Publications by authors named "Xiaoling Li"

706 Publications

IL-27 Promotes Intestinal Barrier Integrity following Ethanol Intoxication and Burn Injury.

Immunohorizons 2022 Aug 16;6(8):600-613. Epub 2022 Aug 16.

Alcohol Research Program, Stritch School of Medicine, Loyola University Chicago Health Sciences Division, Maywood, IL;

Alcohol intoxication combined with burn injury can lead to life-threatening complications, including sepsis, multiple organ failure, and death. After an acute burn, the gastrointestinal system becomes hypoxic because of fluid loss and reduction of intestinal blood flow. This can cause perturbations in the intestinal epithelial barrier, immune function, and the composition of the gut microbiome. Increased gut permeability leads to proinflammatory signaling, contributing to further damage to the intestinal barrier. Recent studies have suggested that IL-27 plays an anti-inflammatory role, which may be beneficial in intestinal barrier repair. Therefore, in this study, we examined the effect of ethanol and burn injury on IL-27 in the small intestine, as well as the potential beneficial role of IL-27 in restoring the intestinal barrier after intoxication and burn. Male C57BL/6 mice were gavaged with 2.9 g/kg ethanol before receiving a ∼12.5% total body surface area scald burn with or without rIL-27 in resuscitation fluid. Our results demonstrate that IL-27-producing cells are reduced in the small intestine after injury. When IL-27 is supplemented in resuscitation fluid, we were able to restore intestinal barrier integrity and transit, mediated through increased intestinal epithelial cell proliferation, reduced inflammatory cytokines, and increased anti-inflammatory cytokine IL-10. We also observed increased gene expression of tight junction proteins. These findings suggest that IL-27 may be a contributor to maintaining proper intestinal barrier function after injury through multiple mechanisms, including preventing excess inflammation and promoting intestinal epithelial cell proliferation and tight junction integrity.
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http://dx.doi.org/10.4049/immunohorizons.2200032DOI Listing
August 2022

Primary large B-cell lymphoma of the central nervous system with positive NMDAR antibody: a case report.

BMC Neurol 2022 Aug 12;22(1):298. Epub 2022 Aug 12.

Department of Pathology, Lanzhou University Second Hospital, Cuiyingmen 82, Chengguan District, 730030, Lanzhou, China.

Background: N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate (Glu) receptor that is widely expressed in the central nervous system (CNS), mainly in the hippocampus. We present a case in which the patient had atypical clinical manifestations and was positive for anti-NMDAR antibodies.

Case Presentation: A 40-year-old male was admitted to the hospital with "dizziness and double vision for 2 months". At admission, the patient was lethargic, had short-term memory loss, exhibited loss of orientation (time, place, and person) and calculation ability, and had limited left eye abduction. After admission, serum anti- NMDAR antibody was 1:32, and cerebrospinal fluid was 1:1. Magnetic resonance imaging (MRI) revealed diffuse abnormal signals in the bilateral basal ganglia, thalamus, brainstem, hippocampus, and temporal lobe, with patchy and heterogeneous enhancement. A stereotactic brain biopsy was performed, and the pathological results indicated normal brain tissue. Preliminary diagnosis suggested anti-NMDAR antibody encephalitis. The patient was treated with methylprednisolone combined with intravenous gamma globulin; the symptoms were alleviated, and the patient was discharged. Two months later, the patient's symptoms worsened, and a second stereotactic brain biopsy was performed. The pathological results showed that the patient had primary diffuse large B-cell lymphoma of the CNS, and the patient was transferred to the Department of Hematology and received chemotherapy combined with rituximab. The patient was in stable condition.

Conclusions: When the primary CNS diffuses large B-cell lymphoma is associated with autoimmune encephalitis, it is very easy to be misdiagnosed. The diagnosis should not be based on the pathological examination that was performed in the early stage of the disease. Therefore, in the diagnosis of immune diseases caused by nervous system infections, it is necessary to dynamically observe the evolution of the disease, perform differential diagnoses when necessary, and ultimately improve our understanding of the disease.
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http://dx.doi.org/10.1186/s12883-022-02821-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9373403PMC
August 2022

The Hypoglycemic Effect of JinQi Jiangtang Tablets Is Partially Dependent on the Palmatine-Induced Activation of the Fibroblast Growth Factor Receptor 1 Signaling Pathway.

Front Pharmacol 2022 22;13:895724. Epub 2022 Jul 22.

College of Life Sciences, Northeast Agricultural University, Harbin, China.

JinQi Jiangtang tablet (JQJTT) is a Chinese patent medicine that has been shown to be beneficial for patients with diabetes both preclinically and clinically; however, the molecular mechanism underlying the effects of JQJTT remains unclear. In this study, surface plasmon resonance fishing was employed to identify JQJTT constituent molecules that can specifically bind to fibroblast growth factor receptor 1 (FGFR1), leading to the retrieval of palmatine (PAL), a key active ingredient of JQJTT. and experiments demonstrated that PAL can significantly stimulate FGFR1 phosphorylation and upregulate glucose transporter type 1 (GLUT-1) expression, thereby facilitating glucose uptake in insulin resistance (IR) HepG2 cells as well as alleviating hyperglycemia in diabetic mice. Our results revealed that PAL functions as an FGFR1 activator and that the hypoglycemic effect of JQJTT is partially dependent on the PAL-induced activation of the FGFR1 pathway. In addition, this study contributed to the understanding the pharmacodynamic basis and mechanism of action of JQJTT and provided a novel concept for future research on PAL.
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http://dx.doi.org/10.3389/fphar.2022.895724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354937PMC
July 2022

Study of the mechanism by which MSCs combined with LITUS treatment improve cognitive dysfunction caused by traumatic brain injury.

Neurosci Lett 2022 Aug 4;787:136825. Epub 2022 Aug 4.

Graduate School of Chengde Medical University, Shuangqiao District, Chengde, Hebei Province, China; First Hospital of Qinhuangdao, Culture Road, Seaport District, Qinhuangdao, Hebei Province, China. Electronic address:

Traumatic brain injury (TBI) substantially affects the quality of life of patients, and an effective therapy is unavailable. Previous studies have shown that mesenchymal stem cells (MSCs) and low-intensity transcranial ultrasound (LITUS) are effective treatments for neurological damage, inflammation, edema and cognitive impairment caused by TBI. However, it is unclear whether the combination of the two treatments exerts an additive effect. In this study, a rat TBI model was established using the controlled cortical impact (CCI) method. Neurological function was assessed by determining the rat modified neurological score (mNSS), and cognitive function was assessed using the Y-maze. Pathological changes in the injured tissue were observed using hematoxylin-eosin (HE) staining and immunohistochemistry (IHC), and western blot was performed to detect the expression levels of Nestin, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), growth-associated protein-43 (GAP-43), postsynaptic density protein (PSD-95), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and aquaporin-4 (AQP-4). Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was performed to detect the expression levels of GAP-43, PSD-95, BDNF, TNF-α, and AQP-4 mRNA to investigate whether MSCs combined with LITUS exert an additive therapeutic effect of alleviating the cognitive dysfunction caused by TBI and the possible mechanisms involved. Rats exhibited cognitive dysfunction 28 days after TBI, and MSCs combined with LITUS treatment ameliorated the cognitive deficits caused by TBI via increasing Nestin, NSE, GAP-43, PSD-95, and BDNF expression and attenuating the inflammatory response and edema caused by TBI via reducing TNF-α and AQP-4 expression. According to these results, MSCs combined with LITUS is more effective than MSCs alone for the treatment of TBI, and the mechanism may be the promotion of neuronal proliferation and differentiation, and the attenuation of the inflammatory response and edema, which ameliorates the spatial learning memory impairment caused by TBI. MSCs combined with LITUS treatment represents a new approach for the clinical treatment of patients with TBI.
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http://dx.doi.org/10.1016/j.neulet.2022.136825DOI Listing
August 2022

Curcumin regulates anti-inflammatory responses by AXL/JAK2/STAT3 signaling pathway in experimental autoimmune encephalomyelitis.

