Olanzapine's effects on hypothalamic transcriptomics and kinase activity.

Olanzapine is a second-generation antipsychotic that disrupts metabolism and is associated with an increased risk of type 2 diabetes. The hypothalamus is a key region in the control of whole-body metabolic homeostasis. The objective of the current study was to determine how acute peripheral olanzapine administration affects transcription and serine/threonine kinase activity in the hypothalamus. Hypothalamus samples from rats were collected following the pancreatic euglycemic clamp, thereby allowing us to study endpoints under steady state conditions for plasma glucose and insulin. Olanzapine stimulated pathways associated with inflammation, but diminished pathways associated with the capacity to combat endoplasmic reticulum stress and G protein-coupled receptor activity. These pathways represent potential targets to reduce the incidence of type 2 diabetes in patients taking antipsychotics.

Tiaogan daozhuo formula attenuates atherosclerosis via activating AMPK -PPARγ-LXRα pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Tiaogan Daozhuo Formula (TGDZF) is a common formulation against atherosclerosis, however, there is limited understanding of its therapeutic mechanism. AIM OF THIS STUDY: To examine the effectiveness of TGDZF in the treatment of atherosclerosis and to explore its mechanisms. MATERIALS AND METHODS: In ApoE-/- mice, atherosclerosis was induced by a high-fat diet for 12 weeks and treated with TGDZF at different doses. The efficacy of TGDZF in alleviating atherosclerosis was evaluated by small animal ultrasound and histological methods. Lipid levels were measured by biochemical methods. The capacity of cholesterol efflux was tested with a cholesterol efflux assay in peritoneal macrophage, and the expression of AMPKα1, PPARγ, LXRα, and ABCA1 was examined at mRNA and protein levels. Meanwhile, RAW264.7-derived macrophages were induced into foam cells by ox-LDL, and different doses of TGDZF-conducting serum were administered. Similarly, we examined differences in intracellular lipid accumulation, cholesterol efflux rate, and AMPKα1, PPARγ, LXRα, and ABCA1 levels following drug intervention. Finally, changes in the downstream molecules were evaluated following the inhibition of AMPK by compound C or PPARγ silencing by small interfering RNA. RESULTS: TGDZF administration reduced aortic plaque area and lipid accumulation in aortic plaque and hepatocytes, and improved the serum lipid profiles of ApoE-/- mice. Further study revealed that its efficacy was accompanied by an increase in cholesterol efflux rate and the expression of PPARγ, LXRα, and ABCA1 mRNA and protein, as well as the promotion of AMPKα1 phosphorylation. Moreover, similar results were caused by the intervention of TGDZF-containing serum in vitro experiments. Inhibition of AMPK and PPARγ partially blocked the regulatory effect of TGDZF, respectively. CONCLUSIONS: TGDZF alleviated atherosclerosis and promoted cholesterol efflux from macrophages by activating the AMPK-PPARγ-LXRα-ABCA1 pathway.

Dehydrocostus lactone (DHC) promotes osteoblastic differentiation and mineralization through p38/RUNX-2 signaling.

Dysregulation of osteoblastic differentiation is an important risk factor of osteoporosis, the therapy of which is challenging. Dehydrocostus lactone (DHC), a sesquiterpene isolated from medicinal plants, has displayed anti-inflammatory and antitumor properties. In this study, we investigated the effects of DHC on osteoblastic differentiation and mineralization of MC3T3-E1 cells. Interestingly, we found that DHC increased the expression of marker genes of osteoblastic differentiation, such as alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Additionally, DHC increased the expressions of collagen type I alpha 1 (Col1a1) and collagen type I alpha 2 (Col1a2). We also demonstrate that DHC increased ALP activity. Importantly, the Alizarin Red S staining assay revealed that DHC enhanced osteoblastic differentiation of MC3T3-E1 cells. Mechanistically, it is shown that DHC increased the expression of Runx-2, a central regulator of osteoblastic differentiation. Treatment with DHC also increased the levels of phosphorylated p38, and its blockage using its specific inhibitor SB203580 abolished the effects of DHC on runt-related transcription factor 2 (Runx-2) expression and osteoblastic differentiation, suggesting the involvement of p38. Based on these findings, we concluded that DHC might possess a capacity for the treatment of osteoporosis by promoting osteoblastic differentiation.

