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Aim: Atractylodes macrocephala Rhizome (AM) has been used to treat hyperlipidemia for centuries, but its functional components and mechanisms are not clear. This research aimed to investigate the active components in AM and the mechanisms that underlie its anti-hyperlipidemia effect. Methods: SD rats were fed a high-sucrose high-fat diet in conjunction with alcohol (HSHFDAC) along with different AM extracts (AMW, AMO, AME, and AMP) for 4 weeks. AM's active components were analyzed using multiple databases, and their mechanisms were explored through network pharmacology. The relationship between AM's effect of enhancing serum HDL-c and regulating the expression of reverse cholesterol transport (RCT)-related proteins (Apo-A1, LCAT, and SR-BI) was further validated in the HSHFDAC-induced hyperlipidemic rats. The kidney and liver functions of the rats were measured to evaluate the safety of AM. Results: AMO, mainly comprised of volatile and liposoluble components, contributed the most significant anti-hyperlipidemia effect among the four extracts obtained from AM, significantly improving the blood lipid profile. Network pharmacology analysis also suggested that volatile and liposoluble components, comprise AM's main active components and they might act on signaling pathways associated with elevated HDL-c. Validation experiments found that AMO substantially and dose-dependently increased HDL-c levels, upregulated the expression of Apo-A1, SR-BI, and LCAT, improved the pathological changes in the kidney and liver, and significantly reduced the serum creatinine levels in rats with hyperlipidemia. Conclusion: The main anti-hyperlipidemia active components of AM are its volatile and liposoluble components, which may enhance serum HDL-c by increasing the expression of the RCT-related proteins Apo-A1, LCAT, and SR-BI.

There is an increasing global trend toward unhealthy lifestyles and dietary decisions, like the overconsumption of alcohol and high-sugar and high-fat diets (ACHSFDs). Poor eating habits can cause an imbalance of the Treg/Th17 immune axis, thereby leading to an imbalance of anti-inflammatory and pro-inflammatory factors, which damages target organs and the vascular endothelium causing MH. Hawthorn has been shown to improve gastrointestinal function, lower blood pressure, and regulate metabolic abnormalities. However, whether it acts on MH by regulating the Treg/Th17 immune axis remains unclear. In this study, the hawthorn extract reduced blood pressure[systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP)] and improved dyslipidemia in rats with ACHSFD-induced MH. In addition, the extract reduced serum AST and ALT levels and liver coefficient and improved liver fat deposition and fibrosis. On the other hand, the hawthorn extract downregulated RORγt expression, upregulated Foxp3 expression, increased IL-10 levels in the aorta, and reduced IL-17, IL-6, and TNF-α content. Moreover, the extract upregulated eNOS expression in the aorta and increased NO content in the serum. These findings indicate that hawthorn extract can inhibit aortic inflammatory injury and improve vascular endothelial function by regulating the Treg/Th17 immune imbalance.

Metabolic hypertension (MH) is the most common type of hypertension worldwide because of unhealthy lifestyles, such as excessive alcohol intake and high-sugar/high-fat diets (ACHSFDs), adopted by humans. Poor diets lead to a decrease in the synthesis of short-chain fatty acids (SCFAs), which are produced by intestinal flora and transferred by G protein-coupled receptors (GPCRs), resulting in impaired gastrointestinal function, disrupted metabolic processes, increased blood pressure (BP), and ultimately, MH. It is not clear whether Dendrobium officinale polysaccharide (DOPS) can mediate its effects by triggering the SCFAs-GPCR43/41 pathway. In this study, DOPS, with a content of 54.45 ± 4.23% and composition of mannose, glucose, and galacturonic acid at mass percentages of 61.28, 31.87, and 2.53%, was isolated from Dendrobium officinale. It was observed that DOPS, given to rats by intragastric administration after dissolution, could lower the BP and improve the abnormal lipid metabolic processes in ACHSFD-induced MH rats. Moreover, DOPS was found to increase the production, transportation, and utilization of SCFAs, while improving the intestinal flora and strengthening the intestinal barrier, as well as increasing the intestinal levels of SCFAs and the expression of GPCR43/41. Furthermore, DOPS improved vascular endothelial function by increasing the expression of GPCR41 and endothelial nitric oxide synthase in the aorta and the nitric oxide level in the serum. However, these effects were all reversed by antibiotic use. These findings indicate that DOPS is the active component of Dendrobium officinale, and it can reverse MH in rats by activating the intestinal SCFAs-GPCR43/41 pathway.

