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1.
Neurochem Res ; 49(8): 2197-2214, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38834846

ABSTRACT

Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.


Subject(s)
Alzheimer Disease , Apoptosis , Blood-Retinal Barrier , Mice, Transgenic , Retina , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Apoptosis/drug effects , Blood-Retinal Barrier/drug effects , Blood-Retinal Barrier/metabolism , Retina/drug effects , Retina/metabolism , Retina/pathology , Mice , Inflammation/metabolism , Inflammation/drug therapy , Mice, Inbred C57BL , Humans , Amyloid beta-Peptides/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Wnt Signaling Pathway/drug effects , Wnt Signaling Pathway/physiology , Male
2.
Heliyon ; 10(7): e28434, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38560099

ABSTRACT

Background: A conclusive evidence regarding the optimal concentration and volume of local anesthetic for quadratus lumborum block is lacking. Methods: In this single-center, prospective, randomized, controlled study, 60 patients scheduled for laparoscopic colorectal surgery were randomly assigned to 3 different combinations of volume and concentration of ropivacaine (3 mg/kg) - Group 0.25%, Group 0.375% and Group 0.5%. All subjects received ultrasound-guided posterior quadratus lumborum block prior to the induction. The primary outcome was the complete sensory block rate of surgical site measured at 30 min after quadratus lumborum block, after extubation, at 12, 24, and 48 h after operation. Secondary outcomes were the changes in hemodynamic parameters before and after incision (ΔSBP, ΔDBP and ΔHR), postoperative pain score, the sufentanil consumption after surgery, length of stay and adverse reactions. Results: The sensory block rate of surgical site at 5 time points differed significantly among the three groups (P < 0.001). Both Group 0.375% (P < 0.001) and Group 0.5% (P < 0.001) had a higher sensory block rate than Group 0.25%, but no significant difference was observed between the former two. Group 0.375% and Group 0.5% had lower postoperative pain scores, lower sufentanil consumption after surgery and shorter length of stay. No statistical difference was observed in ΔSBP, ΔDBP, ΔHR and the incidence of adverse reactions. Conclusions: 0.375% and 0.5% ropivacaine in posterior quadratus lumborum block provide better sensory block of surgical site when compared to 0.25% in laparoscopic colorectal surgery. Trial registration number: Chinese Clinical Trials Registry (ChiCTR2100043949).

3.
RSC Adv ; 13(47): 32850-32851, 2023 Nov 07.
Article in English | MEDLINE | ID: mdl-38025870

ABSTRACT

[This corrects the article DOI: 10.1039/C5RA26521E.].

4.
Arch Esp Urol ; 76(6): 403-410, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37681331

ABSTRACT

BACKGROUND: In this study, the clinical effect of lamivudine combined with leflunomide and methylprednisolone in the treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN) and their influence on renal function indexes was explored. METHODS: Patients with HBV-GN were selected for retrospective analysis and divided into the group B and group A, with 41 cases in each group. The group B was given leflunomide and methylprednisolone, whereas the group A was supplemented with lamivudine. The level of 24 h proteinuria (PRO), albumin (ALB), beta2-microglobulin (ß2-MG), alanine aminotransferase (ALT), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) in two groups was measured. The clinical efficacy, adverse reactions appetite, spirit, sleep and daily life scores of the two groups were recorded. RESULTS: With the extension of treatment time to end of the treatment, the level of 24 h PRO, ALB and ß2-MG in the group A significantly changed compared with that before treatment (p < 0.05). Moreover, the level of ALT, IFN-γ and IL-4 in the two groups significantly decreased compared with that before treatment, and the level of the three indexes in the group A decreased more significantly (p < 0.05). The total effective rate in the group A was higher than that in the group B (p < 0.05). The occurrence of adverse reactions showed no statistically significant difference between the two groups. After treatment, scores of appetite, spirit, sleep and daily living were increased in the two groups, and the increase in the group A was more significant than that in the group B (p < 0.05). CONCLUSIONS: Lamivudine combined with methylprednisolone and leflunomide treatment is conducive to clearing Hepatitis B virus (HBV) and improving renal function.