Neurosci Lett 2022 Jul 28;787:136821. Epub 2022 Jul 28.

Department of Neurology, Lanzhou University Second Hospital, 730030 Lanzhou, China. Electronic address:

Microglia-mediated neuroinflammation plays an important role in multiple sclerosis (MS). This study explored whether curcumin has a protective effect on experimental autoimmune encephalomyelitis (EAE), and the specific mechanism was investigated. We found that curcumin attenuates the severity of EAE mice. It inhibits the activation of microglia in the spinal cord of EAE mice and LPS-stimulated BV-2 cells. The findings clarify that curcumin may inhibit the inflammatory response mediated by microglia by inactivating the AXL/JAK2/STAT3 signaling pathway, which laid a theoretical foundation for the clinical management of MS.
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http://dx.doi.org/10.1016/j.neulet.2022.136821DOI Listing
July 2022

Body mass index and serum markers associated with progression-free survival in lung cancer patients treated with immune checkpoint inhibitors.

BMC Cancer 2022 Jul 28;22(1):824. Epub 2022 Jul 28.

Department of Thoracic Cancer 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, P. R. China.

Background: ICIs have remarkably affected the treatment strategies for numerous malignancies, including lung cancer. However, only a fraction of patients experience durable responses to ICIs; thus, there is an urgent need to identify the parameters related to ICI therapeutic effects. In this study, we investigated nutritional status surrogates and several serum markers to estimate the efficacy of ICIs.

Materials And Methods: The records of 66 patients with stage III/IV lung cancer who received ICIs were retrospectively analyzed. Features of patients' clinical pathology, including age, sex, histology, line of treatment, BMI, serum albumin, serum creatinine, and serum inflammatory markers such as LMR and PLR, were examined. Progression-free survival was the primary endpoint. Relationships among categorical variables were assessed by the chi-squared test. Survival analysis was performed using the Kaplan-Meier method followed by the log-rank test. Cox multivariate analysis was performed to analyze the association between each variable and the survival time of patients.

Results: The patients with BMI ≥ 25 (kg/m2), serum ALB≥37 (g/dL), serum creatinine ≥61.8 (μmol/L), LMR ≥ 2.12 had a significantly prolonged PFS in comparison with BMI<25 (kg/m2), ALB<37 (g/dL), creatinine<61.8 (μmol/L), LMR<2.12 (p < 0.05). No statistically significant difference was detected between patients with PLR < 135 and PLR ≥ 135 (p = 0.612). Multivariate analysis revealed that ALB≥37 (g/dL) and creatinine ≥ 61.8 (μmol/L) were associated with prolonged PFS, while statistical significance was not achieved in the BMI groups.

Conclusions: The current results indicated that high BMI is related to longer PFS in lung cancer patients treated with ICIs, which may be correlated with high levels of serum albumin and creatinine.
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http://dx.doi.org/10.1186/s12885-022-09744-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336031PMC
July 2022

Penpulimab for Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter, Single-Arm, Pivotal Phase I/II Trial (AK105-201).

Front Oncol 2022 7;12:925236. Epub 2022 Jul 7.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China.

Background: Nearly all anti-PD-1 antibodies are of the IgG4 isotype, and thus possess residual FcR effector functions. Such anti-PD-1 antibodies are also associated with immune tolerance and escape due to instability of the CH3 domain and Fc-Fc interaction. In this trial, we examined the efficacy and safety of penpulimab, a novel IgG1 anti-PD-1 antibody that does not bind to the Fc receptor, in patients with refractory or relapsed classical Hodgkin lymphoma (R/R cHL).

Methods: Adult patients (≥18 years of age) with R/R cHL received 200 mg penpulimab once biweekly until disease progression or unacceptable toxicities for a maximum of 24 months. The primary endpoint was objective response rate (ORR) based on the Independent Radiology Review Committee per Lugano 2014 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs).

Results: A total of 94 patients were enrolled. The median follow-up was 15.8 months. The ORR was 89.4% (95% CI 80.8%, 95.0%) in the full analysis set (85 patients). Forty (47.1%) patients achieved complete remission, 36 (42.4%) patients achieved partial remission. The 12-month PFS rate was 72.1% (95% CI 60.5%, 80.8%) and the 18-month OS rate was 100%. Totally 97.9% (92/94) of patients experienced at least one TRAE. The rate of grade 3 and above TRAEs was 26.6% (25/94). In addition, 51 (54.3%) patients experienced an irAE, and 4 (4.3%) patients developed grade 3 or above irAEs. No irAE-related death occurred.

Conclusions: Penpulimab was effective and safe in patients with R/R cHL.
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http://dx.doi.org/10.3389/fonc.2022.925236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301139PMC
July 2022

Evaluation of Clinical Outcomes of Icotinib in Patients With Clinically Diagnosed Advanced Lung Cancer With EGFR-Sensitizing Variants Assessed by Circulating Tumor DNA Testing: A Phase 2 Nonrandomized Clinical Trial.

JAMA Oncol 2022 Jul 21. Epub 2022 Jul 21.

State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Importance: The inability to obtain a pathological diagnosis in a certain proportion of patients with clinically diagnosed advanced lung cancer impedes precision treatment in clinical practice.

Objective: To evaluate the clinical outcome of first-line icotinib in patients with clinically diagnosed advanced lung cancer with unknown pathological status and positive epidermal growth factor receptor (EGFR)-sensitizing variants assessed by circulating tumor DNA (ctDNA).

Design, Setting, And Participants: The Efficiency of Icotinib in Plasma ctDNA EGFR Mutation-Positive Patients Diagnosed With Lung Cancer (CHALLENGE) trial is a prospective, multicentered, open-label, single-arm phase 2 nonrandomized clinical trial conducted between July 1, 2017, and July 31, 2019. Patients with systemic treatment-naive, clinically diagnosed advanced peripheral lung cancer, unknown pathological status, and positive pretreatment plasma EGFR-sensitizing variants were eligible. A total of 391 potentially eligible Chinese patients from 19 centers in China were screened for ctDNA EGFR variants by 3 independent detection platforms (Super amplification refractory mutation system [SuperARMS] polymerase chain reaction, droplet digital polymerase chain reaction, and next-generation sequencing), and those with EGFR variants tested by any platform were included. Analyses were conducted from September 9 to December 31, 2021.

