Neurotensin-loaded collagen dressings reduce inflammation and improve wound healing in diabetic mice

Impaired wound healing is an important clinical problem in diabetes mellitus and results in failure to completely heal diabetic foot ulcers (DFUs), which may lead to lower extremity amputations. In the present study, collagen based dressings were prepared to be applied as support for the delivery of neurotensin (NT), a neuropeptide that acts as an inflammatory modulator in wound healing. The performance of NT alone and NT–loaded collagen matrices to treat wounds in streptozotocin (STZ) diabetic induced mice was evaluated. Results showed that the prepared dressings were not-cytotoxic up to 72 h after contact with macrophages (Raw 264.7) and human keratinocyte (HaCaT) cell lines. Moreover, those cells were shown to adhere to the collagen matrices without noticeable change in their morphology. NT–loaded collagen dressings induced faster healing (17% wound area reduction) in the early phases of wound healing in diabetic wounded mice. In addition, they also significantly reduced inflammatory cytokine expression namely, TNF-α (p < 0.01) and IL-1β (p < 0.01) and decreased the inflammatory infiltrate at day 3 post-wounding (inflammatory phase). After complete healing, metalloproteinase 9 (MMP-9) is reduced in diabetic skin (p < 0.05) which significantly increased fibroblast migration and collagen (collagen type I, alpha 2 (COL1A2) and collagen type III, alpha 1 (COL3A1)) expression and deposition. These results suggest that collagen-based dressings can be an effective support for NT release into diabetic wound enhancing the healing process. Nevertheless, a more prominent scar is observed in diabetic wounds treated with collagen when compared to the treatment with NT alone.     

Healing potential of Pequi (Caryocar coriaceum Wittm.) fruit pulp oil

Caryocar coriaceum Wittm. (Caryocaraceae), popularly known as Pequi, is a common tree frequently used in folk medicine to treat many types of afflictions, such as wound lesions, gastric and inflammatory diseases. The present study was undertaken to evaluate the healing potential of the pulp oil from C. coriaceum (OCC) in rats and mice. OCC was tested by monitoring wound contraction in incised wounds and topical application of OCC accelerated wound contraction in open wounds. The mean values of wound contraction in pulp oil treated rats on day 16 were 6.25 ± 0.51% as against 4.17 ± 0.28% seen in control and the difference was statistically significant (p < 0.01). Gastric lesions induced by ethanol and aspirin were significantly reduced by OCC (200 and 400 mg/kg, p < 0.05). Pretreatment of mice with yohimbine, indomethacin, l-NAME or glibenclamide greatly suppressed the gastroprotective effect of OCC. Thus we provide the first evidence that OCC reduces gastric damage induced by ethanol, at least in part, by mechanisms that involve α₂-receptors, endogenous prostaglandins, nitric oxide and K⁺ATP channels. These results indicate the beneficial effect of C. coriaceum on wound and gastric healing and justify its traditional use for the treatment of wounds and gastric ulcers.     

Utilidad clínica de la micafungina en el tratamiento de las candidiasis invasoras en el paciente oncohematológico

BackgroundInvasive candidiasis is a severe infection among onco-hematological patients, with an attributable mortality around 40%. Micafungin has shown efficacy in antifungal prophylaxis among hematopoietic stem cell transplant recipients and in the treatment of esophageal candidiasis.AimsTo assess the role of micafungin in the treatment of invasive candidiasis among onco-hematological patients.MethodsLiterature review.ResultsIn a study on 126 patients with candidemia treated with micafungin, an overall response rate of 83% was reported. A double-blind study of 531 patients with invasive candidiasis comparing micafungin (100 mg/day) versus liposomal amphotericin B (3 mg/kg/day) reported success in 90% of patients in both arms, with a more favorable safety profile with micafungin. Other double blind randomized, phase III study compared two doses of micafungin (100 mg/day and 150 mg/day) with standard doses of caspofungin (70 mg loading dose, then 50 mg/day) in adults with invasive candidiasis. Overall success rate was 74% for micafungin 100 mg/day, 70% for micafungin 150 mg/day, and 71% for caspofungin. A double blind randomized study compared micafungin (2 mg/kg/day) to liposomal amphotericin B (3 mg/kg/day) in the treatment of invasive candidiasis in children with a predominance of infections with non-albicans Candida spp. Overall success rate was similar (73% for micafungin and 76% for liposomal amphotericin B).ConclusionsComparative phase III studies have demonstrated non-inferiority of micafungin compared to standard antifungal agents for invasive candidiasis. Micafungin is safe and effective in the treatment of children and adults with invasive candidiasis. Effectivity in invasive infections caused by non-albicans Candida spp is especially relevant in onco-hematological patients receiving fluconazole prophylaxis.     

