Beneficial effects of Dendrobium officinale National Herbal Drink on metabolic immune crosstalk via regulate SCFAs-Th17/Treg.

BACKGROUND: The development of gut-liver axis metabolic immune crosstalk is intimately associated with intestinal barrier disorder, intestinal SCFAs-Th17/Treg immunological imbalance, and disorders of the gut microbiota. Prior research has discovered that Dendrobium officinale National Herbal Drink (NHD), a traditional Chinese medicine drink with enhanced immunity, may enhance the immunological response in animals with impaired immune systems brought on by cyclophosphamide by repairing intestinal barrier function and controlling turbulence in the gut microbiota. However, whether NHD can further improve the gut-liver axis metabolic immune crosstalk and its related mechanisms need to be systematically studied. OBJECTIVES: The purpose of this study is to clarify the function and mechanism of NHD in enhancing the gut-liver axis metabolic immunological crosstalk brought on by excessive alcohol intake. METHODS: In this work, we set up a mouse model to analyze the metabolic and immunological crosstalk involving the gut-liver axis across 7 weeks of continuous, excessive drinking. At the same time, high and low doses (20,10 ml/kg) of NHD were given by gavage. The effect of NHD on improving the metabolism of gut-liver axis was evaluated by blood lipid, liver lipid deposition, liver function and intestinal pathophysiology. By measuring serum immunological indices, intestinal barrier, and intestinal immune barrier, the impact of NHD on enhancing immune and intestinal barrier function was assessed. Furthermore, immunohistochemistry, immunofluorescence, 16S rRNA, Western blot, q-PCR and other methods were used to detect gut microbiota, SCFAs-GPR41/43 pathway, intestinal Th17/Treg immune cells and PPAR-α-NPC1L1/SREBP1 pathway to elucidate the mechanism by which NHD enhances the gut-liver axis' metabolic immune crosstalk. RESULTS: Our study demonstrated that NHD has the potential to improve the pathophysiological damage caused by gut-liver axis in model mice. NHD also ameliorated the disorder of lipid metabolism. In addition, it regulated the levels of peripheral blood T cell immunity and serum immune factors. And NHD can restore intestinal mechanical and immune barrier damage. NHD has a favorable impact on the quantity of beneficial bacteria, including uncultured_bacterium_g__norank_f__muribaculacea and uncultured_bacterium_g__Turicibacter. Additionally, it raised the model mice's levels of SCFAs (n-butyric acid, isovaleric acid, etc.). This resulted in the promotion of intestinal GPR41/43-ERK1/2 expression and the reshaping of intestinal CD4+T cell Th17/Treg homeostasis. As a consequence, colon IL-22 and IL-10 levels increased, while colon IL-17A levels decreased. Lastly, NHD raised the amount of intestinal IAP/LPS, regulated the development of PPAR-α-NPC1L1/SREBP1 pathway in gut-liver axis, and improve lipid metabolism disorder. CONCLUSIONS: Our study found that NHD can improve the gut-liver axis metabolic immune crosstalk in model mice caused by excessive drinking. The mechanism might be connected to how NHD controls gut microbiota disorders in model mice, the activation of intestinal SCFAs-GPR41/43 pathway, the remodeling of Th17/Treg immune homeostasis of intestinal CD4+T cells, the improvement of IAP/LPS abnormality, and further mediating the PPAR-α-NPC1L1/SREBP1 pathway of lipid metabolism in gut-liver axis.

The effect of modified Qiyuan paste on mice with low immunity and sleep deprivation by regulating GABA nerve and immune system.