Subject(s)
Glomerulonephritis , Lamivudine , Humans , Lamivudine/therapeutic use , Hepatitis B virus , Interleukin-4 , Leflunomide , Retrospective Studies , Methylprednisolone/therapeutic use , Glomerulonephritis/complications , Glomerulonephritis/drug therapy , Kidney/physiology , Tablets
5.
Arch. esp. urol. (Ed. impr.) ; 76(6): 403-410, 28 aug. 2023. tab, graf
Article in English | IBECS | ID: ibc-224892

ABSTRACT

Background: In this study, the clinical effect of lamivudine combined with leflunomide and methylprednisolone in the treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN) and their influence on renal function indexes was explored. Methods: Patients with HBV-GN were selected for retrospective analysis and divided into the group B and group A, with 41 cases in each group. The group B was given leflunomide and methylprednisolone, whereas the group A was supplemented with lamivudine. The level of 24 h proteinuria (PRO), albumin (ALB), beta2-microglobulin (β2-MG), alanine aminotransferase (ALT), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) in two groups was measured. The clinical efficacy, adverse reactions appetite, spirit, sleep and daily life scores of the two groups were recorded. Results: With the extension of treatment time to end of the treatment, the level of 24 h PRO, ALB and β2-MG in the group A significantly changed compared with that before treatment (p < 0.05). Moreover, the level of ALT, IFN-γ and IL-4 in the two groups significantly decreased compared with that before treatment, and the level of the three indexes in the group A decreased more significantly (p < 0.05). The total effective rate in the group A was higher than that in the group B (p < 0.05). The occurrence of adverse reactions showed no statistically significant difference between the two groups. After treatment, scores of appetite, spirit, sleep and daily living were increased in the two groups, and the increase in the group A was more significant than that in the group B (p < 0.05). Conclusions: Lamivudine combined with methylprednisolone and leflunomide treatment is conducive to clearing Hepatitis B virus (HBV) and improving renal function (AU)


Subject(s)
Humans , Male , Female , Adult , Reverse Transcriptase Inhibitors/administration & dosage , Lamivudine/administration & dosage , Leflunomide/administration & dosage , Methylprednisolone/administration & dosage , Hepatitis B/drug therapy , Glomerulonephritis/drug therapy , Drug Therapy, Combination , Kidney Function Tests , Retrospective Studies
6.
Nat Commun ; 14(1): 4394, 2023 07 20.
Article in English | MEDLINE | ID: mdl-37474626

ABSTRACT

The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Humans , Rats , Animals , Proto-Oncogene Proteins c-fos/genetics , Inflammation , Transcription Factor AP-1/metabolism
7.
Pharmacol Res ; 194: 106850, 2023 08.
Article in English | MEDLINE | ID: mdl-37453674

ABSTRACT

Non-small cell lung cancer (NSCLC) is one of the main malignant tumors with high mortality and short survival time. Immunotherapy has become the standard treatment for advanced NSCLC, but it has the problems of drug resistance and low response rate. Therefore, obtaining effective biomarkers to predict and enhance immune checkpoint inhibitors (ICIs) efficacy in NSCLC is important. Sphingolipid metabolism is recently found to be closely involved in tumor immunotherapy. CERS4, an important sphingolipid metabolizing enzyme, is positively correlated with the efficacy of anti-PD-1 therapy for NSCLC. Upregulation of CERS4 expression could improve the efficacy of anti-PD-1 therapy for NSCLC. High expression of CERS4 could downregulate the expression of Rhob in tumor. Significantly, the ratio of CD4+/CD8+ T cell increased and the ratio of Tim-3+/CD8+ T cell decreased in spleen and peripheral blood cells. When Rhob was knocked out, the efficacy of PD-1 mAb treatment increased, and the frequency of Tim-3+ CD8+ T cell decreased. This finding further confirmed the role of sphingolipid metabolites in regulating the immunotherapeutic function of NSCLC. These metabolites may improve the efficacy of PD-1 mAb in NSCLC by regulating the CERS4/Rhob/Tim-3 axis. Overall, this study provided a potential and effective target for predicting and improving the efficacy of ICIs for NSCLC. It also provided a new perspective for the study on the mechanisms of ICIs resistance for NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/metabolism , CD8-Positive T-Lymphocytes , Immunomodulation , Lung Neoplasms/pathology
8.
Eur J Oncol Nurs ; 64: 102320, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37224788

