Publications by authors named "Hua Jiang"

1,281 Publications

  • Page 1 of 1

Structure-Activity relationship of 1-(Furan-2ylmethyl)Pyrrolidine-Based Stimulation-2 (ST2) inhibitors for treating graft versus host disease.

Bioorg Med Chem 2022 Jul 22;71:116942. Epub 2022 Jul 22.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, United States. Electronic address:

An elevated plasma level of soluble ST2 (sST2) is a risk biomarker for graft-versus-host disease (GVHD) and death in patients receiving hematopoietic cell transplantation (HCT). sST2 functions as a trap for IL-33 and amplifies the pro-inflammatory type 1 and 17 response while suppressing the tolerogenic type 2 and regulatory T cells activation during GVHD development. We previously identified small-molecule ST2 inhibitors particularly iST2-1 that reduces plasma sST2 levels and improved survival in two animal models. Here, we reported the structure-activity relationship of the furanylmethylpyrrolidine-based ST2 inhibitors based on iST2-1. Based on the biochemical AlphaLISA assay, we improved the activity of iST2-1 by 6-fold (∼6 μM in IC values) in the inhibition of ST2/IL-33 and confirmed the activities of the compounds in a cellular reporter assay. To determine the inhibition of the alloreactivity in vitro, we used the mixed lymphocyte reaction assay to demonstrate that our ST2 inhibitors decreased CD4 and CD8 T cells proliferation and increased Treg population. The data presented in this work are critical to the development of ST2 inhibitors in future.
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http://dx.doi.org/10.1016/j.bmc.2022.116942DOI Listing
July 2022

A Comprehensive Review of Microneedling as a Potential Treatment Option for Androgenetic Alopecia.

Aesthetic Plast Surg 2022 Aug 5. Epub 2022 Aug 5.

Department of Plastic Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China.

Background: Microneedling refers to a minimally invasive technique that uses multiple fine needles targeted skin epidermis for mechanical stimulation to obtain therapeutic or cosmetic effects. It is suitable for the treatment of a variety of dermatological conditions, including androgenetic alopecia (AGA).

Objective: This article aims to make a comprehensive review of the relevant studies on microneedling for the management of AGA.

Methods: Extensive literature search was performed using PubMed, Web of Science, and EBSCO databases. 4 in vivo studies and 25 clinical trials were included according to the inclusion and exclusion criteria.

Results: The effects of microneedling on AGA was investigated in animal experiments. Several clinical trials, including randomized controlled trials, strengthen the validity of the findings. Microneedling therapy showed some encouraging results with minor complications when used alone or in combination with topical products.

Conclusions: Microneedling appears to be a safe and effective therapeutic option for AGA. Larger and more randomized controlled trials regarding the role of microneedling in AGA are strongly recommended to provide more definitive evidence.

Level Of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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http://dx.doi.org/10.1007/s00266-022-03042-yDOI Listing
August 2022

Radiation enhances the efficacy of EGFR-targeted CAR-T cells against triple-negative breast cancer by activating NF-κB/Icam1 signaling.

Mol Ther 2022 Aug 3. Epub 2022 Aug 3.

State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China; CARsgen Therapeutics, Shanghai 200032, China. Electronic address:

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options. Epidermal growth factor receptor (EGFR) is reported to be expressed in 50% to 75% of TNBC patients, making it a promising target for cancer treatment. Here we show that EGFR-targeted Chimeric Antigen Receptor (CAR) T cell therapy combined with radiotherapy provides enhanced antitumor efficacy in immunocompetent and immunodeficient orthotopic TNBC mice. Intriguingly, this combination therapy resulted in a substantial increase in the number of tumor-infiltrating CAR-T cells. The efficacy of this combination was independent of tumor radiosensitivity and lymphodepleting preconditioning. Cytokine profiling showed that this combination did not increase the risk of cytokine release syndrome (CRS). RNA-seq analysis revealed that EGFR-targeting CAR-T therapy combined with radiotherapy increased the infiltration of CD8 T and NK cells into tumors. Mechanistically, radiation significantly increased Icam1 expression on TNBC cells via activating NF-κB signaling, thereby promoting CAR-T cell infiltration and killing. These results suggest that CAR-T therapy combined with radiotherapy may be a promising strategy for TNBC treatment.
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http://dx.doi.org/10.1016/j.ymthe.2022.07.021DOI Listing
August 2022

CRMP2 derived from cancer associated fibroblasts facilitates progression of ovarian cancer via HIF-1α-glycolysis signaling pathway.

Cell Death Dis 2022 Aug 4;13(8):675. Epub 2022 Aug 4.

Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.

As the predominant stroma cells of tumor microenvironment (TME), cancer associated fibroblasts (CAFs) are robust tumor player of different malignancies. However, less is known about the regulatory mechanism of CAFs on promoting progression of ovarian cancer (OvCA). In the present study, the conditioned medium of primary CAFs (CAF-CM) from OvCA was used to culture cell lines of epithelial ovarian cancer (EOC), and showed a potent role in promoting proliferation, migration and invasion of cancer cells. Mass spectrum (MS) analysis identified that Collapsin response mediator protein-2 (CRMP2), a microtubule-associated protein involved in diverse malignancies, derived from CAFs was a key regulator responsible for mediating these cell events of OvCA. In vitro study using recombinant CRMP2 (r-CRMP2) revealed that the protein promoted proliferation, invasion, and migration of OvCA cells through activation of hypoxia-inducible factor (HIF)-1α-glycolysis signaling pathway. The CRMP2 was abundantly expressed in OvCA, with a well correlation with metastasis and poor prognosis, as analyzed from 118 patients' samples. Inhibition of the CRMP2 derived from CAFs by neutralizing antibodies significantly attenuated the tumor size, weights, and metastatic foci numbers of mice in vivo. Our finding has provided a novel therapeutic clue for OvCA based on TME.
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http://dx.doi.org/10.1038/s41419-022-05129-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352901PMC
August 2022

Wedelolactone induces apoptosis and pyroptosis in retinoblastoma through promoting ROS generation.

Int Immunopharmacol 2022 Jul 26;111:108855. Epub 2022 Jul 26.