Laminar shear stress induces the expression of aquaporin 1 in endothelial cells involved in wound healing

Laminar shear stress (LSS) due to blood flow contributes to the maintenance of endothelial health by multiple mechanisms including promotion of wound healing. The present study examined the hypothesis that the induction of water channel aquaporin 1 (AQP1) expression by LSS might be functionally associated with endothelial wound healing. When human umbilical vein endothelial cells were exposed to LSS at 12 dyn cm^?2 for 24 h, significant increases in AQP1 expression were observed at the mRNA and protein levels as compared with static control. In the in vitro scratch wound healing assay, LSS treatments before and after wound creation enhanced endothelial wound healing and this effect was significantly attenuated by selective suppression of AQP1 expression using small interfering RNA. Ectopic expression of AQP1 enhanced wound healing in the absence of LSS. This study demonstrated that LSS stimulates the endothelial expression of AQP1 that plays a role in wound healing.     

Urinary parameters predictive of cisplatin-induced acute renal injury in dogs

A 28-day study was conducted to evaluate changes in urinary cytokine/chemokine expression levels in dogs with renal injury due to administration of cisplatin. Animals (n = 17) were administered cisplatin at 0.75 mg/kg/day (i.v.) for five consecutive days. Urine/serum were collected at pre-dosing, 4 h post-dosing and on days 2, 3, 4, 8, 10, 14, 16, 18, 21, 23, 25, 28 and unscheduled terminations. Animals were euthanized when serum creatinine (sCr) levels measured at ⩾1.9 mg/dL, indicating significant loss of renal function (decreased glomerular filtration rate). Relevant clinical observations included lethargy and dehydration. Pre-study sCr levels ranged from 0.6 to 0.8 mg/dL; on days 1 through 4, sCr levels ranged from 0.5 and 1.1 mg/dL; and terminal sCr levels ranged from 0.6 and 6.6 mg/dL. Histologically, cisplatin-related renal changes were characterized as proximal tubule dilatation, vacuolization, degeneration, regeneration, and interstitial inflammation. Increased interleukin (IL)-2, IL-8, monocyte chemoattractant protein-1 (MCP-1), granulocyte–macrophage colony-stimulating factor (GMCSF) and keratinocyte-derived chemokine (KC) occurred on days 3 through 4. Increased IL-7 occurred on day 4. This study showed for the first time that inflammatory cytokines/chemokines in urine positively identified acute renal tubular injury in dogs at time points earlier than sCr, a traditional marker of nephrotoxicity.     

Thymosin beta 4 improves dermal burn wound healing via downregulation of receptor of advanced glycation end products in db/db mice

BackgroundThe delay of dermal burn wound healing caused by vascular disorders is a critical problem for many diabetic patients. Thymosin β₄ (Tβ₄), identified by subtractive cloning of endothelial cells on plastic versus basement membrane substrates, has been found to promote angiogenesis and dermal wound repair in rats, aged mice, and db/db diabetic mice. However, previous studies involving the role of Tβ₄ in wound repair were limited to mechanical damage and dermal impairment. Thus, this study aimed to evaluate the improvement of healing of burn wounds by Tβ₄ in relation to advanced glycation end products (AGE), which are pathological factors in diabetes.MethodsWe adapted a dermal burn wound in vivo model in which the dorsal skin of db/db mice was exposed for 10 s to 100 °C heated water to produce a deep second-degree burn 10 mm in diameter. Five mg/kg of Tβ₄ was then injected intradermally near the burn wound twice a week for 2 weeks.ResultsAfter treatment, Tβ₄ improved wound healing markers such as wound closure, granulation, and vascularization. Interestingly, Tβ₄ reduced levels of receptor of AGE (RAGE) during the wound healing period.ConclusionsTβ₄ exerts effects to remedy burn wounds via downregulation of RAGE.General significanceOur results suggest the potential importance of Tβ₄ as a new therapy for impaired burn wound healing that is associated with diabetes.     

