[The role of Keap1/Nrf2/HO-1 signal pathway in liver injury induced by rare earth neodymium oxide in mice].

Objective: To investigate the role of Keap1/Nrf2/HO-1 signaling pathway in liver injury induced by neodymium oxide (Nd(2)O(3)) in mice. Methods: In March 2021, forty-eight SPF grade healthy male C57BL/6J mice were randomly divided into control group (0.9% NaCl), low dose group (62.5 mg/ml Nd(2)O(3)), medium dose group (125.0 mg/ml Nd(2)O(3)), and high dose group (250.0 mg/ml Nd(2)O(3)), each group consisted of 12 animals. The infected groups were treated with Nd(2)O(3) suspension by non-exposed tracheal drip and were killed 35 days after dust exposure. The liver weight of each group was weighed and the organ coefficient was calculated. The content of Nd(3+) in liver tissue was detected by inductively coupled plasma mass spectrometry (ICP-MS). HE staining and immunofluorescence was used to observe the changes of inflammation and nuclear entry. The mRNA expression levels of Keap1, Nrf2 and HO-1 in mice liver tissue were detected by qRT-PCR. Western blotting was used to detect the protein expression levels of Keap1 and HO-1. The contents of catalase (CAT), glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) were detected by colorimetric method. The contents of interleukin 1ß (IL-1ß), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were determined by ELISA. The data was expressed in Mean±SD. Two-independent sample t-test was used for inter-group comparison, and one-way analysis of variance was used for multi-group comparison. Results: Compared with the control group, the liver organ coefficient of mice in medium and high dose groups were increased, and the Nd(3+) accumulation in liver of mice in all dose groups were significantly increased (P<0.05). Pathology showed that the structure of liver lobules in the high dose group was slightly disordered, the liver cells showed balloon-like lesions, the arrangement of liver cell cords was disordered, and the inflammatory exudation was obvious. Compared with the control group, the levels of IL-1ß and IL-6 in liver tissue of mice in all dose groups were increased, and the levels of TNF-α in liver tissue of mice in high dose group were increased (P<0.05). Compared with the control group, the mRNA and protein expression levels of Keap1 in high dose group were significantly decreased, while the mRNA expression level of Nrf2, the mRNA and protein expression levels of HO-1 were significantly increased (P<0.05), and Nrf2 was successfully activated into the nucleus. Compared with the control group, the activities of CAT, GSH-Px and T-SOD in high dose group were significantly decreased (P<0.05) . Conclusion: A large amount of Nd(2)O(3) accumulates in the liver of male mice, which may lead to oxidative stress and inflammatory response through activation of Keap1/Nrf2/HO-1 signal pathway. It is suggested that Keap1/Nrf2/HO-1 signal pathway may be one of the mechanisms of Nd(2)O(3) expose-induced liver injury in mice.

Dunye Guanxinning Improves Acute Myocardial Ischemia-Reperfusion Injury by Inhibiting Neutrophil Infiltration and Caspase-1 Activity.

Acute myocardial infarction is the most serious manifestation of cardiovascular disease, and it is a life-threatening condition. Dunye Guanxinning (DG) is a protective traditional Chinese patent herbal medicine with high clinical efficacy and suitable for the treatment of myocardial infarction. However, the mechanism through which it is beneficial is unclear. In this study, we hypothesized that DG improves acute myocardial ischemia-reperfusion injury by inhibiting neutrophil infiltration and caspase-1 activity. We found that DG administration decreased infarct size and cardiomyocyte apoptosis and improved left ventricular ejection fraction, fractional shortening, end-systolic volume index, end-systolic diameter, and carotid arterial blood flow output in rats. DG administration also improved hemorheological parameters, myocardial damage biomarkers, and oxidative stress indexes. The findings showed that DG administration inhibited neutrophil infiltration and reduced the serum interleukin-1 beta (IL-1ß) level and myocardial IL-1ß maturation. Moreover, DG administration inhibited caspase-1 activity and activated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in rat hearts. These results suggested that DG administration inhibits inflammasome activity and IL-1ß release through the AMPK pathway. Our findings support the clinical efficacy of DG and partially reveal its mechanism, which is beneficial for understanding the therapeutic effects of this protective traditional Chinese patent drug.

