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As potential candidates for treating ulcerative colitis (UC), polysaccharides from natural Cordyceps sinensis inhibited the activation of the NF-κB pathway, enhanced the intestinal barrier, increased the content of sIgA and modulated the gut microbiota in colitis mice.

As potential candidates for treating ulcerative colitis (UC), polysaccharides have been attracting extensive interest in recent years.

Objective: Previous studies showed acromegaly have significant higher prevalence of ventricular arrhythmias and often complicated by diabetes mellitus (DM) and hypertension (HT). Both HT and DM are notoriously associated with the development of arrhythmias. However, the effect of complication (DM and/or HT) in acromegaly on ventricular arrhythmias and the risk of ventricular arrhythmias in acromegaly accept therapy but no control is largely unknown. Methods: A cross-sectional study with 307 acromegaly and 303 patients with non-functional pituitary adenoma as control group. All subjects were divided into acromegaly with/without complication and controls with/without complication. In the longitudinal study, 30 persistent uncontrolled active acromegaly with at least three months follow-up. Electrocardiographic Measurements, laboratory examination, and clinical data collection were performed in all subjects. QT interval corrected for heart rate (QTc) was analyzed among groups. Results: QTc in acromegaly population significantly increased compared to controls (pConclusions: Acromegaly is an independent risk factor for ventricular arrhythmias and acromegaly with complication have an elevated risk for ventricular arrhythmia. Persistent uncontrolled acromegaly, who have significantly decreased in serum GH/IGF-1 levels relative to pre-treatment, also enhance the risk of ventricular arrhythmia.

Many SCR catalysts without V species are developed and used for the NO abatement. The content of Ca in the real flue gas will result in the deactivation of catalysts. In this work, the effect of Ca(OH)2 on the denitration performance of the Fe–Ce/TiO2 catalyst for SCR reaction was explored. The BET, XRD, XPS, NH3-TPD, Py-IR, UV–Vis DRS, H2-TPR, and SEM–EDS mapping techniques were used to characterize the evolution of active species and the surface properties over the studied catalysts. The gained results demonstrate that the Ca(OH)2 results in serious deactivation of Fe–Ce/TiO2 catalyst for NH3-SCR reaction and the degree of deactivation is closely related to the loading of Ca(OH)2. Such serious deactivation caused by Ca(OH)2 is attributed to the smaller surface area, the declined redox ability and surface acidity, the lower content of Ce3+ and Fe3+, as well as the less surface adsorbed oxygen species. Moreover, the addition of Ca(OH)2 leads to poor dispersion of Ce and Fe species over the catalyst surface, which may also be responsible for the fall of the catalytic performance of the catalyst.

Pituitary neuroendocrine tumors (PitNETs) represent the neoplastic proliferation of the anterior pituitary gland. Transcription factors play a key role in the differentiation of PitNETs. However, for a substantial proportion of PitNETs, the etiology is poorly understood. According to the transcription data of 172 patients, we found the imprinting disorders of the 14q32.2 region and DLK1/MEG3 locus associated with the differentiation of PitNETs. DLK1/MEG3 locus promoted somatotroph differentiation and inhibited tumor proliferation in PIT1(+) patients, furthermore, the level of DLK1 played a critical role in the trend of somatotroph or lactotroph differentiation. Anti-DLK1 monoclonal antibody blockade or siMEG3 both indicated that the DLK1/MEG3 significantly promoted the synthesis and secretion of GH/IGF-1 and inhibited cell proliferation. In addition, loss of DLK1 activated the mTOR signaling pathway in high DLK1-expressing and PIT1(+) GH3 cell lines, a mild effect in the low DLK1-expressing and PIT1(+) MMQ cell lines and no effect in the PIT1(-) ATT20 cell line. These findings emphasize that expression at the DLK1/MEG3 locus plays a key role in the differentiation of PitNETs, especially somatotroph adenomas, and provide potential molecular target data for patient stratification and treatment in the future.

