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Jiaxuan Peng,1,* Kangxian Zhao,2,* Jiling Zhu,3,* Yanben Wang,4,5 Peng Sun,2 Qichang Yang,2 Tan Zhang,4 Weiqi Han,4 Wenjun Hu,4 Wanlei Yang,4 Jianwei Ruan,6 Yu Qian1,2,4 1Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, People’s Republic of China; 2The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China; 3Department of Clinical Medicine, Medical College of Shaoxing University, Shaoxing, Zhejiang 312000, People’s Republic of China; 4Department of Orthopaedics, Shaoxing People’s Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang, People’s Republic of China; 5Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Orthopaedics, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang, Republic of China*These authors contributed equally to this workCorrespondence: Yu QianDepartment of Orthopaedics, Shaoxing People’s Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang, People’s Republic of ChinaEmail doctor120@hotmail.comIntroduction: Osteoclasts are giant polynuclear cells; their main function is bone resorption. An increased number of osteoclasts and enhanced bone resorption exert significant effects on osteoclast-related bone-lytic diseases, including osteoporosis. Given the limitations of current therapies for osteolytic diseases, it is urgently required to develop safer and more effective alternatives. Sarsasapogenin, a major sapogenin from Anemarrhena asphodeloides Bunge, possesses potent antitumor effects and inhibits NF-κB and MAPK signaling. However, the manner in which it affects osteoclasts is unclear.Methods: We investigated the effects of anti-osteoclastogenic and anti-resorptive of sarsasapogenin on bone marrow-derived osteoclasts.Results: Sarsasapogenin inhibited multiple RANKL-induced signaling cascades, thereby inhibiting the induction of key osteoclast transcription factor NFATc1. The in vivo and in vitro results were consistent: sarsasapogenin treatment protected against bone loss in a mouse osteolysis model induced by lipopolysaccharide.Conclusion: Our research confirms that sarsasapogenin can be used as a new treatment for osteoclast-related osteolytic diseases.Keywords: sarsasapogenin, osteoclast, osteoclastogenesis, NF-κB, MAPK, NFATc1, therapeutics

Background: ALK‐tyrosine kinase inhibitors (TKIs) have been proven effective for treating ALK‐positive non‐small cell lung cancer (NSCLC), although patients present with variable responses and disease progression courses. The detailed underlying molecular mechanisms require further investigation to yield a better prognosis. Methods: Targeted next‐generation sequencing (NGS) mutation profiling was performed on samples from 42 NSCLC patients confirmed positive for ALK rearrangements by fluorescence in situ hybridization or immunohistochemistry who experienced disease progression after crizotinib treatment. Results: ALK rearrangements were not confirmed in six patients (14%) with other potential oncogenic drivers identified by NGS, who therefore did not respond to crizotinib and had significantly shorter overall survival (OS) compared to NGS ALK ‐positive patients. Fifteen ALK activating mutations were detected in 8 out of 26 post‐treatment samples (31%), among which ALK L1196M and G1269A were the most common acquired mutations detected in half of the patients with ALK activating mutations. Dynamic monitoring of the genetic evolution in one patient revealed both spatial and temporal heterogeneity of resistant mechanisms during different ALK‐TKI treatment courses. Activation of ALK downstream or bypass pathways was detected in patients without ALK activating mutations, such as genetic alterations in PIK3CA, MET, and KRAS. Interestingly, we identified two patients with acquired mutations in the DNA mismatch repair gene POLE, which resulted in a dramatically increased tumor mutation burden, and might contribute to the poor response to crizotinib. Conclusions: Heterogeneous resistant mechanisms have been identified and correlate to diverse responses to crizotinib. Comprehensive and dynamic mutation profiling is required to better predict clinical outcomes. [ABSTRACT FROM AUTHOR]