Interventions: Enrolled patients were treated with oral icotinib tablets (125 mg 3 times daily) until disease progression, death, or treatment discontinuation due to various reasons, such as toxic effects and withdrawing consent.

Main Outcomes And Measures: The primary end point was objective response rate (ORR). The secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and the concordance among the 3 detection platforms.

Results: Of 116 included patients, 76 (65.5%) were female, and the median (range) age was 64 (37-85) years. The median (IQR) follow-up duration was 36.3 (30.2-40.7) months. The ORR was 52.6% (95% CI, 43.1%-61.9%). The median PFS and OS were 10.3 months (95% CI, 8.3-12.2) and 23.2 months (95% CI, 17.7-28.0), respectively, and the DCR was 84.5% (95% CI, 76.6%-90.5%). The concordance rate among the 3 detection platforms was 80.1% (313 of 391), and the clinical outcomes in patients identified as positive by any platform were comparable.

Conclusions And Relevance: This prospective phase 2 nonrandomized clinical trial suggests that for patients with clinically diagnosed advanced lung cancer with unknown pathological status, ctDNA-based EGFR genotyping could help decision-making in particular clinical situations, while still warranting future larger-scaled real-world exploration.

Trial Registration: ClinicalTrials.gov Identifier: NCT03346811.
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http://dx.doi.org/10.1001/jamaoncol.2022.2719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305594PMC
July 2022

Comparison of efficacy and safety of ripertamab (SCT400) versus rituximab (Mabthera ) in combination with CHOP in patients with previously untreated CD20-positive diffuse large B-cell lymphoma: A randomized, single-blind, phase III clinical trial.

Hematol Oncol 2022 Jul 20. Epub 2022 Jul 20.

Department of Medical Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.

This study compared the efficacy, safety and immunogenicity of ripertamab (SCT400) and rituximab (Mabthera ) combined with CHOP as the first-line treatment for Chinese patients with CD20-positive diffuse large B cell lymphoma (DLBCL). This is a randomized, patient-blind, multicenter, active-control, non-inferiority study with parallel design. Patients were randomly (2:1) to receive ripertamab combined with CHOP (S-CHOP) or rituximab (Mabthera ) combined with CHOP (R-CHOP) for up to 6 cycles. The primary endpoint was the Independent Review Committee (IRC) assessed objective response rate (ORR) in full analysis set (FAS) and the per protocol set (PPS). A total of 364 patients (243 in the S-CHOP and 121 in the R-CHOP groups) were enrolled in this study. In FAS, IRC-assessed ORRs were 93.8% (95% confidence interval (CI) 90.0%, 96.5%) and 94.2% (95% CI: 88.4%, 97.6%) in the S-CHOP and R-CHOP groups (p = 0.9633), respectively. The ORR difference between the two groups -0.4% (95% CI: -5.5%, 4.8%) met the pre-specified non-inferiority margin of -12%. There were no significant differences between the S-CHOP and R-CHOP groups in 1-year progression-free survival rates (81.1% vs. 83.2%, p = 0.8283), 1 year event-free survival rates (56.2% vs. 58.1%, p = 0.8005), and 3-year overall survival rates (81.0% vs. 82.8%, p = 0.7183). The results in PPS were consistent with those in FAS. The rates of treatment-emergent adverse events (TEAEs) and ≥ grade 3 TEAEs were 97.9% and 99.2%, 85.2% and 86.0% in the S-CHOP and R-CHOP groups, respectively in safety set. The percentage of anti-drug antibodies positive patients in the S-CHOP group was numerically lower than the R-CHOP group (10.9% vs. 16.0%). This study demonstrated that S-CHOP was not inferior to R-CHOP in the first-line treatment of Chinese patients with CD20-positive DLBCL in efficacy, safety and immunogenecity. S-CHOP could be an alternative first-line standard treatment regimen for this patient population.
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http://dx.doi.org/10.1002/hon.3054DOI Listing
July 2022

Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases.

Front Cell Neurosci 2022 30;16:852002. Epub 2022 Jun 30.

State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.

Most of the neurodegenerative diseases and aging are associated with reactive oxygen species (ROS) or other intracellular damaging agents that challenge the genome integrity of the neurons. As most of the mature neurons stay in G0/G1 phase, replication-uncoupled DNA repair pathways including BER, NER, SSBR, and NHEJ, are pivotal, efficient, and economic mechanisms to maintain genomic stability without reactivating cell cycle. In these progresses, polymerases are prominent, not only because they are responsible for both sensing and repairing damages, but also for their more diversified roles depending on the cell cycle phase and damage types. In this review, we summarized recent knowledge on the structural and biochemical properties of distinct polymerases, including DNA and RNA polymerases, which are known to be expressed and active in nervous system; the biological relevance of these polymerases and their interactors with neuronal degeneration would be most graphically illustrated by the neurological abnormalities observed in patients with hereditary diseases associated with defects in DNA repair; furthermore, the vicious cycle of the trinucleotide repeat (TNR) and impaired DNA repair pathway is also discussed. Unraveling the mechanisms and contextual basis of the role of the polymerases in DNA damage response and repair will promote our understanding about how long-lived postmitotic cells cope with DNA lesions, and why disrupted DNA repair contributes to disease origin, despite the diversity of mutations in genes. This knowledge may lead to new insight into the development of targeted intervention for neurodegenerative diseases.
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http://dx.doi.org/10.3389/fncel.2022.852002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279898PMC
June 2022

Differential Expression Profiles of mRNA and Noncoding RNA and Analysis of Competitive Endogenous RNA Regulatory Networks in Nonalcoholic Steatohepatitis.

Gastroenterol Res Pract 2022 7;2022:3200932. Epub 2022 Jul 7.

Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.

Nonalcoholic steatohepatitis (NASH) is a liver disease caused by multiple factors, and there is no approved pharmacotherapy. The pathogenesis of NASH remains underexplored. In this study, differentially expressed circular RNAs (circRNAs) were obtained by analyzing NASH-related circRNA datasets, and then, corresponding target microRNAs (miRNAs) and messenger RNAs (mRNAs) were predicted to construct a circRNA-miRNA-mRNA regulatory network. On this basis, a total of 38 circRNAs, 7 miRNAs, and 10 mRNAs were screened out. The present study reveals novel circRNA biomarkers of NASH and reports a potential competing endogenous RNA (ceRNA) regulatory network that might provide insights for further investigation into the underlying pathogenesis of NASH.
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http://dx.doi.org/10.1155/2022/3200932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282983PMC
July 2022

Anlotinib as third- or further-line therapy for short-term relapsed small-cell lung cancer: subgroup analysis of a randomized phase 2 study (ALTER1202).

Front Med 2022 Jul 16. Epub 2022 Jul 16.

Department of Medical Oncology, Liaoning Cancer Hospital, Shenyang, 110042, China.

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ⩾ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gammaglutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.
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http://dx.doi.org/10.1007/s11684-021-0916-8DOI Listing
July 2022

Single-cell profiling of immune cells after neoadjuvant pembrolizumab and chemotherapy in IIIA non-small cell lung cancer (NSCLC).

