Application of CMV-IVIg as prophylaxis against cytomegalovirus reactivation in allogeneic hematopoietic stem cell transplantation patients.

Cytomegalovirus (CMV) reactivation remains one of the major and life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Yet, there is still a lack of safe and effective ways to prevent CMV reactivation in allo-HSCT patients. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our transplant center between 2018 and 2022 to evaluate the efficacy of prophylactic CMV-specific intravenous immunoglobulin (CMV-IVIg) against CMV reactivation. After Propensity Score Matching, the CMV reactivation rate was significantly decreased in the CMV-IVIg group (HR, 2.952; 95% CI,1.492-5.841; P = .002) compared with the control group. Additionally, the time duration of CMV reactivation (P = .001) and bacterial infection rate (P = .013) were significantly lower in the CMV-IVIg group. Moreover, prophylactic CMV-IVIg was more effective in CMV seropositive patients who received ATG as part of GVHD prevention (HR, 8.225; 95% CI,1.809-37.39; P = .006). In conclusion, CMV-IVIg is considered an effective and safe way to prevent CMV reactivation in HSCT recipients, which may be related to the acceleration of immune reconstitution in the early stage after transplantation.

Autophagy is essential for human myelopoiesis.

Emergency myelopoiesis (EM) is essential in immune defense against pathogens for rapid replenishing of mature myeloid cells. During the EM process, a rapid cell-cycle switch from the quiescent hematopoietic stem cells (HSCs) to highly proliferative myeloid progenitors (MPs) is critical. How the rapid proliferation of MPs during EM is regulated remains poorly understood. Here, we reveal that ATG7, a critical autophagy factor, is essential for the rapid proliferation of MPs during human myelopoiesis. Peripheral blood (PB)-mobilized hematopoietic stem/progenitor cells (HSPCs) with ATG7 knockdown or HSPCs derived from ATG7-/- human embryonic stem cells (hESCs) exhibit severe defect in proliferation during fate transition from HSPCs to MPs. Mechanistically, we show that ATG7 deficiency reduces p53 localization in lysosome for a potential autophagy-mediated degradation. Together, we reveal a previously unrecognized role of autophagy to regulate p53 for a rapid proliferation of MPs in human myelopoiesis.

Generation of an NSD2-deficient human embryonic stem cell line using CRISPR/Cas9 technology.

NSD2 is a histone methyltransferase (HMT) and is involved in the epigenetic regulation of hematopoiesis and hematological cancers. To understand and illustrate the precise roles of NSD2 in hematopoietic development, here we constructed a human embryonic stem cell (hESC) line with knockout of NSD2 using CRISPR/Cas9-mediated gene targeting. The cell line maintained typical stem cell morphology and normal karyotype. Furthermore, the pluripotency of the cell line was evidenced by high expression level of pluripotency genes and differentiation potential into three germ layers. The cell line provides a good model for studying roles of NSD2 in embryonic development, especially hematopoiesis.

[Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction].

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

Super-enhancer-associated gene CAPG promotes AML progression.

Acute myeloid leukemia is the most common acute leukemia in adults, the barrier of refractory and drug resistance has yet to be conquered in the clinical. Abnormal gene expression and epigenetic changes play an important role in pathogenesis and treatment. A super-enhancer is an epigenetic modifier that promotes pro-tumor genes and drug resistance by activating oncogene transcription. Multi-omics integrative analysis identifies the super-enhancer-associated gene CAPG and its high expression level was correlated with poor prognosis in AML. CAPG is a cytoskeleton protein but has an unclear function in AML. Here we show the molecular function of CAPG in regulating NF-κB signaling pathway by proteomic and epigenomic analysis. Knockdown of Capg in the AML murine model resulted in exhausted AML cells and prolonged survival of AML mice. In conclusion, SEs-associated gene CAPG can contributes to AML progression through NF-κB.

The Application and Efficacy of Second Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia.

