Publications by authors named "Gang Wang"

4,308 Publications

  • Page 1 of 1

Case Report: Suspected Case of -Associated Immune Reconstitution Inflammatory Syndrome.

Front Immunol 2022 22;13:923341. Epub 2022 Jul 22.

Department of Infectious Disease, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Human brucellosis is one of the most prevalent zoonoses. There are many similarities between the pathogenesis of (MTB) infection and that of brucellosis. Immune reconstitution inflammatory syndrome (IRIS) may occur during the treatment of MTB infection, but it has not been reported in brucellosis cases thus far. We report the case of a 40-year-old male whose condition initially improved after adequate anti- therapy. However, 3 weeks later, the patient presented with exacerbation of symptoms and development of a paravertebral abscess. After exclusion of other possible causes of clinical deterioration, immune reconstitution inflammatory syndrome (IRIS) with brucellosis was presumed. After supplementation with anti- treatment with corticosteroids, the abscess disappeared, and the symptoms completely resolved. Our case suggests that it is necessary to be aware of the possible occurrence of IRIS in patients with brucellosis in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2022.923341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353035PMC
August 2022

Development and validation of a noninvasive prediction model for identifying eosinophilic asthma.

Respir Med 2022 Jul 19;201:106935. Epub 2022 Jul 19.

Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, PR China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu, PR China. Electronic address:

Background: Identification of eosinophilic asthma (EA) using sputum analysis is important for disease monitoring and individualized treatment. But it is laborious and technically demanding. We aimed to develop and validate an effective model to predict EA with multidimensional assessment (MDA).

Methods: The asthma patients who underwent a successful sputum induction cytological analysis were consecutively recruited from March 2014 to January 2021. The variables assessed by MDA were screened by least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a nomogram and an online web calculator. Validation was performed internally by a bootstrap sampling method and externally in the validation cohort. Diagnostic accuracy of the model in different asthma subgroups were also investigated.

Results: In total of 304 patients in the training cohort and 95 patients in the validation cohort were enrolled. Five variables were identified in the EA prediction model: gender, nasal polyp, blood eosinophils, blood basophils and FeNO. The C-index of the model was 0.86 (95% CI: 0.81-0.90) in the training cohort and 0.84 (95% CI: 0.72-0.89) in the validation cohort. The calibration curve showed good agreement between the prediction and actual observation. The decision curve analysis (DCA) also demonstrated that the EA prediction model was clinically beneficial. An online publicly available web calculator was constructed (https://asthmaresearcherlimin.shinyapps.io/DynNomapp/).

Conclusion: We developed and validated a multivariable model based on MDA to help the diagnosis of EA, which has good diagnostic performance and clinical practicability. This practical tool may be a useful alternative for predicting EA in the clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmed.2022.106935DOI Listing
July 2022

Self-Adhesive Hydrogel Biomimetic Periosteum to Promote Critical-Size Bone Defect Repair via Synergistic Osteogenesis and Angiogenesis.

ACS Appl Mater Interfaces 2022 Aug 4. Epub 2022 Aug 4.

School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, China.

The periosteum plays an important role in the regeneration of critical-size bone defects, with functions of recruiting multiple cells, accelerating vascular network reconstruction, and guiding bone tissue regeneration. However, these functions cannot be easily implemented by simply simulating the periosteum via a material structure design or by loading exogenous cytokines. Herein, inspired by the periosteal function, we propose a biomimetic periosteum preparation strategy to enhance natural polymer hydrogel membranes using inorganic bioactive materials. The biomimetic periosteum having bone tissue self-adhesive functions and resembling an extracellular matrix was prepared using dopamine-modified gelatin and oxidized hyaluronan (GA/HA), and micro/nanobioactive glass (MNBG) was further incorporated into the hydrogel to fabricate an organic/inorganic co-crosslinked hydrogel membrane (GA/HA-BG). The addition of MNBG enhanced the stability of the natural polymer hydrogel membrane, resulting in a sustained degradation time, biomineralization, and long-term release of ions. The Ca and SiO ions released by bioactive glass were shown to recruit cells and promote the differentiation of bone marrow stromal cells into osteoblasts, initiating multicentric osteogenic behavior. Additionally, the bioactive ions were able to continuously stimulate the endogenous expression of vascular endothelial growth factor from human umbilical vein endothelial cells through the PI3K/Akt/HIF-1α pathway, which accelerated vascularization of the defect area and synergistically promoted the repair of bone defects. This organic-inorganic biomimetic periosteum has been proved to be effective and versatile in critical-size bone defect repair and is expected to provide a promising strategy for solving clinical issues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.2c08400DOI Listing
August 2022

A Rare Case of Acute Infectious Purpura Fulminans Caused by and Human Herpesvirus Type 5.

J Inflamm Res 2022 26;15:4251-4260. Epub 2022 Jul 26.

Laboratory Bacteria Room, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, People's Republic of China.

Background: Purpura fulminans (PF), a rare, life-threatening disorder, is a hematological emergency in which there is skin necrosis, disseminated intravascular coagulation (DIC), and protein C deficiency. In PF, the skin necrosis and DIC are secondary to protein C deficiency. This may progress rapidly to multiorgan failure caused by the thrombotic occlusion of small- and medium-sized blood vessels.

Case Report: This article presents the case of a 22-year-old male with fever as well as necrotic and purpuric skin lesions. The ultrasound and computed tomography scans revealed infections in the skin wounds as well as venous microthrombosis and thrombosis in multiple intracranial and pulmonary vessels. The laboratory tests showed signs of sepsis, thrombocytopenia, an abnormal decrease in protein C and antithrombin III, DIC, multiple organ and system failures, gastric varices, and gastrointestinal hemorrhage. The blood, sputum, and secretions under the skin lesions were cultured and were positive for . The results of the high-throughput genetic testing of the pathogenic microorganism DNA were consistent. In addition, human herpesvirus type 5 was detected. The histopathological examination of the skin lesions revealed pathological features consistent with PF. After successful treatment by the departments of Dermatology, Emergency Critical Care Medicine, and the Intensive Care Unit, the patient was discharged after 67 days of hospitalization.

