Inhibition of integrated stress response protects against lipid-induced senescence in hypothalamic neural stem cells in adamantinomatous craniopharyngioma.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a benign tumor with malignant clinical manifestations. ACP adjacent to the hypothalamus often presents with more severe symptoms and higher incidence of hypothalamic dysfunction. However, the mechanism underlying hypothalamic dysfunction remains unclear. METHODS: Immunostaining was performed to determine the nerve damage to the floor of the third ventricle (3VF) adjacent to ACP and to examine the recruitment and senescence of hypothalamic neural stem cells (htNSCs). The accumulation of lipid droplets (LDs) in htNSCs was evaluated via BODIPY staining, oil red O staining, and transmission electron microscopy. In vitro and in vivo assays were used to evaluate the effect of cystic fluid or oxidized low-density lipoprotein and that of oxytocin (OXT) on htNSC senescence and the hypothalamic function. The protein expression levels were analyzed using western blotting. RESULTS: htNSCs with massive LD accumulation were recruited to the damaged 3VF adjacent to ACP. The LDs in htNSCs induced senescence and reduced neuronal differentiation; however, htNSC senescence was effectively prevented by inhibiting either CD36 or integrated stress response (ISR) signaling. Furthermore, OXT pretreatment reduced lipotoxicity via the inhibition of ISR signaling and the repair of the blood-brain barrier. CONCLUSIONS: Reduced LD aggregation or ISR signaling inhibition prevented senescence in htNSCs and identified molecular pathways and potential therapeutic targets that may improve hypothalamic dysfunction in ACP patients.

Adult neurogenesis of the median eminence contributes to structural reconstruction and recovery of body fluid metabolism in hypothalamic self-repair after pituitary stalk lesion.

Body fluid homeostasis is critical to survival. The integrity of the hypothalamo-neurohypophysial system (HNS) is an important basis of the precise regulation of body fluid metabolism and arginine vasopressin (AVP) hormone release. Clinically, some patients with central diabetes insipidus (CDI) due to HNS lesions can experience recovery compensation of body fluid metabolism. However, whether the hypothalamus has the potential for structural plasticity and self-repair under pathological conditions remains unclear. Here, we report the repair and reconstruction of a new neurohypophysis-like structure in the hypothalamic median eminence (ME) after pituitary stalk electrical lesion (PEL). We show that activated and proliferating adult neural progenitor cells differentiate into new mature neurons, which then integrate with remodeled AVP fibers to reconstruct the local AVP hormone release neural circuit in the ME after PEL. We found that the transcription factor of NK2 homeobox 1 (NKX2.1) and the sonic hedgehog signaling pathway, mediated by NKX2.1, are the key regulators of adult hypothalamic neurogenesis. Taken together, our study provides evidence that adult ME neurogenesis is involved in the structural reconstruction of the AVP release circuit and eventually restores body fluid metabolic homeostasis during hypothalamic self-repair.

An Engineered Protein-Au Bioplaster for Efficient Skin Tumor Therapy.

Melanoma is the most lethal malignancy in skin cancer and may occur at any site and express melanocytes. Due to malignant melanoma's invasion and migration nature, conventional therapies make it challenging to remove the whole tumor tissue while undertaking the high risks of tumor recurrence. Regarding the emerging targeted therapies and immunotherapy, drug resistance and low immunotherapeutic activity remain significant challenges. It is thus becoming urgently important to develop alternative strategies for melanoma therapy. Herein, a novel bifunctional protein-based photothermal bioplaster (PPTB) is developed for non-invasive tumor therapy and skin tissue regeneration. The complexation of adhesive protein and gold nanorods (GNRs) endow the obtained PPTB with good biocompatibility, controllable near-infrared (NIR) light-mediated adhesion performance, and high photothermal performance. Therefore, the PPTB bioagent facilitates skin adhesion and effectively transfers heat from skin to tumor. This behavior endows PPTB capability to eradicate skin tumors conveniently. Thus, the assembly strategy enables this hybrid bioplaster to hold great potential for skin-related tumor treatment.

A retaining sphenoid and dura procedure in the rat to obtain intact pituitary-infundibulum-hypothalamus preparations.