BACKGROUND: Low immunity and sleep disorders are prevalent suboptimal health conditions in contemporary populations, which render them susceptible to the infiltration of pathogenic factors. LJC, which has a long history in traditional Chinese medicine for nourishing the Yin and blood and calming the mind, is obtained by modifying Qiyuan paste. Dendrobium officinale Kimura et Migo has been shown to improve the immune function in sleep-deprived mice. In this study, based on the traditional Chinese medicine theory, LJC was prepared by adding D. officinale Kimura et Migo to Qiyuan paste decoction. METHODS: Indicators of Yin deficiency syndrome, such as back temperature and grip strength, were measured in each group of mice; furthermore, behavioral tests and pentobarbital sodium-induced sleep tests were performed. An automatic biochemical analyzer, enzyme-linked immunosorbent assay kit, and other methods were used to determine routine blood parameters, serum immunoglobulin (IgG, IgA, and IgM), cont (C3, C4), acid phosphatase (ACP) and lactate dehydrogenase (LDH) levels in the spleen, serum hemolysin, and delayed-type hypersensitivity (DTH) levels. In addition, serum levels of γ-aminobutyric acid (GABA) and glutamate (Glu) were detected using high-performance liquid chromatography (HPLC). Hematoxylin-eosin staining and Nissl staining were used to assess the histological alterations in the hypothalamus tissue. Western blot and immunohistochemistry were used to detect the expressions of the GABA pathway proteins GABRA1, GAD, GAT1, and GABAT1 and those of CD4+ and CD8+ proteins in the thymus and spleen tissues. RESULTS: The findings indicated that LJC prolonged the sleep duration, improved the pathological changes in the hippocampus, effectively upregulated the GABA content in the serum of mice, downregulated the Glu content and Glu/GABA ratio, enhanced the expressions of GABRA1, GAT1, and GAD, and decreased the expression of GABAT1 to assuage sleep disorders. Importantly, LJC alleviated the damage to the thymus and spleen tissues in the model mice and enhanced the activities of ACP and LDH in the spleen of the immunocompromised mice. Moreover, serum hemolysin levels and serum IgG, IgA, and IgM levels increased after LJC administration, which manifested as increased CD4+ content, decreased CD8+ content, and enhanced DTH response. In addition, LJC significantly increased the levels of complement C3 and C4, increased the number of white blood cells and lymphocytes, and decreased the percentage of neutrophils in the blood. CONCLUSIONS: LJC can lead to improvements in immunocompromised mice models with insufficient sleep. The underlying mechanism may involve regulation of the GABA/Glu content and the expression levels of GABA metabolism pathway-related proteins in the brain of mice, enhancing their specific and nonspecific immune functions.

Dendrobium officinale flowers' topical extracts improve skin oxidative stress and aging.

BACKGROUND: Dendrobium officinale flowers (DOF) have the effects of antiaging and nourishing yin, but it lacks pharmacological research on skin aging. OBJECTIVE: Confirming the role of DOF in delaying skin aging based on the "in vitro animal-human" model. METHODS: In this experiment, three kinds of free radical scavenging experiments in vitro, D-galactose-induced aging mouse model, and human antiaging efficacy test were used to test whether DOF can improve skin aging through anti-oxidation. RESULTS: In vitro experiment shows that DOF has certain scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical, hydroxyl free radical, and superoxide free radical, and its IC50 is 0.2090 µg/mL, 15.020, and 1.217 mg/mL respectively. DOF can enhance the activities of T-AOC, SOD, CAT, and GSH Px in the serum of aging mice, increase the content of GSH, and reduce the content of MDA when administered with DOF of 1.0, 2.0, and 4.0 g/kg for 6 weeks. In addition, it can enhance the activity of SOD in the skin of aging mice, increase the content of Hyp, and decrease the content of MDA, activated Keap1/Nrf2 pathway in the skin of aging mice. Applying DOF with a concentration of 0.2 g/mL on the face for 8 weeks can significantly improve the skin water score and elasticity value, reduce facial wrinkles, pores, acne, and UV spots, and improve the facial brown spots and roughness. CONCLUSION: DOF can significantly improve skin aging caused by oxidative stress, and its mechanism may be related to scavenging free radicals in the body and improving skin quality.

Soporific effect of modified Suanzaoren Decoction on mice models of insomnia by regulating Orexin-A and HPA axis homeostasis.

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 < 0.05, 0.01), prolonged the sleep duration of mice (P < 0.05, 0.01), and improve the circadian rhythm disorder relative to placebo-treated animals. Furthermore, MSZRD effectively increased the content of 5-HT and 5-HTR1A protein in the hypothalamus of insomnia mice (P < 0.05, 0.01), while downregulated the content of DA and NE (P < 0.05, 0.01). Importantly, serum GABA concentration was increased by treatment with MSZRD (P < 0.05), as reflected by a decreased Glu/GABA ratio (P < 0.05). Moreover, MSZRD decreased the levels of CORT, ACTH, and CRH related hormones in HPA axis (P < 0.05, 0.01). At the same time, MSZRD significantly downregulated the serum Orexin-A content in insomnia mice (P < 0.05), as well as hypothalamic OX2R expression (P < 0.05). In addition, MSZRD also improved the histopathological changes in hypothalamus in insomnia mice. CONCLUSION: MSZRD has sleep-improvement effect in mice model of insomnia. The mechanism may be that regulating the expression of Orexin-A affects the homeostasis of HPA axis and the release of related neurotransmitters in mice with insomnia.

Flexible endoscope visualization to assist in the removal of a string of 10 schwannomas at the cauda equina: technical case report.