National Herbal Drink (NHD) is a functional food approved by the State Administration for Market Regulation for immune enhancement. In this study, the effects of NHD on Cyclophosphamide (CTX)-induced immune regulation and gut microbiota dysregulation in mice were investigated to elucidate whether the attenuation of immunosuppression was related to the regulation of the gut microbiota by NHD. Our study showed that CTX induced immune organ damage in immunosuppressed mice, with reduced levels of serum immunoglobulins IgG, IgM, and complement C3 and disruption of bone marrow hematopoiesis, accompanied by changes in liver toxicity and shortened colonic length. However, all these changes were reversed to varying degrees by NHD intervention. Delayed-type hypersensitivity (DTH) and serum hemolysins in mice also indicated that NHD could effectively regulate cellular and humoral immunity in the body. In addition, it is noteworthy that NHD can also improve intestinal pathology, elevate the expression of intestinal tight junction proteins Occludin and Claudin-1 to restore intestinal barrier function. Furthermore, α-diversity and β-diversity analysis showed that NHD has a positive regulatory effect on the gut microbiota. At the phylum level, NHD could regulate the abundance of three major phyla, namely, Bacteroidetes, Firmicutes, and Actinobacteriota. At the species level, the abundance of the beneficial genus uncultured_bacterium_g__norank_f__ Muribaculaceae increased and the abundance of the harmful genus unclassified_f__Lachnospiraceae decreased after the NHD intervention. These results provide evidence that NHD modulates the immune response in cyclophosphamide-induced immunocompromised mice by restoring intestinal barrier function and regulating gut microbiota disorders.

Aim: Modified Suanzaoren Decoction (MSZRD) is obtained by improving Suanzaoren Decoction (SZRT), a traditional Chinese herbal prescription that has been used to treat insomnia for more than thousands of years. Our previous study showed that MSZRD can improve the gastrointestinal discomfort related insomnia by regulating Orexin-A. This study is the first study to evaluate the effects and possible mechanisms of MSZRD in mice with insomnia caused by p-chlorophenylalanine (PCPA) combined with multifactor random stimulation. Methods: After 14 days of multifactor stimulation to ICR mice, a PCPA suspension (30 mg/mL) was injected intraperitoneally for two consecutive days to establish an insomnia model. Three different doses of MSZRD (3.6, 7.2, and 14.4 g/kg/day) were given to ICR mice for 24 days. The food intake and back temperature were measured, and behavioral tests and pentobarbital sodium-induced sleep tests were conducted. The levels of Orexin-A, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and adrenocortical hormones (CORT) in the serum and 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in hypothalamus were measured using enzyme-linked immunosorbent assay (ELISA) kits. The levels of γ-aminobutyric acid (GABA) and glutamic acid (Glu) were measured by high-performance liquid chromatography (HPLC). The expression of 5HT1A receptor (5-HTRIA) and orexin receptor 2 antibody (OX2R) was measured by Western blot (WB) and immunohistochemical staining (ICH). Hematoxylin and eosin (H&E) staining and Nissl staining were used to assess the histological changes in hypothalamus tissue. Results: Of note, MSZRD can shorten the sleep latency of insomnia mice (P