BACKGROUND: The histopathological study of brain tissue is a conventional method in neuroscience. However, procedures specifically developed to recover intact hypothalamic-pituitary brain specimens, are not available. NEW METHOD: We describe a detailed protocol for obtaining intact rat brain with pituitary-hypothalamus continuity through an intact infundibulum. The brain is collected via a ventral approach through removing the skull base. Membranous structures surrounding the hypothalamus-pituitary system can be preserved, including vasculature. RESULTS: We report a retaining sphenoid and dura technique to obtain intact hypothalamic-pituitary brain preparations, and we confirm the practicability of this method. By combination of this technique with histological analysis or 3D brain tissue clearing and imaging methods, the functional morphology structure of the hypothalamus-pituitary can be further explored. COMPARISON WITH EXISTING METHOD: The current procedure is limited in showing the connection between the hypothalamus and the pituitary. Our procedure effectively protects the integrity of the fragile infundibulum and thus prevents the pituitary from separating from the hypothalamus. CONCLUSIONS: We present a convenient and practical approach to obtain intact hypothalamus-pituitary brain specimens for subsequent histopathological evaluation.

Dahuang Zhechong Pill suppresses colorectal cancer liver metastasis via ameliorating exosomal CCL2 primed pre-metastatic niche.

ETHNOPHARMACOLOGICAL RELEVANCE: Dahuang Zhechong Pill (DZP) is a classical formula from "Synopsis of Prescriptions of the Golden Chamber". It has been used for treatment of abdominal masses (including tumorous diseases) for thousands of years. AIM OF THE STUDY: Our previous work showed that DZP suppresses CCl-4 induced hepatic fibrosis by downregulating the expression of interleukin-13. We aimed to test if DZP suppresses the metastasis of colorectal cancer (CRC) by ameliorating the fibrosis status of the future metastatic organ. MATERIALS AND METHODS: Liver metastasis was observed by injection of MC38-EGFP cells with stably expressing enhanced green fuorescence protein beneath the splenic capsule of C57BL/6J mice. MC38-EGFP-derived exosomes were analyzed by Label-free comparative proteomics. mRNA expression was determined by Quantitative PCR. Protein expression was determined by immunohistochemistry, immunofuorescence and Western blot. Collagen deposition was determined by Masson staining. All data were statistically analyzed using SPSS. RESULTS: DZP drastically reduced the metastatic tumor number and fluorescence intensity in a splenic liver metastasis model. It also lowered the expression of mature TGF-ß1 and decreased the fibronectin contents & collagen deposition. Exosome proteomics showed that the upregualted CC chemokine ligand-2 (CCL2) was repressed by DZP treatment. Importantly, DZP markedly lowered the expression of CCL2 and its receptor CCR2 in the liver. Exosomal CCL2 activated macrophage recruitment and shifted the M1/M2 paradigm to a M2 phenotype. DZP reduced the macrophage infiltration and attenuated the M2 polarizaion in tumor-bearing mice liver. It decreased the F4/80 positive areas and specifically reduced the ratio of CCR2+ positive macrophage. Anti-fibrosis and inhibition of CCR2 suppress the growth and metastasis of CRC. CONCLUSIONS: DZP inhibits the liver metastasis of CRC by suppressing CCL2 mediated M2-skewing paradigm and ameliorating the pro-fibrotic microenvironment.

Endoplasmic reticulum stress induces apoptosis of arginine vasopressin neurons in central diabetes insipidus via PI3K/Akt pathway.

AIMS: Central diabetes insipidus (CDI), a typical complication caused by pituitary stalk injury, often occurs after surgery, trauma, or tumor compression around hypothalamic structures such as the pituitary stalk and optic chiasma. CDI is linked to decreased arginine vasopressin (AVP) neurons in the hypothalamic supraoptic nucleus and paraventricular nucleus, along with a deficit in circulating AVP and oxytocin. However, little has been elucidated about the changes in AVP neurons in CDI. Hence, our study was designed to understand the role of several pathophysiologic changes such as endoplasmic reticulum (ER) stress and apoptosis of AVP neurons in CDI. METHODS: In a novel pituitary stalk electric lesion (PEL) model to mimic CDI, immunofluorescence and immunoblotting were used to understand the underlying regulatory mechanisms. RESULTS: We reported that in CDI condition, generated by PEL, ER stress induced apoptosis of AVP neurons via activation of the PI3K/Akt and ERK pathways. Furthermore, application of N-acetylcysteine protected hypothalamic AVP neurons from ER stress-induced apoptosis through blocking the PI3K/Akt and ERK pathways. CONCLUSION: Our findings showed that AVP neurons underwent apoptosis induced by ER stress, and ER stress might play a vital role in CDI condition through the PI3K/Akt and ERK pathways.

Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Dapivirine is one of reverse transcriptase inhibitors (RTIs). It is the prototype of diarylpyrimidines (DAPY), formerly known as TMC120 or DAPY R147681 (IUPAC name: 4- [[4-(2, 4, 6-trimethylphenyl) amino]-2-pyrimidinyl] amino]-benzonitrile; CAS no.244767-67-7). AIM: The purpose of this study is to investigate the antitumor activity of dapivirine, one of the RTIs, on U87 glioblastoma (GBM) cells in vitro and in vivo. MATERIALS AND METHODS: U87 GBM cells were cultured and treated with or without dapivirine. Cell viability was evaluated by CCK-8 (Cell Counting Kit 8, CCK-8) assay; apoptosis was analyzed by flow cytometry; cell migration was evaluated by Boyden Chamber assay; Western blotting was performed to detect proteins related to apoptosis, epithelial-to-mesenchymal transition and autophagy. PathScan intracellular signaling array kit was used to detect important and well-characterized signaling molecules. Tumor xenograft model in nude mice was used to evaluate the antitumorigenic effect in vivo. RESULTS: Dapivirine weakened proliferation of glioma cells and induced the apoptosis of U87 glioblastoma cells. Furthermore, dapivirine regulated autophagy and induced Akt, Bad and SAPK/JNK activations. Moreover, the inhibition of glioma cell growth by dapivirine was also observed in nude mice in vivo. CONCLUSION: In summary, in our study dapivirine exposure induces stress, resulting in JNK and PI3K/Akt pathway activation through diminished inhibition of the apoptosis and autophagy cascade in U87 GBM cells, which inhibits cell growth in vitro and in vivo.

Diversity of intestinal bacterial lactase gene in antibiotics-induced diarrhea mice treated with Chinese herbs compound Qi Wei Bai Zhu San.

The current investigation is trying to study the impact of the mixture of Chinese herbs Qi Wei Bai Zhu San (QWBZS) on bacterial lactase gene from antibiotics-induced diarrhea (AAD) mice, as the good curative effect of QWBZS on diarrhea. Mice (6 mice per group) were randomly selected as control, model and treatment groups. To induce diarrhea, mice in both model and treatment groups were intragastrically injected with mixture of gentamycin sulfate and cefradine (23.33 mL kg-1 day-1) twice per day and continuously for totally 5 days. After the success of establishing diarrhea model, the mice in treatment group were gavaged with QWBZS for 3 days. Intestinal contents in all three groups were then collected and DNA was extracted in aseptic environment for the following sequencing. The results showed that mice from QWBZS treatment group had obviously detectable levels of intestinal bacteria, such as Actinobacteria, Firmicutes and Proteobacteria, which produce phyla lactase specifically. In comparison with other groups, the mice in treatment group had more abundant expression of lactase gene from Acidovorax sp. KKs102, Stenotrophomonas sp. LMG11000, Pseudomonas oleovorans, Eggerthella and Burkholderia. Interestingly, the Shannon index decreased significantly after the treatment with QWBZS (P < 0.01 or P < 0.05). 63.1% of lactase genes detected in the mice in treatment group were unclassified, and 32.8% of them were non-homologous to any fragments in the gene bank, which means that most of lactase-producing bacteria are novel. Our results indicate that treatment with QWBZS did not increase the diversity of bacterial lactase gene. Its curative effect on diarrhea may be relevant to its role in facilitating the growth of novel or some key lactase-producing strains.

Effects of alginate on frozen-thawed boar spermatozoa quality, lipid peroxidation and antioxidant enzymes activities.