Fine molecular structure and digestibility changes of potato starch irradiated with electron beam and X-ray.

The change of digestibility of starch irradiated with different types from the perspective of fine structure is not well understood. In this work, the change of internal structure, molecular weight and chain-length distribution, helical structure, lamellar structure, fractal structure and digestibility of native and treated potato starch with electron beam and X-ray was analyzed. Two irradiations caused the destruction of internal structure, the disappearance of growth rings and increase of pores. Irradiation degraded starch to produce short chains and to decrease molecular weight. Irradiation increased double helical content and the thickness and peak area of lamellar structure, resulting in the reorganization of amylopectin and increase of structure order degree. The protected glycosidic linkages increased starch resistance to hydrolase attack, thereby enhancing the anti-digestibility of irradiated starch. Pearson correlation matrix also verified the above-mentioned results. Moreover, X-ray more increased the anti-digestibility of starch by enhancing ability to change fine structure.

[Chrysin alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis in rats].

The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.

Therapeutic applications of transcutaneous auricular vagus nerve stimulation with potential for application in neurodevelopmental or other pediatric disorders.

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) as a newly developed technique involves stimulating the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear, with resulting activation of vagal connections to central and peripheral nervous systems. Increasing evidence indicates that maladaptive neural plasticity may underlie the pathology of several pediatric neurodevelopmental and psychiatric disorders, such as autism spectrum disorder, attention deficit hyperactivity disorder, disruptive behavioral disorder and stress-related disorder. Vagal stimulation may therefore provide a useful intervention for treating maladaptive neural plasticity. In the current review we summarize the current literature primarily on therapeutic use in adults and discuss the prospects of applying taVNS as a therapeutic intervention in specific pediatric neurodevelopmental and other psychiatric disorders. Furthermore, we also briefly discuss factors that would help optimize taVNS protocols in future clinical applications. We conclude from these initial findings that taVNS may be a promising alternative treatment for pediatric disorders which do not respond to other interventions.

Transcutaneous auricular vagus nerve stimulation increases eye-gaze on salient facial features and oxytocin release.

Non-invasive, transcutaneous electrical stimulation of the auricular branch of the vagus nerve (taVNS) via the ear is used therapeutically in epilepsy, pain, and depression, and may also have beneficial effects on social cognition. However, the underlying mechanisms of taVNS are unclear and evidence regarding its role in social cognition improvement is limited. To investigate the impact of taVNS on social cognition we have studied its effects on gaze toward emotional faces in combination with eye-tracking and on the release of the neuropeptide oxytocin which plays a key role in influencing social cognition and motivation. A total of 54 subjects were enrolled (49 were included in the final analysis) in a sham-controlled, participant-blind, crossover experiment, consisting of two treatment sessions 1 week apart. In one session participants received 30-min taVNS (tragus), and in the other, they received 30-min sham (earlobe) stimulation with the treatment order counterbalanced. The proportion of time spent viewing the faces and facial features (eyes, nose, and mouth) was measured together with resting pupil size. Additionally, saliva samples were taken for the measurement of oxytocin concentrations by enzyme-linked immunoassay. Saliva oxytocin concentrations increased significantly after taVNS compared to sham stimulation, while resting pupil size did not. In addition, taVNS increased time spent viewing the nose region irrespective of face emotion, and this was positively correlated with increased saliva oxytocin concentrations. Our findings suggest that taVNS biases visual attention toward socially salient facial features across different emotions and this is associated with its effects on increasing endogenous oxytocin release.

Two birds with one stone: YQSSF regulates both proliferation and apoptosis of bone marrow cells to relieve chemotherapy-induced myelosuppression.