Electrophysiological and anatomical evidence for a direct projection from the nucleus of the basal optic root to the nucleus rotundus in pigeons.

A direct projection of the nucleus of the basal optic root (nBOR) onto the nucleus rotundus (Rt) in the pigeon would link the accessory optic system to the ascending tectofugal pathway and could thus combine self- and object-motion processes. In this study, injections of retrograde tracers into the Rt revealed some cells in central nBOR to project onto the ipsilateral Rt. Contrary, injections into the diencephalic component of the ascending thalamofugal pathway resulted in massive labeling of neurons in dorsal nBOR. Single unit recordings showed that visual nBOR units could be activated by antidromic stimulation through the Rt. Successful collision tests applied to nBOR cells revealed that the connection between nBOR and Rt is direct. These data provide strong evidence for a direct and differential projection of nBOR subcomponents onto the thalamic relays of the two ascending visual pathways.

[Action of fengsuidan granules on experimental anti-oral ulcer].

OBJECTIVE: To explore the anti-oral ulcer action, anti-inflammatory and analgesic effect of Fengsuidan Granules(FSDG). METHODS: FSDG(0.5, 5.0, 10.0 g.kg-1) were administered to experimental animals. The oral ulcer in experimental animals was effected by means of white staphylococcus (sc) and carbolic acid (buming). RESULTS: Such as acetic acid body turning, hot-plate, auricle inflammation by dimethylbenzene and foot swelling by egg white were used. CONCLUSION: Following certain regularities of dose-effect relationship, FSDG has anti-oral ulcer effect, helps reduce and heal the ulcer and works efficaciously in analgesic and anti-inflammatory cases.

[Clinical and experimental study on codonopsis pilosula oral liquor in treating coronary heart disease with blood stasis].

The effects of Codonopsis pilosula oral liquor (CPOL) on tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in the plasma of 25 patients of coronary heart disease with blood stasis were studied. It has been shown that those patients had a significant decrease in t-PA activity (P < 0.01) compared to healthy subjects. After 4 weeks of CPOL therapy, platelet aggregation significantly decreased (P < 0.05), there was no significant difference in t-PA and PAI. From the results shown above, it suggested that one of the effects of CPOL in influencing blood coagulation was its inhibition on platelet aggregation, but not through the elevating of fibrinolytic activity.

Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. Modification of Diet in Renal Disease Study Group.

In the Modification of Diet in Renal Disease Study, a follow-up (mean, 2.2 yr) of 200 study participants with autosomal dominant polycystic kidney disease (ADPKD) was conducted to determine the effect of lowering protein intake and blood pressure on the rate of decline in GFR. The rate of decline was faster in participants with ADPKD than in persons with other diagnoses, reflecting, in part, faster disease progression in the ADPKD group. Baseline characteristics that predicted a faster rate of decline in GFR in persons with ADPKD were greater serum creatinine (independent of GFR), greater urinary protein excretion, higher mean arterial pressure (MAP), and younger age. In patients with initial GFR values between 25 and 55 mL/min per 1.73 m2, neither assignment to a low-protein diet group nor assignment to a low blood pressure group significantly reduced the rate of decline of GFR in ADPKD participants. Similarly, the decline in GFR was not related to achieved protein intake or MAP. In participants with GFR values between 13 and 24 mL/min per 1.73 m2, assignment to the low MAP group led to a somewhat more rapid decline in GFR. However, the more rapid decline in GFR did not appear to be due to a detrimental effect of low blood pressure or the antihypertensive agents used to reach the low blood pressure goal. Lower protein intake, but not prescription of the keto acid-amino acid supplement, was marginally associated with a slower progression of renal disease.

[Animal experiments on meridian-reaching actions of traditional Chinese medicinal herbs].

With the level variations of cAMP and cGMP in cat tissues as the criteria, the meridian actions reaching of Fructus Schisandrae, Radix Stephaniae Tetrandrae and Herba Houttuyniae were studied tentatively in animal experiments. The result obtained in this way approximates to the understanding of the meridian reaching actions of Chinese medicinal herbs as approved by traditional Chinese medicine.