Department of Interventional Radiology and Vascular, The Affiliated Hospital of Guangzhou Medical University, Guangzhou Women and Children's Medical Center, Guangzhou 510060, China. Electronic address:

Retinoblastoma is a most frequently occurring primary intraocular tumor in infancy and children, highlighting the requirement to find and develop novel and more effective therapeutic approaches. Wedelolactone (WDL), a nature compound isolated from E. prostrata, exhibits multiple biological activities through regulating various signaling pathways; however, its potential influences on retinoblastoma progression are still unknown, and thus was investigated in our study, as well as the underlying mechanisms. Here, we found that WDL treatments significantly reduced the proliferation of retinoblastoma cells by inducing apoptosis and pyroptosis through increasing Caspase-3, Caspase-1, gasdermin E (GSDME) and gasdermin D (GSDMD) activation. Mitochondrial impairment and reactive oxygen species (ROS) generation were considerably up-regulated in WDL-incubated retinoblastoma cells through a dose-dependent manner. Notably, we found that ROS scavenge significantly abolished the function of WDL to provoke apoptosis and pyroptosis in retinoblastoma cell lines, revealing that ROS was required for WDL to perform its anti-cancer role in retinoblastoma. Moreover, our in vivo experiments indicated that WDL administration significantly reduced the tumor growth in the established retinoblastoma mouse models with undetectable toxicity. Collectively, these findings highlighted the potential of WDL to inhibit the growth and induce cell death of retinoblastoma in vitro and in vivo, and thereby showed promise as a therapeutic agent for the treatment of retinoblastoma.
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http://dx.doi.org/10.1016/j.intimp.2022.108855DOI Listing
July 2022

A case report on a child with fracture and dislocation of the upper cervical spine accompanied by spinal cord injury.

Medicine (Baltimore) 2022 Jul 29;101(30):e29717. Epub 2022 Jul 29.

School of Clinical Medicine, Guizhou Medical University, Guiyang City, Guizhou Province, People's Republic of China.

Rationale: This study describes an 8-year-old boy with a C2 fracture and dislocation with a left C2-C3 articular process interlocking and spinal cord injury who underwent open reduction and internal fixation using the posterior cervical approach and achieved satisfactory results.

Patient Concerns: An 8-year-old boy underwent an emergency transfer from a previous hospital after a car accident.

Diagnoses: Axial fracture and dislocation with spinal cord injury (American Spinal Injury Association grade C), traumatic shock, brain contusion, intracranial hemorrhage, mandibular fracture, pulmonary contusion and hemorrhage, left vertebral artery stenosis, and multiple fractures throughout the body. Radiological examination revealed a fracture of the lower edge of the C2 vertebral body, fourth-degree anterior spondylolisthesis of the C2 vertebral body, interlocking of the left C2-C3 articular processes, widening of the C2-C3 vertebral space, and occlusion of the V1 and 2 segments of the left vertebral artery.

Interventions: The boy was immediately intubated and transferred to the pediatric intensive care unit for rescue treatment. However, the reduction was unsuccessful with 2 weeks of cranial traction. Thus, an open reduction was performed under general anesthesia. One month after the surgery, the boy was discharged from the hospital on foot after rehabilitation treatment.

Outcomes: The boy was discharged from the hospital 1 month after surgery. At the 8-month follow-up, a radiological examination showed that the corrected C2 vertebral body fracture and dislocation were satisfactorily reduced, and the spinal cord was adequately decompressed. The internal fixation position was also good, and the spinal sequence had recovered well. In summary, except for the muscle strength of the right upper limb, which was slightly worse, the other clinical symptoms were significantly improved.

Lessons: In treating cervical fracture and dislocation with unilateral facet lock, the posterior open reduction of pedicle screw and lateral mass screw internal fixation achieved satisfactory results. Consequently, treating complex cervical spine injuries in children requires an accurate diagnosis and careful treatment strategy.
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http://dx.doi.org/10.1097/MD.0000000000029717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333534PMC
July 2022

Effects of Different Extraction Methods in Pharmacopoeia on the Content and Structure Transformation of Ginsenosides.

Molecules 2022 Jul 6;27(14). Epub 2022 Jul 6.

School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China.

Ginseng ( C. A. Meyer), a perennial herb, possesses immunostimulatory, anticarcinogenic, antiemetic, and antioxidative biological activities. In recent years, more and more people have paid attention to the extraction methods and quality evaluation of ginseng. China, the United States, Europe, Japan, and Korea have all had the quality standards and content determination methods of ginseng. The different treatment methods are adopted before the determination of ginseng samples and the content limits of the index components, such as ginsenoside Rb, ginsenoside Rg, and ginsenoside Re exist differences. The similarities and differences of ginseng content detection methods in pharmacopoeias of different countries have been analyzed by a research group, but the comparison of the effects of different methods on the ginsenoside content and structural transformation has not been reported. In this paper, ginsenosides in ginseng were extracted according to four national pharmacopoeias and analyzed quantitatively and qualitatively by UPLC-Q-Exactive-MS and HPLC-UV. It was illustrated that the pretreatment method has a significant influence on the content determination of ginseng. The yield of rare saponins was increased by heating concluded from both the qualitative and quantitative comparison. Finally, a simple and feasible extraction method was optimized by response surface method at room temperature. The analysis of the preparation method and process optimization of the four pharmacopoeias can provide important reference information for the revision of ginseng standards.
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http://dx.doi.org/10.3390/molecules27144347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351678PMC
July 2022

Protocol for establishing a protein-protein interaction network using tandem affinity purification followed by mass spectrometry in mammalian cells.

STAR Protoc 2022 09 19;3(3):101569. Epub 2022 Jul 19.

Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China.

Identification of protein interactors is fundamental to understanding their functions. Here, we describe a modified protocol for tandem affinity purification coupled with mass spectrometry (TAP/MS), which includes two-step purification. We detail the S-, 2×FLAG-, and Streptavidin-Binding Peptide (SBP)- tandem tags (SFB-tag) system for protein purification. This protocol can be used to identify protein interactors and establish a high-confidence protein-protein interaction network based on computational models. This is particularly useful for identifying interacting proteins for subsequent functional studies. For complete details on the use and execution of this protocol, please refer to Bian et al. (2021).
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http://dx.doi.org/10.1016/j.xpro.2022.101569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304681PMC
September 2022

Luteolin Binds Streptolysin O Toxin and Inhibits Its Hemolytic Effects and Cytotoxicity.