ETHNOPHARMACOLOGICAL RELEVANCE: Yiqi Shengsui formula (YQSSF) is a commonly used formula to treat chemotherapy-induced myelosuppression, but little is known about its therapeutic mechanisms. AIM OF THIS STUDY: This study aims to examine the effect of YQSSF in treating myelosuppression and explore its mechanism. MATERIALS AND METHODS: A myelosuppression BALB/c mouse model was established by intraperitoneal (i.p.) injection of cyclophosphamide (CTX). The efficacy of YQSSF in alleviating chemotherapy-induced myelosuppression was evaluated by blood cell count, immune organ (thymus, spleen, liver) index, bone marrow nucleated cell (BMNC) count and histopathological analysis of bone marrow and spleen. Then, ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to analyze the ingredients of YQSSF extract. Key effects and potential mechanism of YQSSF extract in alleviating myelosuppression were predicted by network pharmacology method. Finally, cell cycle and TUNEL staining of bone marrow cells was detected to verify the key effects, and RT-qPCR or Western blotting were performed to measure the gene and protein expressions of the effect targets respectively to confirm the predicted mechanism of YQSSF for myelosuppression. RESULTS: YQSSF up-regulated the number of peripheral blood leukocytes and BMNC, reduced spleen index and liver index, improved the pathological morphology of bone marrow and spleen. A total of 40 ingredients were isolated from YQSSF extract using UPLC-Q/TOF-MS analysis. Network pharmacology revealed that YQSSF regulated both proliferation and apoptosis to alleviate myelosuppression. Finally, YQSSF decreased G0/G1 ratio, increased the proportion of bone marrow cells in S phase and proliferation index (PI), and reduced apoptotic cells in femur bone marrow. RT-qPCR and Western blotting showed that YQSSF up-regulated the expression levels of CDK4, CDK6, CyclinB1, c-Myc and Bcl-2, as well as down-regulated the expression levels of Cyt-c, Fas, Caspase-8/3 and p53. CONCLUSIONS: YQSSF promotes the proliferation and inhibits the apoptosis of bone marrow cells to relieve chemotherapy-induced myelosuppression.

Deciphering of Key Pharmacological Pathways of Poria Cocos Intervention in Breast Cancer Based on Integrated Pharmacological Method.

OBJECTIVE: Poria cocos (Fuling), a natural plant, has recently emerged as a promising strategy for cancer treatment. However, the molecular mechanisms of Poria cocos action in breast cancer remain poorly understood. METHODS: TCMSP database was used to screen the potential active ingredients in Poria cocos. GEO database was used to identify differentially expressed genes. Network pharmacology was used to identify the specific pathways and key target proteins related to breast cancer. Finally, molecular docking was used to validate the results. RESULTS: In our study, 237 targets were predicted for 15 potential active ingredients found in Poria cocos. An interaction network of predicted targets and genes differentially regulated in breast cancers was constructed. Based on the constructed network and further analysis including network topology, KEGG, survival analysis, and gene set enrichment analysis, 3 primary nodes were identified as key potential targets that were significantly enriched in the PPAR signaling pathway. CONCLUSION: The results showed that potential active ingredients of Poria cocos might interfere with breast cancer through synergistic regulation of PTGS2, ESR1, and FOS.

Curcumin Suppresses Aldosterone-Induced CRP Generation in Rat Vascular Smooth Muscle Cells via Interfering with the ROS-ERK1/2 Signaling Pathway.

Aldosterone regulates the initiation and development of atherosclerosis which is identified as a chronic inflammatory disease by promoting the generation of C-reactive protein in vascular smooth muscle cells. Curcumin is the most active ingredient of turmeric with anti-inflammation and antioxidation effects. Here, the effect of curcumin on aldosterone-induced C-reactive protein generation in vascular smooth muscle and the molecular mechanisms involved were explored. Primary rat vascular smooth muscle cells and hyperaldosteronism model rats were used in this study. The amount of C-reactive protein, reactive oxygen species, and the signaling pathway-related molecules generated were estimated. We found that curcumin inhibited aldosterone-induced C-reactive protein generation in vascular smooth muscle cells by interfering with the reactive oxygen species-ERK1/2 signal pathway. The results provide new evidence for the potential anti-inflammatory and cardiovascular protective effects of curcumin.