Pituitary adenomas (PAs) are slow growing and benign primary intracranial tumors that often cause occupying effects or endocrine symptoms. PAs can be classified into various subtypes according to hormone secretion. Although widespread transcriptional alterations that cause aberrant hormone secretion have been characterized, the impact of genomic variations on transcriptional alterations is unclear due to the rare occurrence of single-nucleotide variations in PA. In this study, we performed whole-genome sequencing (WGS) on 76 PA samples across three clinical subtypes (PRL-PAs; GH-PAs, and NFPAs); transcriptome sequencing (RNA-seq) of 54 samples across these subtypes was also conducted. Nine normal pituitary tissues were used as controls. Common and subtype-specific transcriptional alterations in PAs were identified. Strikingly, widespread genomic copy number amplifications were discovered for PRL-PAs, which are causally involved in transcriptomic changes in this subtype. Moreover, we found that the high copy number variations (CNVs) in PRL-PA cause increased prolactin production, drug resistance and proliferative capacity, potentially through key genes with copy number amplification and transcriptional activation, such as BCAT1. This study provides insight into how genomic CNVs affect the transcriptome and clinical outcomes of PRL-PA and sheds light on the development of potential therapeutics for aberrantly activated targets.

The Fe–Ce/Ti catalysts with different molar ratios of Fe and Ce were synthesized by the precipitation method and impregnation method and used for the SCR reaction. BET, XRD, NH3-TPD, XPS, H2-TPR, UV–Vis, TEM, SEM–EDS mapping techniques were performed to explore the physicochemical properties of catalysts synthesized by different methods. As a result, the catalysts synthesized by precipitation method yields higher catalytic activity than that of the catalysts prepared by the impregnation method. The precipitated catalysts possess larger specific surface areas, higher ratios of Ce3+/Ce4+ and Fe3+/Fe2+ and more surface chemisorbed oxygen, as well as the enhanced surface acid sites and redox ability. Besides these, it holds a high dispersion of active species and more uniform smaller nanoparticles. All mentioned above will result in a higher catalytic performance of catalysts.

Due to its high specific capacity (in theory), molybdenum disulfide (MoS2) has been recognized as a plausible substitute in lithium-ion batteries (LIBs). However, it suffers from an inferior electric conductivity and a substantial volume change during Li+ insertion/extraction. By using a facile hydrothermal method, a flexible free-standing MoS2 electrode has here been fabricated onto a carbon cloth substrate. The grafting of ultrathin MoS2 nanoflakes onto the carbon cloth framework (forming CC@MoS2), was shown to facilitate an improved electron transport, as well as an enhanced Li+ transport. As expected, the as-obtained CC@MoS2 electrode was observed to exhibit an excellent lithium storage performance. It delivers a high discharge specific capacity of 2.42 mA h cm−2 at 0.7 mA cm−2 (even after 100 cycles), which is an impressive result.

Polysaccharide is one of the main bioactive substances in Cordyceps sinensis (C. sinensis). The aim of this study was to investigate the effect of polysaccharide from natural C. sinensis (CSP) on intestinal mucosal immunity and antioxidant activity in cyclophosphamide (Cy)-induced intestinal immunosuppressed mice, further to explore the potential mechanism. Results showed that in mice with Cy-induced intestinal injury, the supplement of CSP (25, 50, 100 mg/kg·bw) significantly increased the levels of goblet cells and mucus in intestine in a dose-dependent manner. The formation of immunoglobulin A (IgA)-secreting cells and the secretory IgA (sIgA) contents were promoted obviously in CSP groups. Furthermore, CSP significantly promoted the secretion or mRNA expression of T helper (Th) 1 style cytokines, including interleukin-2 (IL-2), IL-12 p40, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), in addition to Th1 style transcription factor T-bet. Besides, the levels of Th2 style cytokines, including IL-4, IL-10 and transcription factor GATA-3, were also improved. The value of T-bet/GATA-3, as well as IFN-γ/IL-4 was increased obviously. These results indicated that CSP effectively enhanced intestinal mucosal immunity and regulated polarization of Th1/Th2 cells. The total antioxidant capacity (T-AOC), and the activities of superoxidase dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in liver were increased significantly, and the content of malondialdehyde (MDA) was decreased dose-dependently. In conclusion, CSP effectively ameliorated Cy-induced intestinal injury in mice, which provided a good suggestion of the potential utilization of CSP as a natural immunopotentiator and antioxidant.