BACKGROUND: We retrospectively analyzed the application and clinical efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia patients who relapsed or had primary graft failure (PGF) after first transplantation. METHODS: From 2007 to 2021, eight patients with acute leukemia who received second allo-HSCT in our hospital were collected, including 6 relapsed patients and 2 patients with PGF after the first HSCT. RESULTS: All the patients received complete donor implantation after second transplantation. The median time of neutrophils and platelet implantation were 12 days (10 days - 13 days) and 23 days (12 days - 123 days). Two cases (25.0%) developed grade II aGVHD, and 4 cases (50.0%) developed cGVHD. Leukemia-free survival (LFS) and overall survival (OS) at 1 year both were 71.4% and at 3 years both were 28.6%. After a median follow-up of 1,556 days (range, 257 - 5,252 days), 3 of the patients (37.5%) survived and 5 (62.5%) died. One patient with NR before second transplantation, treated with a conditioning regime of CLAG-M bridging BuCy, has survived for more than 5 years (61 months). Relapse was the main death reason. CONCLUSIONS: Second allo-HSCT is an effective means to treat acute leukemia patients with relapsed and PGF after first transplantation.

CMV infection is a risk factor for hemorrhagic cystitis after hematopoietic stem cell transplantation.

Hemorrhagic cystitis (HC) is a common complication after transplantation. The purpose of this study was to examine the incidence and risk factors for HC after hematopoietic stem cell transplantation (HSCT). The records of patients who underwent allogenic HSCT from January 2012 to December 2018 at our institution were retrospectively reviewed. Cox proportional regression and Kaplan-Meier analyses were performed to determine independent risk factors for HC. The statistical analysis was performed in May 2020. A total of 173 patients underwent HSCT, and 53 (30.6%) developed grade 2 or 3 HC cystitis at a median of 37 days (range - 5 to 98 days) after transplantation. Thirty-two patients developed moderate (grade 2) cystitis and 21 severe (grade 3) cystitis. Of the 173 patients, 61 developed acute graft-versus-host disease (GVHD) (median onset day 24) and 79 experienced cytomegalovirus (CMV) reactivation (median onset day 35). The relative risk (RR) of developing a CMV infection for patients with acute GVHD was 2.77 times that of patients without acute GVHD (P < 0.001). CMV infection was the only independent variable significantly associated with HC in both univariate and multivariate analyses. The estimated hazard ratio (HR) of CMV infection for the development of HC was 5.57 (95% confidence interval [CI]: 2.52 to 12.33, P < 0.001). CMV infection is an independent risk factor for the development of HC after HSCT, and acute GVHD is a risk factor for CMV reactivation. Decreasing the frequency of GVHD after HSCT may result in a lower frequency of HC.

Diagnosis and treatment for the early stage of cytomegalovirus infection during hematopoietic stem cell transplantation.

Cytomegalovirus (CMV) infection remains a frequent complication after hematopoietic stem cell transplantation (HSCT) and causes significant morbidity and mortality in transplantation recipients. In this review, we highlight the role of major risk factors that are associated with the incidence of CMV infection. Advances in immunosurveillance may predict CMV infection, allowing early interventions to prevent severe infection. Furthermore, numerous therapeutic strategies against CMV infection after HSCT are summarized. A comprehensive understanding of the current situation of CMV treatment may provide a hint for clinical practice and even promote the development of novel strategies for precision medicine.

Vitamin C promotes anti-leukemia of DZNep in acute myeloid leukemia.