The Caenorhabditis elegans homolog of human copper chaperone Atox1, CUC-1, aids in distal tip cell migration.

Cell migration is a fundamental biological process involved in for example embryonic development, immune system and wound healing. Cell migration is also a key step in cancer metastasis and the human copper chaperone Atox1 was recently found to facilitate this process in breast cancer cells. To explore the role of the copper chaperone in other cell migration processes, we here investigated the putative involvement of an Atox1 homolog in Caenorhabditis elegans, CUC-1, in distal tip cell migration, which is a key process during the development of the C. elegans gonad. Using knock-out worms, in which the cuc-1 gene was removed by CRISPR-Cas9 technology, we probed life span, brood size, as well as distal tip cell migration in the absence or presence of supplemented copper. Upon scoring of gonads, we found that cuc-1 knock-out, but not wild-type, worms exhibited distal tip cell migration defects in approximately 10-15% of animals and, had a significantly reduced brood size. Importantly, the distal tip cell migration defect was rescued by a wild-type cuc-1 transgene provided to cuc-1 knock-out worms. The results obtained here for C. elegans CUC-1 imply that Atox1 homologs, in addition to their well-known cytoplasmic copper transport, may contribute to developmental cell migration processes.

miR-375 affects the proliferation and invasion of hepatoma cells via targetingYAP / 中国肿瘤生物治疗杂志

@# Objective: To investigate the mechanisms of miR-375 affecting the proliferation and invasion of hepatoma cells via targeting YAP (Yes-associated protein). Methods: The cancerous tissues and corresponding para-cancerous tissues of 70 patients with hepatocellular carcinoma (HCC) who underwent surgical resection at the Second Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2015 to December 2016, as well as the hepatoma cell lines SMMC-7721, Hb611, HepG2 and BEL-7405 were collected for this study. qPCR method was used to detect the expression level of miR-375 in collected HCC tissues and different hepatoma cell lines; Dual luciferase reporter gene assay was used to verify the interaction between miR-375 and YAP; The relationship between miR-375 and clinicopathological features of HCC patients was also analyzed; MTT assay was used to detect the effect of miR375 on the proliferation of hepatoma cells; Transwell invasion assay was used to detect the invasive ability of hepatoma cells after inhibiting the expression of miR-375; Western blotting was used to detect the expression of YAP in HepG2 cells. The nude mouse model of subcutaneously transplanted xenograft was established, and the tumor volume and mass of transplanted hepatoma cells were detected after inhibiting the expression of miR-375. The expression of YAP in xenograft of nude mice was detected by immunohistochemistry and Western blotting. Results: The expression of miR-375 and YAP in HCC tissues was significantly higher than that in para-cancerous tissues (all P<0.05). The expression of miR-375 in HepG2 cells was the highest (P<0.05). miR-375 could specifically bind to the 3' UTR of YAP and regulate the expression activity of YAP. After inhibiting the expression of miR-375, the proliferation and invasion abilities of HepG2 cells were reduced (all P<0.05); The tumor volume and mass of transplanted xenografts were significantly reduced (both P<0.05); The expression of YAP protein in the transplanted xenografts was down-regulated (P<0.05). Conclusion: miR-375 plays an important role in the occurrence and development of liver cancer, and can influence the malignant biological behaviors of hepatoma cells by targeting and regulating the expression ofYAP.

Pinus massoniana Bark Extract: Structure-Activity Relationship and Biomedical Potentials.

Proanthocyanidins (PAs) belong to the condensed tannin subfamily of natural flavonoids. Recent studies have shown that the main bioactive compounds of Pinus massoniana bark extract (PMBE) are PAs, especially the proanthocyanidins B series, which play important roles in cell cycle arrest, apoptosis induction and migration inhibition of cancer cells in vivo and in vitro. PA-Bs are mixtures of oligomers and polymers composed of flavan-3-ol, and the relationship between their structure and corresponding biomedical potentials is summarized in this paper. The hydroxyl at certain positions or the linkage between different carbon atoms of different rings determines or affects their anti-oxidant and free radical scavenging bioactivities. The degree of polymerization and the water solubility of the reaction system also influence their biomedical potential. Taken together, PMBE has a promising future in clinical drug development as a candidate anticancer drug and as a food additive to prevent tumorigenesis. We hope this review will encourage interested researchers to conduct further preclinical and clinical studies to evaluate the anticancer activities of PMBE, its active constituents and their derivatives.