Conclusion: Adults with acquired protein C and/or S deficiency states, including certain bacterial and viral infections, who drink alcohol and take varieties of non-steroidal anti-inflammatory analgesics at the same time, may develop acute infectious PF. Clinicians should be aware of this for early diagnosis and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/JIR.S369986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340174PMC
July 2022

The Role of Long Non-Coding RNAs in Epithelial-Mesenchymal Transition-Related Signaling Pathways in Prostate Cancer.

Front Mol Biosci 2022 18;9:939070. Epub 2022 Jul 18.

Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Prostate cancer (PCa) is one of the most common male malignancies with frequent remote invasion and metastasis, leading to high mortality. Epithelial-mesenchymal transition (EMT) is a fundamental process in embryonic development and plays a key role in tumor proliferation, invasion and metastasis. Numerous long non-coding RNAs (lncRNAs) could regulate the occurrence and development of EMT through various complex molecular mechanisms involving multiple signaling pathways in PCa. Given the importance of EMT and lncRNAs in the progression of tumor metastasis, we recapitulate the research progress of EMT-related signaling pathways regulated by lncRNAs in PCa, including AR signaling, STAT3 signaling, Wnt/β-catenin signaling, PTEN/PI3K/AKT signaling, TGF-β/Smad and NF-κB signaling pathways. Furthermore, we summarize four modes of how lncRNAs participate in the EMT process of PCa regulating relevant signaling pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2022.939070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339612PMC
July 2022

Letter to the Editor Regarding "Andersson Lesion Occurring in the Lumbosacral Segment of a Young Man: A Case Report and Literature Review".

World Neurosurg 2022 Feb;158:331

Department of Rheumatology and Immunology, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou, Hunan, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2021.10.094DOI Listing
February 2022

Fast and Selective Detection of Trace Chemical Warfare Agents Enabled by an ESIPT-Based Fluorescent Film Sensor.

Anal Chem 2022 Aug 3. Epub 2022 Aug 3.

Key Laboratory of Applied Surface and Colloid Chemistry of Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, P. R. China.

Reliable detection of airborne chemical warfare agents (CWAs) at the site and in real-time remains a challenge due to the rarity of miniaturized analytical tools. Herein, an -carborane-functionalized benzothiazole derivative (PCBO) with excited-state intramolecular proton transfer (ESIPT) and AIE characteristics was synthesized. The PCBO-based film sensor showed a highly sensitive response to representative simulants of CWAs, and detection limits were found to be 1.0 mg·m for triphosgene, 6.0 mg·m for chloroethyl ethyl sulfide, and 0.2 mg·m for diethyl chlorophosphite. Moreover, the sensor showed great reusability (>100 cycles) and unprecedented response speed (<0.5 s). The excellent sensing performance was ascribed to the microenvironmental sensitivity of the sensing fluorophore, the porous adlayer structure of the film, and the specific binding of the fluorophore to the analytes. Furthermore, discrimination and identification of the examined CWA simulants were realized via the introduction of another fluorophore (HCBO)-based film. Importantly, a portable fluorescent CWA detector was built with the sensor as the key component, and its applicability was demonstrated by the successful detection of a typical CWA sample (Sarin). The present study indicates that fluorescent film sensors could satisfy reliable onsite and real-time detection of harmful chemicals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.2c00862DOI Listing
August 2022

Inhibition of APLN suppresses cell proliferation and migration and promotes cell apoptosis in esophageal cancer cells in vitro, through activating PI3K/mTOR signaling pathway.

Eur J Histochem 2022 Aug 3;66(3). Epub 2022 Aug 3.

Department of Integrated Traditional Chinese and Western Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University.

Esophageal cancer is the sixth leading cause of cancer mortalities globally with a high incidence rate. Apelin (APLN) plays regulatory roles in different organs. However, its role in esophageal cancer remains unknown. Therefore, our study aims to explore the effect of APLN on esophageal cancer. One hundred and eighty-four (184) esophageal tumor tissues samples from patients with esophageal cancer, and 11 esophageal tissues samples from healthy volunteers were analyzed for the expression of APLN. APLN was highly expressed in the tumor of patients with esophageal cancer and esophageal cancer cells.  Patients with high expressions of APLN had a lower survival rate than the ones with low to medium expressions of APLN.  Human esophageal carcinoma cell lines, TE-1 and ECA-109 cells were transfected with APLN siRNA to knockdown APLN, or transfected with pcDNA-APLN to overexpress APLN. Inhibition of APLN by siRNA-APLN reduced proliferative, migrative, and invasive abilities of esophageal cancer cells and promoted cell apoptosis, which could be all restored by pcDNA-APLN. Moreover, knocking down APLN by siRNA-APLN suppressed the PI3K/mTOR signaling pathway. These findings identify that APLN inhibition might ameliorate esophageal cancer through activating the PI3K/mTOR signaling pathway, thus APLN could be a potential target for esophageal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/ejh.2022.3336DOI Listing
August 2022

Acinar Cell-Derived Extracellular Vesicle MiRNA-183-5p Aggravates Acute Pancreatitis by Promoting M1 Macrophage Polarization Through Downregulation of FoxO1.

Front Immunol 2022 13;13:869207. Epub 2022 Jul 13.

Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, China.

Acute pancreatitis (AP) is a common cause of a clinically acute abdomen. Crosstalk between acinar cells and leukocytes (especially macrophages) plays an important role in the development of AP. However, the mechanism mediating the interaction between acinar cells and macrophages is still unclear. This study was performed to explore the role of acinar cell extracellular vesicles (EVs) in the crosstalk between acinar cells and macrophages involved in the pathogenesis of AP. EVs derived from caerulein-treated acinar cells induced macrophage infiltration and aggravated pancreatitis in an AP rat model. Further research showed that acinar cell-derived EV miR-183-5p led to M1 macrophage polarization by downregulating forkhead box protein O1 (FoxO1), and a dual-luciferase reporter assay confirmed that FoxO1 was directly inhibited by miR-183-5p. In addition, acinar cell-derived EV miR-183-5p reduced macrophage phagocytosis. Acinar cell-derived EV miR-183-5p promoted the pancreatic infiltration of M1 macrophages and increased local and systemic damage . Subsequently, miR-183-5p overexpression in macrophages induced acinar cell damage and trypsin activation, thus further exacerbating the disease. In clinical samples, elevated miR-183-5p levels were detected in serum EVs and positively correlated with the severity of AP. EV miR-183-5p might play an important role in the development of AP by facilitating M1 macrophage polarization, providing a new insight into the diagnosis and targeted management of pancreatitis. Graphical abstract of the present study. In our caerulein-induced AP model, miR-183-5p was upregulated in injured acinar cells and transported by EVs to macrophages. miR-183-5p could induce M1 macrophage polarization through downregulation of FoxO1 and the release of inflammatory cytokines, which could aggravate AP-related injuries. Therefore, a vicious cycle might exist between injured ACs and M1 macrophage polarization, which is fulfilled by EV-transported miR-183-5p, leading to sustainable and progressive AP-related injuries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2022.869207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326086PMC
July 2022