Nω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension and liver injury. This study aimed at investigating the changes of liver lipometabonomics and exploring the underlying mechanisms of liver injury in the L-NAME-treated rats. The male Sprague-Dawley (SD) rats were treated with L-NAME (40 mg/kg, p.o.) for 8 weeks. After that, the liver, aorta, fecal, and serum were collected for analysis. The results showed that L-NAME induced hypertension and disordered the endothelial nitric oxide synthase (eNOS)-NO pathway in the treated rats. L-NAME could also increase the levels of serum total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), and aspartate transaminase (AST). The multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) analysis showed that L-NAME could induce significant changes of the total hepatic lipids and most hepatic triglycerides, as well as fatty acid (FA). A positive correlation was found between the blood pressure and TAG. Immunofluorescence and Western-Blot experiments indicated that the L-NAME treatment significantly influenced some FA β-oxidation, desaturation, and synthesis-related proteins. The increase of intestinal inflammation, decrease of microcirculation and tight junction proteins, as well as alterations of microbial communities were observed in the L-NAME induced hypertensive rats, as well as alterations of microbial communities were notable correlation to TAG and FA species. This study demonstrated that the L-NAME-induced hypertensive rats exhibiting liver injury were the joint action of hepatic abnormal fatty acid metabolism and microcirculation disorder. Furthermore, the gut microflora, as well as the changes of FA β-oxidation (ACOX, CPT1α), desaturation (SCD-1), and synthesis (FAS) may be the potential mechanisms for abnormal fatty acid metabolism.

Objective: To investigate the effect of Xuduan Zhongzi prescription on the expression of HSP60 and HSP90 in testicular spermatogenic cells and semen quality of oligozoospermia and asthenospermia model rats. Methods: A total of 40 SPF male rats were randomly divided into 10 blank control group and 30 model group. After successful modeling, the model group was divided into model control group, levocarnitine group and Xuduan Zhongzi prescription group with 10 rats in each group. The rats in levocarnitine group and Xuduan Zhongzi prescription group were given corresponding drugs by gavage according to the equivalent measurement of humanbody, the blank control group and model control group were given the same amount of normal saline by gavage, and the rats in each group were killed after 8 weeks of continuous administration. Take the left epididymis of each group for sperm quality detection, take the left testis of each group, observe the histomorphological changes by HE staining, and detect the expression of HSP60 and HSP90 in testicular tissue by immunohistochemistry and Western blot. Results: HE staining showed that compared with the blank control group, the convoluted tubules in the model group were significantly atrophic, degenerated and irregularly arranged, the spermatogenic epithelium showed a large number of vacuoles, Sertoli cell degeneration, obvious inflammatory infiltration in stromal cells, stromal cell proliferation, scattered rows of epithelial cells, a large number of exfoliation and degeneration, and sperm were rare. After the intervention of Xuduan Zhongzi prescription, the above lesions were significantly improved, the structure of seminiferous tubules was relatively regular and orderly, denser than that of the model group, sertoli cells and stromal cells increased significantly, the seminiferous epithelium was thicker than that of the model group, with rich layers, and a large number of sperm could be seen in the lumen. Immunohistochemistry and Western Blot showed that the expression of HSP60 and HSP90 increased significantly after the intervention of Xuduan Zhongzi prescription in model rats (P<0.01). The sperm quality test results showed that compared with the blank control group, the sperm concentration and activity rate in the model group decreased significantly, (P<0.01). After continuous seed cutting, the sperm concentration and activity rate of model rats were significantly increased, (P<0.01). Conclusion: Xuduan Zhongzi prescription may inhibit the apoptosis of testicular spermatogenic cells in oligoasthenospermia model rats by increasing the expression of HSP60 and HSP90, so as to improve sperm quality. [ABSTRACT FROM AUTHOR]

The Arp2/3 complex, which nucleates actin filaments, comprises a stable assembly of seven-protein subunits including two actin-related proteins (Arp2 and Arp3). Previous work showed that Arp2/3 binds to the sides of actin filaments and is concentrated at the leading edges of motile cells. In the present study, we show that the Arp2/3 complex is critical for cytokinesis during early embryonic development in porcine parthenotes. The Arp2/3 complex is concentrated at the cortex of each cell at the 1-, 2-, and 4-cell stages, and at the periphery at the morula stage. The amount of Arp2/3 significantly decreased at the blastocyst stage in parthenogenetically activated porcine embryos. Inhibition of the Arp2/3 complex in the pig embryos by the Arp2/3-specific inhibitor CK666 resulted in abnormal cell division, a decrease in developmental rate and total cell numbers, and an increase in the ratio of trophectoderm cell number to inner cell mass number in blastocyst-stage embryos. In addition, 4-cell stage embryos subjected to CK666 treatment exhibited significantly decreased expression of ZGA genes (Pou5f1, Sox2, and Nanog), suggesting that the Arp2/3 complex plays an important role in early porcine embryo development. Thus, our data demonstrate that the Arp2/3 complex is required for early embryonic development in pigs and appears to regulate the expression of pluripotency genes. [ABSTRACT FROM AUTHOR]