Pine bark extracts: nutraceutical, pharmacological, and toxicological evaluation.

Proanthocyanidins are among the most abundant constituents in pine bark extracts (PBEs). This review summarizes medical research on PBEs from Pinus pinaster, Pinus radiata, Pinus massoniana, and other less well characterized species. The precise mechanisms of the important physiologic functions of PBE components remain to be elucidated, but there is evidently great potential for the identification and development of novel antioxidant, anti-inflammatory, cardiovascular, neuroprotective, and anticancer medicines. Although toxicological data for PBEs are limited, no serious adverse effects have been reported. PBEs, therefore, may have potential as nutraceuticals and pharmaceuticals and should be safe for use as food ingredients.

The Beneficial Effects of Electro-acupuncture at PC6 (Neiguan-point) of Gene and Protein Expressions of Classical Inward-rectifier Potassium Channels in Myocardial Ischemic Rats.

This study is aim to investigate the effect of electro-acupuncture at PC6 (Neiguan-point) on the gene and protein expressions of classical inward-rectifier potassium channels (Kir) in myocardial ischemia (MI) rats induced by isoproterenol (ISO). With ten for each one, 50 rats were divided into 5 groups which were control group, MI group, PC6 group, LU7 (Lieque-point) group and non-acupoint group. The control group was injected normal saline solution (85 mg/kg), the other groups were injected ISO (85 mg/kg). All the rats were injected once daily for two days and recorded electrocardiograms (ECGs) after every injection. Electro-acupuncture (EA) was operated at PC6, LU7 and non-acupoint respectively in the rats of PC6 group, LU7 group and non-acupoint group after twice injections. EA was performed to these three groups with disperse-dense wave (4-20 Hz), pulse amplitude of 14V, 20 mins a day remaining 7 days. The gene and protein expressions of Kir2.1, Kir2.2 and Kir2.3 were analyzed by Western Immunoblotting Technology (Western Blot) and Real-time Fluorescence Quantitative Polymerase Chain Reaction (RT-PCR). But it is regrettable that we did not detect meaningful gene and protein expressions Kir2.3, and the expressions of Kir2.1 and Kir2.2 in MI induced groups were lower [The gene and protein decreased 39.4 ± 27.3% and 38.7 ± 17.1% respectively.] than control group (P < 0.05). Compared with MI group, the results of PC6 group and LU7 group increased [PC6 group: the gene and protein increased 42.9 25.0% and 42.2 ± 10.0% respectively. LU7 group: the gene and protein increased 23.8 ± 50.1% and 21.1 ± 32.5% respectively.] obviously (P < 0.05) after EA, furthermore the expressions of PC6 group were higher [The gene and protein increased 15.4 ± 16.7% and 17.3 ± 60% respectively.] than LU7 group (P < 0.05). The results show that PC6 has a better positive effect than LU7 on MI rats, and the mechanism is probably that EA at PC6 can significantly increase the gene and protein expressions of Kir2.1 and Kir2.2.

The beneficial effect of electro-acupuncture given at PC6 (Neiguan-point) by the increase in cardiac transient outward K+ current channel which depends on the gene and protein expressions in artificially induced myocardial ischemia rats.