Endothelial and vascular smooth muscle cell dysfunction mediated by cyclophylin A and the atheroprotective effects of melatonin

AimsThis study evaluated the role of cyclophilin A (CyPA) in early phase of atherosclerosis and also examined the atheroprotective effects of melatonin due to its antioxidant properties.Main methodsAPOE null mice at 6 and 15 weeks of age were treated with melatonin at a dose of 0.1 mg/kg/day or 10 mg/kg/day. We evaluated both histopathological alterations in endothelial and vascular smooth muscle cells by CyPA and rolling mononuclear cell expression during the early phase of atherosclerosis development.Key findingsOur study showed that CyPA expression increases and may modulate inflammatory cell adhesion and interleukin-6 expression inducing vascular smooth muscle cell migration and inflammatory cell extravasation in a time-dependent manner. Moreover, we observed an indirect atheroprotective effect of melatonin on vascular injury; it inhibited CyPA mediated inflammatory cell extravasation and oxidative stress.SignificanceThe melatonin treatment may represent a new atheroprotective approach that contributes to reducing the early phase of atherosclerosis involving the rolling of monocytes, their passage to subendothelial space and inhibition of CyPA expression.     

TNF-α depuration is a predictor of mortality in critically ill patients under continuous veno-venous hemodiafiltration treatment

IntroductionCritically ill patients with acute kidney injury (AKI) present high mortality rates. The magnitude of inflammatory response could determine the prognosis of such patients. Continuous renal replacement therapy (CRRT) may play an important role in removing inflammatory mediators in patients with AKI.AimTo investigate whether the magnitude of inflammatory mediator’s removal is associated with mortality among critically ill patients on CVVHDF, a CRRT modality.MethodsThis study consisted of 64 critically ill patients requiring CVVHDF. Plasma levels of C3a, TNF-α, IL-10, IL-6, IL-1β, sTNFRI and sTNFRII were determined by enzyme-linked immunosorbent assay (ELISA) at the beginning of CVVHDF and after 24 h (outlet). Clearance of cytokines during the first 24 h of CVVHDF was calculated. Clinical and laboratory data were acquired from patient’s records data.ResultsMean age of patients requiring CVVHDF was 63 years, 67.2% were men and 87.3% were Caucasian. Thirty-five (35) patients (54.7%) died. Comparing non-survivors with the group of survivors we observed higher incidence of sepsis (68.6 versus 37.9%, p < 0.05), higher APACHE II score (34.8 ± 7.6 versus 29.2 ± 7.1, p < 0.05) and higher lactate levels (23.2 ± 17.6 versus 16.4 ± 6.6, p < 0.05). According to the inter-tertile range of TNF-α clearance (ITR1 (<0.54); ITR2 (0.54–2.93); ITR3 (>2.93)) we found that those patients with higher TNF-α removal by RRT (ITR3) had a better survival. Multivariable analysis showed that lower clearance of TNF-α remained independently associated with high mortality after adjustment for sex, age, use of vasoactive drugs, APACHE II score sepsis, creatinine and lactate before CVVHDF (HR: 0.179, 95% IC: 0.049–0.661, p < 0.01).ConclusionThe attenuation of inflammatory response may be related to the lower mortality observed on those patients with higher TNF-α removal by CVVHDF.     

Effect of sophora japonica total flavonoids on pancreas,kidney tissue morphology of streptozotocin-induced diabetic mice model

To observe effect of sophora japonica total flavonoids on pancreas, kidney tissue morphology of streptozotocin-induced diabetic mice model. Mice received tail vein injection of streptozotocin (60 mg/kg) for diabetes modeling. The model mice were divided into five groups, to be respectively fed with high, middle and small doses of sophora japonica total flavonoids solution, metformin solution and saline of the same volume. Another blank control group was set to be fed with saline of the same volume. The mice were administered once a day for 30 consecutive days, to be euthanatized after fasting blood glucose level testing on 30th day with pancreas, kidney taken out for pathological section and microscopic examination. The mice chain streptozotocin diabetes modeling was successful, with significant pathological changes (P < 0.01) in pancreas, kidney. Compared with model group, high, middle and small doses of sophora japonica total flavonoids could significantly alleviate streptozotocin-induced pancreas, kidney damage (P < 0.01). Conclusion: Sophora japonica total flavonoids can effectively alleviate pancreas, kidney injury of streptozotocin-induced diabetic mice model.     

