A 7-Day Decitabine-Included Conditioning Regimen Accelerated Donor Hematopoietic Engraftment while Reduced the Occurrence of Mucositis without Interfering with Prognosis.

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the standard and curative treatment strategy for patients with hematologic malignancies. Recently, decitabine-included regimens have been investigated by several studies including ours, which may prevent relapse of primary malignant diseases. METHODS: This study was to retrospectively evaluate a 7-day decitabine-included regimen with reduced dose of idarubicin for patients with hematologic malignancies who underwent allo-HSCT. RESULTS: A total of 84 patients were enrolled, including 24 cases in 7-day and 60 cases in 5-day decitabine groups, respectively. Patients conditioned with 7-day decitabine regimen showed accelerated neutrophil (12.05 ± 1.97 vs. 13.86 ± 3.15; u = 9.309, p < 0.001) and platelet (16.32 ± 6.27 vs. 21.37 ± 8.57; u = 8.887, p < 0.001) engraftment compared with those treated with 5-day decitabine regimen. Patients in the 7-day decitabine group showed a significantly lower incidence rate of total (50.00% [12/24] versus 78.33% [47/60]; χ2 = 6.583, p = 0.010) and grade III or above (4.17% [1/24] vs. 31.67% [19/60]; χ2 = 7.147, p = 0.008) oral mucositis compared to those in the 5-day decitabine group. However, the occurrence of other major complications post-allo-HSCT and outcomes of patients in these two groups were comparable. CONCLUSION: These results demonstrate that this 7-day decitabine-contained new conditioning regimen seems to be feasible and safe for patients with myeloid neoplasms who receive allo-HSCT, and a large-scale prospective study is needed to confirm the findings of this study.

Devosia ginsengisoli sp. nov., isolated from ginseng cultivation soil.

A Gram-stain-negative, strictly aerobic, motile, ivory-coloured and rod-shaped bacterium (designated Gsoil 520T) isolated from ginseng cultivation soil was characterized by using a polyphasic approach to clarify its taxonomic position. Strain Gsoil 520T was observed to grow optimally at 30 °C and pH 7.0 on Reasoner's 2A agar medium. The results of phylogenetic analysis, based on 16S rRNA gene sequence similarities, indicated that Gsoil 520T belongs to the genus Devosia of the family Hyphomicrobiaceae and was most closely related to Devosia epidermidihirudinis E84T (98.0 %), Devosia yakushimensis Yak96BT (97.7 %), Devosia neptuniae J1T (97.7 %) and Devosia chinhatensis IPL18T (96.8 %). The complete genome of strain Gsoil 520T is a presumptive circular chromosome of 4 480 314 base pairs having G+C content of 63.7 mol%. A total of 4 354 genes, 4 303 CDS and 43 rRNA genes were assigned a putative function. The major isoprenoid quinone was Q-10. The main polar lipids were phosphatidylglycerol, diphosphatidylglycerol and two unidentified aminolipids (AL1 and AL3). The predominant fatty acids of strain Gsoil 520T were C18 : 1ω7c 11-methyl, C16 : 0 and C18 : 1ω7c/C18 : 1ω6c (summed feature 8) supporting the affiliation of strain Gsoil 520T to the genus Devosia. The low values of DNA-DNA hybridization distinguished strain Gsoil 520T from the recognized species of the genus Devosia. Thus, the novel isolate represents a novel species of the genus Devosia, for which the name Devosia ginsengisoli sp. nov. is proposed, with the type strain Gsoil 520T (=KACC 19440T=LMG 30329T).

Caballeronia ginsengisoli sp. nov., isolated from ginseng cultivating soil.

