Publications by authors named "Xiaolin Xu"

261 Publications

Spectrum and tissue distribution of RB1 pathogenic alleles in mosaic retinoblastoma patients.

Ophthalmic Genet 2022 Aug 8:1-11. Epub 2022 Aug 8.

Nanjing Geneseeq Technology Inc, Nanjing, China.

To characterize the spectrum of mosaic RB1 pathogenic alleles and map the distribution of mutant cells in available tissues from mosaic patients. Next-generation sequencing was performed on blood samples from 263 retinoblastoma families to identify mosaic RB1 variant alleles. A variety of available tissues were sampled to determine tissue distribution and fraction of mutant cells in five mosaic patients who consented to participate in mosaic pathogenic allele research. Twelve identified mosaic RB1 variants were all "null" pathogenic alleles and displayed reduced expressivity. The use of next-generation deep sequencing increased the sensitivity of mosaicism detection to 0.03% in the case of tissue DNA. In the five mosaic participants, we observed coherent but uneven, bilateral asymmetrical distribution of mutant cells across various tissues. They all carried early-embryonic mosaic pathogenic alleles and had significantly higher variant fractions in blood than in other tissues. Variant fractions of ipsilateral tissue samples were not concordant higher or lower compared with the contralateral side. Only ipsilateral conjunctival and oral epithelial cells showed concordance in mosaicism levels. No associations were observed between the laterality of affected eyes and variant fractions of any tissue type. NGS allows the detection of low-level mosaicism. Mosaic RB1 pathogenic alleles are prone to occur at very early stages of human embryonic development. With respect to genetic counseling, risk prediction should take into account unrecognized mosaicism. The underlying tissue distribution patterns of mosaic RB1 variant alleles remain to be determined.
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http://dx.doi.org/10.1080/13816810.2022.2098985DOI Listing
August 2022

Association between socioeconomic status and health behaviour change before and after non-communicable disease diagnoses: a multicohort study.

Lancet Public Health 2022 Aug;7(8):e670-e682

Department of Big Data in Health Science School of Public Health, and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. Electronic address:

Background: Behavioural risk factors of non-communicable diseases (NCDs) are socially patterned. However, the direction and the extent to which socioeconomic status (SES) influences behaviour changes before and after the diagnosis of NCDs is not clearly understood. We aimed to investigate the influence of SES on behaviour changes (physical inactivity and smoking) before and after the diagnosis of major NCDs.

Methods: In this multicohort study, we pooled individual-level data from six prospective cohort studies across 17 countries. We included participants who were diagnosed with either diabetes, cardiovascular disease, chronic lung disease, or cancer after recruitment. Participants were surveyed every 2 years. Education and total household wealth were used to construct SES. We measured behaviour changes as whether or not participants continued or initiated physical inactivity or smoking after NCD diagnosis. We used multivariable logistic regression models to estimate odds ratios (ORs), prevalence ratios (PRs), and 95% CIs for the associations between SES and continuation or initiation of unfavourable behaviours.

Findings: We included 8107 individuals recruited between March, 2002, and January, 2016. Over the 4-year period before and after NCD diagnosis, 886 (60·4%) of 1466 individuals continued physical inactivity and 1018 (68·8%) of 1480 participants continued smoking; 1047 (15·8%) of 6641 participants with physical activity before diagnosis initiated physical inactivity after diagnosis and 132 (2·0%) of 6627 non-smokers before diagnosis initiated smoking after diagnosis. Compared with participants with high SES, those with low SES were more likely to continue physical inactivity (244 [70·3%] of 347 vs 23 [50.0%] of 46; PR 1·41 [95% CI 1·05-1·99]; OR 2·28 [1·18-4·41]), continue smoking (214 [75·4%] of 284 vs 39 [60·9%] of 64; PR 1·27 [1·03-1·59]; OR 2·08 [1·14-3·80]), but also to initiate physical inactivity (188 [26·1%] of 720 vs 47 [7·4%] of 639; PR 3·59 [2·58-4·85]; OR 4·31 [3·02 - 6·14]).

Interpretation: Low SES was associated with continuing or initiating physical inactivity and continuing smoking after NCD diagnosis. Reducing socioeconomic inequality in health behaviour changes should be prioritised and integrated into NCD-prevention programmes.