Topical Analgesic Containing Methyl Salicylate and L-Menthol Accelerates Heat Loss During Skin Cooling for Exercise-Induced Hyperthermia.

Front Physiol 2022 13;13:945969. Epub 2022 Jul 13.

Integrative Exercise Physiology Laboratory, Department of Physical Education, Jeonbuk National University, Jeonju, South Korea.

Hyperthermia impairs physical performance and, when prolonged, results in heat stroke or other illnesses. While extensive research has investigated the effectiveness of various cooling strategies, including cold water immersion and ice-suit, there has been little work focused on overcoming the cutaneous vasoconstriction response to external cold stimulation, which can reduce the effectiveness of these treatments. Over-the-counter (OTC) topical analgesics have been utilized for the treatment of muscle pain for decades; however, to date no research has examined the possibility of taking advantage of their vasodilatory functions in the context of skin cooling. We tested whether an OTC analgesic cream containing 20% methyl salicylate and 6% L-menthol, known cutaneous vasodilators, applied to the skin during skin cooling accelerates heat loss in exercise-induced hyperthermia. Firstly, we found that cutaneous application of OTC topical analgesic cream can attenuate cold-induced vasoconstriction and enhance heat loss during local skin cooling. We also revealed that core body heat loss, as measured by an ingestible telemetry sensor, could be accelerated by cutaneous application of analgesic cream during ice-suit cooling in exercise-induced hyperthermia. A blunted blood pressure response was observed during cooling with the analgesic cream application. Given the safety profile and affordability of topical cutaneous analgesics containing vasodilatory agents, our results suggest that they can be an effective and practical tool for enhancing the cooling effects of skin cooling for hyperthermia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2022.945969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326359PMC
July 2022

Belowground Root Competition Alters the Grass Seedling Establishment Response to Light by a Nitrogen Addition and Mowing Experiment in a Temperate Steppe.

Front Plant Sci 2022 14;13:801343. Epub 2022 Jul 14.

International Joint Research Laboratory of Global Change Ecology, School of Life Sciences, Henan University, Kaifeng, China.

Predicting species responses to climate change and land use practices requires understanding both the direct effects of environmental factors as well as the indirect effects mediated by changes in belowground and aboveground competition. Belowground root competition from surrounding vegetation and aboveground light competition are two important factors affecting seedling establishment. However, few studies have jointly examined the effect of belowground root and light competition on seedling establishment, especially under long-term nitrogen addition and mowing. Here, we examined how belowground root competition from surrounding vegetation and aboveground light competition affect seedling establishment within a long-term nitrogen addition and mowing experiment. Seedlings of two grasses ( and ) were grown with and without belowground root competition under control, nitrogen addition, and mowing treatments, and their growth characteristics were monitored. The seedlings of the two grasses achieved higher total biomass, height, mean shoot and root mass, but a lower root/shoot ratio in the absence than in the presence of belowground root competition. Nitrogen addition significantly decreased shoot biomass, root biomass, and the survival of the two grasses. Regression analyses revealed that the biomass of the two grass was strongly negatively correlated with net primary productivity under belowground root competition, but with the intercept photosynthetic active radiation in the absence of belowground root competition. This experiment demonstrates that belowground root competition can alter the grass seedling establishment response to light in a long-term nitrogen addition and mowing experiment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2022.801343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331913PMC
July 2022

Safety and efficacy of microwave ablation for lung cancer adjacent to the interlobar fissure.

Thorac Cancer 2022 Aug 1. Epub 2022 Aug 1.

Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China.

Background: This retrospective study aimed to assess the safety and efficacy of microwave ablation for lung tumors adjacent to the interlobar fissures.

Methods: From May 2020 to April 2021, 59 patients with 66 lung tumors (mean diameter, 16.9 ± 7.7 mm; range, 6-30 mm) adjacent to the interlobar fissures who underwent microwave ablation at our institution were identified and included in this study. Based on the relationship between the tumor and the interlobar fissure, tumors can be categorized into close to the fissure, causing the fissure, and involving the fissure. The complete ablation rate, local progression-free survival, complications, and associated factors were analyzed.

Results: All 66 histologically proven tumors were treated using computed tomography-guided microwave ablation. The complete ablation rate was 95.5%. Local progression-free survival at 3, 6, 9, and 12 months were 89.4%, 83.3%, 74.2%, and 63.6%, respectively. The complications included pneumothorax (34.8%), pleural effusion (24.2%), cavity (18.2%), and pulmonary infection (7.6%). There were statistical differences in the incidence of pneumothorax, cavity, and delayed complications between the groups with and without antenna punctures through the fissure.

Conclusions: Microwave ablation is a safe and effective treatment for lung tumor adjacent to the interlobar fissure. Antenna puncturing though the interlobar fissure may be a potential risk factor for pneumothorax, cavity, and delayed complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.14589DOI Listing
August 2022

A randomised, double-blind, placebo-controlled study to evaluate the safety and efficacy of lamotrigine in the maintenance treatment of Chinese adult patients with bipolar I disorder.

Int J Bipolar Disord 2022 Aug 1;10(1):20. Epub 2022 Aug 1.

The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital , Capital Medical University, 100088, Beijing, China.

Background: Lamotrigine is approved as a maintenance therapy for bipolar I disorder in many countries, including China in 2021. This study evaluated the efficacy and safety of lamotrigine in controlling relapse and/or recurrence of mood episodes in Chinese patients with bipolar I disorder.