ABSTRACT

OBJECTIVE: To investigate the efficacy and safety of non-mechanical bowel preparation (non-MBP) in patients undergoing surgery for malignant gynecological tumors. METHODS: Patients undergoing surgery for a gynecological malignancy (n = 105) were randomized to receive mechanical bowel preparation (MBP) or non-MBP. Parameters indicating postoperative gastrointestinal function recovery were the primary outcomes. The secondary outcomes included the number of postoperative complaints, the plasma levels of D-lactate and diamine oxidase (DAO), ease of visualization of the surgical field, involuntary defecation during surgery, operation time, wound healing, surgical site infection, length of hospital stay, and tolerance to MBP. RESULTS: The participants in the non-MBP group exhibited shorter time intervals until the first postoperative bowel movement (27.87 vs. 29.48 h), first passage of flatus (50.96 vs. 55.08 h), and first passage of stool (75.94 vs. 98.50 h) compared with the MBP group, while they also exhibited fewer postoperative gastrointestinal symptoms, including nausea (18.9% vs. 38.5%), vomiting (26.4% vs. 51.9%), abdominal pain (34.0% vs. 78.9%), and bloating (3.8% vs.26.9%). The plasma D-lactate and DAO levels were significantly increased following bowel preparation compared with the baseline levels in the MBP group (2.93 vs. 5.68 nmol/mL and 20.46 vs. 54.49 ng/mL, respectively), but no such differences were observed in the non-MBP group. Compared with the MBP group, surgical field visualization was superior (92.45% vs. 78.85%), and the operation time was shorter (173.58 vs. 203.88 min) in the non-MBP group. The patients undergoing MBP complained of bloating (182.35%), an unpleasant taste (78.43%), sleep disturbance (70.59%), nausea (68.63%), abdominal pain (64.71%), vomiting (45.10%), polydipsia (33.33%), dizziness (25.49%), and headache (7.84%). CONCLUSIONS: The use of non-MBP in patients undergoing surgery for gynecological malignancies is more conducive to the postoperative recovery of gastrointestinal function.


Subject(s)
Genital Neoplasms, Female , Female , Humans , Genital Neoplasms, Female/surgery , Vomiting , Nausea , Abdominal Pain , Lactates , Preoperative Care
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(2): 327-332, 2023 Apr.
Article in Chinese | MEDLINE | ID: mdl-37096501

ABSTRACT

OBJECTIVE: To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored. RESULTS: The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients. CONCLUSION: VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Leukemia, Myeloid, Acute , Adult , Humans , Retrospective Studies , Neoplasm, Residual/chemically induced , Neoplasm, Residual/drug therapy , Bridged Bicyclo Compounds, Heterocyclic/adverse effects , Recurrence , Leukemia, Myeloid, Acute/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
10.
Environ Geochem Health ; 45(1): 41-52, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35124755