This study explored the mechanism of electro-acupuncture (EA) at PC6 to improve the heart function by regulating the cardiac transient outward potassium current (= Ito) channel in myocardial ischemia (MI). Kv1.4 is the main component of the slow Ito (Ito.s) channel. Kv4.2 and Kv4.3 are the main components of the fast Ito (Ito.f) channel. KChIP2 is a compound protein of Ito channel. In this experiment, MI was induced by injecting isoproterenol in rats, and the gene and protein expressions of Kv1.4, Kv4.2, Kv4.3 and KChIP2 were lower [The gene and protein decreased (42.8 ± 4.3)% and (37.2 ± 4.7)% respectively.] than the control rats significantly (p < 0.05). After MI induction, the MI rats were divided into three groups, including PC6, LU7 (Lieque-point) and Non-acupoint group which were acupunctured at once a day for 7 days respectively. After EA at PC6 and LU7, the gene and protein expressions showed obvious increased [EA at PC6: the gene and protein increased (50.24 ± 5.4)% and (39.14 ± 5.3)% respectively. EA at LU7: the gene and protein increased (24.6 ± 2.8)% and (22.04 ± 5.5)% respectively] and they are all higher than MI rats significantly (p < 0.05). EA at PC6 and LU7 showed the same variation, and the effects of EA at PC6 and LU7 were better than Non-acupuncture-point (p < 0.05). The effects of EA at PC6 were significantly better [The gene and protein increased (19.74 ± 2.7)% and (14.14 ± 4.4)% respectively] than LU7 (p < 0.05). PC6 is an acupoint of the pericardium meridian, and the pericardium meridian which corresponds to adrenal gland according to Omura Y's research, can affect the heart function directly LU7 belong to the lung meridian, and the lung plays an important factor in blood circulation according to TCM. So PC6 is more effective than LU7 on heart function regulation. The results suggested that PC6 showed the target effect of meridian specificity on regulating the Kv channel in MI.

[Inhibitory effect of baicalin on germ tube formation and adhesion of Candida albicans].

OBJECTIVE: To investigate the effects of baicalin against Candida albicans germ tube formation, and adherence to buccal epitherial and vaginal epitherial cells. METHOD: Various concentrations of baicalin (100, 50, 10 mg x L(-1)) were incubated with C. albicans suspension, the mixed suspension of C. albicans and human buccal epitherial cells, the mixed suspension of C. albicans and vaginal epitherial cells, respectively. The effects of baicalin on C. albicans germ tube formation, and adherence to buccal epitherial and vaginal epitherial cells were then assessed microscopically. RESULT: All concentrations of baicalin could inhibit C. albicans germ tube formation, and adherent to buccal epitherial and vaginal epitherial cells,while there was no significant difference between standard and clinical strains. CONCLUSION: Baicalin could inhibit C. albicans germ tube formation, and adherence to buccal epitherial and vaginal epitherial cells.

Differences in growth and physiological traits of two poplars originating from different altitudes as affected by UV-B radiation and nutrient availability.

Cuttings of Populus kangdingensis and Populus cathayana originating from altitudes of 3500 and 1500 m in southwestern China, respectively, were grown for one growing season in the field under ambient or ambient plus supplemental ultraviolet-B (UV-B) radiation with two levels of nutrients. In both species, enhanced UV-B radiation significantly increased UV-B absorbing compounds and guaiacol peroxidase (GPX) activity, while no significant effects were observed in photosynthetic pigments and proline content. On the other hand, cuttings grown with high-nutrient availability had larger leaf area, higher total biomass and GPX activity as well as higher water use efficiency (WUE) (as measured by stable carbon isotope composition, delta(13)C) when compared with low-nutrient conditions, while UV-B absorbing compounds and ascorbic acid (AsA) content significantly decreased. Differences in responses to enhanced UV-B radiation and nutrient availability were observed between the two species. Nutrient-induced increases in chlorophyll a, chlorophyll b and total chlorophyll as well as in carotenoids were greater in P. kangdingensis than in P. cathayana. In P. cathayana, enhanced UV-B radiation significantly decreased leaf area and total biomass, while it significantly increased WUE and ascorbate peroxidase (APX). In contrast, such changes were not observed in P. kangdingensis. In addition, the effects of enhanced UV-B radiation on leaf area, total biomass and UV-B absorbing compounds were closely related to the nutrient status. Our results indicated that P. kangdingensis, which originates from the altitude of 3500 m and is apparently adapted to low-nutrient and high-UV-B habitats, exhibits better tolerance to enhanced UV-B radiation and greater growth under low-nutrient availability than does P. cathayana originating from the altitude of 1500 m.