Cell Death Dis 2022 Jul 13;13(7):607. Epub 2022 Jul 13.

Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China.

The combination of immune checkpoint inhibitors (ICIs) with chemotherapy (chemoimmunotherapy) in the neoadjuvant setting have achieved favorable clinical benefits in non-small cell lung cancer (NSCLC), but the mechanism of clinical responses remain unclear. We provide a rich resource of 186,477 individual immune cells from 48 samples of four treatment-naive and eight neoadjuvant chemoimmunotherapy treated IIIA NSCLC patients (responders versus non-responders) by single-cell RNA-seq and TCR-seq. We observed the synergistic increase of B cells and CD4 T cells were associated with a positive therapeutic response of neoadjuvant chemoimmunotherapy. B cell IgG subclasses IgG1 and IgG3 played a critical role in anti-tumor immune response in tumor lesions, and this process was driven by increased IL-21 secreted by infiltrated T follicular helper (Tfh) cells after neoadjuvant chemoimmunotherapy. Furthermore, we uncovered several critical events for positive clinical outcomes, including the diminished activated TNFRSF4 regulatory T cells (Tregs), increased LAMP3 dendritic cells (DCs), and the expansion of intratumoral CD4 T clones and peripheral C3-Cytotoxic CD8 T clones. A validation cohort of 26 treatment-naive and 30 neoadjuvant chemoimmunotherapy treated IIIA/ IIIB NSCLC patients verified these findings. In total, our comprehensive study of the single-cell profile of immune cells provides insights into mechanisms underlying anti-PD-1-based therapies and identified potential predictive factors and therapeutic targets for improving the efficiency of neoadjuvant chemoimmunotherapy in NSCLC.
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http://dx.doi.org/10.1038/s41419-022-05057-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279493PMC
July 2022

Does Schizophrenia Itself Cause Obesity?

Front Psychiatry 2022 23;13:934384. Epub 2022 Jun 23.

Department of Psychiatry, The Third People's Hospital of Foshan, Foshan, China.

Background: Schizophrenia (SC) is considered the most serious of all mental disorders. Some antipsychotics are associated with weight gain and metabolic abnormalities. Whether SC itself causes obesity remains uncertain.

Methods: We collected 185 first-episode drug-naive SC and 59 healthy controls (HCs) from the Third People's Hospital of Foshan, Guangdong, China, and distinguished their course of disease in order to understand the body mass index (BMI) and body fat metabolism of SC.

Results: We found that excluding the drug factors, the longer the course of SC, the more obvious the increase of BMI and the higher the proportion of obesity. BMI was positively correlated with age, course of disease, fasting blood glucose (FBG), low-density lipoprotein (LDL), triglyceride (TG), and total cholesterol (TC), and negatively correlated with high-density lipoprotein (HDL). The results of regression analysis were further proof that age ( = 0.094, < 0.001), duration (B = 0.081, = 0.002), FBG ( = 0.987, = 0.004), and TG ( = 0.918, = 0.002) were the risk factors for the increase of BMI. HDL (B = -2.875, < 0.001) was the protective factor.

Conclusion: SC itself can increase BMI and easily lead to obesity. We should pay more attention to the monitoring of blood metabolism indicators, so as to reduce the risk of obesity and improve the quality of life of patients.
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http://dx.doi.org/10.3389/fpsyt.2022.934384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260012PMC
June 2022

Efficacy and Safety of SH-1028 in Patients With EGFR T790M-Positive NSCLC: A Multicenter, Single-Arm, Open-Label, Phase 2 Trial.

J Thorac Oncol 2022 Jul 5. Epub 2022 Jul 5.

Department of Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.

Introduction: As a novel third-generation EGFR tyrosine kinase inhibitor (TKI), SH-1028 (formerly oritinib) is developed to inhibit both sensitizing EGFR mutations and EGFR T790M mutation.

Methods: This was a multicenter, single-arm, open-label, phase 2 trial (NCT03823807). Eligible patients were those with advanced NSCLC with centrally confirmed EGFR T790M mutation who progressed after first- or second-generation EGFR TKIs or with primary EGFR T790M mutations. Each patient received SH-1028 tablets orally at 200 mg/d until disease progression or intolerable toxicity. Tumor response was evaluated every 6 weeks per the Response Evaluation Criteria in Solid Tumors, version 1.1. The primary end point was objective response rate by an independent review committee. The secondary end points were progression-free survival, overall survival (OS), disease control rate, safety, and so on.

Results: A total of 286 patients with EGFR T790M-positive advanced NSCLC were enrolled in this study, including 59 patients in part A (dose-verification study) and 227 patients in part B (second-line registration study). By data cutoff on September 17, 2021, the independent review committee-assessed objective response rate was 55.9% (95% confidence interval [CI]: 42.4-68.8) in part A and 60.4% (95% CI: 53.7-66.8) in part B. The median progression-free survival was 12.4 months (95% CI: 8.3-20.8) in part A and 12.6 months (95% CI: 9.7-15.3) in part B. The median OS was 26.0 months (95% CI: 23.3-not reached) in part A, and OS was immature in part B. Among the 286 patients, 44 of them experienced at least one grade 3 or higher treatment-related adverse event, with the most common ones as increased serum creatinine phosphokinase level (13 [4.5%]), diarrhea (six [2.1%]), and prolonged QT interval (three [1.0%]). Treatment-related skin rash was reported in 26 patients (9.1%), all grade 1 or 2. There was no interstitial lung disease reported in this study.

Conclusions: SH-1028 is efficacious and tolerable in second-line treatment of patients with advanced NSCLC with positive EGFR T790M.
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http://dx.doi.org/10.1016/j.jtho.2022.06.013DOI Listing
July 2022

Molecular mechanism of CAIF inhibiting myocardial infarction by sponging miR‑488 and regulating AVEN expression.

Mol Med Rep 2022 Aug 7;26(2). Epub 2022 Jul 7.

Intensive Care Unit, Guilin People's Hospital, Xiangshan 541002, P.R. China.

In recent years, the global incidence and mortality of myocardial infarction (MI) has increased and become one of the important diseases threatening public health. Long non‑coding (lnc)RNAs are a type of ncRNA that serve critical roles in the progression of various types of disease. The present study aimed to investigate the effect and mechanism of lncRNA cardiac autophagy inhibitory factor (CAIF) on cardiac ischemia/reperfusion (I/R) injury. CAIF was downregulated in the myocardium of I/R rats and cardiomyocytes treated with hydrogen peroxide (H2O2). Further experiments demonstrated that CAIF overexpression inhibited I/R‑induced cardiac infarction and apoptosis . CAIF decreased HO‑induced apoptosis and oxidative stress of cardiomyocytes. Mechanistically, CAIF sponged microRNA (miR)‑488‑5p; this interaction was confirmed by rescue experiments. Moreover, miR‑488‑5p targeted apoptosis and caspase activation inhibitor (AVEN) and inhibited its expression. In summary, the present data identified a novel CAIF/miR‑488‑5p/AVEN signaling axis as a key regulator of myocyte apoptosis, which may be a potential therapeutic target for the treatment of MI.
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http://dx.doi.org/10.3892/mmr.2022.12786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309535PMC
August 2022

[Determination of five nitroimidazoles and six benzodiazepines in aquatic products using ultra-high performance liquid chromatography-tandem mass spectrometry coupled with dispersive solid-phase extraction].