Summary: Monitoring longitudinal nonadvanced fibrosis is a more common scenario in management of chronic hepatitis B (CHB), for which, however, current evaluation methods generally lack sufficient performance. We conducted a proof‐of‐concept study to evaluate the performance of quantitative fibrous collagen parameters (q‐FP) in the assessment. Data sets from a prior CHB trial (NCT00962533) with mostly mild‐to‐moderate fibrosis participants were used for this study. 301 subjects with paired liver biopsies were consecutively included. Of these, 139 subjects were used to establish the test and the rest for internal validation. Fibrosis change between baseline and week 104 of treatment was blindly assessed with q‐FP and was compared with Ishak fibrosis staging. There were 70% and 93% subjects with Ishak F0‐2 at baseline and week 104, respectively. For the test of the subjects, q‐FP and Ishak staging showed no difference in determining the incidence of fibrosis regression (68% vs 67%; difference = 0.7%, P = 1.00). Q‐FP demonstrated that the regression was independently associated with the antiviral efficacy endpoint (OR 3.0, 95% CI 1.4‐6.5, P = .005), but Ishak failed the detection (OR 0.6, 95% CI 0.3‐1.3, P = .24). Moreover, q‐FP directly revealed a higher fibrosis‐resistance to antiviral treatment in virus genotypes C vs B and in males vs females. These results were confirmed in the validation subjects. Additionally, a functional model built on the test subjects showed an accuracy of 82% in stratifying fibrosis reversibility of the validation subjects. In conclusion, q‐FP could have improved efficiency and accuracy in the longitudinal assessment of mild‐to‐moderate CHB fibrosis, indicating a potential alternative to current evaluation methodologies. [ABSTRACT FROM AUTHOR]

Aims Metformin and acarbose have comparable efficacy as initial therapy for HbA1c reduction in Chinese patients with newly diagnosed Type 2 diabetes. However, not all participants achieved glycaemic control. Our aim was to discover a monotherapy predictor for therapeutic response in Type 2 diabetes on the basis of baseline features. Methods Data from the MARCH trial were collected, resulting in 698 individuals being available for longitudinal analyses. All participants were divided into subgroups based on successful and unsuccessful achievement of the glycaemic target according to primary endpoints at week 24 (HbA1c < 53 mmol/mol; 7.0%). Logistic regression analysis with stepwise variable selection was performed to assess the independent risk factors for good glycaemic control of monotherapy with metformin or acarbose. Results Median HbA1c was 66 ± 1 mmol/mol (8.2 ± 0.07%) in the metformin group at baseline, and 66 ± 1 mmol/mol (8.2 ± 0.07%) in the acarbose group. After 24 weeks of monotherapy, 79.8% of participants in the metformin group achieved glycaemic targets compared with 78.7% of those in the acarbose group. Multivariate regression analysis showed that BMI and fasting blood glucose were significant independent predictors for the maintenance of good glycaemic control in the metformin group, whereas phase I insulin secretion (Insulin/Glucose at 30 min, I30/G30) and duration of diabetes were associated with good glycaemic control in the acarbose group. Conclusions For newly diagnosed Type 2 diabetes, some clinical features and laboratory parameters are important prognostic factors for predicting drug responsiveness. Participants with a higher BMI and lower fasting blood glucose achieved good glycaemic control when metformin was selected as the initial treatment. Acarbose was best for participants with higher phase I insulin secretion (I30/G30) and shorter duration of Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims To test the hypothesis that delivery of integrated care augmented by a web-based disease management programme and nurse coordinator would improve treatment target attainment and health-related behaviour. Methods The web-based Joint Asia Diabetes Evaluation ( JADE) and Diabetes Monitoring Database ( DIAMOND) portals contain identical built-in protocols to integrate structured assessment, risk stratification, personalized reporting and decision support. The JADE portal contains an additional module to facilitate structured follow-up visits. Between January 2009 and September 2010, 3586 Chinese patients with Type 2 diabetes from six sites in China were randomized to DIAMOND ( n = 1728) or JADE, plus nurse-coordinated follow-up visits ( n = 1858) with comprehensive assessments at baseline and 12 months. The primary outcome was proportion of patients achieving ≥ 2 treatment targets (HbA1c < 53 mmol/mol (7%), blood pressure < 130/80 mmHg and LDL cholesterol < 2.6 mmol/l). Results Of 3586 participants enrolled (mean age 57 years, 54% men, median disease duration 5 years), 2559 returned for repeat assessment after a median (interquartile range) follow-up of 12.5 (4.6) months. The proportion of participants attaining ≥ 2 treatment targets increased in both groups ( JADE 40.6 to 50.0%; DIAMOND 38.2 to 50.8%) and there were similar absolute reductions in HbA1c [ DIAMOND −8 mmol/mol vs JADE −7 mmol/mol (−0.69 vs −0.62%)] and LDL cholesterol ( DIAMOND −0.32 mmol/l vs JADE −0.28 mmol/l), with no between-group difference. The JADE group was more likely to self-monitor blood glucose (50.5 vs 44.2%; P = 0.005) and had fewer defaulters (25.6 vs 32.0%; P < 0.001). Conclusions Integrated care augmented by information technology improved cardiometabolic control, with additional nurse contacts reducing the default rate and enhancing self-care. (Clinical trials registry no.: NCT01274364) [ABSTRACT FROM AUTHOR]