Background Recently, a hotspot mutation in prolactinoma was observed in splicing factor 3b subunit 1 (SF3B1R625H), but its functional effects and mechanisms are poorly understood. Methods Using the CRISPR/Cas9 genome editing system and rat pituitary GH3 cells, we generated heterozygous Sf3b1R625H mutant cells. Sanger and whole-genome sequencing were conducted to verify the introduction of this mutation. Transcriptome analysis was performed in SF3B1-wild-type versus mutant human prolactinoma samples and GH3 cells. Quantitative PCR and minigene reporter assays were conducted to verify aberrant splicing. The functional consequences of SF3B1R625H were evaluated in vitro and in vivo. Critical makers of epithelial-mesenchymal transition and key components of relevant signaling pathways were detected by western blot, immunohistochemistry, and immunofluorescence, and were knocked down by siRNA-mediated silencing. Results Transcriptomic analysis of prolactinomas and heterozygous mutant cells revealed that the SF3B1R625H allele led to different alterations in splicing properties, affecting different genes in different species. Consistently between rat cells and human tumor samples, mutant SF3B1 promoted aberrant splicing and the suppression of DLG1. Additionally, mutant SF3B1 with knockdown of DLG1 expression promoted cell migration, invasion, and epithelial-mesenchymal transition by activating the PI3K/Akt pathway. Conclusions Our findings elucidate a mechanism through which mutant SF3B1 promotes tumor progression and may provide a potent molecular therapeutic target for prolactinomas with the SF3B1R625H mutation.

Context Pituitary adenoma (PA) is a common intracranial tumor. The evidence indicates that the tumor immune microenvironment (TIME) is associated with PA and that the intestinal flora influences other tumors' growth through interacting with the TIME. However, how the intestinal microbial flora contributes to the development of PA through the immune response is unknown. Objective and methods Here we used high-throughput Illumina MiSeq sequencing targeting the V3−V4 region of the 16S ribosomal RNA gene to investigate the intestinal flora of patients with growth hormone-secreting pituitary adenoma (GHPA), nonfunctional pituitary adenoma (NFPA), and healthy controls. We determined their effects on tumor growth and the TIME. Fecal microbiota transplantation (FMT) was performed after adoptive transfer via peripheral blood mononuclear cells to tumor-bearing nude mice, which allowed the study of the immune response. Result We discovered differences in the structures and quantities of intestinal flora between patients with GHPA, patients with NFPA, and healthy controls. After FMT, the intestinal flora of GHPA patients promoted the growth of tumors in mouse models. The number of programmed cell death ligand 1 (PD-L1)-positive cells increased in tumor tissues as well as the extent of infiltration of CD8+ cells. Increased numbers of CD3+CD8+ cells and increased levels of sPD-L1 were detected in peripheral blood. Conclusion These findings indicated that the intestinal flora of patients with GHPA promoted tumor growth and that the immune system may mediate this change.

