PPARG is a potential target of Tanshinone IIA in prostate cancer treatment: a combination study of molecular docking and dynamic simulation based on transcriptomic bioinformatics.

Tanshinone IIA is a lipophilic organic compound from the root of Danshen (Salvia miltiorrhiza) and is one of the most well-known Tanshinone molecules by pharmacologists. In recent years, in addition to effects of anti-cardiovascular and neurological diseases, Tanshinone IIA has also shown some degrees of anti-prostate cancer potential. Although they do have some studies focusing on the molecular mechanism of Tanshinone IIA's anti-prostate cancer effects, a further understanding on the transcriptomic and structural level is still lacking. In this study, transcriptomic sequencing technology and computer technology were employed to illustrate the effects of Tanshinone IIA on prostate cancer through bioinformatic analysis and molecular dynamics simulation, and PPARG was considered to be one of the targets for Tanshinone IIA according to docking scoring and dynamic calculation. Our study provides a novel direction to further understand the mechanism of the effects of Tanshinone IIA on prostate cancer, and further molecular biological studies need to be carried on to further investigate the molecular mechanism of Tanshinone IIA's anti-prostate cancer effect through PPARG.

An online questionnaire survey on the sexual function of Chinese male adults in the COVID-19 pandemic with loosened controls.

The coronavirus disease 2019 (COVID-19) may have a negative impact on the sexual health of male adults. An online questionnaire survey was conducted among male adults from February 04, 2023 to March 15, 2023 to analyze the impact of COVID-19 on the sexual health of male adults in China. Participants provided about their medical, social, lifestyle, and family situations information through questionnaires including the Brief Sexual Function Inventory (BSFI). Sexual function problems were defined based on predetermined cutoff values of the BSFI domain scores. A total of 1,250 male adults were included with median age as 32 years. According to the analysis of statistical results, sexual drive and erections firm enough to have sexual intercourse were reported to be present only a few days or less last month among 14.8 % and 11.1 % of COVID-19 survivors, respectively. Compared with uninfected persons, COVID-19 survivors had significantly lower scores on all BSFI domains and an increased risk of problems with sexual drive and erectile. In multivariate models of COVID-19 survivors, age ≥30 years, rural resident, lower education level, manual worker, lower income, and shorter duration from recovery to survey date were significantly associated with poorer overall sexual function. In this study, COVID-19 survivors was reported to have significantly poorer sexual function than uninfected persons. The COVID-19 may have had a significant impact on the sexual health of Chinese male adults. We need to focus on sexual dysfunction in COVID-19 survivors, and proactively provide effective interventions.

Trans-cinnamaldehyde attenuates renal ischemia/reperfusion injury through suppressing inflammation via JNK/p38 MAPK signaling pathway.

Inflammation is the major contributor to the mechanisms of acute kidney injury due to renal ischemia-reperfusion injury (IRI). Trans-cinnamaldehyde (TCA) is a main bioactive component extracted from the bark of cinnamon and has been proved to have good anti-inflammatory properties. The current study was to demonstrate the effect of TCA on renal IRI and explore its specific mechanism. C57BL/6J mice were injected prophylactically intraperitoneally for TCA 3 days, and IRI for 24 h. In parallel, Human Kidney-2 (HK-2) cells were prophylactically treated with TCA, and then exposed to oxygen glucose deprivation/reperfusion (OGD/R) and cobalt chloride (CoCl2). TCA was found to significantly attenuate renal pathological changes and renal dysfunction, and inhibit gene and protein expression of kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, TCA significantly suppressed the expression of TNF-α, IL-6, IL-1ß, COX-2, iNOS, and MCP-1. Mechanistically, the activation of the JNK/p38 MAPK signaling pathway was inhibited by TCA in renal IRI as well as in OGD/R and CoCl2-stimulated cells. However, following pretreatment with anisomycin before OGD/R treatment, we found that the activation of the JNK/p38 MAPK signaling pathway was significantly enhanced, and concomitant abrogation of the TCA inhibitory effect on the JNK/p38 MAPK signaling pathway, which was followed by a worsening of cell injury that was characterized by an increased number of cell necrosis and an increase in the expression of Kim-1, NGAL as well as proinflammatory factors (IL-6, IL-1ß, iNOS). In summary, TCA inhibited renal inflammation via the JNK/p38 MAPK signaling pathway and attenuated renal IRI.

MiR-7-5p attenuates vascular smooth muscle cell migration and intimal hyperplasia after vascular injury by NF-kB signaling.