Objective: Hypersplenism is a common disease. The conventional treatment is splenectomy and partial splenic embolization; however, both of them have high complication rates and technical defects. Therefore, safer and more effective techniques should be considered for the treatment of hypersplenism. High-intensity focused ultrasound (HIFU) may provide an effective and safe way for treatment of hypersplenism. Therefore, we conducted this study to assess the safety and efficacy of HIFU in treatment of secondary hypersplenism. Methods: A to ta l of 28 patients who suffered from secondary hypersplenism were treated w ith HIFU ablation. All patients who underwent HIFU were closely followe dup over a year. MRI scan was performed, and the spleens were observed. Blood counts and liver function tests were also carried out. Results: In the follow-up process, the levels of white blood cells and platelets in the blood after HIFU were significantly higher than those before HIFU, liver function also improved after HIFU treatment. In addition, the symptoms were ameliorated significantly or even disappeared. The MRI showed that the ablation area had turned into a non-perfused volume, and after 12 months of HIFU ablation, the ablated area shrank evidently; the sunken spleen formed a lobulated shape and the splenic volume decreased. Conclusion: HIFU ablation is a safe, effective and noninvasive approach for secondary hypersplenism. Advances in knowledge: For the first time we used HIFU ablation to treat secondary hypersplenism. It not only expands indications of HIFU but also provides better choice for the treatment of secondary hypersplenism. [ABSTRACT FROM AUTHOR]

We sought to investigate the antifibrotic effects of an artificial microRNA (miRNA) targeting connective tissue growth factor (CTGF) using the ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system. Cationic liposomes were conjugated with microbubbles using a biotin-avidin system. Plasmids carrying the most effective artificial miRNA sequences were delivered by ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system to rats with hepatic fibrosis. The results show that this method of gene delivery effectively transported the plasmids to the rat liver. The artificial miRNA reduced hepatic fibrosis pathological alterations as well as the protein and mRNA expressions of CTGF and transforming growth factor β1. Furthermore, the CTGF gene silencing decreased the levels of type I collagen and α-smooth muscle actin (P<0.01). These data suggest that delivery of an artificial miRNA targeted against CTGF using ultrasound-targeted cationic liposome-bearing microbubble destruction may be an efficacious therapeutic method to ameliorate hepatic fibrosis. [ABSTRACT FROM AUTHOR]

This study was performed to assess the efficacy of beraprost sodium ( BPS) in painful diabetic peripheral neuropathy ( DPN) in type 2 diabetes mellitus ( T2DM) patients. In this randomized clinical trial, 99 T2DM patients (41% male, age 60 ± 6 years) with DPN but without evidence of peripheral artery disease were randomized to receive either BPS (40 µg, tid) or placebo for 8 weeks. The primary end point was the improvement of the total symptom score ( TSS), temperature rebound ( TR) and nadir to peak ( NP) above baseline. After 8 weeks treatment, the change of TSS in the BPS group showed a significant improvement compared to the placebo group (2.80 ± 2.48 vs. 1.60 ± 1.94 points, p = 0.009). Furthermore, the number of patients who showed signs of improvement in TSS and the proportion of patients with 50% relief of symptom was also significantly greater in the BPS group than in the placebo group (83.7 vs. 62%, p = 0.015, 36.2 vs. 14%, p = 0.009, respectively). In conclusion, treatment with BPS significantly improved TSS over an 8-week period. [ABSTRACT FROM AUTHOR]

The article discusses the role of pharmacogenetic testing in clinical research and informs that it will be helpful in the expansion of pharmacogenetic variants. It informs that using computational tools integrated with electronic medical record are used for prescribing drugs on the basis of genetic data and this process can increase efficiency for disease interpretation.