Nesfatin-1 improves oxidative skin injury in normoglycemic or hyperglycemic rats

Hyperglycemia is one of the major causes of suppressed angiogenesis and impaired wound healing leading to chronic wounds. Nesfatin-1 a novel peptide was reported to have antioxidant and anti-apoptotic properties. This study is aimed to investigate the potential healing-promoting effects of nesfatin-1 in non-diabetic or diabetic rats with surgical wounds. In male Sprague-Dawley rats, hyperglycemia was induced by intraperitoneal (ip) injection of streptozotocin (55 mg/kg). Under anesthesia, dorsum skin tissues of normoglycemic (n = 16) and hyperglycemic rats were excised (2 × 2 cm, full-thickness), while control rats (n = 16) had neither hyperglycemia nor wounds. Half of the rats in each group were treated ip with saline, while the others were treated with nesfatin-1 (2 μg/kg/day) for 3 days until they were decapitated. Plasma interleukin-1-beta (IL-1β), transforming growth factor-beta (TGF-β-1), IL–6 levels, and dermal tissue malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) and caspase-3 activity were measured. For histological examination, paraffin sections were stained with hematoxylin-eosin or Masson’s trichrome and immunohistochemistry for vascular endothelial growth factor (VEGF) was applied. ANOVA and Student’s t-tests were used for statistical analysis. Compared to control rats, skin MPO activity, MDA and caspase-3 levels were increased similarly in saline-treated normo- and hyperglycemic rats. Nesfatin-1 depressed MDA, caspase-3, MPO activity and IL-1β with concomitant elevations in dermal GSH and plasma TGF-β-1 levels. Histopathological examination revealed regeneration of epidermis, regular arrangement of collagen fibers in the dermis and a decrease in VEGF immunoreactivity in the epidermal keratinocytes of nesfatin-1-treated groups. Nesfatin-1 improved surgical wound healing in both normo- and hyperglycemic rats via the suppression of neutrophil recruitment, apoptosis and VEGF activation.     

Effect of nano-silver hydrogel coating film on deep partial thickness scald model of rabbit

Objective

Observing the effect of nano-silver hydrogel coating film on deep partial thickness scald model of rabbit.

Clomipramine and benznidazole association for the treatment of acute experimental Trypanosoma cruzi infection

Alternative strategies are being designed to identify candidates among drugs already available on the market that could be used in combination to improve the efficacy of Chagas disease treatment. This work evaluates the effect of the association of clomipramine (CLO) with benznidazole (BZN) for the treatment of experimental Chagas disease in the acute stage, in Swiss albino mice infected with Trypanosoma cruzi Tulahuen strain. Infected mice were treated with CLO 5 mg/kg/day and BZN 50 and 100 mg/kg/day, each separately or together. Efficacy of the treatment was evaluated through parasitemia, survival, electrocardiography, histopathological studies, serological and PCR assays at 90 days post-infection (dpi). All treatments significantly (P < 0.05) reduced mortality and decreased parasitemia. Histopathological analysis of liver and kidneys of mice treated with CLO and the drug combination showed less injury than mice treated only with BZN. The lower dose of BZN (50 mg/kg/day) combined with CLO showed the same efficacy as the habitual dose of BZN (100 mg/kg/day) combined with CLO. The therapeutic results from the combination of BZN with CLO presented lesser side effects than the treatment with BZN.     

Interleukin (IL)-19 promoted skin wound healing by increasing fibroblast keratinocyte growth factor expression

BackgroundInterleukin (IL)-19, a member of the IL-10 cytokine family, is involved in keratinocyte proliferation in psoriasis.ObjectivesWe investigated the role of IL-19 in the wound-healing process in vivo and in vitro.MethodsTwo full-thickness circular wounds (4 mm in diameter) were punched into the skin of BALB/C mice. IL-19 and keratinocyte growth factor (KGF) mRNA in wounded skin were determined using real-time PCR. The wounds were treated with PBS, vehicle, IL-19 (400 ng/mL), or IL-20 (400 ng/mL) (n = 6 in each group) twice daily and the percentage of wound healing was measured daily for 7 days. In vitro, human skin fibroblast CCD966-SK cells and keratinocyte HaCaT cells were treated with IL-19 or KGF. Cell proliferation and migration were determined using bromodeoxyuridine (BrdU) and transwell assays, respectively. The expression of IL-19 and KGF mRNA was also analyzed.ResultsIn wounded mouse skin, IL-19 mRNA was upregulated at 12 h, and KGF at 24 h after the injury. Both increases in gene expression declined 72 h after the skin had been wounded. The percentage of wound healing in IL-19-treated mice was higher than in control mice. In vitro, IL-19 upregulated KGF expression in the CCD966-SK cells; IL-19 was upregulated in KGF-treated HaCaT cells. KGF but not IL-19 promoted HaCaT cell proliferation. However, IL-19 significantly increased the migration of HaCaT cells. HaCaT cells treated with the cultured supernatants of IL-19-stimulated CCD966-SK cells showed significantly more proliferation than in controls.ConclusionsIL-19 is important for cutaneous wound healing because it upregulates KGF expression.     