ABSTRACT

Understanding and prediction of mercury (Hg) phytoavailability in vegetable-soil systems is essential for controlling food chain contamination and safe vegetable production as Hg-contaminated soils pose a serious threat to human health. In this study, four typical Chinese soils (Heilongjiang, Chongqing, Yunnan, and Jilin) with varied physicochemical properties were spiked with HgCl2 to grow sweet pepper (Capsicum annuum L.) in a pot experiment under greenhouse condition. The chemical fractionation revealed a significant decrease in exchangeable Hg, while an increase in organically bound Hg in the rhizosphere soil (RS) compared to bulk soil (BS). This observation strongly highlights the vital role of organic matter on the rhizospheric Hg transformation irrespective of contamination levels and soil properties. Stepwise multiple linear regression (SMLR) analysis between Hg concentration in plants, Hg fractions in RS and BS, and soil properties showed that Hg in plant parts was significantly influenced by soil total Hg (THg) (R2 = 0.90), soil clay (R2 = 0.99), amorphous manganese oxides (amorphous Mn) (R2 = 0.97), amorphous iron oxides (amorphous Fe) (R2 = 0.70), and available Hg (R2 = 0.97) in BS. Nevertheless, in the case of RS, Hg accumulation in plants was affected by soil THg (R2 = 0.99), amorphous Mn (R2 = 0.97), amorphous Fe oxides (R2 = 0.66), soil pH, and organically bound Hg fraction (R2 = 0.96). Among all the evaluated soils (n = 04), metal (mercury) concentration in terms of plant uptake was reported highest in the Jilin soil. Based on SMLR analysis, the results suggested that the phytoavailability of Hg was mainly determined by THg and metal oxides regardless of the rhizospheric effect. These findings facilitate the estimation of Hg phytoavailability and ecological risk that may exist from Hg-contaminated areas where pepper is the dominant vegetable.


Subject(s)
Mercury , Soil Pollutants , Biological Availability , China , Mercury/analysis , Oxides/analysis , Soil/chemistry , Soil Pollutants/analysis , Vegetables/metabolism
11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-982062

ABSTRACT

OBJECTIVE@#To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML).@*METHODS@#The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored.@*RESULTS@#The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients.@*CONCLUSION@#VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.


Subject(s)
Adult , Humans , Retrospective Studies , Neoplasm, Residual/drug therapy , Bridged Bicyclo Compounds, Heterocyclic/adverse effects , Recurrence , Leukemia, Myeloid, Acute/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
12.
Chinese Journal of Hematology ; (12): 401-407, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-984636

ABSTRACT

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.


Subject(s)
Humans , Fecal Microbiota Transplantation/methods , Treatment Outcome , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Steroids
13.
Front Oncol ; 12: 941643, 2022.
Article in English | MEDLINE | ID: mdl-35965565

ABSTRACT

Biologically active sphingolipids are closely related to the growth, differentiation, aging, and apoptosis of cancer cells. Some sphingolipids, such as ceramides, are favorable metabolites in the sphingolipid metabolic pathway, usually mediating antiproliferative responses, through inhibiting cancer cell growth and migration, as well as inducing autophagy and apoptosis. However, other sphingolipids, such as S1P, play the opposite role, which induces cancer cell transformation, migration and growth and promotes drug resistance. There are also other sphingolipids, as well as enzymes, played potentially critical roles in cancer physiology and therapeutics. This review aimed to explore the important roles of sphingolipid metabolism in cancer. In this article, we summarized the role and value of sphingolipid metabolism in cancer, including the distribution of sphingolipids, the functions, and their relevance to cancer diagnosis and prognosis. We also summarized the known and potential antitumor targets present in sphingolipid metabolism, analyzed the correlation between sphingolipid metabolism and tumor immunity, and summarize the antitumor effects of natural compounds based on sphingolipids. Through the analysis and summary of sphingolipid antitumor therapeutic targets and immune correlation, we aim to provide ideas for the development of new antitumor drugs, exploration of new therapeutic means for tumors, and study of immunotherapy resistance mechanisms.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-927993