[Relation between traditional Chinese medicinal syndrome differentiation and blood platelet function in 310 cases of blood stasis].

310 patients (153 male, 157 female) of Blood Stasis were divided into various groups by Syndrome Differentiation of TCM and 35 healthy subjects were taken as control. The relationship of TCM Syndrome and function of blood platelet were studied with blood platelet counting, its volume, adherence and aggregation, plasma thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha(6k-PGF1 alpha) as indices of observation. The results were: (1) Blood platelet aggregation of Blood Stasis patients was higher than that in control (P > 0.001). (2) There were some differences of platelet aggregation among different TCM Syndromes. Platelet aggregation of Blood Stasis patients with Qi Deficiency was higher than that with other Syndromes significantly, and the aggregating rate in those patients was higher than that in control (P < 0.05). (3) The platelet aggregation and TXB2 of patient with Heart Qi Deficiency were significantly higher than those of the control (P < 0.05, P < 0.001), and they were also higher than of other groups of blood stasis patient with Spleen, Lung or Kidney Qi Deficiency.

Isolation and characterization of porcine milk lactoferrin.

We purified porcine whey lactoferrin by affinity chromatography on a heparin-Sepharose column, followed by high-performance liquid chromatography. Molecular mass of purified lactoferrin (PLF) is 78,000 daltons. The iron-binding activity of PLF had a UV/visible-light absorption spectrum indistinguishable from that of human and bovine lactoferrins (absorbance ratio [465 nm/280 nm] approx 0.046). The growth ratio of WIL-2 cells in PLF-supplemented medium is 70% of that in serum-containing medium. The aforementioned characteristics are similar to those of human and bovine lactoferrins. Immunoblot analysis, using polyclonal antibody raised in rabbits against porcine whey lactoferrin, revealed high specificity for PLF, and low cross-reactivity with commercial human and bovine lactoferrins.

[Experimental study on effects of 18 kinds of Chinese herbal medicine for synthesis of thromboxane A2 and PGI2].

The effect of 18 kinds of Chinese herbal medicine for the synthesis of TXA2 and PGI2 was studied. The porcine lung microsoma was used as donor of enzymes such as cyclo-oxygenase, thromboxane A2 synthetase and prostacyclin synthetase, etc. It was found that Glehnia littoralis could inhibit the synthesis of TXA2 and increase the formation of PGI2. Rheum palmatum (300 mg group) and Erigeron breviscapus significantly inhibited the synthesis of TXA2, but no apparent effection on the synthesis of PGI2. When Codonopsis pilosulae, Astragalus membracaceus, Angelica sinensis, Ginsenosides and Baicalin, etc. markedly inhibited the formation of TXA2 and mildly affected the formation of PGI2. Some Chinese herbs for promoting blood circulation play an important role on the inhibition of TXA2 synthesis. Some tonic herbs could either inhibit the synthesis of TXA2 and increase the synthesis of PGI2 or inhibit the formation of PGI2. Therefore these tonic herbs had the characteristics of both strengthening the body resistance and eliminating pathogenic factors. In this aspect they are better than the control drug (Aspirin) and other herbs of promoting blood circulation.

Can daily dietary arginine supplement affect the function and subpopulation of lymphocytes in patients with advanced gastric cancer?

Since arginine can stimulate lymphocyte proliferation in the healthy human, its effect on lymphocyte proliferation in vitro was studied in 7 patients with far advanced gastric cancer. These patients with normal nourishment were ambulatory and could consume a regular diet. A daily dietary supplement of 30 g arginine for 7 days did not alter the total lymphocyte counts or the T/B cell ratio in the peripheral blood. Enhancement of lymphocyte proliferation in response to mitogen stimulation was not observed. Furthermore, an in vitro study on the effect of arginine on phytohemagglutinin-stimulated lymphocyte proliferation showed that lymphocytes from gastric cancer patients had poorer responses than those obtained from normal subjects, despite the supplement in the culture medium with normal serum, patient serum, or fetal bovine serum. Arginine ingestion did not impair liver function and had no detectable side effects except transient nausea in 1 patient. These results indicate that dietary arginine supplement appears safe but does not stimulate lymphocyte function in far advanced gastric cancer patients. The suppressed immune function in gastric cancer patients may be the result of their intrinsic lymphocyte defect.