Immobilization of trypsin on polysaccharide film from Anacardium occidentale L. and its application as cutaneous dressing

Polysaccharide obtained from Anacardium occidentale L. gum was used for trypsin entrapment using cellulose (gaze) as a support and this preparation was applied as cutaneous wound healing. Trypsin release in vitro and the influence of pH and temperature on activity, stability and storage time of entrapped enzyme were evaluated. The preparation showed that it was still capable to release enzyme even after 48 h. Entrapped enzyme presented an optimal pH and temperature of 8.6 and 55 °C, respectively. Also, it was stable at high temperature (45 °C for 60 min) and wide range of pH, retaining 80% of its initial activity when stored for 28 days at 25 °C. Histopathological analysis of mice skin wound healing under the entrapped trypsin preparation treatment showed an acceleration of fibroblast proliferation, neovascularization of granulation tissue and stimulating effect on the epithelium formation compared to the skin wound under the treatment using preparations without trypsin. These results demonstrate that the trypsin–polysaccharide–cellulose preparation could be used in cutaneous dressing applications for wound healing.     

Global perspectives on trace element requirements

Trace elements are inorganic constituents of the human body present in concentrations less than 50 mg/kg body weight. An exception is iron that is found in slightly higher amounts, 60 mg/kg body weight, but it is classified within this category due to its physiological roles. Requirements of trace elements can vary according to age, gender, growth, body composition, genetics, pregnancy, lactation, wound healing and burns, alcohol abuse, infections, and diseases (anemia, coronary artery, Keshan, Kashin–Beck). Additionally, interactions may occur with dietary factors, such as other minerals (iron versus copper), phytates (zinc), oxalates (iron), fiber (manganese), and polyphenolic compounds (molybdenum). On a global basis, requirements can vary according to soil and geographical location, food preparation and processing, food accessibility, cultural practices (geophagia) and pollution. Furthermore, global differences exist in body composition, ethnicity, and age of menarche.     

Cleavage of hyaluronan is impaired in aged dermal wounds

Changes in extracellular matrix (ECM) are one of many components that contribute to impaired wound healing in aging. This study examined the effect of age on the glycosaminoglycan hyaluronan (HA) in normal and wounded dermis from young (4–6 month-old) and aged (22–24 month-old) mice. HA content and size were similar in the normal dermis of young and aged mice. Dermal explants labeled with [³H]-glucosamine showed decreased generation of smaller forms of HA in aged explants relative to young explants. Aged mice exhibited delayed wound repair compared with young mice with the greatest differential at 5 days. Expression of hyaluronan synthase (HAS) 2 and 3, and hyaluronidase (HYAL) 1–3 mRNA in wounds of young and aged mice was similar. There was a trend toward a decreased HYAL protein expression in aged wound dermis, which was accompanied by changes in detectable HYAL activity. Total HA content was similar in young and aged wound dermis. There was significantly less HA in the lower MW range (~ 250 kDa and smaller) in 5-day wound dermis, but not in 9-day wound dermis, from aged mice relative to young mice. We propose that decreased cleavage of HA is an additional component of impaired dermal wound healing in aging.     