Background: Cucurbitacin (Cuc) and triterpene-derived natural products exhibit anti-cancer potential in addition to their conspicuous anti-bacterial and anti-inflammatory activity. Recently, inhibition of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling was shown to underlie the effects of Cuc family on inducing cell death in cancer.Method: We purified Cuc IIa, the active component from the medicinal plant Hemsleya amalils Diels, which shows different structural modifications from other Cuc derivatives. We investigated the mechanisms of its inhibitory effects on cancer cells in vitro and tumour growth in vivo.Results: Cuc IIa induced the irreversible clustering of filamentous actin and arrested cell cycle by the increases in G2/M populations. Cuc IIa resulted in the reduced phospho-Histone H3 and markedly increased cleavage of poly-(ADP-ribose) polymerase or PARP, immediate upstream of DNA breakdown as the result of caspase activation, consistent with mitotic blockage-induced cell death. However, unlike other Cuc members, Cuc IIa did not suppress JAK2/STAT3 phosphorylation or alter phosphorylation of mitogen-activated protein kinases. Instead, the expression of the cell cycle-regulated Inhibitor of Apoptosis Protein (IAP) survivin was reduced. Introducing oncoprotein δ-catenin, which increased survivin expression and suppressed small GTPase RhoA, reduced efficacy of Cuc IIa to induce cell death. Supporting the effects of Cuc IIa on actin cytoskeletal signaling, RhoA phosphorylation was reduced suggesting its increased activity.Conclusion: Cuc IIa is a novel class of anti-cancer drug in suppression of cancer cell expansion by disrupting the actin cytoskeleton and directing the cell to undergo PARP-mediated apoptosis through the inhibition of survivin downstream of JAK2/STAT3. [ABSTRACT FROM AUTHOR]

Asparaginase is an important component for treatment of childhood acute lymphoblastic leukemia (ALL). The basis for interindividual differences in asparaginase sensitivity remains unclear. To comprehensively identify genetic variants important in the cytotoxicity of asparaginase, we used a genome-wide association approach using the HapMap lymphoblastoid cell lines (87 CEU trio members) and 54 primary ALL leukemic blast samples at diagnosis. Asparaginase sensitivity was assessed as the drug concentration necessary to inhibit 50% of growth (inhibitory concentration (IC)(50)). In CEU lines, we tested 2,390,203 single-nucleotide polymorphism (SNP) genotypes at the individual SNP (P<0.001) and gene level (P<0.05), and identified 329 SNPs representing 94 genes that were associated with asparaginase IC(50). The aspartate metabolism pathway was the most overrepresented among 199 pathways evaluated (P=8.1 × 10(-3)), with primary involvement of adenylosuccinate lyase and aspartyl-tRNA synthetase genes. We validated that SNPs in the aspartate metabolism pathway were also associated with asparaginase sensitivity in primary ALL leukemic blast samples (P=5.5 × 10(-5)). Our genome-wide interrogation of CEU cell lines and primary ALL blasts revealed that inherited genomic interindividual variation in a plausible candidate pathway can contribute to asparaginase sensitivity. [ABSTRACT FROM AUTHOR]

Garlic and onion, are well known for their medical value, especially in against cancer and anticardiovacular diseases. “Alliins” (S-alk(en)yl-l-cysteine sulphoxides) are sources of major active compounds in Allium plants. Se incorporation into garlic significantly increases activities of garlic in cancer prevention and inhibition. Selenomethionine, selenocysteine and Se-methylselenocysteine have been identified in garlic and onion. Previously we identified γ-glutamyl-Se-methyl-l-selenocysteine, in extracts of garlic cultivated in Se-rich soil [Med. Res. Rev. 16 (1) (1996) 111], suggesting the possible existence of Se-alk(en)yl-l-cysteine selenoxides (Se-“alliins”) in garlic. Several comparative experiments were carried out to demonstrate the existence of Se-“alliins” in Se-enriched garlic and onion. We found that there was one similar time-dependent Se signal in HPLC–inductively coupled plasma MS chromatograms of cold-water extracts of freeze-dried garlic powder and fresh garlic. This signal was lost when the extracts of garlic powder and fresh garlic were stored for 1 day at >4 °C, but remained in fresh onion extract at the same storage conditions. These phenomena and possible mechanisms are discussed. An additional experiment showed that Allium species cultivated in Se-rich soil might contain two different Se-“alliins”. [Copyright &y& Elsevier]

