Exogenous 24-Epibrassinolide Enhanced Drought Tolerance and Promoted BRASSINOSTEROID-INSENSITIVE2 Expression of Quinoa.

Brassinosteroids (BRs) are involved in the regulation of biotic and abiotic stresses in plants. The molecular mechanisms of BRs that alleviate the drought stress in quinoa have rarely been reported. Here, quinoa seedlings were treated with 24-epibrassinolide (EBR) and we transiently transferred CqBIN2 to the quinoa seedlings' leaves using VIGS technology to analyze the molecular mechanism of the BR mitigation drought stress. The results showed that EBR treatment significantly increased the root growth parameters, the antioxidant enzyme activities, and the osmolyte content, resulting in a decrease in the H2O2, O2∙-, and malondialdehyde content in quinoa. A transcriptome analysis identified 8124, 2761, and 5448 differentially expressed genes (DEGs) among CK and Drought, CK and EBR + Drought, and Drought and EBR + Drought groups. WGCNA divided these DEGs into 19 modules in which these characterized genes collectively contributed significantly to drought stress. In addition, the EBR application also up-regulated the transcript levels of CqBIN2 and proline biosynthesis genes. Silenced CqBIN2 by VIGS could reduce the drought tolerance, survival rate, and proline content in quinoa seedlings. These findings not only revealed that exogenous BRs enhance drought tolerance, but also provided insight into the novel functions of CqBIN2 involved in regulating drought tolerance in plants.

Reduced miR-99a-3p levels in systemic lupus erythematosus may promote B cell proliferation via NCAPG and the PI3K/AKT signaling pathway.

BACKGROUND: Systemic lupus erythematosus is an immunologically dysregulated disease characterized by the presence of multiple autoantibodies. In SLE, B lymphocytes contribute to the dysregulated production of autoantibodies and cytokines. Recently, we discovered that miR-99a-3p binds to both EIF4EBP1 and NCAPG mRNA and that lowering miR-99a-3p can promote B cell autophagy in SLE by increasing EIF4EBP1 expression. However, the functions of miR-99a-3p and NCAPG in SLE have not been extensively investigated. OBJECTIVE: This work aims to evaluate the levels of miR-99a-3p and NCAPG expression in SLE B cells and to determine whether the aberrant expression of miR-99a-3p and NCAPG contributes to the pathological mechanisms in SLE. METHODS: B lymphocytes were obtained through immunomagnetic negative selection. Using RT-qPCR, miR-99a-3p and NCAPG mRNA expressions in B lymphocytes and in the BALL-1 cell line were measured. To determine the relative abundance of NCAPG, PI3K, p-PI3K, AKT, and p-AKT, we normalize them to the level of ß-actin using Western blotting. Evaluation of miR-99a-3p and NCAPG's impact on cell proliferation was done utilizing CCK-8 assay. Using flow cytometry, the cell cycle and apoptosis were both measured. RESULTS: Comparing SLE B cells to healthy controls, miR-99a-3p expression was significantly downregulated. Additionally, it was observed that SLE B cells had significantly higher NCAPG mRNA expression. Blocking miR-99a-3p expression in BALL-1 cells with an antagomir elevated NCAPG expression, facilitated PI3K/AKT pathway activation, improved cell proliferation, raised the fraction of S-phase cells, and prevented cell apoptosis. The opposite effects of upregulated miR-99a-3p levels on BALL-1 cells were observed by using an agomir. Furthermore, the effect of decreased miR-99a-3p expression on cell proliferation was partially mediated by elevating NCAPG levels and activating the PI3K/AKT pathway. CONCLUSION: Our research indicates that lower miR-99a-3p expression in SLE B cells appears to boost B cell number via the NCAPG and PI3K/AKT pathways.

Von Willebrand factor promotes radiation-induced intestinal injury (RIII) development and its cleavage enzyme rhADAMTS13 protects against RIII by reducing inflammation and oxidative stress.