Methods: Patients aged ≥ 18 years with bipolar I disorder who met response criteria (Clinical Global Impression-Severity [CGI-S] score of ≤ 3 for ≥ 4 consecutive weeks) during treatment with lamotrigine in a 6-16 week open-label (OL) phase, and who were maintained for ≥ 1 week on lamotrigine 200 mg/day monotherapy, were randomised (1:1) to continue receiving lamotrigine 200 mg/day or switch to placebo in a 36-week randomised double-blind (RD) phase. The primary efficacy outcome measure was time from entry into the RD phase to intervention for relapse and/or recurrence of a mood episode (TIME). Post hoc analyses assessed the impact of OL baseline mood severity on TIME. Safety assessments were conducted throughout the study.

Results: Of 420 patients treated in the OL phase, 264 were randomised to receive lamotrigine (n = 131) or placebo (n = 133). Overall, 112 patients had an intervention for relapse and/or recurrence of a mood episode (lamotrigine, n = 50/130 [38.5%]; placebo, n = 62/133 [46.6%]), with no significant difference in TIME between groups (adjusted hazard ratio [95% confidence interval (CI)] 0.93 [0.64, 1.35]; p = 0.701). Post hoc analyses indicated a significant difference in TIME, favouring lamotrigine over placebo, for patients with baseline CGI-S score ≥ 4 (hazard ratio [95% CI] 0.52 [0.30, 0.89]; p = 0.018) and with baseline Hamilton Depression Rating Scale ≥ 18 or Young Mania Rating Scale ≥ 10 (0.44 [hazard ratio [95% CI] 0.25, 0.78]; p = 0.005). Lamotrigine was well tolerated with no new safety signals.

Conclusions: Lamotrigine was not significantly superior to placebo in preventing relapse and/or recurrence of mood episodes in this study of Chinese patients with bipolar I disorder but post hoc analyses suggested a therapeutic benefit in patients with moderate/severe mood symptoms at baseline. The discrepancy between these findings and the positive findings of the pivotal studies may be attributable to the symptom severity of the bipolar patients recruited, a high dropout rate, and the comparatively short duration of the RD phase rather than race/ethnicity differences. Clinical trial registration ClinicalTrial.gov Identifier NCT01602510; 21st May 2012; https://clinicaltrials.gov/ct2/show/NCT01602510 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40345-022-00266-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339436PMC
August 2022

Relationship of serum copper and zinc with kidney function and urinary albumin to creatinine ratio: Cross-sectional data from the NHANES 2011-2016.

Eur J Clin Nutr 2022 Jul 29. Epub 2022 Jul 29.

Department of Nephrology, University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

Background & Objective: Chronic kidney disease (CKD) is a common condition in worldwide with underlying causes. The role of trace elements such as copper and zinc in CKD is uncertain. We aimed to examine the relationship of serum copper and zinc with kidney function status and explore its possible effect modifiers in the general population.

Methods: Data from 5353 National Health and Nutrition Examination Survey (NHANES) participants from 2011 to 2016 were analyzed for the role of trace elements in the age range 18 to 80 years. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m and increased urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g.

Results: Findings showed a significant positive association between serum copper and urinary ACR (OR = 1.04, 95% CI = 1.00-1.07). Serum copper levels of 18.0 μmol/L (median) or higher (reference level <18.0 μmol/L) were significantly associated with increased urinary ACR (OR = 1.67, 95% CI = 1.21-2.31) after adjusting for confounding factors. In contrast, there was a significant inverse association between serum zinc and reduced eGFR (OR = 0.89,95% CI = 0.81-0.99). Where serum zinc level was greater than 12.3 μmol/L (median), the prevalence of reduced eGFR was lower (OR = 0.65, 95% CI = 0.16-0.60). In addition, a stratified analysis based on various risk factors found that in those individuals with serum albumin greater than 43 g/L or systolic blood pressure greater than 120 mmHg, positive correlations between serum copper and risk of increased urinary ACR was more significant.

Conclusions: Our findings suggest that the reference levels of serum copper and zinc levels in healthy individuals may be different from current understanding. If further studies substantiate the same, the results will be a useful guide for designing future clinical trials and nutritional guidelines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41430-022-01181-8DOI Listing
July 2022

An unusual cause of hemoptysis and hoarseness due to live leech in the glottis: case report.

J Travel Med 2022 Jul 29. Epub 2022 Jul 29.

Department of burn and plastic surgery, Zigong Fourth People's Hospital, Zigong, Sichuan, 643000, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jtm/taac089DOI Listing
July 2022

Leukocyte as an Independent Predictor of Lower-Extremity Deep Venous Thrombosis in Elderly Patients With Primary Intracerebral Hemorrhage.

Front Neurol 2022 12;13:899849. Epub 2022 Jul 12.

Department of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China.

Objective: Due to the interaction of leukocytes with platelets and coagulation factors, they may in turn play a role in hemostasis or the formation of thrombi. This study aimed to investigate the association of leukocytosis on admission with an increased risk of acute lower-extremity deep venous thrombosis (LEDVT) in elderly patients with primary intracerebral hemorrhage (ICH).

Methods: This was a single-center, retrospective observational study of consecutive patients observed with spontaneous ICH aged 60 years or above at Lanzhou University Second Hospital from January 2017 to September 2021. Clinical data and demographic information were collected and analyzed. Univariate and multivariate analyses were conducted to identify independent risk factors of acute LEDVT. One-to-one matching was implemented to balance important patient characteristics by the groups' propensity score matching (PSM) analysis.

Results: A total of 371 elderly patients with primary ICH fulfilled requirements for inclusion and exclusion, of whom 33 (8.89%) experienced LEDVT. Leukocyte counts were statistically higher in the LEDVT group compared to the non-LEDVT group [12.89 (8.80-14.61) × 10 cells/L vs. 8.31 (6.60-10.75) × 10 cells /L, < 0.001]. Multivariate logistic regression models adjusted for several potential confounding factors were performed, and leukocytes were consistently a significant independent predictor of LEDVT. The optimal cut-off value of leukocyte counts calculated from the receiver operating characteristic (ROC) curve to predict LEDVT was 10.22 × 10 cells /L (area under the curve:0.714, 95%CI 0.665-0.759; the sensitivity was 72.73%; the specificity was 71.01%) in elderly patients with primary ICH. After one-to-one PSM, compared to the matched non-LEDVT group, the matched LEDVT group had significantly higher leukocyte counts [11.98 (8.40-13.94) × 10 cells/L vs. 6.12 (4.68-12.00) × 10 cells/L, = 0.003]. After PSM, the ROC curve was plotted for leukocytes as a predictor of LEDVT, with an AUC of 0.722 (95%CI 0.593-0.828, = 0.001; the sensitivity was 87.10%, and the specificity was 61.29%). Elevated leukocytes remained independently significant as predictors of LEDVT in elderly patients with primary ICH.

