.33ï¼½ vs ï¼»16.51 ± 7.36ï¼½ ml/s, P <0.05 and ï¼»10.66 ± 5.82ï¼½ vs ï¼»13.44 ± 6.16ï¼½ ml/s, P <0.05); the HAMD scores were remarkably reduced in the experimental group (22.74 ± 6.37 vs 17.62 ± 5.71 and 12.54 ± 5.22, P <0.05) and the control (23.55 ± 7.14 vs 22.34 ± 6.88 and 21.62 ± 5.63, P <0.05), and so were the HAMA scores (21.37 ± 7.15 vs 18.42 ± 6.35 and 14.63 ± 7.11, P <0.05 and 20.54 ± 6.77 vs 19.87 ± 6.24 and 19.42 ± 7.04, P <0.05). No obvious adverse reactions were observed in either of the two groups during the medication. CONCLUSIONS: № I EPCP deserves promotion and clinical application for its definite effectiveness and safety in the treatment of type Ⅲ refractory chronic prostatitis with damp-heat and blood stasis.