ABSTRACT

Amyloid β-protein(Aβ) deposition in the brain is directly responsible for neuronal mitochondrial damage of Alzheimer's disease(AD) patients. Mitophagy, which removes damaged mitochondria, is a vital mode of neuron protection. Ginsenoside Rg_1(Rg_1), with neuroprotective effect, has displayed promising potential for AD treatment. However, the mechanism underlying the neuroprotective effect of Rg_1 has not been fully elucidated. The present study investigated the effects of ginsenoside Rg_(1 )on the autophagy of PC12 cells injured by Aβ_(25-35) to gain insight into the neuroprotective mechanism of Rg_1. The autophagy inducer rapamycin and the autophagy inhi-bitor chloroquine were used to verify the correlation between the neuroprotective effect of Rg_1 and autophagy. The results showed that Rg_1 enhanced the viability and increased the mitochondrial membrane potential of Aβ-injured PC12 cells, while these changes were blocked by chloroquine. Furthermore, Rg_(1 )treatment increased the LC3Ⅱ/Ⅰ protein ratio, promoted the depletion of p62 protein, up-regulated the protein levels of PINK1 and parkin, and reduced the amount of autophagy adaptor OPTN, which indicated the enhancement of autophagy. After the silencing of PINK1, a key regulatory site of mitophagy, Rg_1 could not increase the expression of PINK1 and parkin or the amount of NDP52, whereas it can still increase the LC3Ⅱ/Ⅰ protein ratio and promote the depletion of OPTN protein which indicated the enhancement of autophagy. Collectively, the results of this study imply that Rg_1 can promote autophagy of PC12 cells injured by Aβ, and may reduce Aβ-induced mitochondrial damage by promoting PINK1-dependent mitophagy, which may be one of the key mechanisms of its neuroprotective effect.


Subject(s)
Animals , Humans , Rats , Amyloid beta-Peptides/toxicity , Ginsenosides/pharmacology , Mitophagy/physiology , PC12 Cells , Protein Kinases/metabolism , Ubiquitin-Protein Ligases/metabolism
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1610-1616, 2021 Oct.
Article in Chinese | MEDLINE | ID: mdl-34627449

ABSTRACT

OBJECTIVE: To evaluate the incidence and clinical characteristics of metabolic syndrome (MS) within one year after hematopoietic stem cell transplantation (HSCT) in order to screen the risk factors for HSCT-MS, provide early intervention and improve the long-term quality of survival of patients. METHODS: The clinical follow-up data of 64 HSCT patients (survival time > 1 year) who received HSCT in our center from January 2007 to August 2018 were collected. Among them, 50 cases were allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 14 cases were autologous hematopoietic stem cell transplantation (auto-HSCT). The changes of MS-related indexes and clinical characteristics before and 1, 3, 6 and 12 months after HSCT were analyzed retrospectively. RESULTS: In allo-HSCT group, 14 cases were diagnosed as MS before operation, including high-density lipoprotein cholesterol (hypo-HDL-C)> hyper triglycerides(hyper-TG)> hyper fasting glucose(hyper-FBG)> abdominal obesity (AO) > hypertension. The preoperative diagnosis of MS in the auto-HSCT group was 5 cases, in the order of hyper-FBG> hyper-TG> AO> hypo-HDL-C> hypertension. Incidence of MS at 1, 3, 6 and 12 months after transplantation: 19, 26, 24 and 20 cases in the allo-HSCT group, respectively; auto-HSCT group were 7, 7, 6 and 6 cases, respectively. Hyper-TG and hypo-HDL-C were prominent in both groups. CONCLUSION: The incidence of HSCT-MS is significantly higher within 1 year after HSCT. Regardless of allo-HSCT and auto-HSCT, the prevention and control of HSCT-MS is emphasized as an important guarantee to improve the long-term survival quality of HSCT patients.