Although alginate was reported to play an important role as free radical scavengers in vitro and could be used as sources of natural antioxidants, there was no study about the cryoprotective effects of alginate on boar spermatozoa freezing. The objective of this research was to evaluate the effects of different concentrations of alginate added to the freezing extenders on boar spermatozoa motility, plasma membrane integrity, acrosomal integrity, mitochondrial activities, lipid peroxidation and antioxidative enzymes activities (SOD and GSH-Px) after thawing. Alginate was added to the TCG extender to yield six different final concentrations: 0, 0.2, 0.4, 0.6, 0.8, and 1.0mg/mL. The semen extender supplemented with various doses of alginate increased (P<0.05) total motility. The spermatozoa plasma membrane integrity and mitochondrial activity were improved at four different concentrations: 0.4, 0.6, 0.8, 1.0mg/mL. The addition of alginate also provided significantly positive effect on post-thaw boar spermatozoa acrosomal integrity at concentrations of 0.6, 0.8, 1.0mg/mL, compared with that of the control (P<0.05). The freezing extenders with the presence of alginate led to higher SOD and GSH-Px activities and lower MDA levels, in comparison to the control (P<0.05). In summary, alginate exhibited a dose-related response on frozen-thawed boar spermatozoa motility, functional integrity and antioxidative capacity at appropriate concentrations. Therefore alginate could be employed as an effective cryoprotectant in boar spermatozoa cryopreservation.

[Sanhuangyinchi decoction pretreatment ameliorates acute hepatic failure in rats by suppressing antioxidant stress and caspase-3 expression].

OBJECTIVE: To observe the effects of Sanhuangyinchi decoction (SHYCD) pretreatment on acute hepatic failure (AHF) induced by D-galactosamine and lipopolysaccharide (LPS) in rats and explore the possible mechanisms involving antioxidant stress and cell apoptosis-related protein expression. METHODS: Forty-eight SD rats were randomized equally into control group, AHF model group, high-, medium- and low-dose SHYCD groups, and Bicyclol group. Five days after administration of the corresponding drugs, the rats were challenged with peritoneal D-galactosamine (700 mg/kg) plus LPS (10 ug/kg) injections to induce AHF acute hepatic failure except for those in the control group. At 48 h after the injections, blood samples were collected from the rats to detect the levels of ALT, AST, TBIL, PT, INR and FIB, and pathological changes and superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the liver were examined; immunohistochemistry and western blotting were used to detect caspase-3 protein expression in the liver. RESULTS: The levels of ALT, AST, TBIL, TP and INR in the 3 SHYCD groups and Bicyclol group significantly decreased (P<0.05) while FIB significantly increased in comparison with those in the model group. SHYCD obviously ameliorated the pathological changes, enhanced SOD activity (P<0.05), and decreased MDA levels (P<0.05) and caspase-3 expression (P<0.05) in the liver tissue. SHYCD at the medium dose produced similar effects to Bicyclol (P>0.05) and showed better effects at the high dose than Bicyclol (P<0.05). CONCLUSION: SHYCD pretreatment can dose-dependently ameliorate AHF in rats possibly by suppressing antioxidant stress and caspase-3 expression to decrease hepatic cell apoptosis.

[GAT-1 and GAD65 mRNA expressions in different brain regions in dogs at brain propofol uptake equilibrium].

OBJECTIVE: To investigate the expressions of gamma aminobutyric acid transporter 1 (GAT-1) and glutamate decarboxylase 65 (GAD65) mRNA in different brain regions at brain propofol uptake equilibrium in dogs. METHODS: Eighteen 12- to 18-month-old healthy hybrid dogs were randomized equally into control group (group C), low dose group (group L), and high dose group (group H). In groups L and H, anesthesia was administered by intravenous injection of 5.5 and 7.0 mg/kg propofol followed by propofol infusion at a constant rate of 55 and 70 mg·kg(-1)·h(-1) for 50 min, respectively. Blood samples were taken from the internal carotid artery and jugular vein to measure plasma propofol concentrations, and the brain tissues of the hypothalamus, sub thalamus, dorsal thalamus, hippocampus, pons, parietal lobe and frontal lobe were examined for GAT-1 and GAD65 mRNA expressions using quantitative real-time PCR. RESULTS: In groups L and H, propofol infusion at a constant rate for 50 min resulted in comparable plasma propofol concentrations between the internal carotid artery and jugular vein (P>0.05), but the concentrations differed significantly between the two groups (P<0.01). GAT-1 mRNA levels in the hypothalamus and hippocampus were significantly higher in groups L and H than in group C (P<0.05 and P<0.01), but comparable between the former two groups. The variations of GAT-1 mRNA levels between the hypothalamus and hippocampus were similar in both group L [(61.26∓7.17)% and (79.34∓39.95)%, P>0.05] and group H [(74.64∓19.63)% and (97.12∓32.31)%, P>0.05]. GAT-1 mRNA levels in other brain regions showed no significant difference among the 3 groups. GAD65 mRNA levels were similar between group L and group H, but both significantly higher than that in group C (P<0.01). GAD65 mRNA in other brain regions had no significant difference among the 3 groups. CONCLUSION: GAT-1 mRNA in the hypothalamus and hippocampus and GAD65 mRNA in the dorsal thalamus are upregulated when propofol uptake reaches an equilibrium in the brain of dogs.