Se Pu 2022 Jul;40(7):625-633

Hunan Fisheries Science Institute, Changsha 410153, China.

Nitroimidazoles (NMZs) are a crucial group of antibacterial compounds from a historical perspective. In the past, they were used for treating and preventing parasitic infections in fish. Benzodiazepines (BZDs) are second-generation sedative-hypnotics. Some fish farmers or vendors use them illegally to keep aquatic products fresh during the transportation of aquatic animals. Aquatic products are one of the most common food sources of protein and can be contaminated by NMZs and BZDs, which could impact humans through the food chain. Until recently, there was limited information on the simultaneous determination of NMZs and BZDs. Thus, it is critical to accurately quantify NMZs and BZDs for risk assessment and risk monitoring of food safety. For the simultaneous determination of five nitroimidazoles and six benzodiazepines in aquatic products, a new approach based on the dispersive solid-phase extraction (dSPE) coupled with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed. First, the samples were extracted with acetonitrile containing 1% (v/v) ammonium hydroxide, and the extracts were purified using dSPE with C18 and primary secondary amine sorbents. Second, the extracts were collected and dried at 45 ℃ under nitrogen flow. Finally, the extracts were redissolved in 1 mL methanol-water (1∶9, v/v) mixture, filtered through a nylon-66 microfiltration membrane, and analyzed using UHPLC-MS/MS. The separation of compounds was conducted on a Kinetex F5 column (100 mm×3.0 mm, 2.6 μm) using gradient elution with 1% (v/v) formic acid aqueous solution and methanol as the mobile phase. The analytes were detected using MS/MS with positive electrospray ionization (ESI) source under the multiple reaction monitoring modes. The matrix-matched external standard approach was used for quantitative analysis. The compounds of five nitroimidazoles and six benzodiazepines could be examined within 8.5 min. Under the optimal conditions, the standard curves were linear in the range of 0.5-20 μg/L, with the correlation coefficients exceeding 0.995. The limits of detection and limits of quantification were 0.2-0.5 μg/kg and 0.5-1.0 μg/kg, respectively. The average recoveries at three spiked levels in blank samples (grass carp, large yellow croaker, and prawn) ranged from 73.2% to 110.6%, with relative standard deviations of less than 15%. The developed approach is simple, sensitive, fast, and inexpensive. It can be used for determining five nitroimidazoles and six benzodiazepines in aquatic products.
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http://dx.doi.org/10.3724/SP.J.1123.2022.01005DOI Listing
July 2022

STAT3-mediated ferroptosis is involved in ulcerative colitis.

Free Radic Biol Med 2022 Aug 30;188:375-385. Epub 2022 Jun 30.

The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong, 524023, China. Electronic address:

Ferroptosis is a form of iron-dependent lipid peroxidation cell death that plays an important role in inflammation. However, the mechanism of ferroptosis in ulcerative colitis (UC) remains to be further investigated. In the present study, we merged the differentially expressed genes (DEGs) of UC in GEO database with the ferroptosis-related genes of FerrDb for bioinformatics analysis and successfully screened out the ferroptosis-related hub gene STAT3 (signal transducer and activator of transcription 3). Then we further validated the role of STAT3-mediated ferroptosis in vitro and in vivo models of colitis. The results showed that ferroptosis was increased in DSS-induced colitis, salmonella typhimurium (S. Tm) colitis and HO-induced IEC-6 cells. And the phosphorylation level of the hub gene STAT3 was down-regulated in IEC-6 cells treated with HO, while Fer-1, an ferroptosis inhibitor, reactivated the phosphorylation level of STAT3. In addition, co-treatment of cells with HO and STAT3 inhibitor (stattic) showed an additive effect on the extent of ferroptosis. Taken together, these findings suggest that ferroptosis is closely associated with the development of colitis and ferroptosis-related gene STAT3 could serve as a potential biomarker for diagnosis and treatment of ulcerative colitis.
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http://dx.doi.org/10.1016/j.freeradbiomed.2022.06.242DOI Listing
August 2022

Regulation of the Intestinal Extra-Adrenal Steroidogenic Pathway Component LRH-1 by Glucocorticoids in Ulcerative Colitis.

Cells 2022 06 12;11(12). Epub 2022 Jun 12.

Innate Immunity Laboratory, Immunology Program, Biomedical Sciences Institute, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) and can be treated with glucocorticoids (GC), although some patients are unresponsive to this therapy. The transcription factor LRH-1/ is critical to intestinal cortisol production (intestinal steroidogenesis), being reduced in UC patients. However, the relationship between LRH-1 expression and distribution with altered corticosteroid responses is unknown. To address this, we categorized UC patients by their steroid response. Here, we found that steroid-dependent and refractory patients presented reduced glucocorticoid receptor (GR)-mediated intestinal steroidogenesis compared to healthy individuals and responder patients, possibly related to increased colonic mucosa GR isoform beta (GRβ) content and cytoplasmic LRH-1 levels in epithelial and lamina propria cells. Interestingly, an intestinal epithelium-specific GR-induced knockout (GR) dextran sodium sulfate (DSS)-colitis mice model presented decreased epithelial LRH-1 expression, whilst it increased in the lamina propria compared to DSS-treated control mice. Mechanistically, GR directly induced gene expression in CCD841CoN cells and human colonic organoids. Furthermore, GR bound to two glucocorticoid-response elements within the promoter in dexamethasone-stimulated CCD841CoN cells. We conclude that GR contributes to intestinal steroidogenesis by inducing LRH-1 in epithelial cells, suggesting LRH-1 as a potential marker for glucocorticoid-impaired response in UC. However, further studies with a larger patient cohort will be necessary to confirm role of LRH-1 as a therapeutic biomarker.
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http://dx.doi.org/10.3390/cells11121905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221003PMC
June 2022

Efficacy and Safety of Befotertinib (D-0316) in Patients With EGFR T790M-Mutated NSCLC That Had Progressed After Prior EGFR Tyrosine Kinase Inhibitor Therapy: A Phase 2, Multicenter, Single-Arm, Open-Label Study.

J Thorac Oncol 2022 Jun 18. Epub 2022 Jun 18.

Department of Medical Oncology/Chemotherapy, The First Affiliated Hospital of University of Science and Technology of China, Anhui Provincial Hospital, Hefei, People's Republic of China.

Introduction: Befotertinib (D-0316) is a novel, third-generation EGFR tyrosine kinase inhibitor (TKI). This study evaluated befotertinib in patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy.

Methods: This was a single-arm, open-label, phase 2 study at 49 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC harboring EGFR T790M mutations with disease progression after prior first- or second-generation EGFR TKI therapy received oral befotertinib of 50 mg (cohort A) or 75 to 100 mg (cohort B) once daily. The primary end point was objective response rate (ORR) assessed by an independent review committee in intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT03861156.