Objectives: to examine the associations of two common CRP gene polymorphisms with CRP levels, frailty and comorbidity in an elderly Chinese population. Design: a population-based cohort study. Setting and participants: we obtained data on 1,723 elderly participants aged 70-84 from the ageing arm of the Rugao Longevity and Ageing study (RuLAS), a population-based observational cohort study conducted in Rugao, Jiangsu province, China. Measurements: the genotyping of two common CRP gene polymorphisms (rs1205 and rs3093059) was performed. Items concerning the frailty index and comorbidity were collected. Results: the mean age of the study population was 75.3 ± 3.9 years, and 53.5% (n = 922) were women. The minor allele frequencies of rs1205 and rs3093059 were 42.4% (C allele) and 16.9% (C allele), respectively. The polymorphisms rs1205 and rs3093059 were significantly associated with CRP levels (β=0.113 and 0.222, all P< 0.001). Non-significant association between rs1205 and rs3093059 and frailty, as well as between rs3093059 and co-morbidity was observed. However, SNP rs1205 CC genotype had an increased odds of co-morbidity compared with the TT genotype (odds ratio (OR):1.53; 95% confidence interval (CI): 1.16--2.02). Each additional copy of the C allele of SNP rs1205 was associated with 1.23 times (95% CI: 1.07--1.41) odds of co-morbidity. The significance remained after controlling for covariates such as education level, etc. Conclusions: among elderly Chinese individuals, two CRP gene polymorphisms were significantly associated with CRP levels. However, none of them was associated with frailty. The preliminary findings warrant further validations. [ABSTRACT FROM AUTHOR]

It was originally thought that no single routine blood test result would be able to indicate whether or not a patient had cancer; however, several novel studies have indicated that the median survival and prognosis of cancer patients were markedly associated with the systemic circulation features of cancer patients. In addition, certain parameters, such as white blood cell (WBC) count, were largely altered in malignant tumors. In the present study, routine blood tests were performed in order to observe the change of blood cells in tumor-bearing mice following the implantation of 4T1 breast cancer cells into the mammary fat pad; in addition, blood flow in breast tumor sites was measured indirectly using laser Doppler perfusion imaging (LDPI), in an attempt to explain the relevance between the blood circulation features and the growth or metastasis of breast cancer in mice model. The LDPI and blood test results indicated that the implantation of 4T1 breast cancer cells into BALB/c mice led to thrombosis as well as high WBC count, high platelet count, high plateletcrit and low blood perfusion. Following implantation of the 4T1 cells for four weeks, the lung metastatic number was determined and the Pearson correlation coefficient revealed that the number of visceral lung metastatic sites had a marked negative association with the ratio of basophils (BASO%; r=-0.512; P<0.01) and the mean corpuscular hemoglobin was significantly correlated with primary tumor weight (r=0.425; P<0.05). In conclusion, the results of the present study demonstrated that tumor growth led to thrombosis and acute anemia in mice; in addition, when blood BASO% was low, an increased number of lung metastases were observed in tumor-bearing mice. [ABSTRACT FROM AUTHOR]