Triptolide inhibits colon cancer cell proliferation and induces cleavage and translocation of 14-3-3 epsilon.

Triptolide is a diterpenoid triepoxide derived from the traditional Chinese medical herb Tripterygium wilfordii. In the present study, we demonstrated that this phytochemical attenuated colon cancer growth in vitro and in vivo. Using a proteomic approach, we found that 14-3-3 epsilon, a cell cycle- and apoptosis-related protein, was altered in colon cancer cells treated with triptolide. In this regard, triptolide induced cleavage and perinuclear translocation of 14-3-3 epsilon. Taken together, our findings suggest that triptolide may merit investigation as a potential therapeutic agent for colon cancer, and its anticancer action may be associated with alteration of 14-3-3 epsilon.

Dingxin recipe ( ) prevents ischemia/reperfusion-induced arrhythmias via up-regulating prohibitin and suppressing inflammatory responses.

OBJECTIVE: To identify the underlying mechanisms of the protective effects of Dingxin Recipe (: , DXR), a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia/reperfusion (I/R)-induced arrhythmias in rat model. METHODS: A total of 30 rats were randomly divided into three groups: sham group, I/R group, and DXR-pretreated I/R (DXR-I/R) group. Rats in the DXR-DXRI/R group were intragastrically administrated with DXR (12.5 g/kg per day) for consecutive 7 days, while rats I/in the sham and I/R groups were administrated with normal saline. Arrhythmias were introduced by I/R and electrocardiograms (ECG) were recorded. Two-dimensional (2-D) polyacrylamide gel electrophoresis and matrix-matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify assisted differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction (RQ-RQPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to analyze proteins PCR), obtained in the above experiments. RESULTS: DXR significantly reduced the incidence and mean duration of ventricular tachycardia and ventricular fibrillation and dramatically decreased the mortality, as well as arrhythmia score, compared with those of the I/R group. Among successfully identified proteins, prohibitin (PHB) and heart fatty acid binding protein (hFABP) were up-regulated in DXR-pretreated I/R rats compared with those of the I/R rats. In addition, compared with the I/R group, the level of glutathione (GSH) was elevated accompanied by reduced expressions of interleukin-6 (IL-6) and neutrophil infiltration in I/R rats with DXR pretreatment. CONCLUSIONS: DXR could alleviate I/R-induced arrhythmias, which might be related to increased expression of PHB. The enhanced expression of PHB prevented against the depletion of GSH and consequently inhibited apoptosis of cardiomyocytes. Furthermore, up-regulation of PHB might ameliorate I/R-induced cell death and leakage of hFABP by suppressing neutrophil infiltration and IL-6 expressions.

Proteomic analysis of protective effects of polysaccharides from Salvia miltiorrhiza against immunological liver injury in mice.

This study was designed to investigate mechanisms of the protective effects of Salvia miltiorrhiza polysaccharide (SMPS) against lipopolysaccharide (LPS)-induced immunological liver injury (ILI) in Bacille Calmette-Guérin (BCG)-primed mice. Two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis showed that three proteins are down-regulated and six proteins are up-regulated by SMPS. SMPS reduces the degree of liver injury by up-regulating the enzymes of the citric acid cycle, namely malate dehydrogenase (MDH) and 2-oxoglutarate dehydrogenase complex. LPS significantly increases nuclear factor kappa B (NF-κB) activation, inducible nitric oxide synthase (iNOS) expression and MDA level in BCG primed mice liver, whereas SMPS treatment protects against the immunological liver injury through inhibition of the NF-κB activation by up-regulation of PRDX6 and the subsequent attenuation of lipid peroxidation, iNOS expression and inflammation.

[Effect of Sanhuangyinchi decoction on liver damage and caspase-3 in rats with acute hepatic failure].