Conclusion: Leukocyte at admission is an independent risk factor of LEDVT in elderly patients with primary ICH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2022.899849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314880PMC
July 2022

Asprosin inhibits macrophage lipid accumulation and reduces atherosclerotic burden by up-regulating ABCA1 and ABCG1 expression via the p38/Elk-1 pathway.

J Transl Med 2022 07 28;20(1):337. Epub 2022 Jul 28.

The First Affiliated Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China.

Background: Asprosin, a newly discovered adipokine, is a C-terminal cleavage product of profibrillin. Asprosin has been reported to participate in lipid metabolism and cardiovascular disease, but its role in atherogenesis remains elusive.

Methods: Asprosin was overexpressed in THP-1 macrophage-derived foam cells and apoE mice using the lentiviral vector. The expression of relevant molecules was determined by qRT-PCR and/or western blot. The intracellular lipid accumulation was evaluated by high-performance liquid chromatography and Oil red O staining. HE and Oil red O staining was employed to assess plaque burden in vivo. Reverse cholesterol transport (RCT) efficiency was measured using [H]-labeled cholesterol.

Results: Exposure of THP-1 macrophages to oxidized low-density lipoprotein down-regulated asprosin expression. Lentivirus-mediated overexpression of asprosin promoted cholesterol efflux and inhibited lipid accumulation in THP-1 macrophage-derived foam cells. Mechanistic analysis revealed that asprosin overexpression activated p38 and stimulated the phosphorylation of ETS-like transcription factor (Elk-1) at Ser383, leading to Elk-1 nuclear translocation and the transcriptional activation of ATP binding cassette transporters A1 (ABCA1) and ABCG1. Injection of lentiviral vector expressing asprosin diminished atherosclerotic lesion area, increased plaque stability, improved plasma lipid profiles and facilitated RCT in apoE mice. Asprosin overexpression also increased the phosphorylation of p38 and Elk-1 as well as up-regulated the expression of ABCA1 and ABCG1 in the aortas.

Conclusion: Asprosin inhibits lipid accumulation in macrophages and decreases atherosclerotic burden in apoE mice by up-regulating ABCA1 and ABCG1 expression via activation of the p38/Elk-1 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12967-022-03542-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331044PMC
July 2022

Recent Advancements and Development in Nano-Enabled Agriculture for Improving Abiotic Stress Tolerance in Plants.

Front Plant Sci 2022 11;13:951752. Epub 2022 Jul 11.

Horticulture Department, Faculty of Agriculture, Minia University, El-Minia, Egypt.

Abiotic stresses, such as heavy metals (HMs), drought, salinity and water logging, are the foremost limiting factors that adversely affect the plant growth and crop productivity worldwide. The plants respond to such stresses by activating a series of intricate mechanisms that subsequently alter the morpho-physiological and biochemical processes. Over the past few decades, abiotic stresses in plants have been managed through marker-assisted breeding, conventional breeding, and genetic engineering approaches. With technological advancement, efficient strategies are required to cope with the harmful effects of abiotic environmental constraints to develop sustainable agriculture systems of crop production. Recently, nanotechnology has emerged as an attractive area of study with potential applications in the agricultural science, including mitigating the impacts of climate change, increasing nutrient utilization efficiency and abiotic stress management. Nanoparticles (NPs), as nanofertilizers, have gained significant attention due to their high surface area to volume ratio, eco-friendly nature, low cost, unique physicochemical properties, and improved plant productivity. Several studies have revealed the potential role of NPs in abiotic stress management. This review aims to emphasize the role of NPs in managing abiotic stresses and growth promotion to develop a cost-effective and environment friendly strategy for the future agricultural sustainability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2022.951752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310028PMC
July 2022

Association between baseline C-reactive protein and the risk of lung cancer: a prospective population-based cohort study.

Cancer Prev Res (Phila) 2022 Jul 27. Epub 2022 Jul 27.

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

C-reactive protein (CRP), a systemic marker of diagnosing chronic inflammation, has been associated with the incidence of multiple types of cancer. However, little is known about the impact of CRP on lung cancer incidence in Chinese population. A total of 97,950 participants without cancer at baseline (2006-2007) of the Kailuan Cohort Study were followed up. The concentration of plasma high-sensitivity CRP (hsCRP) was tested for all participants at baseline interview. Multivariable Cox proportional hazards regression models were used to assess the association between levels of hsCRP and incident lung cancer. During 8.7-year follow-up, 890 incident lung cancer cases occurred and were divided into three groups according to the level of hsCRP. The risk of incident lung cancer was significantly increased with elevated levels of hsCRP [hazard ratio (HR)Medium/Low=1.21, 95% confidence interval (CI)=1.03-1.42; HRHigh/Low=1.42, 95%CI=1.20-1.68; Ptrend<0.001], compared to the low group after adjusting confounders. Moreover, after stratifying by BMI, the significantly positive associations between the hsCRP level and the risk of lung cancer were found among those with BMI<24 (HRHigh/Low=1.51, 95%CI=1.18-1.94; Ptrend=0.001) and BMI=24-28 (HRHigh/Low=1.47, 95%CI=1.13-1.92; Ptrend=0.003), but not among those with BMI≥28 (HRHigh/Low=1.01, 95%CI=0.64-1.57; Ptrend=0.991). There was an antagonistic interaction between hsCRP levels and BMI that contributed to development of lung cancer (Pinteraction=0.049). In conclusion, these findings indicate a dose-dependent relationship between hsCRP and lung cancer risk among Chinese population, especially in non-obese participants, suggesting that CRP could serve as a potential biomarker for prediction of lung cancer risk and identification of high-risk population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1940-6207.CAPR-21-0533DOI Listing
July 2022

Discovery of a First-in-Class Degrader for Nuclear Receptor Binding SET Domain Protein 2 (NSD2) and Ikaros/Aiolos.