Results: A total of 176 patients and 290 patients were included in cohorts A (50 mg) and B (75-100 mg), respectively. At data cutoff (August 15, 2021), independent review committee-assessed ORR was 67.6% (95% confidence interval [CI]: 61.9%-72.9%) in cohort B. The investigator-assessed ORR was 54.0% (95% CI: 46.3%-61.5%) in cohort A and 65.9% (95% CI: 60.1%-71.3%) in cohort B. The median investigator-assessed progression-free survival was 11.0 (95% CI: 9.6-12.5) months in cohort A and 12.5 (95% CI: 11.1-13.8) months in cohort B. The median independent review committee-assessed progression-free survival in cohort B was 16.6 (95% CI: 15.0-not evaluable [NE]) months. The intracranial ORR was 26.7% (95% CI: 7.8%-55.1%) in cohort A by investigator assessment, while 57.1% (95% CI: 34.0%-78.2%) and 55.9% (95% CI: 37.9%-72.8%) in cohort B by investigator and independent review committee assessment, respectively. The median investigator-assessed intracranial progression-free survival was 16.5 (95% CI: 8.6-NE) months in cohort A, while the median intracranial progression-free survival was not evaluable in cohort B due to immature data regardless of investigator or independent review committee assessment. and NE (95% CI: 13.8-NE) in cohort B. The overall survival was immature. Grade 3 or higher treatment-related adverse events and treatment-related serious adverse events occurred in 20.5% and 11.4% of patients in cohort A and in 29.3% and 10.0% of patients in cohort B, respectively.

Conclusions: Befotertinib of 75 to 100 mg has satisfying efficacy and manageable toxicity in patients with locally advanced or metastatic NSCLC harboring T790M mutation with resistance to first- or second-generation EGFR TKIs. A phase 3 randomized trial is underway (NCT04206072).
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http://dx.doi.org/10.1016/j.jtho.2022.06.002DOI Listing
June 2022

HA/CD44 Regulates the T Helper 1 Cells Differentiation by Activating Annexin A1/Akt/mTOR Signaling to Drive the Pathogenesis of EAP.

Front Immunol 2022 26;13:875412. Epub 2022 May 26.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

CD44 partcipates in multiple inflammatory reactions. Here, we aimed to investigate the role of CD44 and the ligand, hyaluronan (HA), on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) pathogenesis. We found that CD44 was universally expressed in CD4 lymphocytes in the peripheral blood of CP/CPPS patients. After silencing CD44 expression or delivering 4-methylumbelliferone (4-MU), the pain severity and prostatic inflammation were significantly relieved. assay found that HA/CD44 was able to regulate T helper 1 (Th1) cells differentiation, the deficiency of which diminished experimental autoimmune prostatitis (EAP) susceptibility. Bioinformatic analysis suggested that after HA or 4-MU treatment, mTOR signaling was significantly altered, and these results were confirmed by subsequent Western blotting assay. Besides, mass spectrometry and co-immunoprecipitation assays found that CD44 was able to interact with Annexin A1 (ANX A1), and this kind of interaction stabilized ANX A1 protein and maintained the activation of Akt/mTOR pathway. Meanwhile, HA-treatment-enhanced prostatic inflammation, Th1 cell differentiation, and Akt/mTOR pathway activation were reversed after silencing the expression of ANX A1 using shANX A1-lentivirus. The present study systematically investigates the functional role of HA/CD44 in CP/CPPS and identifies novel mechanisms for HA/CD44 promoting Th1 cell differentiation. Targeting the HA/CD44/ANX A1/Akt/mTOR signaling represents novel potential therapeutic strategies for patients with CP/CPPS.
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http://dx.doi.org/10.3389/fimmu.2022.875412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178196PMC
May 2022

Dietary inflammatory potential and the incidence of depression and anxiety: a meta-analysis.

J Health Popul Nutr 2022 May 28;41(1):24. Epub 2022 May 28.

Department of Nutrition, Hebei Province Key Laboratory of Nutrition and Health, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, Hebei Province, China.

The potential modifiable role of diet in common psychological disorders, including depression and anxiety, has attracted growing interest. Diet may influence the occurrence of mental disorders through its inflammatory characteristics. The purpose of this meta-analysis was to explore whether dietary inflammatory potential is associated with the risk of depression and anxiety. A systematic literature search was conducted in PubMed, Web of Science, and Embase databases up to February 2021. Articles related to dietary inflammatory potential and risk of depression or anxiety were included. After the elimination of repetitive and irrelevant literature, we conducted quality assessment, publication bias, and sensitivity analysis. In total, 17 studies with a total of 157,409 participants were included in the final analysis. Compared with the lowest inflammatory diet group, the highest group was significantly associated with the incidence of depression and anxiety, with the following pooled odds ratios (ORs) and 95% confidence intervals (95% CIs): 1.45 (1.30 ~ 1.62) for depression and 1.66 (1.41 ~ 1.96) for anxiety. A subgroup analysis by gender showed that this association was more prominent in women. For depression, the increased risk was 49% in women (OR 1.49, 95% CI 1.28 ~ 1.74) and 27% in men (OR 1.27, 95% CI 1.06 ~ 1.52). As for anxiety, the increased risk was 80% in women (OR 1.80, 95% CI 1.30 ~ 2.49) and 47% in men (OR 1.53, 95% CI 0.81 ~ 2.89). As a result, long-term anti-inflammatory eating patterns may prevent depression and anxiety, whereas pro-inflammatory eating patterns may promote these conditions. People should add more fish, fish oil, fresh fruit, walnuts, and brown rice to their diet.
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http://dx.doi.org/10.1186/s41043-022-00303-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148520PMC
May 2022

Effect of BCG HSP70 Gene Transfection on Dendritic Cells Derived From Bone Marrow in Children With Acute Leukemia.

J Pediatr Hematol Oncol 2022 Aug 11;44(6):e939-e944. Epub 2022 May 11.

Hematology Department, the Children's Hospital of Soochow University, Suzhou, Jiangsu Province.

Objectives: In this study, immature dendritic cells (imDCs) were transfected with the Bacillé Calmette-Guérin (BCG) heat shock protein 70 (HSP70) gene to investigate the impact on the maturity and function of imDCs from the bone marrow of pediatric patients with acute leukemia.

Materials And Methods: Bone marrow mononuclear cells were isolated from pediatric patients with acute lymphoblastic leukemia who had achieved complete remission at least 6 months prior. The recombinant vector pDisplay-HSP70 was transfected into imDCs. The test groups included 5 subgroups: imDCs (imDCs without special processing), imDC-neos (imDCs transfected with the pDisplay vector), HSP70 (imDCs transfected with the pDisplay-HSP70 vector), tumor necrosis factor α (TNF-α) (imDCs induced with rhTNF-α), and HSP70+TNF-α. Mature dendritic cells (mDCs) from different groups (HSP70, TNF-α, and HSP70+TNF-α) and T cells were cultured. An equal number of lymphocytes and mDCs were used as controls. The proliferation indices of T cells and the cytokine contents (interleukin-12 and interferon-γ) were determined.