Patients with abdominopelvic cancer undergoing radiotherapy commonly develop radiation-induced intestinal injury (RIII); however, its underlying pathogenesis remains elusive. The von Willebrand factor (vWF)/a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) axis has been implicated in thrombosis, inflammation, and oxidative stress. However, its role in RIII remains unclear. In this study, the effect of radiation on vWF and ADAMTS13 expression was firstly evaluated in patients with cervical cancer undergoing radiotherapy and C57BL/6J mice exposed to different doses of total abdominal irradiation. Then, mice with the specific deletion of vWF in the platelets and endothelium were established to demonstrate the contribution of vWF to RIII. Additionally, the radioprotective effect of recombinant human (rh) ADAMTS13 against RIII was assessed. Results showed that both the patients with cervical cancer undergoing radiotherapy and RIII mouse model exhibited increased vWF levels and decreased ADAMTS13 levels. The knockout of platelet- and endothelium-derived vWF rectified the vWF/ADAMTS13 axis imbalance; improved intestinal structural damage; increased crypt epithelial cell proliferation; and reduced radiation-induced apoptosis, inflammation, and oxidative stress, thereby alleviating RIII. Administration of rhADAMTS13 could equally alleviate RIII. Our results demonstrated that abdominal irradiation affected the balance of the vWF/ADAMTS13 axis. vWF exerted a deleterious role and ADAMTS13 exhibited a protective role in RIII progression. rhADAMTS13 has the potential to be developed into a radioprotective agent.

NCOA4-mediated ferritinophagy is involved in ionizing radiation-induced ferroptosis of intestinal epithelial cells.

Ferroptosis is a newly recognized form of regulated cell death that is characterized by severe lipid peroxidation initiated by iron overload and the generation of reactive oxygen species (ROS). However, the role of iron in ionizing radiation (IR)-induced intestinal injury has not been fully illustrated yet. In this study, we found that IR induced ferroptosis in intestinal epithelial cells, as indicated by the increase in intracellular iron levels and lipid peroxidation, upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, reduced glutathione peroxidase 4 (GPX4) mRNA and glutathione (GSH) levels, and significant mitochondrial damage. In addition, the iron chelator deferoxamine (DFO) attenuated IR-induced ferroptosis and intestinal injury in vitro and in vivo. Intriguingly, pharmacological inhibition of autophagy with 3-methyladenine (3-MA) mitigated IR-induced ferritin downregulation, iron overload and ferroptosis. IR increased the levels of nuclear receptor coactivator 4 (NCOA4) mRNA and protein. NCOA4 knockdown significantly inhibited the reduction of ferritin, decreased the level of intracellular free iron, and mitigated ferroptosis induced by IR in HIEC cells, indicating that NCOA4-mediated autophagic degradation of ferritin (ferritinophagy) was required for IR-induced ferroptosis. Furthermore, cytoplasmic iron further activated mitoferrin2 (Mfrn2) on the mitochondrial membrane, which in turn increased iron transport into the mitochondria, resulting in increased ROS production and ferroptosis. In addition, mice fed with an iron-deficient diet for 3 weeks showed a significant reversal in the intestinal injury induced by abdominal IR exposure. Taken together, ferroptosis is a novel mechanism of IR-induced intestinal epithelial cytotoxicity, and is dependent on NCOA4-mediated ferritinophagy.

Identification of a distal enhancer that determines the expression pattern of acute phase marker C-reactive protein.

C-reactive protein (CRP) is a major acute phase protein and inflammatory marker, the expression of which is largely liver specific and highly inducible. Enhancers are regulatory elements critical for the precise activation of gene expression, yet the contributions of enhancers to the expression pattern of CRP have not been well defined. Here, we identify a constitutively active enhancer (E1) located 37.7 kb upstream of the promoter of human CRP in hepatocytes. By using chromatin immunoprecipitation, luciferase reporter assay, in situ genetic manipulation, CRISPRi, and CRISPRa, we show that E1 is enriched in binding sites for transcription factors STAT3 and C/EBP-ß and is essential for the full induction of human CRP during the acute phase. Moreover, we demonstrate that E1 orchestrates with the promoter of CRP to determine its varied expression across tissues and species through surveying activities of E1-promoter hybrids and the associated epigenetic modifications. These results thus suggest an intriguing mode of molecular evolution wherein expression-changing mutations in distal regulatory elements initiate subsequent functional selection involving coupling among distal/proximal regulatory mutations and activity-changing coding mutations.