OBJECTIVE: To investigate effect of Sanhuangyinchi decoction (SHYCD) on liver damage and the pro-apoptotic factor caspase-3 in rats with acute hepatic failure. METHODS: SD rats were randomly divided into blank control group, model group, Angongniuhuang group (AGNH) and SHYCD group. Acute hepatic failure was induced in the rats by intraperitoneal injections of D-GaLN and LPS, and the death rate, ALT, TBIL, PT and caspase-3 activity was observed or tested. RESULTS: At 36 h after the injections, the death rate of the rats was 74.29% (26/35) in the model group, 31.43% (11/35) in AGNH group and 28.57%(10/35) in SHYCD group. The death rate, ALT, TBIL, PT and caspase-3 activity in AGNH and SHYCD groups were significantly lower than those in the model group (P<0.01). SHYCD showed stronger effect than AGNH in depressing TBIL and the activity of caspase-3 (P<0.05). CONCLUSION: SHYCD can improve the liver function and inhibit the activity of caspase-3 in rats, which can be the possible mechanism for its therapeutic effect against acute hepatic failure.

Rosiglitazone attenuates development of polycystic kidney disease and prolongs survival in Han:SPRD rats.

Although pioglitazone, a PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) agonist, has been shown to prolong survival in two rapidly progressive pkd1 (polycystic kidney disease 1)-knockout mice models through disparate mechanisms, these studies lacked data on therapeutic potential and long-term safety because of a short observation period. In the present study, we have used another potent PPAR-gamma agonist, rosiglitazone, to treat Han:SPRD rats, a slowly progressive ADPKD (autosomal dominant PKD) animal model, and confirmed that short-term treatment was able to delay the progression of kidney cysts and protect renal function, which may relate to down-regulating the abnormally activated beta-catenin signalling pathway and its anti-inflammatory and anti-fibrosis effects. Long-term administration significantly prolonged the survival of Han:SPRD rats. Moreover, early therapy in rats with normal renal function had a better outcome than delayed therapy, while initiating therapy in rats with mild impaired renal function still protected renal function. The efficacy of rosiglitazone depended on continuous drug administration; withdrawal of the drug caused accelerated deterioration of renal function in effectively treated rats and shortened their survival to an untreated state. Long-term administration led to cardiac enlargement, probably due to rosiglitazone-mediated sodium re-absorption. In conclusion, these results indicate that rosiglitazone was able to effectively delay the progression of kidney disease and protect renal function in Han:SPRD rats, but its adverse effect of inducing cardiac enlargement should also be monitored closely.

[Prophylactic immunization of dangguibuxue decoction against Cryptosporidium infection in immune suppressed mice].

OBJECTIVE: To explore the prophylaxis of dangguibuxue decoction, a traditional Chinese medicine made from Angelica sinensis and Radix astragalus, on immunosuppressed mice infected by Cryptosporidium parvum. METHODS: 48 BALB/c mice were randomly divided into 4 groups: normal control (A), immunosuppressed control (B), high dose (C), and low dose (D). Mice in groups B, C and D were intragastrically administered with dexamethasone (DXM) for 8 days, and in the same time mice in groups C and D were given high dose (2 g/kg) and low dose (1 g/kg) dangguibuxue decoction respectively. On the ninth day all mice in groups B, C and D were orally inoculated by 1 x 10(6) oocysts of C. parvum. The amount of oocysts in feces was examined daily since being infected. 11 days after infection, the subset of T lymphocytes in peripheral blood was analyzed with flow cytometry, sIL-2R in serum and sIgA of intestinal fluid were detected by ELISA. Pathological change of duodenum and jejunum was observed microscopically. RESULTS: Compared with the immuno-suppressed control group, there were less oocysts in feces (35.0 +/- 4.21) (P < 0.01) and lighter injury in the intestinal mucosa in mice of the high dose dangguibuxue decoction group. Both the number of CD4+ T lymphocytes (47.483 +/- 4.082) and the ratio of CD4+/CD8+ (2.271 +/- 0.378) increased, sIgA [(320.19 +/- 1.94) ng/ml] in the intestinal fluid elevated and sIL-2R [(321.34 +/- 6.66) ng/ml] in peripheral blood decreased in the high dose group, with a significant difference in comparison to the immunosuppressed group (P < 0.01). All the above-mentioned indices in low dose dangguibuxue decoction group showed no significant difference with the immunosuppressed control group (P > 0.05). CONCLUSION: Administration of high dose dangguibuxue decoction plays a role of prophylaxis on the infection of C. parvum in immunosuppressed mice through improving the immune status.