Background: Atherosclerosis (AS) is the primary cause of coronary artery disease, which is featured by aberrant proliferation, differentiation, and migration of vascular smooth muscle cells (VSMCs). MicroRNAs play crucial roles in AS, but the function of miR-7-5p in AS remains unclear. Here, we aimed to explore the effect of miR-7-5p on AS and VSMCs in vitro and in vivo. Methods: The in vivo rat AS model and apoE-/- mouse model were established. The carotid artery injury was checked by immunohistochemistry staining. The RNA levels of miR-7-5p and p65 were measured by qPCR assay. Protein levels were checked by western blotting. Cell apoptosis was evaluated by flow cytometry. Cell migration was checked by Transwell assay and wound healing assay. The potential interaction between miR-7-5p with p65 was checked by luciferase reporter gene assay. Results: MiR-7-5p was downregulated and NF-κB p65 was upregulated in injured carotid arteries in rat model. The carotid artery injury in the AS rats and the treatment of miR-7-5p attenuated the phenotype in the model. Immunohistochemistry staining and Western blot analysis revealed that PCNA levels were increased in injured carotid arteries of the model rats and miR-7-5p could reverse the levels. The cell viability of VSMCs was induced by PDGF-BB but miR-7-5p blocked the phenotype. PDGF-BB decreased apoptosis of VSMCs, while miR-7-5p was able to restore the cell apoptosis in the model. PDGF-BB-induced migration of VSMCs was attenuated by miR-7-5p. miR-7-5p mimic remarkably repressed the luciferase activity of p65 in VSMCs. The levels of p65 were inhibited by miR-7-5p in the cells. The PDGF-BB-promoted cell viability and migration of VSMCs was repressed by miR-7-5p and p65 overexpression reversed the phenotype. Conclusion: We concluded that miR-7-5p attenuates vascular smooth muscle cell migration and intimal hyperplasia after vascular injury by NF-kB signaling.

Altered spontaneous brain activity in major depressive disorder: An activation likelihood estimation meta-analysis.

BACKGROUND: Wide application of resting-state functional magnetic resonance imaging (fMRI) in psychiatric research has revealed that major depressive disorder (MDD) manifest abnormal neural activities in several brain regions involving key resting state networks. However, inconsistent results have hampered our understanding of the exact neuropathology associated with MDD. Therefore, our aim was to conduct a meta-analysis to identify the consistent vulnerable brain regions of MDD in resting state, and to reveal the potential pathogenesis of MDD. METHODS: A systematic review analysis was conducted on studies involving brain resting-state changes in MDD using low-frequency amplitude (ALFF), fractional low-frequency amplitude (fALFF) and regional homogeneity (ReHo) analysis. The meta-analysis was based on the activation likelihood estimation method, using the software of Ginger ALE 2.3. RESULTS: 25 studies (892 MDD and 799 healthy controls) were included. Based on the meta-analysis results of ReHo, we found robust reduction of resting-state spontaneous brain activity in MDD, including the left cuneus and right middle occipital gyrus (cluster size = 216, 256 mm3, uncorrected P < 0.0001), while no increased spontaneous activation in any of the brain regions. We also found reduced ALFF in the left middle occipital gyrus (cluster size = 224 mm3, uncorrected P < 0.0001), and no increased spontaneous brain activation in any regions. CONCLUSION: Our meta-analysis study using the activation likelihood estimation method demonstrated that MDD showed significant abnormalities in spontaneous neural activity, compared with healthy controls, mainly in areas associated with visual processing, such as the cuneus and the middle occipital gyrus. Dysfunction of these brain regions may be one of the pathogenesis of MDD.

Lipoxin A4 regulates M1/M2 macrophage polarization via FPR2-IRF pathway.

Lipoxin A4 (LXA4) has been shown to have anti-inflammatory activity, but its underlying molecular mechanisms are not clear. Herein, we investigated the potential role of LXA4 in macrophage polarization and elucidated its possible molecular mechanism. The RAW264.7 macrophage cell line was pretreated with LXA4 with or without lipopolysaccharides (LPSs) and interleukin-4 (IL-4). In cultured macrophages, LXA4 inhibited LPS-induced inflammatory polarization, thereby decreasing the release of proinflammatory cell factors (IL-1ß, IL-6, TNF-α) and increasing the release of anti-inflammatory cytokines (IL-4 and IL-10). Notably, the inhibitory effect of LXA4 on inflammatory macrophage polarization was related to the downregulation of p-NF-κB p65 and IRF5 activity, which reduced the LPS-induced phenotypic and functional polarization of M1 macrophages via the FPR2/IRF5 signaling pathway. Moreover, LXA4 also induced the IL-4-induced polarization of M2 macrophages by promoting the FPR2/IRF4 signaling pathway. Therefore, LXA4 regulates M1/M2 polarization of macrophages via the FPR2-IRF pathway.

Microencapsulated islet transplantation alleviates podocyte injury in diabetic nephropathy via inhibiting Notch-1 signaling.