A Gram-stain-negative, strictly aerobic, non-motile, ivory colored and rod-shaped bacterium (designated Gsoil 652T) isolated from ginseng cultivating soil, was characterized using a polyphasic approach to clarify its taxonomic position. Strain Gsoil 652T was observed to grow optimally at 30 °C and at pH 7.0 on R2A agar medium. Phylogenetic analysis, based on 16S rRNA gene sequences similarities, indicated that Gsoil 652T belongs to the genus Caballeronia of the family Burkholderiaceae and was most closely related to Caballeronia choica LMG 22940T (98.9%), Caballeronia udeis LMG 27134T (98.9%), Caballeronia sordidicola LMG 22029T (98.2%) and Caballeronia humi LMG 22934T (98.1%). The DNA G+C content was 62.1 mol% and Q-8 was the major isoprenoid quinone. The main polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, unidentified aminophospholipid, and unidentified phospholipid. The predominant fatty acids were C16:0, C17:0 cyclo and C19:0 cyclo ω8c. The DNA-DNA relatedness value between strain Gsoil 652T and closely related type strains of Caballeronia species were less than 36.0%. Moreover, strain Gsoil 652T could be distinguished phenotypically from the recognized species of the genus Caballeronia. The novel isolate, therefore, represents a novel species, for which the name Caballeronia ginsengisoli sp. nov. is proposed, with the type strain Gsoil 652T (= KACC 19441T = LMG 30326T).

Coding and Noncoding Variants in CFH Act Synergistically for Complement Activation in Immunoglobulin A Nephropathy.

BACKGROUND: In immunoglobulin A nephropathy (IgAN), complement activation occurs in both the systemic circulation and in situ (glomerular). A recent IgAN-genome-wide association study (GWAS) identified 1q32 as an IgAN susceptible locus that contained the complement regulatory protein coding gene complement factor H (CFH). Here, we explored the combined genetic effects of coding and noncoding variants in CFH, rs6677604 and rs800292 on complement activation in IgAN. METHODS: In total, 1,194 IgAN patients and 900 healthy controls who were the same as the Beijing Discovery Cohort in our recent IgAN-GWAS were recruited. The genotyping information of rs800292 and rs6677604 were extracted from GWAS data, while the information regarding plasma C3 levels and mesangial C3 deposits were collected from medical records. RESULTS: We found both rs800292-GG and rs6677604-GG were risk genotypes for complement activation in IgAN patients, as represented by lower plasma C3 levels in IgAN patients with rs800292-GG and a higher intensity of glomerular C3 deposits in those with rs6677604-GG, respectively. Additionally, IgAN patients with 2 risk genotypes (rs800292-GG and rs6677604-GG) showed a higher degree of complement activation compared to those with no risk genotypes (rs800292-AA/AG and rs6677604-AA/AG), as represented by both lower plasma C3 levels and a higher intensity of glomerular C3 deposits. Moreover, when compared to rs800292 or rs6677604 alone, the combined genetic effects of rs800292 and rs6677604 showed a stronger association with IgAN susceptibility. CONCLUSIONS: Our findings suggested that both coding and noncoding variants in CFH acted synergistically to regulate the degree of complement activation and thereby contributed to IgAN susceptibility.

Terrabacter ginsengisoli sp. nov., isolated from ginseng cultivating soil.

A Gram-positive, strictly aerobic, nonmotile, yellowish, coccus-rod-shaped bacterium (designated Gsoil 653T) isolated from ginseng cultivating soil was characterized using a polyphasic approach to clarify its taxonomic position. The strain Gsoil 653T exhibited optimal growth at pH 7.0 on R2A agar medium at 30°C. Phylogenetic analysis based on 16S rRNA gene sequence similarities, indicated that Gsoil 653T belongs to the genus Terrabacter of the family Humibacillus, and was closely related to Terrabacter tumescens DSM 20308T (98.9%), Terrabacter carboxydivorans PY2T (98.9%), Terrabacter terrigena ON10T (98.8%), Terrabacter terrae PPLBT (98.6%), and Terrabacter lapilli LR-26T (98.6%). The DNA G + C content was 70.5 mol%. The major quinone was MK-8(H4). The primary polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidyl-ethanolamine. The predominant fatty acids were iso-C15:0, iso-C16:0, iso-C14:0, and anteiso-C15:0, as in the case of genus Terrabacter, thereby supporting the categorization of strain Gsoil 653T. However, the DNA-DNA relatedness between Gsoil 653T and closely related strains of Terrabacter species was low at less than 31%. Moreover, strain Gsoil 653T could be both genotypically and phenotypically distinguished from the recognized species of the genus Terrabacter. This isolate, therefore, represents a novel species, for which the name Terrabacter ginsengisoli sp. nov. is proposed with the type strain Gsoil 653T (= KACC 19444T = LMG 30325T).