Background: Pulmonary sarcomatoid carcinoma (SC) consists of both carcinomatous and sarcomatous tumors with high degree of malignancy, rapid progression, and poor prognosis. However, little is known regarding how pulmonary SC develops and progresses.Case Presentation: A 66-year-old male was initially diagnosed with stage IIIa lung cancer containing both adenocarcinoma (ADC) and SC. Adjuvant chemotherapy was administrated post-surgery, however, recurrence with SC only soon followed. Mutation profiling of the patient's microdissected ADC and SC components of the primary lesion and recurrent tumor was performed by targeted next-generation sequencing (NGS) of 416 cancer-relevant genes. Our data showed that primary SC/ADC and the recurrent SC shared multiple gene mutations including EGFR, NF1, TP53, CDKN2B, and SMARCA4, while both primary and recurrent SCs had a unique TP53 exon 4 splicing mutation frequently observed in sarcoma. Interestingly, a novel PHF20-NTRK1 fusion was acquired in the recurrent SC, which may be a potential driver for SC recurrence.Conclusions: The molecular genetic characteristics of tumor tissues at different stages reveals a linear tumor evolution model in this case, and support that the primary SC derived from the original lung ADC during the evolution of the tumor. We also identified a novel PHF20-NTRK1 fusion, which may contribute to the disease recurrence, and that can be potentially targeted with NTRK1 inhibitors for treatment. [ABSTRACT FROM AUTHOR]

Nephrotoxicity is a major concern for patients with psoriasis using cyclosporine. Here, we evaluated the impact of intermittent cyclosporine treatment on nephrotoxicity risk among patients with psoriasis in real‐world clinical practice. We retrospectively reviewed 611 patients with psoriasis treated with cyclosporine between January 2013 and January 2017, 398 of whom were considered eligible for analysis. Eighteen (4.5%) patients showed a greater than 25% increase in serum creatinine levels. Age over 60 years (relative risk [RR], 1.6; p = .015), diabetes (RR, 2.3; p < .001), and obesity (RR, 1.7; p = .011) were the significant risk factors of increased serum creatinine levels in patients with psoriasis. There was no significant association of the treatment duration or cumulative dose of cyclosporine with increased serum creatinine levels. In real clinical practice, intermittent cyclosporine use with regular serum creatinine tests can be used to treat psoriasis relatively safely. Age over 60 years, diabetes and obesity are significant risk factors for cyclosporine‐induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 36-year-old man with a history of psoriasis and treated with acitretin, phototherapy and methotrexate. He was diagnosed with central retinal vein occlusion (CRVO) after receiving treatment with adalimumab. It notes that retinal vein occlusion occurs after taking infliximab. It also mentions that CRVO is a side-effect of adalimumab.