Front Pharmacol 2022 7;13:942180. Epub 2022 Jul 7.

College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.

Group A (GAS, ) is a common pathogen that can cause a variety of human diseases. Streptolysin O (SLO) is an exotoxin produced by GAS. It is a pore-forming toxin (PFT) that exhibits high toxicity. SLO enables GAS to evade phagocytosis and clearance by neutrophils, induces eukaryotic cell lysis, and activates inflammatory bodies. Luteolin is a natural compound that is produced by a wide range of plant species, and recent studies have shown that luteolin can inhibit the growth and alter the morphological of GAS. Here, we reported that luteolin can weaken the cytotoxicity and hemolytic activity of SLO . Briefly, luteolin bound SLO with high affinity, inhibited its dissolution of erythrocytes, affected its conformational stability and inhibited the formation of oligomers. To further verify the protective effect of luteolin, we used an SLO-induced human laryngeal carcinoma epithelial type-2 cells (HEp-2) model. Notably, our results showed luteolin protected HEp-2 cells from SLO induced cytotoxicity and changed in cell membrane permeability. In addition, we explored the role of luteolin in protecting mice from GAS-mediated injury using an aerosolized lung delivery model, and our results indicate that luteolin increases murine survival rate following inoculation with a lethal dose of GAS, and that survival was also associated with decreased pathological damage to lung tissue. Our results suggest that luteolin may be a novel drug candidate for the treatment of GAS infection.
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http://dx.doi.org/10.3389/fphar.2022.942180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300923PMC
July 2022

Clinical Metagenomic Next-Generation Sequencing for Diagnosis of Secondary Glaucoma in Patients With Cytomegalovirus-Induced Corneal Endotheliitis.

Front Microbiol 2022 5;13:940818. Epub 2022 Jul 5.

The Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China.

Glaucoma is the second leading cause of blindness globally. Growing scientific evidence indicated that inflammation of the trabecular meshwork induced by corneal endotheliitis could lead to secondary glaucoma. Cytomegalovirus (CMV) has been identified as the most common herpes virus in corneal endotheliitis patients. Early detection is critical in preventing endothelial cell loss, and patient management should vary based on different pathological factors. However, routine culture and real-time polymerase chain reaction (qPCR) have difficult in distinguishing whether CMV, Varicella Zoster Virus (VZV) or Herpes Simplex Virus (HSV) causes endothiliitis. This may result in inappropriate treatment, which may prolong or aggravate the status of disease. We compared the sensitivity and specificity of qPCR and Metagenomic Next-Generation Sequencing (mNGS) in the aqueous humor of patients with suspected CMV endotheliitis in this study. Our results showed that four out of 11 (36.4%) of our patients were positive for CMV by qPCR, whereas mNGS had a 100% detection rate of CMV. Our findings implied that mNGS could be a useful diagnostic tool for CMV-induced endotheliitis.
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http://dx.doi.org/10.3389/fmicb.2022.940818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295740PMC
July 2022

Effects of microneedling with 5% minoxidil topical solution combination therapy in treatment of androgenetic alopecia.

J Cosmet Dermatol 2022 Jul 21. Epub 2022 Jul 21.

Department of Plastic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Microneedling (MN) therapy is one of minimal invasive operations with needles rolled over skin to puncturing the epidermis, and it is becoming a widely used treatment during various dermatological diseases includes androgenetic alopecia (AGA).

Objective: The purpose of the current study is to investigate the clinical observation and safety of MN combined with 5% minoxidil on triggering hair growth in AGA patients.

Material And Methods: This retrospective study has analyzed 18 AGA patients who were treated by MN in combination with 5% minoxidil topical solution between July 2021 and February 2022. All patients received six sessions of treatment under aseptic condition at an interval of one week. Assessment of hair regrowth was done at the baseline and 10 weeks by photography, investigator and patient assessment global scoring table on clinical improvement, and the patient's final satisfaction was investigated.

Results: According to the standardized 7-point scale, mean scores of investigator and participant assessments were 1.44±0.61 and 1.66±0.59 respectively, indicating that the hair appearance was considerably improved by MN combined with 5% minoxidil treatment. 15 patients (83.3%) were satisfied with the improvement in hair growth. No severe adverse events were noted in patients during and after the procedure.

Conclusion: The combination of the length of 1.5 mm MN and 5% minoxidil in the treatment of AGA showed efficacy with high safety, which is worthy of clinical application.
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http://dx.doi.org/10.1111/jocd.15263DOI Listing
July 2022

Monocytic myeloid-derived suppressive cells mitigate over-adipogenesis of bone marrow microenvironment in aplastic anemia by inhibiting CD8 T cells.

Cell Death Dis 2022 Jul 18;13(7):620. Epub 2022 Jul 18.

Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China.

Aplastic anemia (AA) is a blood disorder resulted from over-activated T-cell related hematopoietic failure, with the characterization of hypocellularity and enhanced adipogenic differentiation of mesenchymal stroma cells (MSCs) in bone marrow (BM). However, little is known about the relationship between immune imbalance and polarized adipogenic abnormity of BM microenvironment in this disease entity. In the present study, we differentiated BM-MSCs into osteoblastic or adipogenic lineages to mimic the osteo-adipogenic differentiation. Activated CD8 T cells and interferon-γ (IFN-γ) were found to stimulate adipogenesis of BM-MSCs either in vitro or in vivo of AA mouse model. Interestingly, myeloid-derived suppressive cells (MDSCs), one of the immune-regulating populations, were decreased within BM of AA mice. We found that it was not CD11bLy6GLy6C granulocytic-MDSCs (gMDSCs) but CD11bLy6GLy6C monocytic-MDSCs (mMDSCs) inhibiting both T cell proliferation and IFN-γ production via inducible nitric oxide synthetase (iNOS) pathway. Single-cell RNA-sequencing (scRNA-seq) of AA- and mMDSCs-treated murine BM cells revealed that mMDSCs transfusion could reconstitute BM hematopoietic progenitors by inhibiting T cells population and signature cytokines and decreasing immature Adipo-Cxcl12-abundant reticular cells within BM. Multi-injection of mMDSCs into AA mice reduced intra-BM T cells infiltration and suppressed BM adipogenesis, which subsequently restored the intra-BM immune balance and eventually prevented pancytopenia and hypo-hematopoiesis. In conclusion, adoptive transfusion of mMDSCs might be a novel immune-regulating strategy to treat AA, accounting for not only restoring the intra-BM immune balance but also improving stroma's multi-differentiating microenvironment.
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http://dx.doi.org/10.1038/s41419-022-05080-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293984PMC
July 2022

Characterization of a novel bispecific antibody targeting tissue factor-positive tumors with T cell engagement.