Results: The HSP70 group and the TNF-α group expressed higher levels of HLA-DR, CD80, and CD86 but lower levels than the HSP70+TNF-α group; there was no significant difference between the HSP70 group and the TNF-α group. The combination of HSP70 and TNF-α induced the highest levels of interleukin-12 and interferon-γ.

Conclusions: The outcomes of this study indicated that gene transfection with BCG HSP70 evidently promoted imDC maturity and the antitumor effects of mDC-mediated T cells. It could serve as a candidate gene-modified cell vaccine for tumor immunotherapy.
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http://dx.doi.org/10.1097/MPH.0000000000002479DOI Listing
August 2022

Berberine chloride (dual topoisomerase I and II inhibitor) modulate mitochondrial uncoupling protein (UCP1) in molecular docking and dynamic with in-vitro cytotoxic and mitochondrial ATP production.

J Biomol Struct Dyn 2022 May 25:1-11. Epub 2022 May 25.

Department of Endocrinology and Metabolism, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Obesity initiates numerous diseases like cardiovascular, metabolic, and type 2 diabetes, and obesity is a vital cause of death worldwide. Plants are necessary to the source of life. Several drug compounds isolated from plants are called phytochemicals which are safe, effective drug moieties to treat several diseases. Berberine chloride is a dual topoisomerase I and II inhibitor, that exhibited potent antitumor activities against several malignancies. However, the effect of Berberine on mitochondria remains unknown. The focus of this study was to determine the role of Berberine on mitochondrial uncoupling protein (UCP1), ATP production, and cytotoxic effect of HEK293T cell at a time and dose-dependent manner analysis by CCK8 assay. The upregulation of mitochondrial UCP1 gene expression reduces adipocyte content by initiating thermogenesis. In this study, berberine chloride significantly up-regulates UCP1 gene expression in brown adipocytes. AT 10 µM concentration of Berberine 48 h treatment demonstrated significant cell death. The decreased level of ATP production leads to mitochondrial uncoupling. Initiate thermogenesis reducing fat droplets in adipocytes. The first time, we used molecular docking and dynamic of Berberine with UCP1 gene in this study and revealed therapeutic potential of Berberine via modulation of mitochondrial UCP1 gene. Further investigation will reveal new insight into mechanisms to treat metabolic-related diseases.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.2024255DOI Listing
May 2022

IMU Motion Capture Method with Adaptive Tremor Attenuation in Teleoperation Robot System.

Sensors (Basel) 2022 Apr 27;22(9). Epub 2022 Apr 27.

School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an 710000, China.

Teleoperation robot systems can help humans perform tasks in unstructured environments. However, non-intuitive control interfaces using only a keyboard or joystick and physiological tremor reduce the performance of teleoperation. This paper presents an intuitive control interface based on the wearable device gForcePro+ armband. Two gForcePro+ armbands are worn at the centroid of the upper arm and forearm, respectively. Firstly, the kinematics model of the human arm is established, and the inertial measurement units (IMUs) are used to capture the position and orientation information of the end of the arm. Then, a regression model of angular transformation is developed for the phenomenon that the rotation axis of the torsion joint is not perfectly aligned with the limb segment during motion, which can be applied to different individuals. Finally, to attenuate the physiological tremor, a variable gain extended Kalman filter (EKF) fusing sEMG signals is developed. The described control interface shows good attitude estimation accuracy compared to the VICON optical capture system, with an average angular RMSE of 4.837° ± 1.433°. The performance of the described filtering method is tested using the xMate3 Pro robot, and the results show it can improve the tracking performance of the robot and reduce the tremor.
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http://dx.doi.org/10.3390/s22093353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100553PMC
April 2022

Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

Lancet Oncol 2022 06 13;23(6):739-747. Epub 2022 May 13.

Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, China. Electronic address:

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is associated with poor prognosis and treatment options are scarce. Immunotherapy has shown robust clinical activity in ES-SCLC in previous phase 3 trials. We aimed to assess the efficacy and safety of adebrelimab (SHR-1316), a novel anti-PD-L1 antibody, with standard chemotherapy as a first-line treatment for ES-SCLC.

Methods: The CAPSTONE-1 study was a randomised, double-blind, placebo-controlled, phase 3 trial, done in 47 tertiary hospitals in China. Key inclusion criteria were patients aged 18-75 years, with previously untreated histologically or cytologically confirmed ES-SCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Eligible patients were randomly assigned (1:1) to receive four to six cycles of carboplatin (area under the curve of 5 mg/mL per min, day 1 of each cycle) and etoposide (100 mg/m of body-surface area, on days 1-3 of each cycle) with either adebrelimab (20 mg/kg, day 1 of each cycle) or matching placebo, followed by maintenance therapy with adebrelimab or placebo. All treatments were given intravenously in 21-day cycles. Randomisation was done using a centralised interactive web response system with a block size of four, stratified by liver metastases, brain metastases, and lactate dehydrogenase concentration. The primary endpoint was overall survival in patients who received at least one dose of study medication. Safety was analysed in the as-treated population. This study is complete and registered with ClinicalTrials.gov, NCT03711305.

Findings: Between Dec 26, 2018, and Sept 4, 2020, 462 eligible patients were enrolled and randomly assigned: 230 (50%) patients received adebrelimab plus chemotherapy (adebrelimab group) and 232 (50%) patients received placebo plus chemotherapy (placebo group). At data cutoff (Oct 8, 2021), median follow-up was 13·5 months (IQR 8·9-20·1). Median overall survival was significantly improved in the adebrelimab group (median 15·3 months [95% CI 13·2-17·5]) compared with the placebo group (12·8 months [11·3-13·7]; hazard ratio 0·72 [95% CI 0·58-0·90]; one-sided p=0·0017). The most common treatment-related grade 3 or 4 adverse events were decreased neutrophil count (174 [76%] patients in the adebrelimab group and 175 [75%] patients in the placebo group), decreased white blood cell count (106 [46%] and 88 [38%]), decreased platelet count (88 [38%] and 78 [34%]), and anaemia (64 [28%] and 66 [28%]). Treatment-related serious adverse events occurred in 89 (39%) patients in the adebrelimab group and 66 (28%) patients in the placebo group. Four treatment-related deaths were reported: two each in the adebrelimab group (respiratory failure and interstitial lung disease and pneumonia) and placebo group (multiple organ dysfunction and unknown cause of death).

Interpretation: Adding adebrelimab to chemotherapy significantly improved overall survival with an acceptable safety profile in patients with ES-SCLC, supporting this combination as a new first-line treatment option for this population.

Funding: Jiangsu Hengrui Pharmaceuticals.
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http://dx.doi.org/10.1016/S1470-2045(22)00224-8DOI Listing
June 2022

Early severity prediction of BPD for premature infants from chest X-ray images using deep learning: A study at the 28th day of oxygen inhalation.

Comput Methods Programs Biomed 2022 Jun 10;221:106869. Epub 2022 May 10.

Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai 200438, China; Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address:

Background And Objective: Bronchopulmonary dysplasia is a common respiratory disease in premature infants. The severity is diagnosed at the 56th day after birth or discharge by analyzing the clinical indicators, which may cause the delay of the best treatment opportunity. Thus, we proposed a deep learning-based method using chest X-ray images of the 28th day of oxygen inhalation for the early severity prediction of bronchopulmonary dysplasia in clinic.