OBJECTIVE: Podocyte injury has a critical role in the pathogenesis of diabetic nephropathy (DN). Microencapsulated islet transplantation (MIT) is identified as an effective method for improving the clinical condition of DN. This study aimed to explore the role and mechanism of MIT in alleviating podocyte injury in DN. METHODS: A mouse model of DN was constructed using streptozotocin (STZ). Mice were divided into 3 groups: the untreated diabetic nephropathy group (DN group), the microencapsulated islet transplantation-treated group (MIT group) and the control group. The mice were raised for 6 weeks posterior to islet transplantation to identify the role of MIT. Renal function and structure of glomerular filtration barrier were assessed by urine analysis, histopathological examination, and transmission electron microscopy. The expression levels of several proteins including Caspase-3, Bcl2/Bax, ß-galactosidase, Ki-67, synaptopodin, WT-1, Jagged-1, Notch-1, and Hes-1 in renal tissues were identified via immunohistochemistry (IHC), immunofluorescence (IF), and western blotting techniques. RESULTS: Compared with the DN group, the MIT group presented decreased levels of blood glucose, urinary albumin/creatinine, urea nitrogen, and serum creatinine while their body weight gradually increased. Glomerular injury in the MIT group was significantly better than that in the DN group. The MIT group indicated significantly decreased expression of Caspase-3, ß-galactosidase, Bax/Bcl-2, and Ki-67 when compared with DN group, while the proportion of synaptopodin- and WT-1-positive cells was significantly increased (P < 0.05). The protein expression of Jagged-1, Notch-1, and Hes-1 in the glomerulus of the MIT group was significantly lower than that in the DN group (P < 0.05). CONCLUSION: MIT alleviates podocyte injury induced by DN by inhibiting Notch-1 signaling. The identification of signaling pathways influencing podocyte restoration can help evaluate personalized medicine efficacy for patients treated with islet transplantation.

Transcriptome Sequencing Reveals the Potential Mechanisms of Modified Electroconvulsive Therapy in Schizophrenia.

OBJECTIVE: Schizophrenia (SCZ) is one of the most common and severe mental disorders. Modified electroconvulsive therapy (MECT) is the most effective therapy for all kinds of SCZ, and the underlying molecular mechanism remains unclear. This study is aim to detect the molecule mechanism by constructing the transcriptome dataset from SCZ patients treated with MECT and health controls (HCs). METHODS: Transcriptome sequencing was performed on blood samples of 8 SCZ (BECT: before MECT; AECT: after MECT) and 8 HCs, weighted gene co-expression network analysis (WGCNA) was used to cluster the different expression genes, enrichment and protein-protein interaction (PPI) enrichment analysis were used to detect the related pathways. RESULTS: Three gene modules (black, blue and turquoise) were significantly associated with MECT, enrichment analysis found that the long-term potentiation pathway was associated with MECT. PPI enrichment p-value of black, blue, turquoise module are 0.00127, <1×10-16 and 1.09×10-13, respectively. At the same time, EP300 is a key node in the PPI for genes in black module, which got from the transcriptome sequencing data. CONCLUSION: It is suggested that the long-term potentiation pathways were associated with biological mechanism of MECT.

Comparison between Tramadol and Butorphanol for Treating Postoperative Catheter-Related Bladder Discomfort: A Randomized Controlled Trial.

BACKGROUND: Intraoperative catheterization often leads to postoperative catheter-related bladder discomfort (CRBD) during the restoration period. This study aimed to assess the curative effect of butorphanol as a K receptor agonist in the treatment of postoperative CRBD. Patients and Approaches. Sixty patients with CRBD who underwent elective nonurological surgery at the postanesthesia care unit were randomly and evenly assigned to two groups. The control group was slowly injected with tramadol 1.5 mg/kg using a Murphy dropper, whereas the experimental group was intravenously injected with butorphanol 0.02 mg/kg. Severity, pain score, and sedation score of CRBD were evaluated at 0 min, 5 min, 15 min, 30 min, 1 h, and 6 h later. RESULTS: The severity score of CRBD and visual analog scale pain score were lower in the butorphanol group than in the control group, whereas the sedation score was higher in the butorphanol group than in the control group. CONCLUSION: Butorphanol relieves on postoperative urination discomfort and pain compared with tramadol.

Synthesis of indium borate and its application in photodegradation of 4-chlorophenol.

Indium borate has been prepared by a sol-gel method. The structure, morphology, and photophysics of the resultant photocatalysts have been studied via the techniques of X-ray diffraction (XRD), transmission electron microscopy (TEM), and diffuse reflectance UV-visible light spectroscopy. These photocatalysts have been used to photodegrade 4-chlorophenol. The photocatalytic activity depends on the annealing temperature during preparation. It is found that borates can exhibit a high photodegradation activity under UV-light irradiation, for which the efficiency can be higher than that of as-prepared TiO(2). This is explained according to the results of fluorescence spectra and valence band X-ray photoelectron spectroscopy (XPS). It is confirmed by the results of time-resolved photoluminescence decay spectra; i.e., the lifetime of electrons and holes involved in the radiative process can be longer for the borates than that for TiO(2). This implies that indium borate can be a promising photocatalyst for future applications in treatment of environment contaminants.