Subject(s)
Hematopoietic Stem Cell Transplantation , Metabolic Syndrome , Hematopoietic Stem Cells , Humans , Retrospective Studies , Transplantation, Homologous
16.
PLoS One ; 16(3): e0248675, 2021.
Article in English | MEDLINE | ID: mdl-33735325

ABSTRACT

BACKGROUND: In December 2019, a new disease named coronavirus disease 2019 (COVID-19) was occurred. Patients who are critically ill with COVID-19 are more likely to die, especially elderly patients. We aimed to describe the effect of age on the clinical and immune characteristics of critically ill patients with COVID-19. METHODS: We retrospectively included 32 patients with COVID-19 who were confirmed to have COVID-19 by the local health authority and who were admitted to the first affiliated hospital of Zhengzhou University in Zhengzhou, China between January 3 and March 20, 2020. Clinical information and experimental test data were retrospectively collected for the patients. The 32 patients in this study were all in a critical condition and were classified as severe, according to the guidelines of 2019-nCoV infection from the National Health Commission of the People's Republic of China. Data were compared between those <60 years old and ≥60 years old. RESULTS: Of 32 patients, 13 were under 60 years old, and 19 patients were ≥60 years old. The most common symptom among all patients upon admission was fever (93.8%, 30/32). Compared to younger patients, older patients exhibited increased comorbidities. Among patients who were 60 years and older, platelet count, direct bilirubin (DBIL), indirect bilirubin(IBIL), lactate dehydrogenase (LDH), B-type natriuretic peptide (BNP), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-10 (IL-10) were significantly higher than in younger patients who were less than 60 years old. CD4+ T lymphocytes, CD8+ T lymphocytes, and NKT lymphocytes were decreased, CD4+/CD8+ T lymphocytes were significantly increased in all 32 patients, while there were no evident differences between younger and older patients. The CURB-65 (confusion, urea, respiratory, rate, blood pressure plus age ≥65 years), Acute Physiology and Chronic Health Evaluation (APACHE) II and pH value were significantly higher in older patients than in patients who were under 60 years old. However, the PaO2 and PaO2:FiO2 were lower in older patients than the younger. Compared to patients under 60 years old, patients who were 60 years and older tended to develop ARDS (15 [78.9%] vs 5 [38.5%]), septic shock (7 [36.8%] vs 0 [0.0%]) and were more likely to receive mechanical ventilation (13 [68.4%] vs 3[23.1%]). Dynamic trajectories of seven laboratory parameters were tracked on days 1, 3, 5 and 7, and significant differences in lymphocyte count (P = 0.026), D-dimer (P = 0.010), lactate dehydrogenase (P = 0.000) and C-reactive protein (P = 0.000) were observed between the two age groups. CONCLUSIONS: A high proportion of critically ill patients were 60 or older. Furthermore, rapid disease progression was noted in elderly patients. Therefore, close monitoring and timely treatment should be performed in elderly COVID-19 patients.


Subject(s)
COVID-19/epidemiology , Age Factors , Aged , CD4-CD8 Ratio , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Critical Illness , Female , Humans , Immunity , Lymphocyte Count , Male , Middle Aged , Preliminary Data , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index
17.
Virus Genes ; 57(2): 194-204, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33559837

ABSTRACT

The structural protein VP3 of infectious bursal disease virus (IBDV) plays a critical role in viral assembly, replication, immune escape, and anti-apoptosis. Interaction between VP3 and host protein factors can affect stages in the viral replication cycle. In this study, 137 host proteins interacting with VP3 protein were screened through liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics approach. The functions and relevance of the proteins were obtained through bioinformatics analysis. Most VP3-interacting proteins were linked to binding, catalytic activity, and structural molecular activity, and performed functions in cell parts and cells. Biological functions of VP3-interacting proteins were mainly relevant to "Cytoskeleton", "Translation", and "Signal transduction mechanisms", involving ribosomes, "Tight junction", regulation of actin cytoskeleton, and other pathways. Six potential VP3-interacting proteins in host cells were knocked down, and vimentin, myosin-9, and annexin A2 were found to be related to IBDV replication. This study would help explore regulatory pathways and cellular mechanisms in IBDV-infected cells, and also provided clues for the in-depth study of VP3 biological functions and IBDV replication or pathogenesis.


