[Research progress on structures, activities, and biosynthesis of blazeispirol compounds from Agaricus blazei].

Agaricus blazei is a rare medicinal and edible fungus with a crispy taste and delicious flavor. Both fruiting body and mycelium are rich in polysaccharides, sterols, terpenoids, peptides, lipids, polyphenols, and other active ingredients, which have strong pharmacological activities such as anti-tumor, lipid-lowering, glucose-lowering, immunomodulation, optimization of intestinal flora, and anti-oxidation. Therefore, it is a kind of fungal resource with a great prospect of edible and medicinal development. Among the reported chemical components of A. blazei, blazeispirol is a series of sterol compounds unique to A. blazei, which has a spiral structure and is different from classical steroids. It is an important active ingredient found in the mycelium of A. blazei and has significant hepatoprotective activity. It can be used as a phylogenetic and chemotaxonomic marker of A. blazei strains and is considered an excellent lead compound for drug development. According to the skeleton structure characteristics, the 17 discovered blazeispirol compounds can be divided into two types: blazeispirane and problazeispirane. In order to further explore the resource of blazeispirol compounds of A. blazei, the discovery, isolation, structure, biological activity, and biosynthetic pathways of blazeispirol compounds of A. blazei were systematically reviewed. Besides, the metabolic regulation strategies related to the fermentation synthesis of blazeispirol A by A. blazei were discussed. This review could provide a reference for the efficient synthesis and development of blazeispirol compounds, the research and development of related drugs and functional foods, and the quality improvement of A. blazei and other medicinal and edible fungi resources and derivatives.

Puerarin Suppresses Glycolysis and Increases Cisplatin Chemosensitivity in Oral Squamous Cell Carcinoma via FBXW7/mTOR Signaling.

This study aimed to observe the effects of puerarin on glycolysis and cisplatin sensitivity in oral squamous cell carcinoma (oSCC) cells and to explore the underlying mechanisms. CAL27 cells over- or under-expressing FBXW7 were treated with cisplatin or puerarin, and the levels of proteins involved in glycolysis as well as the activity of the respective enzymes were assessed. Glucose uptake and lactate production were also evaluated, and the IC50 value of cisplatin in CAL27 cells was determined. FBXW7 overexpression significantly downregulated HK2, PKM2, and LDH; suppressed the activity of the corresponding enzymes hexokinase, pyruvate kinase, and lactate dehydrogenase; as well as reduced glucose uptake and lactate production. FBXW7 overexpression was also associated with decreased mTOR phosphorylation and increased cisplatin sensitivity. These effects were partially antagonized by lactate or the mTOR agonist MHY1485. Puerarin suppressed glycolysis by reducing glucose uptake and lactate production, while it promoted cisplatin sensitivity and activated the FBXW7/mTOR signal pathway in a concentration-dependent manner. These effects were antagonized by FBXW7 downregulation or treatment with MHY1485. Our results suggest that FBXW7 improves cisplatin chemosensitivity and suppresses glycolysis in oSCC cells, indicating its promising potential as a target for puerarin to regulate the cisplatin sensitivity of oSCC cells.

Total Barley Maiya Alkaloids Prevent Increased Prolactin Levels Caused by Antipsychotic Drugs and Reduce Dopamine Receptor D2 via Epigenetic Mechanisms.

Background: The dopamine D2 receptor (DRD2) plays an important role in the increased prolactin (PRL) levels associated with the pathogenesis of antipsychotic drugs (ADs). Elevated prolactin levels can affect people's quality of life. Maiya alkaloids has been used to treat diseases associated with high PRL levels. Maiya, is a processed product of the mature fruits of Hordeum vulgare L. (a gramineous plant) after sprouting and drying and also a common Chinese herbal drug used in the clinic, is traditionally used to treat abnormal lactation, and is currently used clinically for the treatment of abnormal PRL levels. Aims: Epigenetic mechanisms can be related to DRD2 expression. We investigated the role of DRD2 methylation in the induction of PRL expression by ADs and the mechanism underlying the effects of total barley maiya alkaloids (TBMA) on this induction. Methods: The methylation rate of DRD2 in 46 people with schizophrenia who took risperidone was detected by MassARRAY sequencing. Humans were long term users of Ris. Seventy Sprague Dawley female rats were divided into seven groups. A rat model of risperidone-induced PRL was established, and the potential protective effects of TBMA and its components [e.g., hordenine (Hor)] on these increased PRL levels were investigated. The PRL concentration was detected by Enzyme-linked immunosorbent assay. PRL, DRD2, and DNA methyltransferase (DNMT1, DNMT3α, and DNMT3ß) protein and mRNA expression were detected by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. The positive rate of methylation in the DRD2 promoter region of rats was detected by MassARRAY sequencing. Results: Clinical studies showed that the positive rate of DRD2 methylation associated with increased PRL levels induced by ADs was significantly higher than in the normal prolactinemia (NPRL) group. In vivo and vitro, TBMA and Hor inhibited this induction of PRL expression and increased DRD2 expression by inhibiting the expression of the DNMTs. Conclusions: TBMA and hordenine increased DRD2 expression by inhibiting DNMT-dependent DRD2 methylation.