Bead-like schwannomas at the cauda equina are rare but benign intraspinal tumors. They can involve multiple nerve roots and spread within the spinal canal, and open resection would cause significant trauma. The authors have successfully applied a novel minimally invasive technique for the total removal of such schwannomas. A 68-year-old woman presented with a 1-month history of left waist and leg pain. MRI demonstrated multiple intraspinal lesions located from L1 to S1. The diagnosis was bead-like schwannomas at the cauda equina. Two incisions were made at the T12 and L5 levels. A flexible endoscope was introduced into the spinal canal following hemisemilaminectomy under a microscope to identify the relationship between the tumors and the carrying nerves. After dissecting both cranial and caudal ends of the carrying nerve, the string of bead-like tumors was gently pulled out from the caudal end as a whole. The endoscope was reintroduced into the spinal canal to ensure complete tumor removal. The patient recovered quickly, and no tumor residual was found at postoperative MRI. Flexible endoscope-assisted visualization plus microscopic hemisemilaminectomy via 2 incisions is a feasible minimally invasive approach for selected patients with bead-like schwannomas at the cauda equina.

Recombinant OX40 attenuates neuronal apoptosis through OX40-OX40L/PI3K/AKT signaling pathway following subarachnoid hemorrhage in rats.

Subarachnoid hemorrhage (SAH) is the most devastating form of stroke. Reducing neuronal apoptosis is an important countermeasure against early brain injury (EBI) after SAH. Recent evidence indicates that OX40-OX40L coupling is critical for cell survival and proliferation. Current study was performed to detect the role of recombinant OX40 (ReOX40) against neuronal apoptosis after SAH. The endovascular perforation model of SAH was performed on Sprague-Dawley (SD) rats. ReOX40 was injected intracerebroventricularly (i.c.v) 1 h after SAH induction and the following methods were employed: neurological function evaluation, immunofluorescence staining, fluoro-Jade C staining, and western blot. To study the underlying precise molecular mechanism, small interfering ribonucleic acid (siRNA) for OX40L and a specific inhibitor of PI3K, LY294002, were injected i.c.v. into SAH + ReOX40 rats before induction of SAH. When compared with sham rats, the expression of OX40 and OX40L was seen to decrease in the brain at 24 h after SAH induction. Administration of ReOX40 (5 µg/kg) increased expression of the OX40L, reduced the neuronal apoptosis, and improved short and long-term neurological function deficits. Furthermore, ReOx40 heightened activation of OX40L/PI3K/AKT axis, increased the downstream anti-apoptotic protein (Bcl2, Bcl-XL), and depressed the apoptotic protein (cleaved caspase 3, Bax). However, the protective effects of ReOX40 were abolished by the administration of OX40L siRNA and LY294002, respectively. These results demonstrate that ReOX40 attenuates neuronal apoptosis through OX40-OX40L/PI3K/AKT pathway in EBI after SAH.

Osteopontin attenuates early brain injury through regulating autophagy-apoptosis interaction after subarachnoid hemorrhage in rats.

AIM: To determine the effect of osteopontin (OPN) on autophagy and autophagy-apoptosis interactions after SAH. METHODS: The endovascular perforation model of SAH or sham surgery was performed in a total of 86 Sprague-Dawley male rats. The temporal expressions of endogenous OPN and autophagy-related proteins (Beclin 1, ATG5, LC3 II to I ratio) were measured in sham and SAH rats at different time points (3, 6, 12, 24, and 72 hours). Rats were randomly divided into three groups: Sham, SAH + Vehicle (PBS, phosphate-buffered saline), and SAH + rOPN (5 µg/rat recombinant OPN). Neurobehavioral tests were performed 24 hours after SAH, followed by the collection of brain samples for assessment of autophagy and apoptosis proteins. These tests assessed whether an autophagy-apoptosis relationship existed on the histological level in the brain. RESULTS: Endogenous OPN and autophagy-related proteins all increased after SAH. rOPN administration improved neurological dysfunction, increased the expression of autophagy-related proteins (Beclin 1, ATG5, LC3 II to I ratio) and antiapoptotic protein Bcl-2, while decreasing the expression of proapoptotic proteins (cleaved Caspase-3 and Bax). rOPN also regulated autophagy-apoptosis interactions 24 hours after SAH. CONCLUSION: rOPN attenuates early brain injury and inhibits neuronal apoptosis by activating autophagy and regulating autophagy-apoptosis interactions.

Pyruvate oral rehydration solution improved visceral function and survival in shock rats.