MicroRNA-497-5p Is Downregulated in Hepatocellular Carcinoma and Associated with Tumorigenesis and Poor Prognosis in Patients.

BACKGROUND: MicroRNAs (miRNAs) have been demonstrated to exhibit important regulatory roles in multiple malignancies, including hepatocellular carcinoma (HCC). hsa-miR-497-5p was reported to involve in cancer progression and poor prognosis in many kinds of tumors. However, the expression and its clinical significance of hsa-miR-497-5p in HCC remain unclear. METHODS: In the present study, we investigated the expression of hsa-miR-497-5p in HCC and analyzed the correction of clinical features with prognosis. The expression levels of hsa-miR-497-5p and potential target genes were analyzed in HCC and adjacent noncancerous tissues using The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze hsa-miR-497-5p levels in 328 HCC tissues and 30 paired adjacent noncancer tissues. Overall survival (OS) and progression-free survival (PFS) of patients with HCC were assessed using the Kaplan-Meier method and the log-rank test. RESULTS: The hsa-miR-497-5p expression levels were decreased, and its target genes ACTG1, CSNK1D, PPP1CC, and BIRC5 were upregulated in HCC tissues compared with normal tissues. Lower levels of hsa-miR-497-5p expression and higher levels of the four target genes were significantly associated with higher tumor diameter. Moreover, patients with lower hsa-miR-497-5p expression and higher target genes levels had shorter OS. CONCLUSION: The expression levels of hsa-miR-497-5p may play an important regulatory role in HCC and are closely correlated with HCC progression and poor prognosis in patients. The hsa-miR-497-5p may be a specific therapeutic target for the treatment of HCC.

Novel p.G1344E mutation in FBN1 is associated with ectopia lentis.

BACKGROUND: Ectopia lentis refers to dislocation or subluxation of the crystalline lens. Fibrillin-1, encoded by FBN1, is an important microfibrillar structural component that is specifically required for the suspensory ligament of the lens. FBN1 mutations may cause abnormal structure of microfibrils and has been associated with a broad spectrum of clinical phenotypes. In this study, we characterised a Chinese dominant family with late-onset isolated ectopia lentis caused by a novel missense FBN1 mutation. METHODS: Eight family members, including four patients with suspected isolated ectopia lentis, were recruited from Shanghai. Clinical data and family history of the proband and other affected family members were collected. Ophthalmic examination, systemic examination and echocardiography were performed. Whole exome sequencing and Sanger sequencing were used to detect potential pathogenic variants. RESULTS: A novel heterozygous missense mutation c.4031 G>A/p.Gly1344Glu in exon 33 of FBN1 was identified. This mutation was detected in all affected family members and led to specific ocular system phenotypes (ectopia lentis, microspherophakia and secondary glaucoma) with minor skeletal involvement (hallux valgus). CONCLUSION: The novel c.4031G>A mutation in FBN1 is a likely pathogenic mutation for isolated ectopia lentis. Our study expands the spectrum of FBN1 mutations and contributes to better comprehension of genotype-phenotype correlations of ectopia lentis disease.

[48,XXYY syndrome: A report of four cases].

OBJECTIVE: To explore the clinical characteristics and prognosis of the 48,XXYY syndrome and gain a deeper insight into this condition. METHODS: This retrospective study included 4 cases of 48,XXYY syndrome confirmed between 2011 and 2018. We analyzed the general information, clinical manifestations, laboratory results, imaging features and outcomes of assisted reproductive technology (ART) of the patients and reviewed the relevant literature. RESULTS: The 4 patients with 48,XXYY syndrome were characterized by low literacy, soft texture and small volume of the testis, high levels of FSH and LH, and low level of serum T. Two of them were diagnosed with ejaculatory dysfunction and aspermia, and the other 2 with normal ejaculatory function but azoospermia. Biochemical analysis of seminal plasma indicated normal quantifications of both fructose and neutral α glucosidase. ART with donor sperm was performed for all the 4 cases and 3 of them got full-term babies. CONCLUSIONS: The 48,XXYY syndrome is often complicated by hypergonadotropic hypogonadism, with the clinical manifestations of aspermia or non-obstructive azoospermia. ART with donor sperm can be employed to help the patient with 48,XXYY syndrome get their non-biological offspring.