Objectives: To investigate the expression levels of neuropilin 1 (NRP1) and vascular endothelial growth factor (VEGF) in the placentas of women with pre-eclampsia (PE), determine whether homocysteine (Hcy) contributes to the development of PE in mice, and detect alterations in placental NRP1 and VEGF in Hcy-treated mice.Study Design: Placental tissue samples were obtained from 16 patients with and without PE. Using reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, the expression levels of NRP1 and VEGF in PE and control placental tissues were examined. Immunohistochemical (IHC) assay was used to detect the localization of NRP1 and VEGF proteins. Pregnant mice were treated with DL-Hcy on embryonic day 7.5. The symptoms of the treated mice were examined. The expression levels of Ddah1, Ddah2, eNos, Cbs and Cse were determined by quantitative RT-PCR to study the possible mechanism of hyperhomocysteinemia (HHcy). Nrp1 and Vegf expression levels in the placentas of treated mice were measured by quantitative RT-PCR, western blot analysis and IHC.Results: NRP1 and VEGF were expressed at lower levels in women with PE compared with control women. The immunoreactivity of NRP1 was detected in villous trophoblast cells and villous capillary endothelial cells (ECs). Immunoreactive VEGF was observed mainly in vascular ECs within the villi. The pregnant mice treated with DL-Hcy showed PE-like symptoms such as higher systolic blood pressure and proteinuria in late pregnancy. Compared with the control mice, Ddah1, Ddah2 and eNos mRNA were expressed at lower levels, and Cbs and Cse mRNA were expressed at significantly higher levels in the placentas of the Hcy-treated group. Expression levels of Nrp1 and Vegf in mice placentas were decreased in the Hcy-treated group.Conclusions: DL-Hcy can induce PE-like symptoms in mice. Both placental NRP1 and VEGF were expressed at lower levels in women with PE and Hcy-treated mice, which may contribute to endothelial damage. [ABSTRACT FROM AUTHOR]

Abstract: Mesenchymal stem cells (MSCs) are multipotent stromal elements that can differentiate into a variety of cell types. MSCs are good sources of therapeutic cells for degenerative diseases. For these reason, many researchers have focused on searching for other sources of MSCs. To obtain MSCs for clinical use requires surgery of the donor that therefore can induce donor morbidity, since the common sources at present are bone marrow and adipose tissues. In this study, we investigated the existence of MSCs in postoperative discarded tissues. Subacromial bursal tissues were obtained from the shoulders of 3 injured patients. The cells from the bursa tissues were isolated through treatment with collagenase. The isolated cells were then seeded and expanded by serial passaging under normal culture system. To evaluate MSC characteristics of the cells, their MSC markers were confirmed by mRNA and protein expression. Multipotent ability was assessed using differentiation media and immunohistochemistry. Cells from the bursa expressed MSCs markers—CD29, CD73, CD90, and PDGFRB (platelet-derived growth factor receptor-beta). Moreover, as to their multipotency, bursal cells differentiated into adipocytes (fat cells), osteocytes (bone cells), and chondrocytes (cartilage cells). In summary, we showed that MSCs could be generated from the subacromial bursa, which is medical waste after surgery. [Copyright &y& Elsevier]

A study using 144 one-day-old Arbor Acres broilers was conducted to assess the effects of dried ginger root (Zingiber officinale) that was processed to particle sizes of 300, 149, 74, 37, and 8.4 μm on growth performance, antioxidant status, and serum metabolites of broiler chickens. The birds were housed in 24 wire cages in an environmentally controlled room. Dietary treatments were no supplementation (control) and supplementation with ginger root processed to 5 particle sizes at the level of 5 g/kg of diet. Average daily gain, ADFI, and feed conversion rate of chicks of each cage were measured weekly. Blood samples from 8 broilers per treatment were obtained at d 21 and 42 of the experiment to determine antioxidant enzymatic activities and metabolites in the serum, and the birds were subsequently killed to determine carcass yield and abdominal fat content. All broilers had similar ADFI or feed conversion rate over the entire experimental period. However, broilers supplemented with ginger powder tended to have higher ADO and had greater (P = 0.014) carcass yield compared with that of the control. Supplementation of ginger increased (P < 0.001) activities of total superoxide dismutase and glutathione peroxidase but reduced (P < 0.01) concentrations of malondialdehyde and cholesterol in serum of broilers at 21 and 42 d of age. Concentration of total protein in serum of ginger-supplemented broilers tended (P = 0.092) to be higher at 21 d and was higher (P 0.002) at 42 d of age compared with that of control broilers. Reducing particle size of ginger powder linearly reduced (P < 0.05) cholesterol (d 21) and linearly increased (P < 0.05) glutathione peroxidase (d 21), total superoxide dismutase (d 42), and total protein (d 21 and 42). Supplementation of ginger at the level of 5 g/kg improved antioxidant status of broilers and the efficacy was enhanced as the particle size was reduced from 300 to 37 pm. [ABSTRACT FROM AUTHOR]