Ataxia-telangiectasia mutated (ATM) is critical for the DNA damage response, cell cycle checkpoints, and apoptosis. Significant effort has focused on elucidating the relationship between ATM and other nuclear signal transducers; however, little is known about the connection between ATM and oocyte meiotic maturation. We investigated the function of ATM in porcine oocytes. ATM was expressed at all stages of oocyte maturation and localized predominantly in the nucleus. Furthermore, the ATM-specific inhibitor KU-55933 blocked porcine oocyte maturation, reducing the percentages of oocytes that underwent germinal vesicle breakdown (GVBD) and first polar body extrusion. KU-55933 also decreased the expression of DNA damage-related genes (breast cancer 1, budding uninhibited by benzimidazoles 1, and P53) and reduced the mRNA and protein levels of AKT and other cell cycle-regulated genes that are predominantly expressed during G2/M phase, including bone morphogenetic protein 15, growth differentiation factor 9, cell division cycle protein 2, cyclinB1, and AKT. KU-55933 treatment decreased the developmental potential of blastocysts following parthenogenetic activation and increased the level of apoptosis. Together, these data suggested that ATM influenced the meiotic and cytoplasmic maturation of porcine oocytes, potentially by decreasing their sensitivity to DNA strand breaks, stimulating the AKT pathway, and/or altering the expression of other maternal genes. [ABSTRACT FROM AUTHOR]

Background: Zinc-alpha2-glycoprotein (AZGP1, ZAG) was recently demonstrated to be an important factor in tumor carcinogenesis. However, AZGP1 expression in hepatocellular carcinoma (HCC) and its significance remain largely unknown. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine mRNA level of AZGP1 in 20 paired fresh HCC tissues. Clinical and pathological data of 246 HCC patients were collected. Tissue-microarray-based immunohistochemistry (IHC) was performed to examine AZGP1 expression in HCC samples. Relationship between AZGP1 expression and clinicopathological features was analyzed by Chi-square test, Kaplan-Meier analysis and Cox proportional hazards regression model. Results: AZGP1 expression was significantly lower in 80.0% (16/20) of tumorous tissues than that in the corresponding adjacent nontumorous liver tissues (P<0.001). Consistently, IHC data revealed that decreased expression of AZGP1 was present in 80.1% (197/246) of HCC patient tissues (P<0.001). Furthermore, AZGP1 expression in HCC significantly associated with several clinicopathological parameters, including serum AFP level (P = 0.013), liver cirrhosis (P = 0.002) and tumor differentiation (P = 0.025). Moreover, HCC patients with high AZGP1 expression survived longer, with better overall survival (P = 0.006) and disease-free survival (P = 0.025). In addition, low AZGP1 expression associated with worse relapse-free survival (P = 0.046) and distant metastatic progression-free survival (P = 0.036). Conclusion: AZGP1 was downregulated in HCC and could be served as a promising prognostic marker for HCC patients. [ABSTRACT FROM AUTHOR]

Aim: Diabetes osteoporosis (DOP) is a chronic bone metabolic disease induced by diabetes, whose morbidity continues to increase. Epimedium brevicornum Maxim (EB), a popular Chinese traditional medicine, has been used to treat bone diseases in China for thousands of years. But its material basis and specific mechanism of action are not clear. Methods: Epimedium brevicornum crude polysaccharide (EPE) is the main component, in this research the characterized the structure of EBPC1 purified from EPE was detected and its effects on cell proliferation, differentiation, and cytoskeletal in osteoblasts induced by high glucose. Results: The molecular weight of EBPC1 was 10.5 kDa. It was mainly comprised of glucose and galactose, and the backbone of EBPC1 was→4)-α-D-Galp-(1→4)-α-D-Galp-(1→6)-β-D-Galp-(1→6)-β-D-Galp-(1→4)-α-D-Glcp-(1→4)-α-D-Glcp-(1→. The results from in vitro experiments revealed that EBPC1 significantly increased alkaline phosphatase (ALP) activity and mineralized nodule formation in primary osteoblasts, also significantly up-regulated expression of Alp mRNA and Runx2 mRNA in the presence of EBPC1 pretreatment. Moreover, EBPC1 modulated apoptosis via the regulation of Bax/Bcl2. Conclusion: These results indicate that EBPC1 treatment can promote osteogenesis during DOP, which can ameliorate apoptosis by regulating Bax/Bcl2 and accelerating osteogenesis in osteoblasts.