Intraocular Pharmacokinetics and Safety of Subretinal Injection Compared with Intravitreal Application of Conbercept in Vitrectomized Rabbit Eyes.

PURPOSE: To evaluate the ocular pharmacokinetic properties of subretinal conbercept injection in vitrectomized rabbit eyes and to compare them with those by intravitreal injection. METHODS: The following groups of New Zealand white rabbits received conbercept injections (0.5 mg/0.05 ml): a subretinal group (subretinal injection in vitrectomized eyes), an intravitreal group (intravitreal injection in vitrectomized eyes), and a control group (intravitreal injection in nonvitrectomized eyes). Drug concentrations in the aqueous humor (AH), the vitreous humor (VH), and the retina were measured by the enzyme-linked immunosorbent assay (ELISA), and pharmacokinetic parameters were calculated. Ophthalmic B-ultrasonography, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to evaluate the safety of subretinal injection. RESULTS: On the 28th day after injection, the drug level in the subretinal group was significantly higher than that in the intravitreal group in the AH (0.90 ± 0.25 µg/ml and 0.11 ± 0.07 µg/ml and 0.11 ± 0.07 P < 0.001, respectively) and the VH (5.00 ± 3.86 µg/ml and 0.11 ± 0.07 µg/ml and 0.11 ± 0.07 P < 0.001, respectively) and the VH (5.00 ± 3.86 P < 0.001, respectively) and the VH (5.00 ± 3.86 P < 0.001, respectively) and the VH (5.00 ± 3.86 . CONCLUSIONS: Our study indicates that applying conbercept by subretinal injection can reduce the drug clearance rate and sustain a long maintenance period in ocular tissue, which suggests that subretinal conbercept injection may be a potentially valuable treatment option.

Traumatic endophthalmitis and the outcome after vitrectomy in young children.

AIM: To explore the traumatic endophthalmitis in young children and the outcome of pars plana vitrectomy (PPV). METHODS: Twenty-two eyes of 22 cases of young children consecutive pediatric traumatic endophthalmitis treated and followed up between September 2014 and May 2018 were included. Aqueous humor or vitreous samples were taken for bacterial culture and sensitivity tests. Intravitreal antibiotics (norvancomycin and ceftazidime) injection, combined with 23-gauge PPV, were administered in 22 eyes. Silicone oil (SO; 5000 centistoke) tamponade or perfluoropropane gas (C3F8) was used in all patients. Main outcome measures were best-corrected visual acuity (BCVA) and retinal attachment, the ratio of penetrating injury, and the existence of intraocular foreign body. RESULTS: The mean age of patients was 6.9±2.2 (range, 3-10)y. All injured eyes suffered from penetrating ocular injury with retained intraocular foreign body in one eye. Bacterial culture was positive in only 2 eyes. The mean follow-up time was 21.1±4.7 (range, 12-30)mo. In the primary PPV, intravitreal antibiotics was administrated in all eyes, SO in 18 eyes, and C3F8 in 4 eyes. The secondary operation of SO removal and C3F8 endotamponade was performed in 16 eyes and a second SO endotamponade due to emulsification of the oil and retinal detachment (RD) was operated in 7 eyes underwent 3 to 11.5mo after primary PPV. A third operation was done in 7 eyes. The final intraocular pressure (IOP) was 8.9±1.8 (range, 6.9-11.4) mm Hg. The final BCVAs were 20/200 or better in 5, counting fingers in 2, and light perception to hand movement in 8 eyes. Whose (66.7%) had retinal injury exhibited worse BCVA (P=0.019, Fisher's exact test). Eyes underwent SO tamponade exhibited worse final BCVA than that with C3F8 in the primary PPV (P=0.026, Fisher's exact test). CONCLUSION: Traumatic endophthalmitis in children is generally more severe and associated with more complicated surgical procedures. Most patients have retinal injury need multiple operations and the final BCVA is poor. Prevention of ocular trauma, especially in children, is still critical.