A polysaccharide from Cordyceps sinensis (NCSP) was reported to attenuate intestinal injury and regulate the balance of T helper (Th)1/Th2 cells in immunosuppressed mice. However, whether it influences Th17 and regulatory T (Treg) cells as well as gut ecology remains unknown. In the present study, the intestinal injury mouse model was also established by intraperitoneal injection of cyclophosphamide (Cy) for three consecutive days. NCSP was found to increase the number of CD4+ T cells, stimulate the secretion of interleukins (IL)-17 and IL-21, and the expression of transcription factor (retinoic acid-related orphan receptor (ROR)-γt). The levels of transforming growth factor (TGF)-β3 and transcription factor (forkhead box (Fox)p-3) were increased in NCSP-treated groups. Moreover, NCSP upregulated the mRNA expression of toll like receptors (TLR-2, -6 and -9), while it downregulated the TLR-4 expression. In addition, NCSP modulated the intestinal microbiota composition and increased the levels of SCFAs. These findings indicated that NCSP may enhance intestinal immunity and have the potential to become a prebiotic to regulate intestinal microbiota.

Non-functioning pituitary adenoma (NFPA) is a very common type of intracranial tumor. Monitoring and predicting the postoperative recurrence of NFPAs is difficult, as these adenomas do not present with serum hormone hypersecretion. Long non-coding RNAs (lncRNAs) and protein-coding genes (PCGs) play critical roles in the development and progression of numerous tumors. However, the complex network of RNA interactions related to the mechanisms underlying the postoperative recurrence of NFPA is still unclear. In the present study, 73 patients with NFPA were investigated using high-throughput sequencing and follow-up investigations. In total, 6 of these patients with recurrence within 1 year after surgery were selected as the fast recurrence group, and 6 patients with recurrence 5 years after surgery were selected as the slow recurrence group. By performing differential expression analysis of the fast recurrence and slow recurrence groups, a set of differentially expressed PCGs and lncRNAs were obtained (t-test, P

Pituitary tumors are the third most common intracranial tumors in adults. Treatment of refractory pituitary tumors is known to be difficult due to limited treatment options. As a promising therapeutic method, tumor immunotherapy has been applied in the treatment of many tumors, including pituitary tumors. Immune checkpoint blocking is one of the effective strategies to activate antitumor immunity. Immune checkpoints prevent tissue damage by regulating the immune response of peripheral tissues and participate in the maintenance of a normal immune environment. In the presence of a tumor, inhibition of T cell activity by tumor cells binding to immune checkpoints and their ligands is an important mechanism for tumor cells to escape immune injury. In this review, we summarize the latest findings of immune checkpoints and their potential as immunotherapeutic targets for pituitary tumors.

In the present work, fresh and Ca poisoned Fe–Ce/Ti catalysts were prepared and used for the NH3-SCR reaction to investigate the effect of Ca doping on the catalytic activity of catalysts. And these catalysts were characterized by BET, XRD, Raman, UV-vis DRS, XPS, H2-TPR, and NH3-TPD techniques. The obtained results demonstrate that Ca doping could lead to an obvious decrease in the catalytic activity of catalysts. The reasons for this may be due to the smaller specific surface area and pore volume, the decreased ratio of Fe3+/Fe2+ and Ce3+/Ce4+, as well as the reduced redox ability and surface acidity.

In the present work, fresh and Ca poisoned Fe-Ce/Ti catalysts were prepared and used for the NH

Pit-1 (POU1F1) is a POU-homeodomain transcription factor, and it is one of the most important tissue-specific transcription factors in pituitary development. Cyclin-dependent kinase 5 (CDK5) is a protein kinase that can phosphorylate many key transcription factors, but the mechanism under which CDK5 phosphorylates Pit-1 is unclear. To investigate whether CDK5 can regulate cell proliferation and promote hormone secretion through phosphorylation of Ser126-Pit-1 in prolactinomas, we generated an antibody that specifically recognizes phosphorylated serine at position 126 of Pit-1 (Ser126-Pit-1). We used western blotting to detect the level of Pit-1 phosphorylation and observed the proliferation and apoptosis of GH3 cells with different levels of Pit-1 phosphorylation by clone formation experiments, cell viability assays, and flow cytometry. ELISA was used to measure the level of PRL in the supernatant of GH3 cells. Tissue microarrays and immunohistochemistry were used to evaluate the expression of the phosphorylation level of Ser126-Pit-1 (pSer126-Pit-1) in prolactinomas. Our data indicated that Ser126-Pit-1 is specifically phosphorylated by CDK5 and high-level pSer-126-Pit-1 can promote cell proliferation and PRL secretion. In addition, a higher level of pSer-126-Pit-1 correlates with a worse prognosis in patients with prolactinoma. Our results show that CDK5 mediated Ser126-Pit-1 phosphorylation and regulated prolactinoma progression and PRL secretion.