BACKGROUND: Recent findings showed advantages of a novel pyruvate-enriched oral rehydration solution (Pyr-ORS) in resuscitation of burns. This study focused on effects of Pyr-ORS on the visceral blood perfusion (VBP), gastrointestinal function, and survival rate, compared with the bicarbonate-based World Health Organization-guided oral rehydration solution (WHO-ORS), during intragastric rehydration of lethal hemorrhagic shock in rats. METHODS: Sixty adult rats were subjected to 45% total blood volume loss and were randomly allocated to the following three groups (n = 20): group NR (no fluid resuscitation), group PORS (oral Pyr-ORS rehydration), and group BORS (oral WHO-ORS rehydration), respectively. Other 10 rats were served as group NH (the sham group). Enteral rehydration lasted for 4 h after hemorrhage. The mean arterial pressure (MAP), VBP, and plasma enzymes activities of heart, liver, and kidney, and intestinal fatty acid binding protein were measured. Liver, kidney, and ileum were harvested for the evaluation of activities of oxidative enzymes and intestinal barrier protein (ZO-1). Other 84 rats with identical procedures without sampling were observed for their 24-h survival rates. RESULTS: Pyr-ORS was more effective in enhancing the MAP and VBP, inhibiting tissue oxidative damage, and improving organ function, compared with WHO-ORS. Hypoxic lactic acidosis was fully corrected in group PORS in 4 h, whereas it worsened in group BORS, and the 24-h survival rate was twice higher in group PORS than in group BORS (45.8 versus 20.8%, P < 0.05). CONCLUSIONS: A small amount of pyruvate in Pyr-ORS was more therapeutically beneficial than equivalent bicarbonate in WHO-ORS and greatly raised survival in enteral rehydration of lethal hemorrhagic shock. The Pyr-ORS may be an ideal oral fluid in resuscitation of hypovolemic shock, especially in prehospital and resource-poor settings.

[Titrating positive end-expiratory pressure after recruitment maneuver according to end-tidal carbon dioxide and its related indicators in acute respiratory distress syndrome dog model].

OBJECTIVE: To investigate the relationship between end-tidal carbon dioxide with its related indicators and ventilation/perfusion of the acute respiratory distress syndrome (ARDS) lung, and to explore a feasible way to titrate positive end-expiratory pressure (PEEP) in clinical practice. METHODS: Five mixed-breed dogs with oleic acid lung injury model were mechanically ventilated at a serial PEEP trial including a recruitment maneuver (RM) before each PEEP level changed. The value of blood dynamics, end-tidal carbon dioxide partial pressure (PetCO2) and arterial carbon dioxide pressure under different PEEP levels were recorded. Arterial end-tidal carbon dioxide gradient (Pa-etCO2) and dead space fraction (Vd/Vt%) were calculated. All dogs received CT scan. Lung volume under different pressure levels, and ratio and volume of alveolar closing pressure, collapsed alveoli, sufficiently and insufficiently ventilated alveoli were obtained. Alveolar opening and closing analysis were performed by non-liner regression equation. RESULTS: The mean pressure when Vd/Vt% obtained lowest level were (11.2 ± 4.4) cm H2O (1 cm H2O = 0.098 kPa), which had no significant difference when compared to alveolar closing pressure [(11.5 ± 3.2) cm H2O](P > 0.05). The fraction of insufficiently ventilated and collapsed alveoli showed a significant linear correlation with the Vd/Vt% when PEEP was lower than P(min) (r = 0.632, P = 0.004). There was a linear correlation between the Vd/Vt% and the fraction of over-distended alveoli when PEEP was higher than P(min) (r = 0.770, P = 0.001). CONCLUSIONS: Closing pressure is in accordance with PEEP level after RM having reached the best ventilation/circulation ratio. The characteristics of lung collapse can be revealed by Vd/Vt% changes after RM. To titrate PEEP for the lowest Vd/Vt% after RM may be a feasible way to match the best ventilation and circulation effects of PEEP.

[Effect of endothelial nitric oxide synthase gene polymorphisms upon disease severity and outcome in septic patients].