Intraocular pharmacokinetics of anti-vascular endothelial growth factor agents by intraoperative subretinal versus intravitreal injection in silicone oil-filled eyes of proliferative diabetic retinopathy: a randomized controlled pilot study.

PURPOSE: Intraoperative subretinal anti-vascular endothelial growth factor (VEGF) injections have been used clinically in some case, but the pharmacokinetic characteristics have not yet been determined. In this pilot study, we investigate the pharmacokinetic parameters of anti-VEGF agents by intraoperative subretinal or intravitreal injection in silicone oil (SiO)-filled eyes of patients with proliferative diabetic retinopathy (PDR). METHODS: Randomized controlled trial including 13 patients (16 eyes) with PDR underwent pars plana vitrectomy (PPV) with SiO tamponade and randomly received a subretinal (8 eyes) or intravitreal (8 eyes) conbercept injection (0.5 mg/0.05 ml) intraoperatively. Aqueous humour (AH) was obtained on the 1st, 3rd, 7th, 10th, 14th, 21st and 28th day after the injection. Drug concentrations in the AH were determined by enzyme-linked immunosorbent assay (ELISA). The last best-corrected visual acuity (BCVA) was examined 6 months postoperatively. RESULTS: The clearance rate of anti-VEGF agents by subretinal injection was reduced in vitrectomized eyes with SiO tamponade (p < 0.05). With the same drug dose, subretinal injection (5.49 ± 6.11 µg/ml) resulted in higher drug concentrations in the AH when compared with intravitreal injection (0.42 ± 0.46 µg/ml, p = 0.001) 4 weeks after the treatment. The mean residence time last (MRT0-t ) by subretinal injection (11.57 ± 0.83 days) was significantly longer than the mean MRT0-t by intravitreal injection (7.10 ± 1.00 days, p < 0.001). A self-paired analysis showed that subretinal injection led to the BCVA improvement by +28.59 letters 6 months postoperatively (p = 0.028) while the BCVA did not improve significantly by intravitreal injection (p = 0.715). CONCLUSIONS: The drug maintenance phase was prolonged by intraoperative subretinal injection in SiO-filled eyes of PDR. The results suggest that subretinal injection might be a valuable treatment option for the management of PDR.

A modified intrascleral intraocular lens fixation technique with fewer anterior segment manipulations: 27-gauge needle-guided procedure with built-in 8-0 absorbable sutures.

BACKGROUND: To report a modified surgical technique for intrascleral intraocular lens (IOL) fixation with fewer anterior segment manipulations in eyes lacking sufficient capsular support. METHODS: Eyes from 14 patients who underwent 27-gauge needle-guided intrascleral IOL fixation with built-in 8-0 absorbable sutures were studied. The 8-0 absorbable sutures were inserted into 27-gauge round needles and used to create sclerotomies at the 4 o'clock and 10 o'clock positions under the scleral flap. The sutures were used to tie knots at the end of each haptic and guide haptic externalization through the sclerotomy. After externalization, a sufficient flange was created at the end of each haptic and fixed under the scleral flaps. The best corrected visual acuity (BCVA), corneal endothelial cell density (ECD), IOL tilt and decentration, previous surgery history, and complications were determined. RESULTS: Fourteen cases were analyzed. The majority of eyes exhibited an improvement in the BCVA after surgery. When comparing the last follow-up to preoperative visual acuity, the mean change in BCVA was + 26.32 letters (p = 0.011). Postoperative complications included postoperative hypotony in 3 eyes, ocular hypertension in 2 eyes. No cases of postoperative cystoid macular edema (CME), vitreous hemorrhage (VH), IOL dislocation, or endophthalmitis were observed. CONCLUSIONS: The 27-gauge needle-guided intrascleral IOL fixation technique with built-in 8-0 absorbable sutures is easy to perform with fewer anterior chamber manipulations and achieves both anatomical and optical stability.

Oxygen-laden mesenchymal stem cells enhance the effect of gastric cancer chemotherapy in vitro.