Subject(s)
Infectious bursal disease virus/metabolism , Viral Structural Proteins/metabolism , Animals , Cell Line , Chick Embryo , Chromatography, Liquid , Fibroblasts/virology , Protein Binding , Protein Interaction Maps , Proteins/metabolism , Proteome/metabolism , Tandem Mass Spectrometry , Virus Replication
19.
Journal of Experimental Hematology ; (6): 1610-1616, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-922304

ABSTRACT

OBJECTIVE@#To evaluate the incidence and clinical characteristics of metabolic syndrome (MS) within one year after hematopoietic stem cell transplantation (HSCT) in order to screen the risk factors for HSCT-MS, provide early intervention and improve the long-term quality of survival of patients.@*METHODS@#The clinical follow-up data of 64 HSCT patients (survival time > 1 year) who received HSCT in our center from January 2007 to August 2018 were collected. Among them, 50 cases were allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 14 cases were autologous hematopoietic stem cell transplantation (auto-HSCT). The changes of MS-related indexes and clinical characteristics before and 1, 3, 6 and 12 months after HSCT were analyzed retrospectively.@*RESULTS@#In allo-HSCT group, 14 cases were diagnosed as MS before operation, including high-density lipoprotein cholesterol (hypo-HDL-C)> hyper triglycerides(hyper-TG)> hyper fasting glucose(hyper-FBG)> abdominal obesity (AO) > hypertension. The preoperative diagnosis of MS in the auto-HSCT group was 5 cases, in the order of hyper-FBG> hyper-TG> AO> hypo-HDL-C> hypertension. Incidence of MS at 1, 3, 6 and 12 months after transplantation: 19, 26, 24 and 20 cases in the allo-HSCT group, respectively; auto-HSCT group were 7, 7, 6 and 6 cases, respectively. Hyper-TG and hypo-HDL-C were prominent in both groups.@*CONCLUSION@#The incidence of HSCT-MS is significantly higher within 1 year after HSCT. Regardless of allo-HSCT and auto-HSCT, the prevention and control of HSCT-MS is emphasized as an important guarantee to improve the long-term survival quality of HSCT patients.


Subject(s)
Humans , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Metabolic Syndrome , Retrospective Studies , Transplantation, Homologous
20.
Huan Jing Ke Xue ; 41(12): 5668-5676, 2020 Dec 08.
Article in Chinese | MEDLINE | ID: mdl-33374084

ABSTRACT

In order to explore the impacts of nitrogen fertilizer and straw returning methods on N2O emissions, a two-factor split-zone design was adopted for experimentation under the winter wheat-summer maize rotation model in the Guanzhong area of Shanxi, China. The main areas of interest were conventional nitrogen (G) and reduced nitrogen (70% G); the sub-areas were straw no return (N), straw return (S), and straw return + biochar (SB); we analyzed their impacts on N2O emissions and crop yield, and the relationships with related impact factors. The results showed that the N2O emissions peaks appeared in the wheat season and maize season treatments within 5-16 days after fertilization, and also appeared after rainfall. The N2O flux was significantly and positively correlated with soil temperature and NH4+-N content. Regardless of the wheat season, maize season, or annual total N2O emissions, the 70% GSB treatment was the lowest and the GS treatment was the highest. At the same level of nitrogen application, S treatment increased N2O emissions, SB treatment could reduce N2O emissions, both S and SB treatments could significantly increase crop yields, and SB production increased more; 70%G-level annual N2O emissions, when compared with the G level, had been reduced by 40% to 48%, while the yield has not decreased significantly. Through comprehensive consideration, a reduction of nitrogen by 30% was achieved through the combination of straw + biochar on the basis of conventional nitrogen application, while ensuring high crop yields and the best N2O emissions reduction.


Subject(s)
Fertilizers , Soil , Agriculture , China , Nitrogen , Nitrous Oxide/analysis , Triticum , Zea mays
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