Funding: Zhejiang University and Fundamental Research Funds for the Central Universities.
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http://dx.doi.org/10.1016/S2468-2667(22)00157-8DOI Listing
August 2022

Special issue "The advance of solid tumor research in China": Discoidin domain receptor 2 promotes colorectal cancer metastasis by regulating epithelial mesenchymal transition via activating AKT signaling.

Int J Cancer 2022 Jul 29. Epub 2022 Jul 29.

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

Tumor metastasis is one of the main reasons for the high mortality rate associated with colorectal cancer (CRC). However, its underlying mechanisms have not been fully understood. Here, we reported that the expression of discoidin domain receptor 2 (DDR2) was significantly upregulated in CRC tissues compared with that in normal adjacent tissues. The expression level of DDR2 was negatively associated with prognosis of CRC patients. Therefore, DDR2 may play an oncogenic role in CRC development. Furthermore, DDR2 induced epithelial mesenchymal transition in CRC cells and regulated their invasive and metastatic capacity in vitro and in vivo. Mechanistically, increased DDR2 expression level activated the AKT/GSK-3β/Slug signaling pathway. In conclusion, these findings showed that DDR2 promoted CRC metastasis and DDR2 inhibition might represent an effective therapeutic strategy for local advanced and metastatic CRC treatment. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ijc.34227DOI Listing
July 2022

Label-Free and Homogeneous Electrochemical Biosensor for Flap Endonuclease 1 Based on the Target-Triggered Difference in Electrostatic Interaction between Molecular Indicators and Electrode Surface.

Biosensors (Basel) 2022 Jul 15;12(7). Epub 2022 Jul 15.

Ministry of Education Key Laboratory for Analysis Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection for Food Safety, College of Chemistry, Fuzhou University, Fuzhou 350116, China.

Target-induced differences in the electrostatic interactions between methylene blue (MB) and indium tin oxide (ITO) electrode surface was firstly employed to develop a homogeneous electrochemical biosensor for flap endonuclease 1 (FEN1) detection. In the absence of FEN1, the positively charged methylene blue (MB) is free in the solution and can diffuse onto the negatively charged ITO electrode surface easily, resulting in an obvious electrochemical signal. Conversely, with the presence of FEN1, a 5'-flap is cleaved from the well-designed flapped dumbbell DNA probe (FDP). The remained DNA fragment forms a closed dumbbell DNA probe to trigger hyperbranched rolling circle amplification (HRCA) reaction, generating plentiful dsDNA sequences. A large amount of MB could be inserted into the produced dsDNA sequences to form MB-dsDNA complexes, which contain a large number of negative charges. Due to the strong electrostatic repulsion between MB-dsDNA complexes and the ITO electrode surface, a significant signal drop occurs. The signal change (Δ) shows a linear relationship with the logarithm of FEN1 concentration from 0.04 to 80.0 U/L with a low detection limit of 0.003 U/L (S/N = 3). This study provides a label-free and homogeneous electrochemical platform for evaluating FEN1 activity.
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http://dx.doi.org/10.3390/bios12070528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313405PMC
July 2022

Compound Glycyrrhiza Oral Solution alleviates oxidative stress and inflammation by regulating SRC/MAPK pathway in chronic obstructive pulmonary disease.

Immunopharmacol Immunotoxicol 2022 Jul 15:1-30. Epub 2022 Jul 15.

Department of Pharmacy, Ji'an Hospital of Shanghai East Hospital, Shanghai, P.R. China.

Objectives: Patients with chronic obstructive pulmonary disease (COPD) suffer from persistent cough and breathlessness, which can be ameliorated by the Chinese herbal medicine glycyrrhiza. Furthermore, the SRC/MAPK pathway is activated in the process of oxidative stress and inflammation, which afflict COPD progression. Thus, this research aimed at dissecting the mechanism of compound glycyrrhiza oral solution (CGOS) relieving oxidative stress and inflammation in COPD via the SRC/MAPK pathway.