Acta Pharm Sin B 2022 Apr 3;12(4):1928-1942. Epub 2021 Nov 3.

Engineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

T cell engaging bispecific antibody (TCB) is an effective immunotherapy for cancer treatment. Through co-targeting CD3 and tumor-associated antigen (TAA), TCB can redirect CD3 T cells to eliminate tumor cells regardless of the specificity of T cell receptor. Tissue factor (TF) is a TAA that involved in tumor progression. Here, we designed and characterized a novel TCB targeting TF (TF-TCB) for the treatment of TF-positive tumors. , robust T cell activation, tumor cell lysis and T cell proliferation were induced by TF-TCB. The tumor cell lysis activity was dependent upon both CD3 and TF binding moieties of the TF-TCB, and was related to TF expression level of tumor cells. , in both tumor cell/human peripheral blood mononuclear cells (PBMC) co-grafting model and established tumor models with poor T cell infiltration, tumor growth was strongly inhibited by TF-TCB. T cell infiltration into tumors was induced during the treatment. Furthermore, efficacy of TF-TCB was further improved by combination with immune checkpoint inhibitors. For the first time, our results validated the feasibility of using TF as a target for TCB and highlighted the potential for TF-TCB to demonstrate efficacy in solid tumor treatment.
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http://dx.doi.org/10.1016/j.apsb.2021.10.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279644PMC
April 2022

The Outcome of Allogeneic Hematopoietic Stem Cell Transplantation From Different Donors in Recipients With Mucopolysaccharidosis.

Front Pediatr 2022 30;10:877735. Epub 2022 Jun 30.

Department of Hematology and Oncology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

There is limited information regarding hematopoietic stem cell transplantation (HSCT) for mucopolysaccharidosis (MPS) IV and VI. This study examined the full donor chimerism, specific lysosomal enzyme levels, and the survival of different MPS children after HSCT from various donor sources and compared the prognosis. A total of 42 children with MPS underwent HSCT, 9 cases were type I, 14 were type II, 15 were type IV, and 4 were type VI. A total of 24 patients received peripheral blood stem cells (PBSC) and 18 patients received umbilical cord blood (UCB). Patients who received PBSC were conditioned with intravenous (IV) busulfan every 6 h for a total of 16 doses, IV cyclophosphamide (CY, 200 mg/kg), and antihuman thymocyte globulin (ATG, 10 mg/kg). While conditioning regimen of patients who received UCB was adjusted to ATG (preposed, pre-) + busulfan + fludarabine + Cy, which includes IV ATG (pre-, 6 mg/kg), IV busulfan every 6 h for a total of 16 doses, IV fludarabine (200 mg/m) and CY (200 mg/kg). Also, 95.2% (40 of 42) of patients achieved full donor chimerism, and all patients' specific lysosomal enzyme levels reached normal. The estimated overall survival (OS) at 1 year was 92.9%. There was no significant difference in 1-year OS between patients who received PBSC transplantation and those who received UCB grafts (87.5% vs. 100%, = 0.0247). The incidence of acute and chronic GVHD did not differ between them. The incidences of pneumonia in PBSC recipients and UCB recipients were 45.8 and 33.3%, respectively, but there few patients suffering from respiratory failure (4.2 and 5.6%, respectively) due to pneumonia. The incidence of cytomegaloviremia was also high in both groups, 58.3 and 44.4% respectively, However, no patient developed CMV disease. All deaths (3 of 42) occurred in patients receiving PBSC grafts, and there was no death in patients receiving UCB grafts. There was no death after transplantation in patients with MPS IV and VI. In addition, respiratory and nervous system functions were improved, whereas valvular heart disease was improved in some patients but progressed in more patients after transplantation. In summary, HSCT is a good therapeutic option for MPS, not only for patients with MPS I or II but also for those with MPS IV or VI. The specific lysosomal enzyme levels can be completely restored to normal, which is the basis for patients to resolve a broad range of clinical outcomes. Moreover, UCB with suitable HLA (HLA-match above 7/10 and 4/6) is a suitable donor source for MPS. Patients who underwent UCB transplantation using the conditioning regimen ATG (pre-) + busulfan + fludarabine + Cy can achieve a higher proportion of full donor chimerism and survival with less severe complications. HSCT can improve organs function in patients with MPS, but it is still worth exploring.
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http://dx.doi.org/10.3389/fped.2022.877735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279935PMC
June 2022

Comparison Analysis of Different DNA Extraction Methods on Suitability for Long-Read Metagenomic Nanopore Sequencing.

Front Cell Infect Microbiol 2022 28;12:919903. Epub 2022 Jun 28.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China.