Assessment of functional recovery in tennis elbow

Objectives: (a) To investigate changes in muscular strength, fatigue and activity in recovered tennis elbow (RTE); (b) to assess the appropriateness of EMG and strength measurements in monitoring functional recovery in tennis elbow (TE).Methods: Study included three age-matched female groups of Control (C) (n = 8, no history of musculoskeletal problems), TE (n = 7, local tenderness at the lateral epicondyle and pain with resisted wrist and middle finger extension) and RTE (n = 6, asymptomatic for at least 6 months, no lateral epicondyle tenderness). Measurements included metacarpophalangeal (MCP), wrist, shoulder and grip isometric strength and EMG measures of muscle fatigue and activity for five forearm muscles (wrist extensors and flexors).Results: Strength was greater (p < 0.05) for all measurements in C compared to RTE and TE except for MCP extension. Only MCP extension was stronger in RTE than TE. EMG revealed increased activity of extensor carpi radialis (ECR) in RTE, decreased in TE.Conclusions: Despite attenuation of pain, global upper limb weakness in RTE indicated incomplete functional recovery. Increased strength of MCP extension may protect weakened wrist extensors from further injury. Monitoring the ECR activity as well as strength measurements may provide a useful assessment of functional recovery in TE.     

The effect of active hexose correlated compound in modulating cytosine arabinoside-induced hair loss,and 6-mercaptopurine- and methotrexate-induced liver injury in rodents

Background: Active hexose correlated compound (AHCC) (a mixture of polysaccharides, amino acids, lipids and minerals derived from cultured mycelia of a Basidiomycete mushroom, Lentinula edodes) was used to assess amelioration of alopecia (hair loss) caused by cytosine arabinoside (Ara-C) and modulation of liver injury caused by single doses 6-mercaptopurine (6-MP) plus methotrexate (MTX). Methods: Follicular integrity and hair growth was assessed in male and female SD neonatal rats (8 days old) treated with a single dose of Ara-C (30 mg/kg/day, i.p.) and AHCC (500 mg/kg/day, p.o.) for 7 consecutive days. The side effects of a single oral dose of 6-MP (2.5 mg/kg body weight) plus MTX (30 mg/kg body weight) and their amelioration by treatment with AHCC (1000 mg/kg body weight) for 28 days were assessed in male ddY mice (8 weeks old). Results: Of the Ara-C treated rats 71.4% showed severe alopecia and 28.6% showed moderate alopecia. However, the AHCC (p.o.)-treated Ara-C group was significantly protected from alopecia. Ara-C treated rats had profound loss of hair follicles but the Ara-C plus AHCC-treated group had mild losses of follicles. AHCC supplementation to the 6-MP- and MTX-treated mice significantly increased body weight, erythrocytes, leukocytes and serum albumin, improved liver hypertrophy and degeneration, normalized the activities of serum glutamic oxaloacetic transaminase (sGOT) and serum glutamic pyruvic transaminase (sGPT), and enhanced liver drug-metabolizing enzymes. Conclusion: Co-administration of AHCC significantly reduced the side effects associated with Ara-C, 6-MP and MTX. However, the molecular mechanism for AHCC activity and its clinical integrity for use needs defining.     

Genetic correlation and path analysis of transpiration efficiency for wheat flag leaves

A 4 × 4 complete diallel cross was set up with four different types of drought-resistant winter wheat varieties to define mutual relations among main quantitative traits and the contribution of each trait to the flag leaf transpiration efficiency (TE) in the grain filling phase. Through genetic correlative and path analysis, the influence of five physiological traits, net photosynthesis rate (Pn), stomatal conductance (Gs), intercellular CO₂ concentration (Ci), transpiration rate (Tr), and leaf temperature (Tl), on flag leaf TE was observed. The results of variance analysis showed that there were very significant differences between TE and the related five traits, as well as between these five traits. The results of genetic correlation analysis showed also that the absolute values of the correlation coefficients of corresponding traits to TE should be ordered as Pn > Gs > Tl > Tr > Ci in the early grain filling stage, Ci > Tr > Pn > Gs > Tl in the middle grain filling stage, and Pn > Ci > Tl > Tr > Gs in the late grain filling stage, respectively. The results of the combined analysis of genetic correlation and path analysis showed that at the early filling stage, there existed a strong positive genetic correlation between Pn and TE, and at the same time Pn had a direct positive contribution to TE. With the progression of grain filling, the stress of high temperature and drought strengthened and the function of flag leaves weakened, so that at the late grain filling phase Ci, Tr and Tl were strongly negatively correlated with TE and all these traits conferred direct negative contributions to TE. The results of this research showed that the selection of wheat genetic materials with slow-ageing, high-photosynthesis, low-transpiration and low leaf temperature should assist breeding of wheat with more efficient use of water in north western China.