Methods: We first adopted a two-step lung field extraction method by combining digital image processing and human-computer interaction to form the one-to-one corresponding image and label. The designed XSEG-Net model was then trained for segmenting the chest X-ray images, with the results being used for the analysis of heart development and clinical severity. Therein, Six-Point cardiothoracic ratio measurement algorithm based on corner detection was designed for the analysis of heart development; and the transfer learning of deep convolutional neural network models were used for the early prediction of clinical severities.

Results: The dice and cross-entropy loss value of the training of XSEG-Net network reached 0.9794 and 0.0146. The dice, volumetric overlap error, relative volume difference, precision, and recall were used to evaluate the trained model in testing set with the result being 98.43 ± 0.39%, 0.49 ± 0.35%, 0.49 ± 0.35%, 98.67 ± 0.40%, and 98.20 ± 0.47%, respectively. The errors between the Six-Point cardiothoracic ratio measurement method and the gold standard were 0.0122 ± 0.0084. The deep convolutional neural network model based on VGGNet had the promising prediction performance, with the accuracy, precision, sensitivity, specificity, and F1 score reaching 95.58 ± 0.48%, 95.61 ± 0.55%, 95.67 ± 0.44%, 96.98 ± 0.42%, and 95.61±0.48%, respectively.

Conclusions: These experimental results of the proposed methods in lung field segmentation, cardiothoracic ratio measurement and clinic severity prediction were better than previous methods, which proved that this method had great potential for clinical application.
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http://dx.doi.org/10.1016/j.cmpb.2022.106869DOI Listing
June 2022

Antibacterial Cellulose Nanocrystal-Incorporated Hydrogels With Satisfactory Vascularization for Enhancing Skin Regeneration.

Front Bioeng Biotechnol 2022 26;10:876936. Epub 2022 Apr 26.

Stomatological Hospital, Southern Medical University, Guangzhou, China.

Wound healing of skin defects remains a significant clinical problem due to inflammation, infection, and dysangiogenesis; especially, the promotion of microvasculature formation in healing of chronic wound or deep skin defects is critical as it supplies oxygen and nutrients to the impaired tissue, relieving uncontrolled inflammatory responses. The cellulose nanocrystals (CNCs) in the liquid crystalline phase, which facilitates cell proliferation and migration, has been shown to improve vascularization effectively. Therefore, we developed a novel injectable hydrogel based on Schiff base and coordination of catechol and Ag. The obtained hydrogels (CCS/CCHO-Ag) exhibited forming properties, satisfactory mechanical performance, controlled release of Ag, antibacterial capacity, and biocompatibility. In addition, the hydrogels could also entirely cover and firmly attach wounds with irregular shapes, so as to reduce the re-injury rate. More importantly, experiments and demonstrated that CCS/CCHO-Ag hydrogels can promote neovascularization and tissue regeneration, thanks to their anti-inflammatory and antibacterial effects. In conclusion, these multifunctional hydrogels are well on the way to becoming competitive biomedical dressings, which show tremendous potential application in the field of tissue engineering.
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http://dx.doi.org/10.3389/fbioe.2022.876936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086275PMC
April 2022

Uterine-specific SIRT1 deficiency confers premature uterine aging and impairs invasion and spacing of blastocyst, and stromal cell decidualization, in mice.

Mol Hum Reprod 2022 06;28(7)

Department of Animal Science, North Carolina State University, Raleigh, NC, USA.

A distinct age-related alteration in the uterine environment has recently been identified as a prevalent cause of the reproductive decline in older female mice. However, the molecular mechanisms that underlie age-associated uterine adaptability to pregnancy are not known. Sirtuin 1 (SIRT1), a multifunctional NAD+-dependent deacetylase that regulates cell viability, senescence and inflammation during aging, is reduced in aged decidua. Thus, we hypothesize that SIRT1 plays a critical role in uterine adaptability to pregnancy and that uterine-specific ablation of Sirt1 gene accelerates premature uterine aging. Female mice with uterine ablation of Sirt1 gene using progesterone receptor Cre (PgrCre) exhibit subfertility and signs of premature uterine aging. These Sirt1-deficient mothers showed decreases in litter size from their 1st pregnancy and became sterile (25.1 ± 2.5 weeks of age) after giving birth to the third litter. We report that uterine-specific Sirt1 deficiency impairs invasion and spacing of blastocysts, and stromal cell decidualization, leading to abnormal placentation. We found that these problems traced back to the very early stages of hormonal priming of the uterus. During the window of receptivity, Sirt1 deficiency compromises uterine epithelial-stromal crosstalk, whereby estrogen, progesterone and Indian hedgehog signaling pathways are dysregulated, hampering stromal cell priming for decidualization. Uterine transcriptomic analyses also link these causes to perturbations of histone proteins and epigenetic modifiers, as well as adrenomedullin signaling, hyaluronic acid metabolism, and cell senescence. Strikingly, our results also identified genes with significant overlaps with the transcriptome of uteri from aged mice and transcriptomes related to master regulators of decidualization (e.g. Foxo1, Wnt4, Sox17, Bmp2, Egfr and Nr2f2). Our results also implicate accelerated deposition of aging-related fibrillar Type I and III collagens in Sirt1-deficient uteri. Collectively, SIRT1 is an important age-related regulator of invasion and spacing of blastocysts, as well as decidualization of stromal cells.
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http://dx.doi.org/10.1093/molehr/gaac016DOI Listing
June 2022

Refined-JinQi-JiangTang tablet ameliorates hypertension through activation of FGF21/FGFR1 axis in fructose-fed rats.

J Nat Med 2022 May 9. Epub 2022 May 9.

College of Food Engineering, Harbin University of Commerce, Harbin, 150076, China.

The aim of this study was to investigate the therapeutic effect of JQ-R on metabolic hypertension and its correlation with Fibroblast growth factor 21/Fibroblast growth factor receptors 1(FGF21/FGFR1) pathway. In this study, fructose-induced metabolic hypertension rats were used as hypertension models to detect the regulation effect of JQ-R on hypertension. The effects of JQ-R on blood glucose, blood lipids, serum insulin levels and other metabolic indicators of rats were also measured. The effects of JQ-R on FGF21/FGFR1 signaling pathway in model animals were detected by Real-time quantitative PCR and Western blotting. The results showed that JQ-R significantly reduce the blood pressure of model rats in a dose-dependent manner. Meanwhile, fasting insulin, fasting blood glucose, insulin resistance index, total cholesterol and triglyceride levels were significantly decreased, and glucose and lipid metabolism abnormalities were also significantly improved. JQ-R induces these changes along with FGFR1 phosphorylation, which was also detected in JQ-R treated FGF21 knockout mice. These results suggest that JQ-R can reduce blood pressure and improve glucose and lipid metabolism in fructose-induced hypertension rats. Activation of FGF21/FGFR1 signaling pathway to regulate downstream blood pressure and glucolipid metabolism-related pathways may be one of the important mechanisms of JQ-R in regulating blood pressure.
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http://dx.doi.org/10.1007/s11418-022-01626-1DOI Listing
May 2022
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