J Med Chem 2022 Aug 27;65(15):10611-10625. Epub 2022 Jul 27.

Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.

Overexpression of nuclear receptor binding SET domain protein 2 (NSD2) is frequent in multiple myeloma (MM). However, existing NSD2 inhibitors are largely ineffective in suppressing MM cell proliferation. Here, we report the discovery of a first-in-class NSD2 proteolysis targeting chimera (PROTAC) degrader, (MS159), and two structurally similar controls, (MS159N1) and (MS159N2), with diminished binding to the cereblon (CRBN) E3 ligase and NSD2, respectively. Compound , but not and , effectively degraded NSD2 in a concentration-, time-, CRBN-, and proteasome-dependent manner. Compound also effectively degraded CRBN neo-substrates IKZF1 and IKZF3, but not GSPT1. Importantly, compound was much more effective in suppressing the growth in cancer cells than the parent NSD2 binder. Moreover, compound was bioavailable in mice. Altogether, compound and its two controls and are valuable chemical tools for exploring the roles of NSD2 in health and disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.2c00807DOI Listing
August 2022

Prediction of Long-Term Tensile Properties of Glass Fiber Reinforced Composites under Acid-Base and Salt Environments.

Polymers (Basel) 2022 Jul 26;14(15). Epub 2022 Jul 26.

Central Research Institute of Building and Construction (Shenzhen) Co. Ltd. MCC Group, Shenzhen 518055, Guangdong, China.

This study investigates the effects of deionized water, seawater, and solutions with various concentrations (5% and 10% by mass) of HCl and NaOH on the physical and mechanical properties of glass fiber reinforced polymers (GFRPs) through aging tests at 20 °C, 50 °C, and 80 °C. The tensile properties of GFRP were assessed by tensile testing at room temperature, and the strain during the tensile process was observed using digital image correlation. Additionally, the degradation mechanism was analyzed using scanning electron microscopy, and long-term tensile properties were predicted based on the Arrhenius model. The results indicated that the tensile strength of the GFRP decreased by 22%, 71%, and 87% after 56 d of exposure to 5% NaOH solutions at 20 °C, 50 °C, and 80 °C, respectively. The alkaline solutions had a more severe effect on the GFRP than deionized water, seawater, and acidic solutions. The experimental values and Arrhenius model predictions were found to be in good agreement with each other.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym14153031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331005PMC
July 2022

Systems Genetic Identification of Mitochondrion-Associated Alzheimer's Disease Genes and Implications for Disease Risk Prediction.

Biomedicines 2022 Jul 24;10(8). Epub 2022 Jul 24.

Hubei Key Laboratory of Agricultural Bioinformaics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China.

Cumulative evidence has revealed the association between mitochondrial dysfunction and Alzheimer's disease (AD). Because the number of mitochondrial genes is very limited, the mitochondrial pathogenesis of AD must involve certain nuclear genes. In this study, we employed systems genetic methods to identify mitochondrion-associated nuclear genes that may participate in the pathogenesis of AD. First, we performed a mitochondrial genome-wide association study (MiWAS, = 809) to identify mitochondrial single-nucleotide polymorphisms (MT-SNPs) associated with AD. Then, epistasis analysis was performed to examine interacting SNPs between the mitochondrial and nuclear genomes. Weighted co-expression network analysis (WGCNA) was applied to transcriptomic data from the same sample ( = 743) to identify AD-related gene modules, which were further enriched by mitochondrion-associated genes. Using hub genes derived from these modules, random forest models were constructed to predict AD risk in four independent datasets ( = 743, = 542, = 161, and = 540). In total, 9 potentially significant MT-SNPs and 14,340 nominally significant MT-nuclear interactive SNPs were identified for AD, which were validated by functional analysis. A total of 6 mitochondrion-related modules involved in AD pathogenesis were found by WGCNA, from which 91 hub genes were screened and used to build AD risk prediction models. For the four independent datasets, these models perform better than those derived from AD genes identified by genome-wide association studies (GWASs) or differential expression analysis (DeLong's test,   <  0.05). Overall, through systems genetics analyses, mitochondrion-associated SNPs/genes with potential roles in AD pathogenesis were identified and preliminarily validated, illustrating the power of mitochondrial genetics in AD pathogenesis elucidation and risk prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biomedicines10081782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330299PMC
July 2022

Novel Prognosis and Therapeutic Response Model of Immune-Related lncRNA Pairs in Clear Cell Renal Cell Carcinoma.

Vaccines (Basel) 2022 Jul 21;10(7). Epub 2022 Jul 21.

Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal carcinoma. It is particularly important to accurately judge the prognosis of patients. Since most tumor prediction models depend on the specific expression level of related genes, a better model therefore needs to be constructed. To provide an immune-related lncRNA (irlncRNAs) tumor prognosis model that is independent of the specific gene expression levels, we first downloaded and sorted out the data on ccRCC in the TCGA database and screened irlncRNAs using co-expression analysis and then obtained the differently expressed irlncRNA (DEirlncRNA) pairs by means of univariate analysis. In addition, we modified LASSO penalized regression. Subsequently, the ROC curve was drawn, and we compared the area under the curve, calculated the Akaike information standard value of the 5-year receiver operating characteristic curve, and determined the cut-off point to establish the best model to distinguish the high- or low-disease-risk group of ccRCC. Subsequently, we reassessed the model from the perspectives of survival, clinic-pathological characteristics, tumor-infiltrating immune cells, chemotherapeutics efficacy, and immunosuppressed biomarkers. A total of 17 DEirlncRNAs pairs (AL031710.1|AC104984.5, AC020907.4|AC127-24.4,AC091185.1|AC005104.1, AL513218.1|AC079015.1, AC104564.3|HOXB-AS3, AC003070.1|LINC01355, SEMA6A-AS1|CR936218.1, AL513327.1|AS005785.1, AC084876.1|AC009704.2, IGFL2-AS1|PRDM16-DT, AC011462.4|MMP25-AS1, AL662844.3I|TGB2-AS1, ARHGAP27P1|AC116914.2, AC093788.1|AC007098.1, MCF2L-AS1|AC093001.1, SMIM25|AC008870.2, and AC027796.4|LINC00893) were identified, all of which were included in the Cox regression model. Using the cut-off point, we can better distinguish patients according to different factors, such as survival status, invasive clinic-pathological features, tumor immune infiltration, whether they are sensitive to chemotherapy or not, and expression of immunosuppressive biomarkers. We constructed the irlncRNA model by means of pairing, which can better eliminate the dependence on the expression level of the target genes. In other words, the signature established by pairing irlncRNA regardless of expression levels showed promising clinical prediction value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/vaccines10071161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325030PMC
July 2022

Effect of Bi, Sb, and Ti on Microstructure and Mechanical Properties of SAC105 Alloys.