Metagenomic next-generation sequencing (mNGS) is a novel useful strategy that is increasingly used for pathogens detection in clinic. Some emerging mNGS technologies with long-read ability are useful to decrease sequencing time and increase diagnosed accuracy, which is of great significance in rapid pathogen diagnosis. Reliable DNA extraction is considered critical for the success of sequencing; hence, there is thus an urgent need of gentle DNA extraction method to get unbiased and more integrate DNA from all kinds of pathogens. In this study, we systematically compared three DNA extraction methods (enzymatic cell lysis based on MetaPolyzyme, mechanical cell lysis based on bead beating, and the control method without pre-cell lysis, respectively) by assessing DNA yield, integrity, and the microbial diversity based on long-read nanopore sequencing of urine samples with microbial infections. Compared with the control method, the enzymatic-based method increased the average length of microbial reads by a median of 2.1-fold [Inter Quartile Range (IQR), 1.7-2.5; maximum, 4.8) in 18 of the 20 samples and the mapped reads proportion of specific species by a median of 11.8-fold (Inter Quartile Range (IQR), 6.9-32.2; maximum, 79.27]. Moreover, it provided fully (20 of 20) consistent diagnosed results to the clinical culture and more representative microbial profiles ( < 0.05), which all strongly proves the excellent performance of enzymatic-based method in long-read mNGS-based pathogen identification and potential diseases diagnosis of microbiome related.
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http://dx.doi.org/10.3389/fcimb.2022.919903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273838PMC
July 2022

Identification and antibiotic resistance of Cronobacter spp. isolated from dried edible mushrooms.

J Food Sci 2022 Jul 14. Epub 2022 Jul 14.

Department of Nutrition, School of Public Health, Xuzhou Medical University, Xuzhou, China.

Cronobacter spp. is an important foodborne pathogen that can cause life-threatening diseases in infants and immunocompromised adults. The present study was carried out to understand the prevalence and characterization of Cronobacter spp. in dried edible mushrooms in Jiangsu province, China. Cronobacter isolates were identified and genotyped by multilocus sequence typing (MLST); the antimicrobial susceptibility of Cronobacter strains was determined by the disk diffusion method; the biofilm formation ability of Cronobacter spp. was assessed using the microtiter plate method. The overall prevalence of Cronobacter spp. in dried edible mushrooms was 14.8%, with the highest contamination rate of after 37.2% found in Auricularia auricular. The Cronobacter isolates were identified as C. sakazakii (n = 26), C. malonaticus (n = 2), C. dublinensis (n = 2) and C. turicensis (n = 1). The MLST scheme produced 20 sequence types (STs), two of which were newly identified. ST148 was the most prevalent ST (n = 5), followed by ST4 (n = 3), ST17 (n = 3), ST64 (n = 3), and ST540 (n = 2). One (3.2%) and 15 (48.4%) Cronobacter isolates were resistant to tetracycline and meropenem, respectively. In contrast, all of the tested isolates were susceptible to the remaining 14 antibiotics. Moreover, 20 (64.5%) Cronobacter isolates showed weak ability to produce biofilm, but no isolates showed strong or moderate biofilm-forming ability. PRACTICAL APPLICATION: Our findings revealed a high genetic diversity of Cronobacter spp. in dried edible mushrooms and provided new epidemiological evidence for the widespread existence of Cronobacter spp. in such products. The presence of Cronobacter spp. in dried edible mushrooms may pose potential risks to human health and enhancing the hygiene of such products are necessary to ensure food safety.
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http://dx.doi.org/10.1111/1750-3841.16251DOI Listing
July 2022

Current Definitions and Clinical Implications of Biomarkers in Graft-versus-Host Disease.

Transplant Cell Ther 2022 Jul 11. Epub 2022 Jul 11.

Departments of (1)Microbiology and Immunology and (2)Pediatrics, Medical University of South Carolina, Charleston, South Carolina. Electronic address:

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for many hematologic and nonhematologic disorders. Graft-versus-host-disease (GVHD) in its acute or chronic form remains the most important nonrelapse post-HCT complication. Biomarkers offer objective, unbiased information on systemic disorders, and significant attention has focused on identifying biomarkers for GVHD. Ideally, a GVHD biomarker is actionable, with the results of biomarker testing used to guide clinical management of disease and clinical trial design. Although many GVHD biomarkers have been identified, none have been properly qualified for clinical use. The National Institutes of Health (NIH) and Food and Drug Administration (FDA) have provided biomarker subtype definitions; however, confusion remains about the proper definition and application of these subtypes in the HCT field. The 2014 NIH consensus development project provided a framework for the development of biomarkers for clinical practice. This review aims to clarify the biomarker subtype definitions and reemphasize the developmental framework. Armed with this knowledge, clinicians can properly translate GVHD biomarkers for clinical use.
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http://dx.doi.org/10.1016/j.jtct.2022.07.008DOI Listing
July 2022

Cytokine storm and targeted therapy in hemophagocytic lymphohistiocytosis.

Immunol Res 2022 Jul 11. Epub 2022 Jul 11.

Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome. The central pathogenesis is an explosive cytokine storm characterized by a significant increase in proinflammatory cytokines, including IL-1β, IL-6, IL-18, IFN-γ, and TNF-α. Meanwhile, negative regulatory factors, such as IL-10 and TGF-β, are also related to the production of HLH. Exploring the specific mechanism of cytokine storms could provide ideas regarding targeted therapy, which could be helpful for early treatment to reduce the mortality of HLH. Although some research has focused on the advantages of targeted therapies, there is still a lack of a comprehensive discourse. This article attempts to summarize the mechanisms of action of various cytokines and provide a therapeutic overview of the current targeted therapies for HLH.
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http://dx.doi.org/10.1007/s12026-022-09285-wDOI Listing
July 2022

Modifying the physicochemical properties, solubility and foaming capacity of milk proteins by ultrasound-assisted alkaline pH-shifting treatment.

Ultrason Sonochem 2022 Jun 30;88:106089. Epub 2022 Jun 30.

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China. Electronic address:

This study investigated the effects of different treatment of alkaline pH-shifting on milk protein concentrate (MPC), micellar casein concentrate (MCC) and whey protein isolate (WPI) assisted by the same ultrasound conditions, including changes in the physicochemical properties, solubility and foaming capacity. The solubility of milk proteins had a significant increase with gradual enhancement of ultrasound-assisted alkaline pH-shifting (p < 0.05), especially for MCC up to 99.50 %. Also, treatment made a significant decline in the particle size of MPC and MCC, as well as the turbidity of the proteins (p < 0.05). The foaming capacity of MPC, MCC, and WPI was all improved, especially at pH 11, and at this pH, the milk protein also showed the highest surface hydrophobicity. The best foaming capacity at pH 11 was the result of the combined effect of particle size, potential, protein conformation, solubility, and surface hydrophobicity. In conclusion, ultrasound-assisted pH-shifting treatment was found to be effective in improving the physicochemical properties and solubility and foaming capacity of milk proteins, especially MCC, with promising application prospect in food industry.
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http://dx.doi.org/10.1016/j.ultsonch.2022.106089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9272034PMC
June 2022

Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2).