The epigenetic treatment by 3-Deazaneplanocin A (DZNep), a histone methyltransferase inhibitor, shows great potential against acute myeloid leukemia (AML). However, the variant sensitivity and incomplete response to DZNep are commonly observed. Here, we reveal that vitamin C (Vc) dramatically promotes DZNep response against leukemic cells in different cell lines and primary AML samples. Vc enhances apoptosis and differentiation induced by DZNep in different AML cell lines in vitro and reduces leukemia progression in vivo. At the molecular level, Vc downregulates an enzyme of serine synthesis named D-3-phosphoglycerate dehydrogenase (PHGDH), as well as BCL2, an anti-apoptotic gene. Over-expression of PHGDH reverses the Vc-enhanced anti-leukemic effect of DZNep in AML cells. Therefore, our findings provide an effective approach to reduce the resistance against epigenetic treatment by Vc, which shows a potential improvement of their combination in AML patients.

New structurally diverse photoactive cadmium coordination polymers.

Four structurally diverse coordination polymers 1-4 (CP1-CP4) were designed and constructed from Cd(II) ions and various carboxyl ligands (H2oba, 4,4'-oxydibenzoic acid; H2bpa, (E)-4,4'-(ethene-1,2-diyl)dibenzoic acid; H2pbda, 4,4'-((1,3-phenylenebis(methylene))bis(oxy))dibenzoic acid) and the alkene containing ligand (CH3-bpeb, 4,4'-((1E,1'E)-(2,5-dimethyl-1,4-phenylene)bis(ethene-2,1-diyl))dipyridine). CP1-CP4 possess Cd2 binuclear secondary building units (SBUs). The geometry of the dicarboxylate ligands and the reaction conditions determined the final structure with a variety of motifs. CP1 possesses an interdigitated 2D structure, while CP2 consists of a 1D channel-like motif with isolated CH3-bpeb molecules embedded in the channels. The solid-state structure of CP3 consists of two unique layers interpenetrated to form a 2D + 2D → 2D polycatenated backbone, while a 1D channel-like motif filled by isolated CH3-bpeb molecules was observed for CP4. In all four coordination polymers pairs of CH3-bpeb molecules were bound or encapsulated by the Cd2 secondary building units at an appropriate distance and orientation for solid-state [2 + 2] photodimerization of one pair of CC bonds. Desolvation of CP3 with heat resulted in a decrease in solid-state fluorescence and a slowing of the rate of solid-state photodimerization.

Runt-Related Transcription Factor 3 Promotes Acute Myeloid Leukemia Progression.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with high relapse/refractory rate. Genetic and epigenetic abnormalities are driving factors for leukemogenesis. RUNX1 and RUNX2 from the Runt-related transcription factor (RUNX) family played important roles in AML pathogenesis. However, the relationship between RUNX3 and AML remains unclear. Here, we found that RUNX3 was a super-enhancer-associated gene and highly expressed in AML cells. The Cancer Genome Atlas (TCGA) database showed high expression of RUNX3 correlated with poor prognosis of AML patients. We observed that Runx3 knockdown significantly inhibited leukemia progression by inducing DNA damage to enhance apoptosis in murine AML cells. By chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we discovered that RUNX3 in AML cells mainly bound more genes involved in DNA-damage repair and antiapoptosis pathways compared to that in normal bone marrow cells. Runx3 knockdown obviously inhibited the expression of these genes in AML cells. Overall, we identified RUNX3 as an oncogene overexpressed in AML cells, and Runx3 knockdown suppressed AML progression by inducing DNA damage and apoptosis.

A novel intensive conditioning regimen for allogeneic hematopoietic stem cell transplantation in the treatment of relapsed/refractory acute myeloid leukemia.

We conducted a prospective study to evaluate the efficacy and safety of cladribine, cytarabine, mitoxantrone, and granulocyte colony-stimulating factor (CLAG-M) regimen combined with busulfan and cyclophosphamide (BuCy) as new intensive conditioning before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML). 24 patients were enrolled. The median follow-up was 15.2 months (range 1.9-67.0 months). Except for one patient who died before graft infusion, the evaluable 23 patients (96%) achieved complete remission (CR). The two-year overall survival (OS) rate and leukemia-free survival (LFS) rate were 61.4% and 59.4%, respectively. The non-relapse mortality (NRM) was 9.1%. Univariate analysis revealed that the myeloid blast phase of chronic myelomonocytic leukemia (CMML), an EVI1 mutated, blood blasts ≥20% at transplant, and extramedullary disease were risk factors for LFS.