Protective effects of Garcinol against neuropathic pain - Evidence from in vivo and in vitro studies.

Neuroinflammatory processes have a vital role in the pathogenesis of neuropathic pain. Garcinol, harvested from Garcinia indica, is known to exert potent anti-inflammatory properties. Recent studies have indicated that Garcinol may inhibit activation of nuclear factor-κB (NF-κB) by inhibiting NF-κB/p65 acetylation. These findings prompted us to evaluate the protective effects of Garcinol in the lumbar fifth spinal nerve ligation (SNL)-induced rat model of neuropathic pain and Lipopolysaccharide(LPS)-stimulated primary cultured microglia. In the present study, we found that intrathecal administration of Garcinol significantly attenuated SNL-induced nociceptive behaviors. Garcinol suppressed microglial activation as well as the expression of interleukin (IL)-1ß, IL-6, inducible nitric oxide synthase (iNOS)/nitric oxide (NO), and cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) in the spinal cord of SNL rats. It also reduced the nuclear translocation of NF-κB by decreasing acetyl-p65 protein expression. Similarly, in the in vitro study, Garcinol decreased the production of NO/iNOS, PGE2/COX-2, and proinflammatory cytokines in LPS-exposed microglia. Likewise, Garcinol inhibited the NF-κB signaling pathway by downregulating acetyl-p65 levels in LPS-challenged microglia. Our findings suggest that Garcinol may have protective effects against neuropathic pain that are associated with the inhibition of neuroinflammation in microglia. Therefore, Garcinol could be a promising agent in the treatment of neuropathic pain.

Identification and isolation of kidney-derived stem cells from transgenic rats with diphtheria toxin-induced kidney damage.

Adult stem cells have been well characterized in numerous organs, with the exception of the kidneys. Therefore, the present study aimed to identify and isolate kidney-derived stem cells. A total of 12 Fischer 344 transgenic rats expressing the human diphtheria toxin receptor in podocyte cells of the kidney, were used in the present study. The rats were administered 5-bromo-2'-deoxyuridine (BrdU) in order to detect cellular proliferation. After 60 days, the rats were treated with the diphtheria toxin (DT), in order to induce kidney injury. Immunohistochemical analysis indicated that the number of BrdU-positive cells were increased following DT treatment. In addition, the expression of octamer-binding transcription factor 4 (Oct-4), a stem cell marker, was detected and suggested that kidney-specific stem cells were present in the DT-treated tissue samples. Furthermore, tissue samples exhibited repair of the DT-induced injury. Further cellular culturing was conducted in order to isolate the kidney-specific stem cells. After 5 weeks of culture, the majority of the cells were non-viable, with the exception of certain specialized, unique cell types, which were monomorphic and spindle-shaped in appearance. The unique cells were isolated and subjected to immunostaining and reverse transcription-polymerase chain reaction analyses in order to reconfirm the expression of Oct-4 and to detect the expression of Paired box 2 (Pax-2), which is necessary for the formation of kidney structures. The unique cells were positive for Oct-4 and Pax-2; thus suggesting that the identified cells were kidney-derived stem cells. The results of the present study suggested that the unique cell type identified in the kidneys of the DT-treated rats were kidney-specific stem cells that may have been involved in the repair of DT-induced tissue injury. In addition, these cells may provide a useful cell line for studying the fundamental characteristics of kidney stem cells, as well as identifying kidney-specific stem cell markers.

[Impact of morphine on the reproductivity of male rats].