Methods: After a COPD rat model was established using lipopolysaccharide and cigarette smoke, rats underwent intragastric administration with CGOS and intratracheal injection with LV-NC and LV-SRC lentivirus into lungs. Then, pulmonary function-related indexes were evaluated, followed by analyses of arterial blood and inflammatory cell number in prepared bronchoalveolar lavage fluids. Meanwhile, the contents of oxidative stress-related indicators (malondialdehyde, 3NT, 8-Isoprostane, glutathione, NO, and SOD) in pulmonary tissues were measured, along with RT-qPCR and ELISA detection of the expression of inflammatory factors (TNF-α, IL-1β, IL-4, and IL-10). Moreover, western blot assay was utilized to assess p-SRC/SRC and p-p38/p38 ratios in pulmonary tissues.

Results: CGOS treatment enhanced PaO and reduced PaCO in COPD rats, accompanied by declines in the number of total cells, neutrophils, and macrophages. CGOS improved pulmonary function, decreased malondialdehyde, 3NT, 8-Isoprostane, TNF-α, and IL-1β levels, and increased GSH, NO, IL-4, and IL-10 levels and SOD activity. Mechanistically, CGOS suppressed the SRC/MAPK pathway, and SRC overexpression reversed the alleviating function of CGOS in COPD rats.

Conclusions: In conclusion, CGOS might alleviate oxidative stress and inflammation in COPD rats by inhibiting the SRC/MAPK pathway.
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http://dx.doi.org/10.1080/08923973.2022.2102992DOI Listing
July 2022

Vaginal Microbiota Changes Caused by HPV Infection in Chinese Women.

Front Cell Infect Microbiol 2022 21;12:814668. Epub 2022 Jun 21.

Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. After studying 602 unvaccinated Chinese women using 16S rRNA to detect cervical-vaginal microecology, we analyzed the relationship between HPV infection and vaginal microecology including 20 HPV types. In Chinese women, dominated and dominated clusters were significantly absence. Microbial alpha diversity was significantly higher in HPV-infected and cervical intraepithelial neoplasia (CIN)-diagnosed groups than in healthy control group. Certain bacteria were associated with HPV infection and CIN, including , , , , , and With the development of disease, the proportions of community state type III (CST-III) and CST-IV-B gradually increased, whereas the proportions of CST-I and CST-IV-A gradually decreased. In addition, age was an influential factor for HPV infection. With aging, the probability of HPV infection and the proportion of CST-IV-B increase. In conclusion, our study was a large cross-sectional study that evaluated the relationship between vaginal microbiota and HPV infection, and brought essential comparable data.
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http://dx.doi.org/10.3389/fcimb.2022.814668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253274PMC
June 2022

Lipid-coated albumin-paclitaxel nanoparticles loaded with sorcin-siRNA reverse cancer chemoresistance via restoring intracellular calcium ion homeostasis.

J Nanobiotechnology 2022 Jul 7;20(1):319. Epub 2022 Jul 7.

Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai, 201508, People's Republic of China.

Chemoresistance is often a cause of the failure of chemotherapy in cancer treatment. Sorcin (SRI) is a soluble resistance-related calcium-binding protein involved in chemoresistant processes and is overexpressed in many chemoresistant cancer cells, including paclitaxel (PTX)-resistant ovarian cancer. Increased SRI can reduce the concentration of calcium ions in the cytosol and mitochondria and the decrease of calcium ion concentration prevents the occurrence of apoptosis. Here we examined the SRI expression in multiple cancers using a human TissueArray and found that SRI expression was significantly higher in malignant tumor tissues. Furthermore, SRI was overexpressed, while intracellular calcium concentration was decreased, in chemoresistant cancer cells. To restore intracellular calcium homeostasis and overcome chemoresistance, we developed lipid-coated albumin-PTX nanoparticles loaded with SRI-siRNA (LANP-PTX-siSRI) for PTX and SRI-siRNA co-delivery. LANP-PTX-siSRI had dual-target roles in the regulation of SRI and the delivery of PTX into chemoresistant cells. The LANP-PTX-siSRI inhibited the expression of SRI and enhanced intracellular calcium, leading to the induction of apoptosis and the inhibition of the growth of PTX-resistant cancer cells in vitro and in vivo. In addition, the mechanism study revealed that the overexpression of SRI was associated with an impaired TGF-β signaling pathway. The administration of TGF-β1 inhibited two calcium-binding proteins SRI and S100A14. In conclusion, our data unveil that restoring intracellular calcium ion homeostasis via reducing SRI expression can reverse chemoresistance. Thus, the fabricated LANP-PTX-siSRI has a potentially therapeutical application.
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http://dx.doi.org/10.1186/s12951-022-01487-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264675PMC
July 2022

GDF-15 as a Therapeutic Target of Diabetic Complications Increases the Risk of Gallstone Disease: Mendelian Randomization and Polygenic Risk Score Analysis.