Bone Marrow Mesenchymal Stem Cells-Derived Exosomal miR-425-5p Inhibits Acute Myeloid Leukemia Cell Proliferation, Apoptosis, Invasion and Migration by Targeting WTAP.

INTRODUCTION: Acute myeloid leukemia (AML) is a predominant blood malignancy with high mortality and severe morbidity. AML is affected by microRNAs (miRNAs) loaded in exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs). MiR-425-5p has been reported to participate in different cancer models. However, the function of BM-MSCs-derived exosomal miR-425-5p in AML is unclear. METHODS: The expression of miR-425-5p was measured by qRT-PCR in clinical AML samples. The immunophenotype of BM-MSCs was analyzed using antibodies against CD44, CD90, and CD105. The exosome was isolated from BM-MSCs. The effect of BM-MSCs-derived exosomal miR-425-5p on AML was analyzed by CCK-8 assay, Edu assay, transwell assay, flow cytometry in AML cells. qRT-PCR, luciferase reporter gene assay and Western blot analysis were also conducted in AML cells. RESULTS: The expression levels of miR-425-5p were decreased in CD34 + CD38-AML cells from primary AML patients compared to that from the bone marrow of healthy cases, and were reduced in exosomes from AML patients compared that from healthy cases. Similarly, miR-425-5p was also down-regulated in AML cell lines compared with BM-MSCs. MiR-425-5p was able to express in exosomes from BM-MSCs. CCK-8, Edu, transwell assay and flow cytometry analysis revealed that BM-MSCs-derived exosomal miR-425-5p significantly inhibited cell viability, Edu positive cells, invasion and migration, and induced apoptosis of AML cells. Meanwhile, the expression levels of cleaved PARP and cleaved caspase3 were increased by BM-MSCs-derived exosomal miR-425-5p in cells. MiR-425-5p inhibited the expression of Wilms tumor 1-associated protein (WTAP). Moreover, overexpression of WTAP could reverse the miR-425-5p-induced inhibition effect on AML cell proliferation, apoptosis, migration and invasion. CONCLUSION: BM-MSCs-derived exosomal miR-425-5p inhibits proliferation, invasion and migration of AML cells and induced apoptosis of AML cells by targeting WTAP. Therapeutically, BM-MSCs-derived exosomal miR-425-5p may serve as a potential target for AML therapy.

Blocking DNA Damage Repair May Be Involved in Stattic (STAT3 Inhibitor)-Induced FLT3-ITD AML Cell Apoptosis.

The FMS-like tyrosine kinase 3 (FLT3)- internal tandem duplication (ITD) mutation can be found in approximately 25% of all acute myeloid leukemia (AML) cases and is associated with a poor prognosis. The main treatment for FLT3-ITD-positive AML patients includes genotoxic therapy and FLT3 inhibitors, which are rarely curative. Inhibiting STAT3 activity can improve the sensitivity of solid tumor cells to radiotherapy and chemotherapy. This study aimed to explore whether Stattic (a STAT3 inhibitor) affects FLT3-ITD AML cells and the underlying mechanism. Stattic can inhibit the proliferation, promote apoptosis, arrest cell cycle at G0/G1, and suppress DNA damage repair in MV4-11cells. During the process, through mRNA sequencing, we found that DNA damage repair-related mRNA are also altered during the process. In summary, the mechanism by which Stattic induces apoptosis in MV4-11cells may involve blocking DNA damage repair machineries.

Characterization and generation of human definitive multipotent hematopoietic stem/progenitor cells.