Hypoxia is an important factor that results in failure of chemotherapy for the majority of solid tumor types, particularly for gastric cancer. In the present study, mesenchymal stem cells (MSCs), which have the ability to migrate to cancer tissues were used as a vehicle to supply oxygen to gastric cancer. The hemoglobin genes were transfected into MSCs as MSC-hemo groups. Subsequently, MSC-hemo groups were induced by isopropyl-b-D-thiogalactopyranoside and hemin to express hemoglobin. The hemoglobin was detected by western blotting method. Following this, the MSC-hemo groups were placed in an atmosphere containing 100% oxygen and were used to investigate the effect of the function of the oxygen-laden MSC-hemo group on gastric cancer chemotherapy with an MTT assay. As a first approach to investigate the possibility of MSCs as a vehicle to supply oxygen to anoxic cancer types, including gastric, liver, breast cancer, the results indicated that the oxygen-laden MSC-hemo group significantly enhanced the effect of chemotherapeutic treatments on gastric cancer cells. Utilizing MSCs as a svehicle to supply oxygen to the solid tumor may be a novel method to improve the hypoxia conditions of tumor tissues and improve the effect of chemotherapy on tumor cells.

[Oxidative Stress Status and Its Effect on Regulation of Hepcidin in Patients with HbHCS].

OBJECTIVE: To investigate the oxidative stress status and its effects on hepcidin in patients with hemoglobin H Constant Spring disease (HbH-CS). METHODS: A total of 35 patients were enrolled in the study, including 15 splenectomized cases and 20 non-splenectomized cases. 20 healthy volunteers were selected as controls. Serum superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG) levels, erythropoietin (EPO), serum free transferrin receptor (sFTR), growth differentiation factor 15 (GDF15) as well as the level of hepcidin were detected. Correlation analysis and multiple factor regression analysis were performed to investigate the factors affecting the iron metabolism and erythropoiesis. RESULTS: Compared with healthy control, the SOD and GSH levels in patients with HbHCS decreased, while MDA and GSSG levels increased. The levels of SOD, MDA, GSG and GSSG were not significantly different between the patients with splenectomy and those without splenectomy. Correlation analysis showed that inpatients with HbHCS, EPO, sFTR and GDF15 correlated negatively with SOD level and positively with MDA level. EPO and sFTR levels negatively correlated with Hepcidin. CONCLUSION: Excessive oxidative stress is present in patients with HbHCS, and hepcidin is inhibited by the upregulation of EPO and sFTR, and hence involved in iron overload in patients.

RETRACTED: miR-208b targets Bax to protect H9c2 cells against hypoxia-induced apoptosis.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Concerns were raised about the background pattern of the Western Blots from Figures 3D and 5A. Given the comments of Dr Elisabeth Bik regarding this article "This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.

Exogenous 24-Epibrassinolide alleviates oxidative damage from copper stress in grape (Vitis vinifera L.) cuttings.

Copper (Cu) stress is the most common abiotic stress experienced in vineyards owing to the copper-based fungicides application. Plant hormones, including 24-Epibrassinolide (EBR), may alleviate the adverse impacts of heavy metal stress on plants. We investigated the effects of EBR pretreatment on root morphological parameters, active oxygen metabolism, osmolytes contents, antioxidant enzyme activity, endogenous phytohormone contents, and ascorbate-glutathione (AsA-GSH) cycle activity of one-year-old grape (Vitis vinifera L.) cuttings under Cu stress. Pretreatment with EBR significantly enhanced root morphological parameters (total root length, root surface area, root diameter, root volume, and tip number), increased soluble protein and proline contents, and significantly decreased the contents of H2O2, O2⋅-, and malondialdehyde (MDA) in roots and leaves. EBR pretreatment increased the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase oxidase (POD), and the contents of the endogenous phytohormones abscisic acid, jasmonic acid, and salicylic acid in the leaves. In addition, EBR regulated the balance of the AsA-GSH cycle by increasing the activities of monodehydroascorbate reductase (MDHAR), glutathione peroxidase (GR), ascorbate peroxidase (APX), and dehydroascorbate reductase (DHAR), and the contents of the antioxidant ascorbate (AsA) and dehydroascorbic acid (DHA), but the contents of glutathione (GSH) and oxidized glutathione (GSSG) decreased. Among the treatments tested, pretreatment with 0.10 mg/L EBR showed the optimal performance for alleviation of Cu toxicity. The results show that exogenous brassinosteroids reduce oxidative damage and improve the tolerance of Cu stress of grapevine cuttings.