Front Genet 2022 13;13:814457. Epub 2022 Jun 13.

Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Growth differentiation factor 15 (GDF-15) levels have been revealed as a robust biomarker for metformin use. We conducted Mendelian randomization (MR) analysis to explore the association between GDF-15 and gallstone disease to inform potential therapeutic effects targeting GDF-15. Four genetic variants associated with GDF-15 levels at < 5 × 10 were selected as instrumental variables from a genome-wide association meta-analysis including 21,758 individuals. Two-sample MR analysis was conducted using summary-level data from UK Biobank (10,520 gallstone cases and 350,674 controls) and FinnGen consortium (19,023 gallstone cases and 195,144 controls). Polygenic risk score analysis using individual-level data in UK biobank was performed to complement the MR findings by examining the non-linearity of the association. Diabetic complications were taken as positive controls to validate the therapeutic effect of targeting GDF-15. Linear and nonlinear associations between genetically predicted GDF-15 levels and gallstones were estimated with stratification by the diabetic status. In the two-sample MR analysis, the odds ratio (OR) of gallstones was 1.09 (95% confidence interval (CI), 1.03-1.15; = 0.001) for one standard deviation increase in genetically predicted GDF-15 levels in the meta-analysis of two datasets. Polygenic risk score analysis found this association to be U-shaped ( = 0.037). The observed association was predominantly seen in nondiabetic population (OR = 1.11, 95% CI: 1.01-1.21; = 0.003). An inverse association between genetically predicted GDF-15 levels and diabetic complications (OR = 0.77, 95% CI: 0.62-0.96; = 0.023) was observed, validating the potential therapeutic effects of targeting GDF-15 levels. This MR study indicates that the increased risk of gallstone disease should be taken into account when considering GDF-15 as a therapeutic target for diabetic complications.
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http://dx.doi.org/10.3389/fgene.2022.814457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234303PMC
June 2022

Uveal Effusion Syndrome: Clinical Characteristics, Outcome of Surgical Treatment, and Histopathological Examination of the Sclera.

Front Med (Lausanne) 2022 9;9:785444. Epub 2022 Jun 9.

Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Medical Artificial Intelligence Research and Verification Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Purpose: In this study, we aimed to investigate clinical characteristics and histopathology and evaluate surgical outcomes of quadrantic lamellar-sclerectomy with sclerostomy for uveal effusion syndrome (UES).

Design: Retrospective, cohort study.

Participants: Overall, 106 eyes of 66 patients diagnosed with UES were treated at the Beijing Tongren Hospital between January 1, 2001 and June 26, 2021.

Methods: Patients were examined by routine ophthalmologic examinations, fluorescein and indocyanine green angiography (FFA/ICGA); axial length determination; color Doppler ultrasound (CDU); ultrasound biomicroscopy (UBM), optical coherence tomography (OCT), and optical coherence tomographic angiography (SD/SS-OCTA). Quadrantic lamellar-sclerectomy with sclerostomy was performed at the equator in all patients and histopathological examination of the excised sclera was analyzed in all samples.

Main Outcome Measures: The reattachment of the choroid and retina with resolution of the serous fluid, best corrected visual acuity (BCVA), choroidal thickness, and recurrence of ciliochoroidal detachment were the main outcome measures.

Results: Two subgroups were identified: (1) type 1 (nanophthalmic eye), wherein the eyeball was small (average axial length 15.83 ± 1.45 mm) with high hypermetropia (average 12.6 diopters) and (2) type 2 (non-nanophthalmic eye), wherein the eyeball size was normal (average axial length 23.45 ± 1.68 mm) with or without refractive error, combined with or without systemic symptoms. Histopathologically, types 1 and 2 demonstrated similarly abnormal sclera with the disorganization of collagen fiber bundles and deposits of proteoglycans in the matrix. Quadrantic lamellar-sclerectomy with sclerostomy was effective in both types 1 and 2, inducing post-operative resolution of the subretinal fluid accumulation and increasing the useful BCVA. The choroidal thickness was significantly different before and after surgery ( < 0.05). Approximately 98.1% of cases attained permanent reattachment within 6 months after one operation through this procedure. The single operation success rate was 96.2%, and success with one or two operations was 100%.