Background: Pituitary neuroendocrine tumors (PitNETs) represent the neoplastic proliferation of the anterior pituitary gland. Transcription factors play a key role in the differentiation of PitNETs according to the 2017 WHO classification of tumors of endocrine organs. However, for a substantial proportion of PitNETs, the etiology is poorly understood.Methods: To analyze the diversity genes and pathways based on transcriptomic data of 172 patients by transcriptome sequencing, difference, correlation, and enrichment analysis. The transcriptomic data and clinical characteristics are applied to find the clinical significance of key genes by correlation analysis and ROC curve. Series functional experiments demonstrated the role of DLK1/MEG3 locus through antibody blocking and RNA interference in GH3, MMQ and ATT20 cell line.Results: In this study, we found the imprinting disorders of the 14q32.2 region and DLK1/MEG3 locus associated with the differentiation of PitNETs. As being specific feature change in somatotroph adenomas compared with other subtype adenomas, DLK1/MEG3 locus promoted somatotroph differentiation and inhibited tumor proliferation in PIT1(+) PitNET patients, furthermore, the level of DLK1 played a critical role in the trend of somatotroph differentiation or lactotroph differentiation in PIT1(+) PitNET patients. Anti-DLK1 monoclonal antibody blockade or siMEG3 both indicated that the DLK1/MEG3 domain significantly induced the synthesis and secretion of growth hormone/insulin-like growth factor-1 (GH/IGF-1) and inhibited cell growth and colony formation and that the loss of DLK1 activated the mTOR signaling pathway in high DLK1-expressing and PIT1(+) GH3 cell lines. There was a mild effect in the low DLK1-expressing and PIT1(+) MMQ cell lines and no effect in the PIT1(-) ATT20 cell line, regardless of whether anti-DLK1 monoclonal antibody blockade or siMEG3 was used. Conclusions: These findings emphasize that expression at the DLK1/MEG3 locus plays a key role in the differentiation of PitNETs in patients depending on the level of PIT1. In addition, these findings provide potential molecular target data for patient stratification and treatment in the future.

The altered cell cycle is associated with aberrant growth factor signaling in somatotroph adenoma, which is the primary cause of acromegaly. The aim of the present study was to investigate the pathological role of the INK4 family and evaluate the effectiveness of CDK4 inhibitor, palbociclib, in somatotroph adenoma. RNA‑Seq, RT‑PCR, and immunohistochemistry were applied to measure the levels and correlations of the INK4 family with angiogenesis, CDKs, EMT, and therapeutic targets. MTS, flow cytometry, and ELISA were used to investigate the bio‑activity in GH3 and GT1‑1 cell lines after palbociclib treatment. Compared with lactotroph adenoma, gonadotroph adenoma, and corticotroph adenoma, somatotroph samples demonstrated higher expression of CDKN2A and SSTR2 but a lower expression of EGFR, CDK4, and CDH2 (P

Cordyceps sinensis is a traditional Chinese edible food with many bioactive constituents. The study aimed to explore the restorative effects of eight fractions, including the raw material. The content of bioactive constituents was measured, and their effects on intestinal restorative activities was evaluated. Results showed that all fractions decreased the crypt depth, increased the villus height and goblet cells. The number of CD4+, CD8+ T lymphocytes, levels of transcription factor and cytokines in small intestine were also enhanced. Furthermore, the concentration of short-chain fatty acids in feces promoted after given the extracted fractions. The results indicated that the extracted fractions from natural Cordyceps sinensis could alleviate intestinal injury in immunosuppressed mice, and the effect was generally better than that of the raw material. These findings may provide fundamental aspect of Cordyceps sinensis utilization.