Clinical trial on the effects of thalidomide on hemoglobin synthesis in patients with moderate thalassemia intermedia.

To investigate the efficacy and safety of thalidomide in patients with thalassemia intermedia (TI). Patients with a confirmed diagnosis of TI who met the trial criteria and signed consent forms were prescribed oral thalidomide 50 mg qn for 3 months from February 2017. Complete blood counts, Hb analysis, and liver and kidney functions were monitored monthly during treatment and any differences were compared before and after treatment. Patients with Hb increments > 2.0 g/dL were termed main responders (MaR), and those with Hb increments between 1.0 and 2.0 g/dL as minor responders (MiR), otherwise they were termed non-responders. Relevance analysis was performed to explore parameters predicting Hb increments after treatment. Adverse effects during treatment were carefully recorded. The overall response rate (ORR = MaR + MiR) and MaR rates were 78.6 and 50% after 1 month of treatment, respectively, and 85.7 and 71.4% after 3 months treatment. At the end of the treatment period, Hb and HbF increased by 2.5 ± 1.8 g/dL and 2.5 ± 1.6 g/dL, while bilirubin, lactate dehydrogenase, and the nucleated red blood cell count (NRBC) were significantly decreased, while the reticulocyte count significantly increased. Correlation analysis showed that the Hb increments correlated significantly with the ratio of HbF before treatment (r = 0.683, P = 0.007) rather than age, Hb, reticulocyte count, and NRBC before treatment. Adverse events during treatment were mild, and drug reduction or withdrawal from the trial was not required. Thalidomide had rapid and significant effects in patients with TI, and also, it is safe and convenient. But larger scale clinical trials will be required to confirm our conclusions. TRIAL REGISTRATION: NCT02995707, https://www.clinicaltrials.gov/ct2/show/NCT03184844?term=thalidomide+thalassemia&rank=1 .

Up-regulation of SR-BI promotes progression and serves as a prognostic biomarker in clear cell renal cell carcinoma.

BACKGROUND: Scavenger receptor class B type I (SR-BI) has been reported to be involved in carcinogenesis of several human cancers. However, it is currently unknown whether SR-BI plays a role in clear cell renal cell carcinoma (ccRCC). Here, we aimed to evaluate a tumor promotive mechanism for SR-BI in ccRCC. METHODS: The expression of SR-BI was evaluated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC) in ccRCC tissues and cell lines. Lipid droplets in ccRCC tissues and normal kidney tissues were examined by Oil Red O (ORO) and hematoxylin-eosin (HE) staining. The correlation between SR-BI mRNA levels and clinicopathological features was analyzed by Pearson's chi-square test or Fisher's exact test. Kaplan-Meier analysis and Cox model were used to evaluate the difference in progression-free survival (PFS) associated with expression of SR-BI. Inhibition of SR-BI was conducted by using small interfering RNA (siRNA). In vitro assays were performed to assess the impact of SR-BI knockdown on cell biological behaviors. High density lipoprotein (HDL)-cholesterol content in ccRCC cells and extracellular media was also measured after transfection with siRNA. RESULTS: The expression of SR-BI was markedly up-regulated in ccRCC tissues and tumor cell lines. ORO and HE staining revealed huge amounts of lipid droplets accumulation in ccRCC. Clinical analysis showed that over-expression of SR-BI was positively associated with tumor size, grade, distant metastasis and inversely correlated with PFS. Furthermore, SR-BI was proved to be an independent prognostic marker in ccRCC patients. The inhibition of SR-BI attenuated the tumorous behaviors of ccRCC cells, expression of metastasis and AKT pathway related proteins. The content of HDL-cholesterol was reduced in cells while increased in extracellular media after transfection with si-SR-BI. CONCLUSIONS: Our results demonstrate that SR-BI functions as an oncogene and promotes progression of ccRCC. SR-BI may serve as a potential prognostic biomarker and therapeutic target for ccRCC.