Materials (Basel) 2022 Jul 6;15(14). Epub 2022 Jul 6.

Yunnan Tin Group (Holding) Co., Ltd., Kunming 650000, China.

The Sn-Ag-Cu (SAC) solder alloys with a low Ag (Ag < 3 wt.%) content have attracted great attention owing to their low cost, increased ability in bulk compliance, and plastic energy dissipation. However, some of their mechanical properties are generally lower than the SAC alloys with a higher Ag content. Adding alloying elements is an effective approach for improving the mechanical properties of the SAC alloys. In this study, the effect of Bi, Sb, and Ti on Sn-1 wt.%Ag-0.5 wt.%Cu (SAC105) solder alloys was investigated. The SAC solders with four compositions: SAC105-1 wt.%Bi, SAC105-1 wt.%Sb, SAC105-1 wt.%Bi-1 wt.%Sb, SAC105-1 wt.%Bi-1 wt.%Sb-0.4 wt.%Ti were prepared. The microstructure and phase compositions were characterized using electron scanning microscopy, and X-ray diffraction. The thermal properties and wettability were also examined. Uniaxial tensile tests and nano-indentation tests were conducted to evaluate the mechanical properties. The results show that adding Bi or Sb could increase the strength of SAC105 alloys mainly due to the solid solution strengthening effect. The creep resistance of SAC105 alloys was also improved with the additions of Bi and Sb. The co-additions of Bi and Sb into SAC105 alloys exhibit an enhanced creep resistance than that calculated by the theoretical calculation. The further addition of Ti into SAC105-1Bi-1Sb alloys demonstrated a much-improved creep resistance, which could be attributed to the synergistic effects of both solid solution strengthening and the precipitation hardening effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma15144727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317400PMC
July 2022

Generation of an mESC model with a human hemophilia B nonsense mutation via CRISPR/Cas9 technology.

Stem Cell Res Ther 2022 07 26;13(1):353. Epub 2022 Jul 26.

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi Province, China.

Background: Hemophilia B is a rare inherited genetic bleeding disorder caused by a deficiency or lack of coagulation factor IX, the gene for which (F9) is located on the X chromosome. Hemophilia B is currently incurable and the standard treatment is coagulation factor replacement therapy. Although gene therapy has the potential to cure hemophilia, significant barriers are still needed to be overcome, e.g., off-target effects and immunoreactivity, so new approaches must be explored. Nonsense mutations account for 8% of all the hemophilia B mutation types and can result in the development of coagulation factor inhibitors. In this study, CRISPR/Cas9 technology was used to construct a mouse embryonic stem cell model with a hemophilia B nonsense mutation (F9 c.223C > T) in humans to investigate the pathogenesis and treatment of nonsense mutations in hemophilia B.

Methods: First, a donor plasmid with a mutation (F9 c.223 C > T) and sgRNAs were constructed. Second, both the donor plasmid and the px330-sgRNA were electroporated into mouse embryonic stem cell, and the mutant cells were then screened using puromycin and red fluorescence. Third, the mutant cell lines were tested for pluripotency and the ability to differentiate into three layers. Finally, the effect of mutation on gene function was studied in the differentiation system.

Results: The mutant vector and effective sgRNA were constructed, and the mutant cell line was screened. This mutant cell line exhibited pluripotency and the ability to differentiate into three layers. This point mutation affects F9 expression at both the RNA and protein levels in the differentiation system.

Conclusions: The mutant cell line obtained in the current study had a single-base mutation rather than a base deletion or insertion in the exon, which is more similar to clinical cases. In addition, the mutant has the characteristics of mouse embryonic stem cells, and this point mutation affects F9 gene transcription and translation, which can be used as a disease model for studying the pathogenesis and treatment of hemophilia at the stem cell level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-022-03036-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327398PMC
July 2022

hsa-miR-34a-5p Ameliorates Hepatic Ischemia/Reperfusion Injury Via Targeting HNF4α.

Turk J Gastroenterol 2022 Jul;33(7):596-605

Department of Ultrasound, The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, China.

Background: To investigate the relationship between the expression level of hsa-miR-34a-5p and liver injury and to further explore its regulatory signaling pathways Methods: Liver tissue and blood were collected from 60 patients undergoing hepatectomy. We constructed a rat HIRI model and treated it with an intraperitoneal injection of agomir-miR-34a-5p or agomir-normal control (NC) for 7 days after the surgery. The pathological changes of agomir-miR-34a-5p or agomir-normal control (NC) groups were compared. 7702 and AML12 cells were transfected with mimics NC or miR-34a-5p mimics and then treated with H2O2 for 6 hours. Cell apoptosis was detected by flow cytometry, Western blot, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, respectively. Furthermore, the target genes of miR- 34a-5p were identified by luciferase reporter gene assay and were verified in vitro.