Antiprolactinoma Effect of Hordenine by Inhibiting MAPK Signaling Pathway Activation in Rats.

Prolactinomas are harmful to human health, and the clinical first-line treatment drug is bromocriptine. However, 20% prolactinomas patients did not respond to bromocriptine. Hordenine is an alkaloid separated from Fructus Hordei Germinatus, which showed significant antihyperprolactinemia activity in rats. The aim of this study was to explore the effect and mechanism of hordenine on prolactinomas in rats. The study used estradiol to induce prolactinomas, which caused the activation of the pituitary mitogen-activated protein kinase (MAPK) pathway in rats significantly. The treatment of hordenine restored estradiol, induced the overgrowth of pituitary gland, and reduced the prolactin (PRL) accumulation in the serum and pituitary gland of rats by blocking the MAPK (p38, ERK1/2, and JNK) activation and production of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). The antiprolactinoma effect of hordenine was mediated by inhibiting the MAPK signaling pathway activation in rats.

Relationships of Non-coding RNA with diabetes and depression.

In order to study the molecular differences between type 2 diabetes mellitus (T2DM) and T2DM with depression (DD), we aimed to screen the differential expression of lncRNA, mRNA, and circRNA in the blood of patients with T2DM and DD. Based on the self-rating depression scale (SDS), patient health questionnaire 9 (PHQ9), blood glucose and HbA1c, we divided the patients into T2DM and DD group. Peripheral blood was collected from the two groups of patients to perform lncRNA, mRNA, and circRNA expression profiling and screening DD-related specific molecules. Subsequently, bioinformatics analysis was performed to investigate the functions of differentially expressed genes (DEgenes). Finally, RT-PCR and lncRNA-mRNA regulatory network was performed to verify the expressions of lncRNAs and mRNAs related to the occurrence and development of DD. 28 lncRNAs, 107 circRNAs, and 89 mRNAs were identified in DD differential expression profiles. GO and pathway analysis found that 20 biological process (BP) related entities and 20 pathways associated with DD. The analysis shows that the genes that are differentially expressed in the DD group involved in the development of the neuropsychiatric system, immunity, and inflammation. Then, we screening for the important DElncRNA and mRNA associated with DD were verified by RT-PCR experiments and the results of RT-PCR were consistent with the sequencing results. LncRNA, circRNA, and mRNA differential expression profiles exist in DD patients compared with T2DM. The lncRNA-mRNA regulatory network analysis confirmed the crosslinking and complex regulation patterns of lncRNA and mRNA expression and verified the authenticity of the regulatory network.

Candesartan cilexetil prevents diet-induced insulin resistance via peroxisome proliferator-activated receptor-γ activation in an obese rat model.

Angiotensin II type 1 receptor (AT1R) blockers (ARBs) have been shown to reduce the incidence of type 2 diabetes mellitus; however, the underlying molecular mechanism is unknown. Peroxisome proliferator-activated receptor γ (PPARγ) is the central regulator of insulin and glucose metabolism, which improves insulin sensitivity. Whether candesartan cilexetil, as a prodrug of the AT1R blocker candesartan, has PPARγ-activating properties remains to be elucidated. The aim of the present study was to investigate the effects of oral administration of candesartan cilexetil on glucose tolerance and the actions of PPARγ on liver and adipose tissue in the insulin-resistant obese rat induced by high-fat diet. Animals treated with candesartan cilexetil showed an improved glucose tolerance after oral glucose challenge. Whole-body insulin sensitivity was evaluated using the hyperinsulinemic-euglycemic clamp technique. During high-fat feeding in high-fat diet (HF) rats, the glucose infusion rate (GIR) was 52.3% lower than that in normal chow (NC) rats. However, the GIR was significantly enhanced following candesartan cilexetil treatment. Angiotensin II receptor antagonism also resulted in significant increases in PPARγ protein expression in adipose and liver tissue. These results indicate that PPARγ activation by candesartan cilexetil may provide novel therapeutic options in the treatment of patients with metabolic syndrome.

Synthesis of in-plane and stacked graphene/hexagonal boron nitride heterostructures by combining with ion beam sputtering deposition and chemical vapor deposition.