J Hematol Oncol 2022 07 6;15(1):86. Epub 2022 Jul 6.

Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China.

Background: LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years.

Methods: LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 10 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy.

Results: As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer.

Conclusions: The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285.
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http://dx.doi.org/10.1186/s13045-022-01301-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261106PMC
July 2022

Mesenchymal stromal cell treatment improves outcomes in children with pneumonia post-hematopoietic stem cell transplantation: a retrospective cohort study.

Stem Cell Res Ther 2022 06 28;13(1):277. Epub 2022 Jun 28.

Department of Hematology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China.

Background: Hematopoietic stem cell transplantation (HSCT) is a standard therapy strategy for most malignant disorders in children. However, transplant-related pneumonia remains a major therapy challenge and mesenchymal stromal cells (MSCs) are rarely reported in HSCT-related pneumonia. The aim of our study was to assess the efficacy of MSC for HSCT-related pneumonia in children.

Methods: We retrospectively retrieved HSCT-related (severe and non-severe) pneumonia cases (aged < 18 years), which underwent MSC treatment (MSC group) or non-MSC treatment (non-MSC group) in Guangzhou Women and Children's Medical Center, from December 2017 to December 2019. We investigated outcomes of the two different treatments among severe cases and non-severe cases, respectively. The primary endpoints were differences in overall cure rate and time to cure between MSC and non-MSC groups. The secondary endpoints were 180-day overall survival and cumulative cure rate.

Results: Finally, 31 severe pneumonia cases (16 in MSC group, 15 in non-MSC group) and 76 non-severe cases (31 in MSC group, 45 in non-MSC group) were enrolled in this study. Among severe pneumonia cases, overall cure rate in MSC group was significant higher than that in non-MSC group (12[75.0%] vs. 5[33.3%]; OR = 6.00, 95% CI [1.26-28.5]; p = 0.020); the time (days) to cure in MSC group was dramatically reduced compared with that in non-MSC group (36 [19-52] vs. 62 [42-81]; OR = 0.32, 95% CI [0.12-0.88]; p = 0.009); the 180-day overall survival in MSC group was better than that in non-MSC group (74.5% [45.4-89.6] vs. 33.3% [12.2-56.4]; p = 0.013). Among non-severe pneumonia cases, the time (days) to cure in MSC group was notably decreased compared with that in non-MSC group (28 [24-31] vs. 33 [26-39]; OR = 0.31, 95% CI [0.18-0.56]; p = 0.003). Compared with non-MSC group, MSC-treated patients achieved significant improvements of cumulative cure rate not only in severe pneumonia cases (p = 0.027), but also in non-severe cases (p < 0.001).

Conclusions: This study revealed that MSC treatment could contribute to improving outcomes in children with pneumonia post-HSCT, especially in severe cases. These findings suggest MSC treatment as a promising therapy for HSCT-related pneumonia in children.
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http://dx.doi.org/10.1186/s13287-022-02960-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241242PMC
June 2022

Reduced Dose Intensity of Daunorubicin During Remission Induction for Low-Risk Patients With Acute Lymphoblastic Leukemia: A Retrospective Cohort Study of the Chinese Children's Cancer Group.

Front Oncol 2022 7;12:911567. Epub 2022 Jun 7.

Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China.

It is urgently necessary to reduce the adverse effects of chemotherapy while maintaining their cure high rates for children with acute lymphoblastic leukemia (ALL). The present study aimed to determine whether the dose intensity of daunorubicin during the remission-induction phase could be reduced for low-risk patients with ALL. A total of 2396 eligible patients, who participated in CCCG-ALL-2015 study and were provisionally assigned to the low-risk group, were included and divided into single-dose group and double-dose group according to the dosage of daunorubicin during the remission-induction phase. For patients with positive ALL or hyperdiploidy ALL, there were no significant differences in outcomes between the two groups. For other patients, the 5-year event-free survival rate was significantly better and the 5-year cumulative risk of any relapse was significantly lower in the double-dose group compared with the single-dose group. Both the 5-year overall survival rate and the risk of early deaths were not significantly different between the two groups. Our results suggested that only B-lineage ALL patients with positivity or hyperdiploidy who achieved an early negative minimal residual disease status were suitable candidates for dosage reduction of daunorubicin during the remission-induction phase.

Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=10115, identifier ChiCTR-IPR-14005706.
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http://dx.doi.org/10.3389/fonc.2022.911567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209708PMC
June 2022

Suilyin Disrupts the Blood-Brain Barrier by Activating Group III Secretory Phospholipase A2.

Life (Basel) 2022 Jun 20;12(6). Epub 2022 Jun 20.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.

Serious diseases caused by serotype 2 ( 2) include septicaemia and meningitis, which are associated with high morbidity and mortality. Proliferation in the blood can result in a breach of the blood-brain barrier (BBB) and provide entry into the cerebrospinal fluid (CSF), where bacteria cause inflammation of the meningeal membranes resulting in meningitis. The molecular mechanisms of how this pathogen crosses the BBB remain unclear. Suilysin (SLY) has been identified as an important secreted virulence factor of 2 and may play a vital role in provoking meningitis. In this investigation, we demonstrate that SLY can increase the paracellular permeability of BBB, both in vivo and in vitro, via the activation of group III secretory phospholipase A2 (PLA2G3). Our results indicate that at lower, sublytic concentrations, the toxin can stimulate cerebral microvascular endothelial cells to release TNF-α, thereby inducing high level expressions of PLA2G3. Abnormal elevations of PLA2G3 might further injure tissues through direct cytolytic effectors or other responses.
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http://dx.doi.org/10.3390/life12060919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229629PMC
June 2022

An Injectable Epigenetic Autophagic Modulatory Hydrogel for Boosting Umbilical Cord Blood NK Cell Therapy Prevents Postsurgical Relapse of Triple-Negative Breast Cancer.

Adv Sci (Weinh) 2022 Jun 16:e2201271. Epub 2022 Jun 16.