OBJECTIVE: To explore the effect of morphine on male reproductive ability and its mechanisms in the rat model of morphine tolerance. METHODS: Twenty male SD rats were equally randomized to groups I (control) and II (morphine tolerance). On the 1st day, the basic paw withdrawal thermal latency (PWTL) was obtained from all the rats followed by subcutaneous injection of morphine at 10 mg/kg and then calculation of the percentage of the maximal possible effect (MPE) at 30 min after administration. On the 2nd day, the rats of group I were injected subcutaneously with saline and those of group I with morphine at 10 mg/kg bid for 7 days. Then all the rats were killed after behavioral tests and their testes and epididymides harvested for sperm counting and determina- tion of the expressions of Bax and Caspase-3 by immunohistochemistry. RESULTS: On the 1st day, no obvious differences were ob- served between the two groups in the basic PWTL or the percentage of MPE. On the 7th day, the percentage of MPE was significantly decreased in group II as compared with group I (P < 0.05), while the basic PWTL showed no marked difference between the two groups. Group II also exhibited a significantly reduced epididymal perm count (P < 0.05) and remarkably upregulated expressions of Bax and Caspase-3 in comparison with group I. CONCLUSION: Morphine might increase testicular cell apoptosis and reduce sperm concentration by upregulating the expressions of Bax and Caspase-3 in the rat model of morphine tolerance.

[L-carnitine improves the reproductive function of male rats with ornidazole-induced asthenospermia].

OBJECTIVE: To explore the protective effect of L-carnitine (LC) on the reproductive function of male rats with asthenospermia induced by ornidazole (ORN). METHODS: Forty male SD rats (200-230 g) were randomly divided into Groups A (control: 0.5% carboxymethylcellulose solution), B (medium-dose ORN: 400 mg/kg/d), C (medium-dose ORN + LC: ORN 400 mg/kg/d + LC 100 mg/kg/d), D (high-dose ORN: 800 mg/kg/d), and E (high-dose ORN + LC: ORN 800 mg/kg/d + LC 100 mg/kg/d). All the rats were treated via gastric gavage for 20 days consecutively, and then killed for the detection of sperm motility and the sperm count of the cauda epididymis. RESULTS: Compared with Group A, there was a significant decrease in sperm motility and sperm count in Groups B and D (P < 0.05), while Group C showed a significant increase in both the parameters as compared with B (P < 0.05), but with no significant difference from A (P > 0.05). Group E exhibited no obvious improvement in sperm motility and sperm count, with no difference from D (P > 0.05). CONCLUSION: L-carnitine can improve the sperm motility and sperm count of the male rats with ornidazole-induced asthenospermia.

[Protective effect of L-carnitine on the testis and epididymis against ornidazole-induced injury in male rats].

OBJECTIVE: To investigate the protective effect of L-carnitine on the testis and epididymis against ornidazole (ORN)-induced injury in male rats. METHODS: Forty male SD rats weighing 200 -230 g were randomly divided into 5 groups, Group A treated with 0.5% sodium carboxymethyl cellulose, and Groups B, C, D and E with ORN at the daily dose of 400 mg/kg, 800 mg/kg, 400 mg/kg plus LC 100 mg/kg and 800 mg/kg plus LC 100 mg/kg, respectively, all by oral gavage for 20 days continuously. Twenty-four hours after the last administration, all the rats were put to death, their testes and epididymides harvested, weighed and subjected to HE staining. The indexes of the testes and epididymides were obtained and their histopathological changes observed. RESULTS: Compared with Group A, Groups B and C showed significant decreases in the indexes of the testis and epididymis (P < 0.05 and P < 0.01), while Group D exhibited no difference and Group E extremely significant difference (P < 0.01). HE staining revealed that the spermatogenic cells at all levels of testicular seminiferous tubules were neatly arranged in Group B, caduceus in some seminiferous tubules, with decreased number of sperm and sporadic spermatogenic cells in the epididymal duct. Necrotic and caduceus spermatogenic cells were observed in the seminiferous tubules of Group C, with significantly decreased number of sperm and lots of non-sperm cell components in the epididymal duct. No obvious changes were found in the testicular seminiferous tubules, nor evident reduction in the number of sperm in the epididymal duct of Group D. Group E showed decreased number of sperm in the testicular seminiferous tubules, necrotic and caduceus spermatogenic cells, obviously reduced number of sperm and a lot of non-sperm cell components in the epididymal duct. CONCLUSION: ORC can induce histopathological changes in the testis and epididymis of male rats, and L-carnitine plays a role in protecting the testis and epididymis from ORN-induced injury in male rats.