Lentinula edodes (L. edodes) is a type of edible mushroom which is known to beneficially support the immune system. In this study, three polysaccharide fractions (F1, F2 and F3) were isolated from L. edodes water extracts. Their molecular weights distribution (F1 > F2 > F3) and their immunomodulatory properties were investigated. Thymus index, thickness of footpad, proliferation of splenocytes, immunoglobulin (Ig) content and cytotoxicity of natural killer (NK) cells were measured to evaluate the immunomodulatory effects of the polysaccharides. All three polysaccharide fractions protected host from immunosuppression. F1 had significant effects in enhancing cellular immunity only, while F2 and F3 improved cellular immunity, humoral immunity and innate immunity. The immunomodulatory effects became more significant in the order F1

Chondroma of the dural convexity (CDC) is a benign and extremely rare type of intracranial chondroma. In this study, we reported five CDCs in a single center and reviewed the available literature to determine the clinical characteristics and surgical outcomes and possible origins of the disease. The clinical data of five patients (4 females) who confirmed to be CDC between 2000 and 2019 in our single center was collected together with 22 cases from literatures. The clinical characteristics and surgical outcomes were reviewed and analyzed. Among all the available CDC cases, the mean age was 31 ± 13.7 years ; the mean tumor volume was 42.3 ± 40.9 c m 3 , showing a female predominance (63% vs. 37%). The tumors showed calcification in 88.2% cases (15/17) on CT scans and hypointense on T1WI (15/19, 78.9%), mixed intense on T2WI (10/18, 55.6%), and inhomogeneous enhancement without dural tail sign after administration of gadolinium (20/21, 95.2%). Almost all the tumors were misdiagnosed as meningiomas preoperatively. In addition, almost all image available CDC lesions (24/25, 96%) located across the cranial sutures indicating that the tumor originated from ectopic chondrocytes from adjacent skull sutures. No tumors recurred after total resection in follow-up. CDCs are characterized with female predominance and may originate from ectopic chondrocytes from adjacent skull sutures. The lesion with inhomogeneous contrast enhancement without dural tail sign and avascular in cerebral angiography are key points to be differentiated from meningioma. The most effective treatment is total resection.

Due to its high specific capacity (in theory), molybdenum disulfide (MoS

ContextProlactinomas are the most common functional pituitary adenomas; the aggressive tumors still present challenge to clinicians. Aberrant expression of miRNAs has been functionally associated with prolactinomas.ObjectiveHere we explored the role of miR-137 on the proliferation, invasion, and apoptosis of prolactinomas and its possible mechanism.ResultsLow expression of miR-137 was correlated with the invasive behavior of human prolactinomas and predicted high recurrence. MiR-137 inhibited cell proliferation, invasion, and survivals of MMQ and GH3 cells and reduced tumor volume in F344 rat prolactinomas. The luciferase reporter assay confirmed that microphthalmia-associated transcription factor (MITF) was the direct target of miR-137. In addition, miR-137 mimics could inhibit MITF expression in vivo and in vitro. Upregulation of MITF expression promoted cell proliferation, invasion, and survivals and reversed the antitumor effect of miR-137 in vivo and in vitro. Furthermore, miR-137 could also upregulate wnt-inhibitory factor-1 and inhibit nuclear translocation of β-catenin. Upregulation of wnt-inhibitory factor-1 with decitabine can enhance the inhibition on cell proliferation of miR-137. A glycogen synthase kinase-3 inhibitor, SB 216763, promoted cell proliferation by upregulation of total/cytoplasmic/nuclear β-catenin and reversed tumor suppression of miR-137 mimics.ConclusionsOur data suggest that miR-137 possesses a tumor invasive suppressor function with a prognostic value in prolactinomas by targeting MITF and modulating Wnt-β-catenin signaling pathway.