Definitive hematopoiesis generates hematopoietic stem/progenitor cells (HSPCs) that give rise to all mature blood and immune cells, but remains poorly defined in human. Here, we resolve human hematopoietic populations at the earliest hematopoiesis stage by single-cell RNA-seq. We characterize the distinct molecular profiling between early primitive and definitive hematopoiesis in both human embryonic stem cell (hESC) differentiation and early embryonic development. We identify CD44 to specifically discriminate definitive hematopoiesis and generate definitive HSPCs from hESCs. The multipotency of hESCs-derived HSPCs for various blood and immune cells is validated by single-cell clonal assay. Strikingly, these hESCs-derived HSPCs give rise to blood and lymphoid lineages in vivo. Lastly, we characterize gene-expression dynamics in definitive and primitive hematopoiesis and reveal an unreported role of ROCK-inhibition in enhancing human definitive hematopoiesis. Our study provides a prospect for understanding human early hematopoiesis and a firm basis for generating blood and immune cells for clinical purposes.

Late-onset severe hepatic sinusoidal obstruction syndrome in an allogeneic stem cell transplant recipient: A case report.

RATIONALE: Hepatic sinusoidal obstruction syndrome (SOS) is a rare and potentially fatal complications after hematopoietic stem cell transplantation (HSCT). Most severe SOS result in multi-organ dysfunction and are associated with a high mortality rate (>80%). PATIENT CONCERNS: A 31-year-old man was diagnosed with chronic myeloid leukemia blast crisis. He presented with severe thrombocytopenia on day 42 post-HSCT (on days +42), gradually developed with painful hepatomegaly, ascites, and weight gain. DIAGNOSES: The abdominal computerized tomography showed hepatomegaly, hepatic congestion, periportal edema, narrow hepatic vein, and ascites suggestive of SOS/hepatic vein occlusion. According to the EBMT revised diagnostic criteria, the patient was diagnosed as late-onset severe SOS. INTERVENTIONS: Comprehensive treatment including low molecular weight heparin was initiated. OUTCOMES: The patient had good response with resolution of his hepatomegaly, increase of platelet, weight and transaminase loss after 4 weeks treatment. LESSONS: In SOS patients with nonspecific clinical and biochemical findings, computerized tomography scans can be useful in differentiating SOS from other complications after HSCT. low molecular weight heparin is effective for the treatment of SOS.

RAD52 aptamer regulates DNA damage repair and STAT3 in BRCA1/BRCA2­deficient human acute myeloid leukemia.

RAD52 (Radiation sensitive 52) is a key factor in DNA damage repair (DDR) bypass, which participates in single­strand annealing (SSA) after DNA damage end excision, while breast cancer type 1 susceptibility protein (BRCA1)/breast cancer type 2 susceptibility protein (BRCA2) play critical roles in homologous recombination (HR) repair. The present study aimed to determine whether RAD52­induced regulation of repair bypass occurs in acute myeloid leukemia (AML) cells and to explore the underlying mechanism. Herein, we applied an RAD52 aptamer to AML cells with downregulated BRCA1/2. RAD52 aptamer inhibited AML cell proliferation detected by cell counting, promoted cell apoptosis obtained by flow cytometry, and suppressed DNA damage repair behavior measured by comet assay and flow cytometry, after drug intervention during low expression of BRCA1/2. During this process, DDR­related cell cycle checkpoint proteins were activated, and the cells were continuously arrested in the S/G2 phase, which affected the cell damage repair process. Concurrently, the expression levels of apoptosis­related proteins were also altered. Furthermore, the expression of STAT3 and p­STAT3 was downregulated by the RAD52 aptamer, suggesting that RAD52 affects the STAT3 signaling pathway. In summary, we present a possible role for RAD52 in DDR of BRCA1/2­deficient AML cells that involves the STAT3 signaling pathway.