Results: The relatively high miR-34a-5p expression group revealed a lower level of alanine aminotransferase and aspartate aminotrans- ferase compared with the relatively low miR-34a-5p expression group. HIRI+agomir-miR-34a-5p rats exhibited significantly higher miR-34a-5p expression, lower serum alanine aminotransferase, aspartate aminotransferase, alleviated hepatic necrosis, reduced hepa- tocyte apoptosis, and decreased expression of apoptosis-related proteins, when compared with HIRI+agomir-NC rats (P < .05). After hydrogen peroxide treatment, alpha mouse liver-12 cell (AML-12) and normal liver cell line LO2 (LO2) cells transfected with miR-34a-5p mimics had significantly lower apoptosis rate compared with miR-34a-5p mimics NC group (P < .05). Hepatocyte nuclear factor 4α was identified as a miR-34a-5p target gene. Hepatocyte nuclear factor 4α expression was significantly downregulated in AML12 and HL-7702 (7702) cells transfected with miR-34a-5p (P < .05). Moreover, AML12 and 7702 cells transfected with miR-34a-5p signifi- cantly showed higher c-Jun N-terminal kinase (JNK), P38, cleavage cas-3, and BCL2 associated X (Bax) protein levels compared with AML12 and 7702 cells transfected with agomir-NC.

Conclusion: miR-34a-5p possibly protected the liver from I/R injury through downregulating Hepatocyte nuclear factor 4α to inhibit the JNK/P38 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5152/tjg.2022.21169DOI Listing
July 2022

Single-Cell Transcriptomics of Immune Cells Reveal Diversity and Exhaustion Signatures in Non-Small-Cell Lung Cancer.

Front Immunol 2022 6;13:854724. Epub 2022 Jul 6.

Laboratory of Omics Technology and Bioinformatics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Understanding immune cell phenotypes in the tumor microenvironment (TME) is essential for explaining and predicting progression of non-small cell lung cancer (NSCLC) and its response to immunotherapy. Here we describe the single-cell transcriptomics of CD45 immune cells from tumors, normal tissues and blood of NSCLC patients. We identified three clusters of immune cells exerting immunosuppressive effects: CD8 T cells with exhausted phenotype, tumor-associated macrophages (TAMs) with a pro-inflammatory M2 phenotype, and regulatory B cells (B regs) with tumor-promoting characteristics. We identified genes that may be mediating T cell phenotypes, including the transcription factors ONECUT2 and ETV4 in exhausted CD8 T cells, TIGIT and CTL4 high expression in regulatory T cells. Our results highlight the heterogeneity of CD45 immune cells in the TME and provide testable hypotheses about the cell types and genes that define the TME.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2022.854724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299430PMC
July 2022

Differential Gene Analysis of Trastuzumab in Breast Cancer Based on Network Pharmacology and Medical Images.

Front Physiol 2022 8;13:942049. Epub 2022 Jul 8.

Shanghai Eighth People's Hospital, Shanghai, China.

The purpose of this study was to use network pharmacology, biomedical images and molecular docking technology in the treatment of breast cancer to investigate the feasible therapeutic targets and mechanisms of trastuzumab. In the first place, we applied pubchem swisstarget (http://www.swisstargetprediction.ch/), (https://pubchem.ncbi.nlm.nih.gov/) pharmmapper (http://lilab-ecust.cn/pharmmapper/), and the batman-tcm (http://bionet.ncpsb.org.cn/batman-tcm/) database to collect the trastuzumab targets. Then, in NCBI-GEO, breast cancer target genes were chosen (https://www.ncbi.nlm.nih.gov/geo/). The intersection regions of drug and disease target genes were used to draw a Venn diagram. Through Cytoscape 3.7.2 software, and the STRING database, we then formed a protein-protein interaction (PPI) network. Besides, we concluded KEGG pathway analysis and Geen Ontology analysis by using ClueGO in Cytospace. Finally, the top 5 target proteins in the PPI network to dock with trastuzumab were selected. After screening trastuzumab and breast cancer in databases separately, we got 521 target genes of the drug and 1,464 target genes of breast cancer. The number of overlapping genes was 54. PPI network core genes include GAPDH, MMP9, CCNA2, RRM2, CHEK1, etc. GO analysis indicated that trastuzumab treats breast cancer through abundant biological processes, especially positive regulation of phospholipase activity, linoleic acid metabolic process, and negative regulation of endothelial cell proliferation. The molecular function is NADP binding and the cellular component is tertiary granule lumen. The results of KEGG enrichment analysis exhibited four pathways related to the formation and cure of breast cancer, containing Drug metabolism, Glutathione metabolism, Pyrimidine metabolism and PPAR signaling pathway. Molecular docking showed that trastuzumab has good binding abilities with five core target proteins (GAPDH, MMP9, CCNA2, RRM2, CHEK1). This study, through network pharmacology and molecular docking, provides new pieces of evidence and ideas to understand how trastuzumab treats breast cancer at the gene level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2022.942049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304584PMC
July 2022

Elevation of TRIM44 potentiates propagation of gastric cancer stem cells.

Genes Dis 2022 Sep 27;9(5):1156-1159. Epub 2021 Nov 27.

Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, PR China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gendis.2021.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293703PMC
September 2022

The performance and perspectives of dendritic cell vaccines modified by immune checkpoint inhibitors or stimulants.

Biochim Biophys Acta Rev Cancer 2022 Jul 21;1877(5):188763. Epub 2022 Jul 21.

Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China. Electronic address:

Therapeutic dendritic cell (DC) vaccines stimulate the elimination of tumor cells by the immune system. However, while antigen-specific T cell responses induced by DC vaccines are commonly observed, the clinical response rate is relatively poor, necessitating vaccine optimization. There is evidence that the suppression of DC function by immune checkpoints hinders the anti-tumor immune responses mediated by DC vaccines, ultimately leading to the immune escape of the tumor cells. The use of immune checkpoint inhibitors (ICIs) and immune checkpoint activators (ICAs) has extended the immunotherapeutic range. It is known that both inhibitory and stimulatory checkpoint molecules are expressed by most DC subsets and can thus be used to manipulate the effectiveness of DC vaccines. Such manipulation has been investigated using strategies such as chemotherapy, agonistic or antagonistic antibodies, siRNA, shRNA, CRISPR-Cas9, soluble antibodies, lentiviruses, and adenoviruses to maximize the efficacy of DC vaccines. Thus, a deeper understanding of immune checkpoints may assist in the development of improved DC vaccines. Here, we review the actions of various ICIs or ICAs shown by preclinical studies, as well as their potential application in DC vaccines. New therapeutic interventional strategies for blocking and stimulating immune checkpoint molecules in DCs are also described in detail.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbcan.2022.188763DOI Listing
July 2022
-->