OBJECTIVE: To investigate the association of eNOS 894G-->T, -786T-->C gene polymorphisms with disease severity and outcome in septic patients. METHODS: A total of 117 patients with severe sepsis were randomly selected from ICUs at 9 academic hospitals in Beijing during April 2007 to May 2009. PCR-RFLP and PCR-SSCP were used to analyze the alleles and genotypes in eNOS 894G-->T and -786T--> C gene polymorphisms. Recorded clinical data included demographics, pathogens, APACHE II score within 24 hours and SOFA score within 7 days after ICU admission, percentage of shock patients, days to shock onset (from infection to shock onset), duration of shock and the mortality at Days 7 and 28. RESULTS: In comparison with genotype GT carriers, the patients with genotype GT in eNOS 894G-->T polymorphism had a incremental trend in frequency of shock (87% vs 68.1%, P = 0.071) and a significantly shortened days to shock onset [1.0 (0.1 - 6.5) vs 2.0 (0.10 - 27.0) days, median (range), P < 0.05]. Those patients had been shown to have a significantly high APACHE II score (23.61 +/- 7.00 vs 19.50 +/- 6.99, P < 0.05), SOFA score (9.43 +/- 3.42 vs 5.26 +/- 2.94, P < 0.001) and mortality at Day 7 (34.8% vs 0%, P < 0.001) and Day 28 (78.3% vs 23.4%, P < 0.001). Multivariate analyses revealed that age in years, SOFA score and genotype GT in eNOS 894G-->T polymorphism were independent high-risk factors for the outcome in septic patients. However, eNOS -786T-->C gene polymorphism was not associated with disease severity and outcome in septic patients. CONCLUSION: Carriage of genotype GT in eNOS 894G-->T polymorphism is associated with the occurrence of shock and impaired organ function.

[The application of pulmonary artery catheterization in treatment of septic shock patients].

OBJECTIVE: To compare the differences of hemodynamic pattern and metabolic alteration between the survivors and nonsurvivors of septic shock so as to explore the value of pulmonary artery catheterization (PAC). METHODS: A total of 70 patients with septic shock in whom PAC was carried out after initial resuscitation were retrospectively studied during a 5-year sequential period from 2001 to 2006 in a 15-bed general intensive care unit of a teaching hospital in Beijing, China. Hemodynamic data, lactate concentration and APACHEII score were obtained at the beginning and 24 hours later of PAC after the initial resuscitation period. The patients' outcome were recorded at the 28th day of hospitalization after diagnosis. RESULTS: The overall mortality rate was 60%. There were no age and sex differences between the survivors and nonsurvivors. The nonsurvivor group had higher initial heart rate, APACHEII score and lactate concentration than the survivor group. After 24 hours, mean arterial pressure (MAP) was significantly lower, but central venous pressure (CVP), pulmonary arterial wedge pressure (PAWP), lactate concentration and APACHEII score of were significantly higher in the nonsurvivor group than those in the survivor group. There were no differences of the other hemodynamic date between the two groups in the beginning and 24 hours later. More patients received superhigh dosage of norepinephrine or dopamine in the nonsurvivor group. Achievement of superhigh concentration of oxygen delivery or early-goal directed therapy (EGDT) indices had no beneficial effect on survival. Multiple stepwise linear regression analysis showed 24-hour MAP, PAWP and initial heart rate were independent predictors of the outcome. CONCLUSION: PAC can not display the differences of hemodynamic patterns between the survivors and nonsurvivors of septic shock after initial resuscitation, but 24 hours later nonsurvivors had higher PAWP significantly. Whether there are differences of hemodynamic pattern between the survivors and nonsurvivors was not the basis of PAC. The value of PAC monitoring is to balance the relationship between the requirement of hyperdynamic circulation and cardiac suppression state.

[Enhanced phytoextraction of heavy metal contaminated soil by chelating agents and auxin indole-3-acetic acid].

The environmental risk of chelating agents such as EDTA application to the heavy metals polluted soils and the stress on plant roots due to the abrupt increase metals concentration limit the wide commercial use of chelate-induced phytoextraction. Chelating agent ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid (NTA) and auxin indole-3-acetic acid (IAA) were used for enhancing heavy metals uptake from soils by Zea mays L. (corn) in pot experiments. The metals content in plant tissues was quantified using an inductively coupled plasma mass spectrometer (ICP-MS). The results showed that the combination of IAA and EDTA increased the biomass by about 40.0% and the contents of Cu, Zn, Cd and Pb in corn shoots by 27.0%, 26.8%, 27.5% and 32.8% respectively, as compared to those in EDTA treatment. While NTA&IAA treatment increased the biomass by about 29.9% and the contents of Cu, Zn, Cd and Pb in corn shoots by 31.8%, 27.6%, 17.0% and 26.9% respectively, as compared to those in NTA treatment. These results indicated that corn growth was promoted, and the biomass and the accumulation of heavy metals in plant shoots were increased significantly with the addition of IAA, which probably helps to change the cell membrane properties and the biomass distribution, resulting in the alleviation of the phytotoxicity of metals and the chelating agents.