The identification of PAF-release-enhancing activity in culture supernatant of mononuclear cells from asthmatics. Correlation between lymphocyte responses and immediate type hypersensitivity.

Cytokines from asthmatic mononuclear cells (MNC) cultured with Bermuda Grass pollen extract (BG), were tested for their effect on leukotriene B4 (LTB4) and platelet-activating factor (PAF) generation by neutrophil under calcium ionophore stimulation. Three groups were enrolled in this study: 9 allergic asthmatics showing skin intradermal test positive to BG, 12 non-allergic asthmatics and 5 normal individuals. Results showed that the stimulation index of BG on MNC and the mediator-release enhancing activity from both allergic and non-allergic asthmatics were similar; neither showed significant increase when compared to that of normal individuals. However, there was a significant increase in PAF-release-enhancing activity in unstimulated MNC supernatant from both allergic and non-allergic asthmatics (618 +/- 75 pg/10(6) neutrophils and 569 +/- 60 pg/10(6) neutrophils) when compared to that of normal individuals (460 +/- 40 pg/10(6) neutrophils). This PAF-release-enhancing activity did not correlate with either skin test reactivity or the amount of BG specific IgE antibodies. The PAF-release-enhancing activity in unstimulated MNC supernatants from asthmatics suggesting that there is a pre-activation of MNC which might contribute to the asthmatic reaction through generation of PAF by neutrophils.

90-Day toxicity study of dichloroacetate in dogs.

Male and female juvenile beagle dogs were dosed daily for 90 days with dichloroacetate (DCA). The compound was administered orally via gelatin capsules at doses of 0, 12.5, 39.5, and 72 mg/kg/day. Each dose group consisted of five males and five females. The dogs were observed clinically and blood samples were taken at 15-day intervals for hematologic and serum chemistry values. Decreased total erythrocyte count and hemoglobin levels were observed in mid- and high-dose dogs beginning at Day 30. Serum concentrations of LDH were elevated at Days 30 and 45 in females and at Day 75 in males treated with DCA at 72 mg/kg/day. One female of the high-dose group died at Day 50 and two high-dose males died at Days 51 and 74. Hindlimb partial paralysis was observed in many high-dose dogs. Vacuolization of myelinated white tracts of cerebrum, cerebellum, and/or spinal cord was observed in many high-dose dogs as well as some mid- and low-dose subjects. Degeneration of testicular germinal epithelium and syncytial giant cell formation was noted in males of all dose groups. Hepatic vacuolar change and chronic hepatitis appeared only in DCA-treated dogs. In addition, suppurative bronchopneumonia and chronic pancreatitis were noted in many high-dose and some middose subjects. A "no-adverse-effect level" was not determined in this study.

The lack of antiplatelet effect of crude extracts from ganoderma lucidum on HIV-positive hemophiliacs.

Effects of the extracts from Ganoderm lucidum (GL-P) to influence immune status of the hemophiliacs with positive HIV antibody and reversed helper/suppressor T-lymphocyte ratio were studied. Since the extracts from G. lucidum have been reported to contain high levels of adenosine, the untoward antiplatelet effect of the extracts on hemophiliacs were highly concerned. Five patients of hemophilia A voluntarily received the extracts which has been analyzed to contain 150 mg of adenosine in 100 gm of the extracts. Patients were estimated to take 1.35 mg of the adenosine daily. Platelet aggregation tests before and after the trial of the extracts showed no significant change. Our crude extracts of the Ganoderma lucidum was considered not to have untoward antiplatelet effect in vivo despite the high contents of adenosine.

Clinical and experimental studies of coronary heart disease treated with yi-qi huo-xue injection.