Department of Hepatic Surgery and Liver Transplantation Center & Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.

Triple-negative breast cancer (TNBC) exhibits resistance to conventional treatments due to the presence of cancer stem cells (CSCs), causing postsurgical relapse and a dismal prognosis. Umbilical cord blood natural killer (UCB-NK) cell-based immunotherapy represents a promising strategy for cancer treatment. However, its therapeutic efficacy is greatly restrained by downregulation of the NK cell activation ligand MHC class I-related chain A/B (MICA/B) and autophagy-mediated degradation of NK cell-derived granzyme B (GZMB) in CSCs. Herein, it is demonstrated that suberoylanilide hydroxamic acid (SAHA) epigenetically downregulates let-7e-5p and miR-615-3p to increase MICA/B expression and that 3-methyl adenine (3MA) inhibits autophagy-mediated GZMB degradation, thereby sensitizing breast CSCs to UCB-NK cells. Then, an injectable hydrogel is designed to codeliver SAHA and 3MA to enhance UCB-NK cell infusion efficacy in TNBC. The hydrogel precursors can be smoothly injected into the tumor resection bed and form a stable gel in situ, allowing for a pH-sensitive sustained release of SAHA and 3MA. Moreover, UCB-NK cell infusion in combination with the hydrogel efficiently controls postsurgical relapse of TNBC. In addition, the hydrogel exhibits good hemostasis and wound-healing functions. Therefore, the work provides proof of concept that an injectable epigenetic autophagic modulatory hydrogel augments UCB-NK cell therapy to combat postsurgical relapse of TNBC.
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http://dx.doi.org/10.1002/advs.202201271DOI Listing
June 2022

Downregulation of lncRNA in the placentas of pregnant women with non‑diabetic fetal macrosomia promotes trophoblast cell proliferation.

Mol Med Rep 2022 08 8;26(2). Epub 2022 Jun 8.

State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.

Macrosomia is a common perinatal complication, with a series of adverse effects on newborns and pregnant women. However, the effects of long non‑coding RNAs (lncRNAs) on non‑diabetic fetal macrosomia (NDFMS) remain unclear. The aim of the present study was to investigate whether aberrant lncRNA expression in the placenta is involved in the pathogenesis of NDFMS and to elucidate its biological mechanisms. The expression profile of lncRNAs in the placentas of pregnant women with NDFMS was investigated using an Agilent Human LncRNA Microarray. Differentially expressed lncRNAs were selected for validation using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Additionally, the function of lncRNA ubiquitin‑specific peptidase 2 antisense RNA 1 () was investigated using a trophoblast cell line. The results revealed that 763 lncRNAs were upregulated and 129 lncRNAs were downregulated in the placentas of women in the NDFMS group (|FC| ≥2.0). A total of 10 lncRNAs (|FC| ≥4.0, signal value ≥50) were selected for validation using two‑stage RT‑qPCR, indicating that the expression trends of the 10 differentially expressed lncRNAs in the NDFMS group (n=8 vs. 8 and 48 vs. 48) were consistent with the microarray data. In addition, a significant downregulation in the levels of lncRNA was observed in both the microarray data and second‑stage verification. The overexpression of lncRNA induced G1 phase cell cycle arrest and the number of cells entering S phase was reduced. In addition, the viability of HTR‑8/SVneo cells was significantly inhibited when lncRNA was overexpressed. Therefore, these findings demonstrated that lncRNAs were significantly differentially expressed in the placentas of pregnant women with NDFMS and that the downregulation of lncRNA may be involved in the pathogenesis of NDFMS, by promoting trophoblast cell viability.
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http://dx.doi.org/10.3892/mmr.2022.12766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218729PMC
August 2022

Solute Carrier Family 35 Member F2 Regulates Cisplatin Resistance and Promotes Malignant Progression of Pancreatic Cancer by Regulating RNA Binding Motif Protein 14.

J Oncol 2022 27;2022:5091154. Epub 2022 May 27.

Department of Geriatrics, Shanghai Oriental Clinical Medical School of Nanjing Medical University, Shanghai, China.

We aimed to explore the role of Solute Carrier Family 35 Member F2 (SLC35F2) in pancreatic cancer (PCa) and to further study whether SLC35F2 regulates cisplatin resistance of PCa cells through the modulation of RNA binding motif protein 14 (RBM14) expression. SLC35F2 expression in 60 pairs of PCa tissues and adjacent ones was studied by RT-PCR analysis. Meanwhile, SLC35F2 expression levels in PCa cell lines were also evaluated by qPCR assay. In addition, SLC35F2 knockdown models were constructed in PCa cisplatin-resistant cells. Furthermore, we determined the interaction between SLC35F2 and RBM14 via luciferase assay. The findings of the present study demonstrated that SLC35F2 was significantly upregulated in PCa tissues. High level of SLC35F2 indicated higher incidence of metastasis and shorter survival rates. In vitro cell experiments revealed that knockdown of SLC35F2 suppressed cell invasion and metastasis capacity of cisplatin-resistant PCa cell lines PANC-1/DDP and CFPAC-1/DDP. It was also suggested that the key protein RBM14 in the SLC35F2 knockdown group was remarkably reduced. SLC35F2 can bind to RBM14 specifically. Overexpression of RBM14 partially reversed the effects of knockdown of SLC35F2 on the development of PCa. SLC35F2 expression in PCa tissues and cell lines is remarkably increased. In addition, it was also suggested that SLC35F2 may regulate cisplatin resistance of PCa cells through modulating RBM14 expression. In conclusion, it is conceivable from the study that SLC35F2 was remarkably upregulated in PCa and promoted the malignancy of PCa via regulating RBM14.
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http://dx.doi.org/10.1155/2022/5091154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166975PMC
May 2022

Exosome Mimetics-Loaded Hydrogel Accelerates Wound Repair by Transferring Functional Mitochondrial Proteins.

Front Bioeng Biotechnol 2022 20;10:866505. Epub 2022 May 20.

Department of Plastic and Reconstructive Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai, China.