Conclusions: UES is caused by abnormalities of the sclera and increased resistance to transscleral fluid outflow, combined with increased choroidal thickness. Quadrantic lamellar-sclerectomy with sclerostomy is an effective treatment for UES that can rescue correct the useful visual acuity.
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http://dx.doi.org/10.3389/fmed.2022.785444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218343PMC
June 2022

Alcohol consumption, blood DNA methylation and breast cancer: a Mendelian randomisation study.

Eur J Epidemiol 2022 Jul 16;37(7):701-712. Epub 2022 Jun 16.

Department of Big Data in Health Science School of Public Health, and Centre of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Alcohol intake is thought to be a risk factor for breast cancer, but the causal relationship and carcinogenic mechanisms are not clear. We performed an up-to-date meta-analysis of prospective studies to assess observational association, and then conducted MR analysis to make causal inference based on the genetic predisposition to alcohol consumption ("drinks per week") and pathological drinking behaviours ("alcohol use disorder" and "problematic alcohol use"), as well as genetically predicted DNA methylation at by alcohol-related CpG sites in blood. We found an observational dose-response association between alcohol intake and breast cancer incidence with an additional risk of 4% for per 10 g/day increase in alcohol consumption. Genetic predisposition to alcohol consumption ("drinks per week") was not causally associated with breast cancer incidence at the OR of 1.01 (95% CI 0.84, 1.23), but problematic alcohol use (PAU) was linked to a higher breast cancer risk at the OR of 1.76 (95% CI 1.04, 2.99) when conditioning on alcohol consumption. Epigenetic MR analysis identified four CpG sites, cg03260624 near CDC7 gene, cg10816169 near ZNF318 gene, cg03345232 near RIN3 gene, and cg26312998 near RP11-867G23.13 gene, where genetically predicted epigenetic modifications were associated with an increased breast cancer incidence risk. Our findings re-affirmed that alcohol consumption is of high risk for breast cancer incidence even at a very low dose, and the pathogenic effect of alcohol on breast cancer could be due to pathological drinking behaviour and epigenetic modification at several CpG sites, which could be potential intervention targets for breast cancer prevention.
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http://dx.doi.org/10.1007/s10654-022-00886-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329409PMC
July 2022

A Practical CEUS Thyroid Reporting System for Thyroid Nodules.

Radiology 2022 Jun 14:212319. Epub 2022 Jun 14.

From the Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University (J.R., X.X., M.L., W.Z., R.L., P.L., B.O., B.L.), Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation (J.R., X.X., M.L., W.Z., R.L., B.O., B.L.), and Department of Otolaryngology, Head and Neck Surgery (P.L.), No. 33 Yingfeng Rd, Guangzhou 510289, China; Department of Ultrasound, Central People's Hospital of Zhanjiang, Zhanjiang, China (Y.C., Y.X.); and Department of Ultrasound, Affiliated Huadu Hospital of Southern Medical University, Guangzhou 510810, China (H.Z., Q.Y.).

Background The role of contrast-enhanced US (CEUS) in reducing unnecessary biopsies of thyroid nodules has received little attention. Purpose To construct and externally validate a thyroid imaging reporting and data system (TI-RADS) based on nonenhanced US and CEUS to stratify the malignancy risk of thyroid nodules. Materials and Methods This retrospective study evaluated 756 patients with 801 thyroid nodules who underwent nonenhanced US, CEUS, and fine-needle aspiration and received a final diagnosis from January 2018 to December 2019. Qualitative US features of the thyroid nodules were analyzed with univariable and multivariable logistic regression to construct a CEUS TI-RADS. The CEUS TI-RADS was validated with use of internal cross-validation and external validation. Results A total of 801 thyroid nodules in 590 female (mean age, 44 years ± 13) and 166 male (mean age, 47 years ± 13 [SD]) patients were included. Independent predictive US features included nodule composition at CEUS, echogenicity, nodule shape, nodule margin, echogenic foci, extrathyroidal extension, enhancement direction, peak intensity, and ring enhancement. The CEUS TI-RADS showed a higher area under the receiver operating characteristic curve of 0.93 (95% CI: 0.92, 0.95; < .001 in comparison with all other systems), a biopsy yield of malignancy of 66% (157 of 239 nodules), and an unnecessary biopsy rate of 34% (82 of 239 nodules). In the external validation, the area under the receiver operating characteristic curve, biopsy yield of malignancy, and unnecessary biopsy rate of CEUS TI-RADS were 0.89 (95% CI: 0.84, 0.92), 61% (65 of 106 nodules), and 39% (41 of 106 nodules) for the first external validation set and 0.90 (95% CI: 0.85, 0.94), 57% (56 of 99 nodules), and 43% (43 of 99 nodules) for the second external validation set. Conclusion A contrast-enhanced US (CEUS) thyroid imaging reporting and data system was created with thyroid nodule malignancy risk stratification according to the simplified regression coefficients of nonenhanced US and qualitative features of CEUS. Clinical trials registration no. ChiCTR2000028712 Published under a CC BY 4.0 license.
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http://dx.doi.org/10.1148/radiol.212319DOI Listing
June 2022