The purpose of the present work was to evaluate the clinical efficacy and the mechanism of Yi-qi Huo-xue Injection (YHI) in treatment of coronary heart disease. YHI consists of Ginseng, Astragalus and Angelicae Sinensis. The 10% dextrose serves as a placebo. The results were as follows: 1. the frequency and severity of angina episodes were reduced by 90.63%; 2. the ischemic ST-T in ECG was improved in 56.25% of cases; 3. the tolerance to treadmill exercise was increased from 348.50 to 503.50 M.; 4. the left ventricular function was strengthened, PEP/LVET ratio reduced from 0.45 to 0.36, the activity of (Na(+)-K+) ATPase in myocardial cell membrane of rats inhibited by 19.2%; 5. the blood viscosity and erythrocyte electrophoretic time lowered; 6. the adhesion and aggregation of platelet in patients with CHD were inhibited by 27% and 59.4% respectively; 7. the plasma TXB2 level in CHD was reduced from 260.28 +/- 164.4 to 139.29 +/- 57.01 pg/ml; 8. the plasma 6-keto-PGF1 alpha level in CHD was increased from 33.45 +/- 22.5 to 57.48 +/- 13.1 pg/ml, and in rats from 185.77 to 366.33 pg/ml. The differences were all statistically significant (P less than 0.05-0.01) in comparison with the placebo group.

Identification of allergens and antigens of Bermuda grass (Cynodon dactylon) pollen by immunoblot analysis.

Allergens and antigens of Bermuda grass pollen fractionated by SDS-polyacrylamide gel electrophoresis and transferred to nitrocellulose membranes were identified using twenty-one sera of Bermuda grass pollen-allergic patients. The IgE- and IgG-binding pollen components transferred to nitrocellulose were detected by reaction with enzyme-labelled anti-human IgE and anti-human IgG, respectively. There was heterogeneity in both IgE- and IgG-binding patterns of the allergic sera tested. Fourteen pollen components, ranging in molecular weight from 16,000 to 88,000 daltons, bound to IgE antibodies. Only two of the fourteen allergens identified reacted with IgE antibodies of more than 50% of the twenty-one allergic sera. The pollen component with a molecular weight of 32,000 daltons showed by far the highest frequency of IgE binding, being recognized by sixteen (76%) of the twenty-one sera examined. Fifteen (71%) of the twenty-one sera tested had IgE antibodies that reacted with more than one of the fourteen allergenic components identified. Pollen components recognized by IgE antibodies also reacted with IgG antibodies, and there were components only recognized by IgG antibodies. Results obtained from this study should be useful both clinically and in research.

Visual responses of neurons in the avian nucleus isthmi.

Electrophysiological responses of neurons to visual and auditory stimulation are extracellularly recorded from the pigeon isthmic area. Cobalt sulfide markings show that only visual units are localized within the nucleus isthmi pars parvocellularis (Ipc) and pars magnocellularis (Imc), while visual-auditory bimodal units are localized outside. Visual units respond to black or white targets moving through their receptive fields (RFs). The RF centers are mainly distributed in the contralaterally lower visual field. The rostral Ipc and Imc receive information from the nasal visual field, and the caudal part of the Ipc and Imc corresponds to the temporal field. Therefore, both Ipc and Imc are visual centers instead of auditory centers as described before.

Microiontophoresis and single-unit analysis of cholinergic drugs in the optic tectum of frog.

Microiontophoresis of acetylcholine (ACh), atropine, or curare was accompanied by single-unit analysis of visual neuronal responses in the optic tectum of Rana nigromaculata. In 71% of the units tested, ACh enhanced responses to visual stimuli, while atropine suppressed visual responses. Twenty-two percent of the remainder showed no ACh- or atrophin-induced effects and were recorded within 125 microns of the pial surface. The majority of ACh-enhanced, atropine-suppressed units were recorded from visually responsive units localized in the postsynaptic cellular layer 8. The iontophoretic effects of curare were considerably more varied, with approximately equal numbers of units showing an increase (33%), a decrease (35%) or no change (32%) in visually activated responses. The specific effects of curare were also related to the depth from which unit recordings were obtained. These findings indicate that ACh functions as a modulatory neurotransmitter in the frog optic tectum, with a predominantly muscarinic mode of action at postsynaptic levels.