Graphene/hexagonal boron nitride (h-BN) heterostructures have attracted a great deal of attention in recent years due to their unique and complementary properties for use in a wide range of potential applications. However, it still remains a challenge to synthesize large-area high quality samples by a scalable growth method. In this work, we present the synthesis of both in-plane and stacked graphene/h-BN heterostructures on Cu foils by sequentially depositing h-BN via ion beam sputtering deposition (IBSD) and graphene with chemical vapor deposition (CVD). Due to a significant difference in the growth rate of graphene on h-BN and Cu, the in-plane graphene/h-BN heterostructures were rapidly formed on h-BN domain/Cu substrates. The large-area vertically stacked graphene/h-BN heterostructures were obtained by using the continuous h-BN film as a substrate. Furthermore, the well-designed sub-bilayered h-BN substrates provide direct evidence that the monolayered h-BN on Cu exhibits higher catalytic activity than the bilayered h-BN on Cu. The growth method applied here may have great potential in the scalable preparation of large-area high-quality graphene/h-BN heterostructures.

Effects of a multivitamin/multimineral supplement on young males with physical overtraining: a placebo-controlled, randomized, double-blinded cross-over trial.

OBJECTIVE: To investigate the effects of vitamin-mineral supplement on young males with physical overtraining. METHODS: Two hundred and forty male Chinese field artillery personnel who undertook large scale and endurance military training and were on ordinary Chinese diet were randomized to receive a multivitamin/multimineral supplement or a placebo for 1 week. After a 1-week wash-out period, a cross-over with 1 week course of a placebo or multivitamin/multimineral supplement was conducted. Blood and urine samples were analyzed for adrenal, gonadal and thyroid hormones. In addition, cellular immune parameters (CD3+, CD3+CD4+, CD3+CD8+, CD4/CD8, CD3-CD56+, CD3-CD19+) were examined and psychological tests were performed before and after the training program and nutrition intervention. RESULTS: After a large scale and endurance military training, the participants showed significantly increased thyroid function, decreased adrenal cortex, testosterone and immunological function, and significantly increased somatization, anger and tension. Compared to placebo, multivitamin/ multimineral intervention showed significant effects on functional recovery of the pituitary - adrenal axis, pituitary-gonadal axis, pituitary- thyroid axis and immune system as well as psychological parameters. CONCLUSION: High-intensity military operations have significant impacts on the psychology, physical ability and neuroendocrine-immune system in young males. Appropriate supplementation of multivitamin/multimineral can facilitate the recovery of the psychology, physical ability and neuroendocrine-immune system in young males who take ordinary Chinese diet.

Experimental study on neuroendocrinological and immunological characteristics of the military-trained artillerymen.

BACKGROUND: Over one million soldiers were treated for battle- or training-fatigue during World War II. Of all ground combat troops, 37% were discharged for psychiatric reasons due to fatigue. The neuroendocrinological and immunological systems played important roles in the work-related fatigue of military personnel. The aim of this study was to investigate the characteristics of fatigue associated with military operations, and we observed changes in the regulatory functions of the neuroendocrinological and immunological systems that may provide theoretical support for improving the combat effectiveness of armies. METHODS: A total of 240 soldiers from the Field Artillery regiment were selected as subjects. Researchers and subjects received training before participating in the study. Data of the subjects' medical histories, physical examinations, scores on a fatigue assessment scale, and assessments of pituitary-adrenal hormones (adrenal cortical hormone (ACTH), cortical hormone (F), and 24-hour urine-free cortisol (UFC)), pituitary-gonadal hormones (luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol (E2), and prolactin (PRL)), pituitary-thyroid hormones (thyroid-stimulating hormone (TSH), thyroxine (TT4), triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine (FT3)), and cellular immune parameters (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), B, and NK cells) were investigated before and after large-scale and high-intensity field exercises. Data were statistically analyzed with Student's t test using SPSS software (version 13.0), and P values < 0.05 were deemed to be significant. RESULTS: After the high-intensity military training, the scores on the fatigue scale reflected significant increases of feeling of unpleasantness among soldiers. Additionally, the symptom checklist showed notable increases in somatization scores and significant decreases in psychoticism scores. After intensive military work, levels of plasma ACTH, F, and UFC of soldiers were decreased (P < 0.01). The level of testosterone decreased significantly after the maneuver ((23.51 ± 6.49) versus (18.89 ± 5.89) nmol/L; P < 0.001), whereas the thyroid function (TT3, FT4, and FT3) was markedly increased after the maneuver (P < 0.01). The number of CD3(+), CD4(+), CD4(+)/CD8(+) cells, and B lymphocytes were decreased (P < 0.05), and NK cells were increased (P < 0.001) after the maneuver. CONCLUSIONS: Following high-intensity military operations, the psychological tolerance of soldiers was depressed. And the hypoadrenocorticism (the functional decreases of hypothalamic-pituitary-gonadal and abnormal pituitary-thyroid axis) contributed to the increased levels of fatigue. Hypoimmunity may increase the susceptibility to diseases after high-intensity military operations.