Clinical analysis and literature review of a case with the myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

Objective: Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a new disease entity in the 2016 WHO classification, characterized by anemia, thrombocytosis and bone marrow ring sideroblasts. We herein reported a case of MDS/MPN-RS-T and discuss its clinical characteristics. Methods: A 69-year-old woman presented to our hospital with recurrent dizziness and fatigue. Hematologic investigations, bone marrow analysis and genomic DNA sequencing studies were performed. Results: Peripheral blood testing showed normocytes anemia and thrombocytosis, and bone marrow analysis revealed hypercellular with clusters of megakaryocytes and 95% ring sideroblasts (RS). She had a normal karyotype and was found to have SF3B1 mutations. Decitabine therapy produced a clinical response and disease remission in this patient. Conclusions: Our report provides a definite conceptual framework for a better understanding of the characteristics of MDS/MPN-RS-T.

Effect of Phacoemulsification on Anterior Chamber Angle in Eyes with Medically Uncontrolled Filtered Primary Angle-Closure Glaucoma.

PURPOSE: To evaluate the effect of phacoemulsification and intraocular lens (IOLs) implantation in eyes with medically uncontrolled primary angle-closure glaucoma (PACG) previously treated with trabeculectomy and to quantify the anatomical changes in the anterior chamber angle by ultrasound biomicroscopy (UBM). METHODS: Forty-four eyes of 37 consecutive patients with medically uncontrolled PACG coexisting cataracts with a surgical history of trabeculectomy were included in this study. Each patient underwent phacoemulsification and IOL implantation. Indentation gonioscopy and UBM were performed preoperatively and then again 3 months after surgery. The main outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP), number of antiglaucoma medications and anatomical changes in the anterior chamber angle. RESULTS: The mean logarithm of the minimum angle of resolution BCVA significantly improved from 0.52 ± 0.30 preoperatively to 0.26 ± 0.23 postoperatively (p < 0.001). The mean IOP significantly decreased from 24.33 ± 9.65 mmHg preoperatively to 18.04 ± 7.86 mmHg postoperatively (p < 0.05). 001). The median number of antiglaucoma medications decreased from 2 preoperatively to 1 postoperatively (p < 0.001). There was no significant difference in the extent of peripheral anterior synechia after the surgery (p > 0.05). Some parameters, including anterior central chamber depth, angle opening distance at 500 µm, trabecular-iris angle, and scleral ciliary process angle, were significantly higher after than before surgery (p < 0.001). However, the crystalline lens rise was significantly smaller following the surgery (p < 0.001). CONCLUSIONS: Phacoemulsification and IOL implantation reduced the IOP and improved vision in eyes with medically uncontrolled filtered PACG. The mechanism underlying the outcomes observed following surgery might be related to the anterior chamber deepening, widened drainage angle, and improved aqueous fluid flow to the trabecular meshwork.

Vitellaria paradoxa Nut Triterpene-Rich Extract Ameliorates Symptoms of Inflammation on Post-Traumatic Osteoarthritis in Obese Rats.

PURPOSE: To investigate the ameliorative effects of Vitellaria paradoxa (VP) nut extract for an anterior cruciate ligament transection with medial meniscectomy (ACLT+MMx)-induced osteoarthritis (OA) in high-fat diet (HFD)-induced obese rats. METHODS: The rats were fed by HFD for 5 weeks before surgery-induced OA. Rats were treated orally with three different doses of VP nut extract (111.6, 223.2, and 446.4 mg/kg) for 8 weeks. RESULTS: The VP nut triterpene-rich extract decreased the level of triglycerides and increased high-density lipoprotein-cholesterol. The level of nitric oxide, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α decreased after treatment with VP nut triterpene-rich extract, especially in high-doses. The VP nut triterpene-rich extracts also alleviated swelling in the knee OA, weight-bearing difference, and suppressed cartilage degradation. CONCLUSION: The Vitellaria paradoxa nut triterpene-rich extract suppressed proinflammatory mediators and attenuated the cartilage degradation and pain in osteoarthritis with an obesity rat model. As such, Vitellaria paradoxa nut triterpene-rich extract can be used as an alternative for osteoarthritis treatment.