Loading human umbilical mesenchymal stem cell (hUMSC) derived exosomes onto hydrogel scaffolds is a strategy for rapid wound healing. The clinical application of exosomes is hindered by low production, and exosome mimetics could be substituted for exosomes. Here, the therapeutic effects of exosome-loaded hydrogels and exosome mimetic-loaded hydrogels on wounds are evaluated. Our results revealed that exosome mimetic-loaded hydrogels promote wound healing more efficiently than exosome-loaded hydrogels. Exosome mimetics can promote the proliferation and migration of dermal fibroblasts (hDF-a) cells . To investigate how exosome mimetics play a role, proteomics analysis was applied, and the obtained results suggested that exosome mimetics significantly enrich mitochondrial-derived oxidative phosphorylation-related proteins in comparison to exosomes. Overall, our work envisages the emerging potential of exosome mimetics, which take the advantage of exosomes and can be promising candidates for exosomes. It also suggests that hUMSC-derived exosome mimetic-loaded hydrogels have remarkable prospects for clinical application.
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http://dx.doi.org/10.3389/fbioe.2022.866505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163684PMC
May 2022

Rapid Detection of Bacterial Pathogens and Antimicrobial Resistance Genes in Clinical Urine Samples With Urinary Tract Infection by Metagenomic Nanopore Sequencing.

Front Microbiol 2022 17;13:858777. Epub 2022 May 17.

College of Life Science, Yantai University, Yantai, China.

Urinary tract infections (UTIs) are among the most common acquired bacterial infections in humans. The current gold standard method for identification of uropathogens in clinical laboratories is cultivation. However, culture-based assays have substantial drawbacks, including long turnaround time and limited culturability of many potential pathogens. Nanopore sequencing technology can overcome these limitations and detect pathogens while also providing reliable predictions of drug susceptibility in clinical samples. Here, we optimized a metagenomic nanopore sequencing (mNPS) test for pathogen detection and identification in urine samples of 76 patients with acute uncomplicated UTIs. We first used twenty of these samples to show that library preparation by the PCR Barcoding Kit (PBK) led to the highest agreement of positive results with gold standard clinical culture tests, and enabled antibiotic resistance detection in downstream analyses. We then compared the detection results of mNPS with those of culture-based diagnostics and found that mNPS sensitivity and specificity of detection were 86.7% [95% confidence interval (CI), 73.5-94.1%] and 96.8% (95% CI, 82.4-99.9%), respectively, indicating that the mNPS method is a valid approach for rapid and specific detection of UTI pathogens. The mNPS results also performed well at predicting antibiotic susceptibility phenotypes. These results demonstrate that our workflow can accurately diagnose UTI-causative pathogens and enable successful prediction of drug-resistant phenotypes within 6 h of sample receipt. Rapid mNPS testing is thus a promising clinical diagnostic tool for infectious diseases, based on clinical urine samples from UTI patients, and shows considerable potential for application in other clinical infections.
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http://dx.doi.org/10.3389/fmicb.2022.858777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152355PMC
May 2022

Clinical and Pathological Features of Primary Renal Well-Differentiated Neuroendocrine Tumor.

Authors:
Hua Jiang He Zhang

Onco Targets Ther 2022 27;15:587-596. Epub 2022 May 27.

Department of Urology, The Fifth Affiliated Hospital of Zunyi Medical University (Zhuhai Sixth People's Hospital), Zhuhai, People's Republic of China.

Primary carcinoid tumor of the kidney is an extremely rare well-differentiated neuroendocrine tumor, which is generally a low-grade malignant cancer with a good prognosis. Carcinoid tumors are rarely found in the urinary system. Here, we report a 34-year-old woman with primary renal well-differentiated neuroendocrine tumor who underwent nephron sparing surgery and no evidence of recurrence or distant metastasis was found during routine follow-up. We searched the case of renal carcinoid with the search phrase "carcinoid [title] and kidney [title]" and "carcinoid [title] and renal [title]" using the PubMed and restricted the search to articles published in English since 2013. The clinical manifestations, age, sex, tumor size, location, gross pathology, light microscopy and immunohistochemistry were analyzed. A total of 28 cases of renal carcinoid were retrieved from PubMed. Higher proportion of positive labeling of CgA, Syn, NSE and CD56 are most valuable in the diagnosis of primary renal well-differentiated neuroendocrine tumor. At present, radical nephrectomy remains the gold standard in the curative-intent therapy for well-differentiated neuroendocrine carcinoma of kidney, in metastatic renal carcinoid, long-term use of octreotide may be an effective adjuvant therapy.
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http://dx.doi.org/10.2147/OTT.S364545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9153994PMC
May 2022

H3K9 demethylases IBM1 and JMJ27 are required for male meiosis in Arabidopsis thaliana.

New Phytol 2022 May 31. Epub 2022 May 31.

Leibniz Institute of Plant Genetics and Crop Plant Research, Gatersleben, 06466, Germany.

Dimethylation of histone H3 lysine 9 (H3K9me2), a crucial modification for heterochromatin formation and transcriptional silencing, is essential for proper meiotic prophase progression in mammals. We analyzed meiotic defects and generated genome-wide profiles of H3K9me2 and transcriptomes for the mutants of H3K9 demethylases. Moreover, we also identified proteins interacting with H3K9 demethylases. H3K9me2 is usually found at transposable elements and repetitive sequences but is absent from the bodies of protein-coding genes. In this study, we show that the Arabidopsis thaliana H3K9 demethylases IBM1 and JMJ27 cooperatively regulate crossover formation and chromosome segregation. They protect thousands of protein-coding genes from ectopic H3K9me2, including genes essential for meiotic prophase progression. In addition to removing H3K9me2, IBM1 and JMJ27 interact with the Precocious Dissociation of Sisters 5 (PDS5) cohesin complex cofactors. The pds5 mutant shared similar transcriptional alterations with ibm1 jmj27, including meiosis-essential genes, yet without affecting H3K9me2 levels. Hence, PDS5s, together with IBM1 and JMJ27, regulate male meiosis and gene expression independently of H3K9 demethylation. These findings uncover a novel role of H3K9me2 removal in meiosis and a new function of H3K9 demethylases and cohesin cofactors in meiotic transcriptional regulation.
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http://dx.doi.org/10.1111/nph.18286DOI Listing
May 2022
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