De novo transcriptome sequencing of Capsicum frutescens. L and comprehensive analysis of salt stress alleviating mechanism by Bacillus atrophaeus WU-9.

Physiol Plant 2022 Jun 8:e13728. Epub 2022 Jun 8.

School of Environmental and Chemical Engineering, Xi'an Polytechnic University, Xi'an, PR China.

Salt stress, as one of the most severe environmental stresses, can cause a series of changes in plants. However, the explanation of plant salt stress alleviating mechanism of plant growth-promoting rhizobacteria (PGPR) was hindered by the limited availability of transcriptomic information for salt stress-treated plants grown in a microorganism-controled environment. Our previous reports have selected Bacillus atrophaeus WU-9 as PGPR significantly alleviating pepper (Capsicum frutescens. L) salt stress. In this work, the RNA-seq analysis of salt stress-treated and untreated plants, grown with and without WU-9 in a microorganism-controled environment, was used to reveal the plant salt stress alleviating mechanisms of WU-9. Twelve sequencing libraries, prepared by treating with WU-9 and salt (150 mM NaCl for 36 h), were constructed by RNA-Seq technique. Non-inoculated seedlings mainly respond to salt stress through regulation of signal transduction, such as ethylene-activated signaling pathway, signaling and cell communication, etc. And ethylene signal participated in salt stress response in pepper through regulating defense responses, fruit ripening and senescence. WU-9 inoculation under salt stress mainly improves salt tolerance and plant growth by regulating salt stress-responding ethylene and auxin signal transduction, utilization of proline, photosynthesis, antioxidant enzyme activities and cell enlargement. Furthermore, 86 differentially expressed genes (DEGs) and 20 transcription factors were identified as associated with salt stress response and tolerance. Thus, this innovative transcriptomic study identified the salt stress response and alleviation in C. frutescens. L with PGPR inoculation. This result provided novel insights into the salinity alleviation in pepper regulated by PGPR. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/ppl.13728DOI Listing
June 2022

Anesthetic management of hip fracture in geriatric patient with respiratory and heart failure using pericapsular nerve group block: A case report.

Medicine (Baltimore) 2022 Jun 3;101(22):e29478. Epub 2022 Jun 3.

Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Introduction: Hip fracture with severe cardiopulmonary and cerebral dysfunction is a relatively common problem in the elderly population and poses a great challenge to anesthetic management. Pericapsular nerve group (PENG) block combined with nerve blocks of the hip region has recently attracted significant interest from anesthesiologists, and very few reports on its anesthetic management exist.

Patient Concerns: Patient suffered from the right femoral neck fracture, combined with respiratory failure, heart failure, moderate-to-severe pulmonary hypertension, cerebral infarction, atrial fibrillation, and cognitive dysfunction.

Diagnosis: Because of right femoral neck fracture, artificial femoral head replacement was scheduled for this patient.

Interventions: Ultrasound-guided PENG block combined with sacral plexus, thoracic 11 to 12 paravertebral block, and lateral femoral cutaneous block were performed to a high-risk elderly patient.

Outcomes: The patient successfully received artificial femoral head replacement with our effective anesthesia techniques and no postoperative complication was reported.

Conclusions: Among elderly patients with multiple organ dysfunction undergoing hip surgery, PENG block combined with nerve blocks of the hip region is an ideal anesthesia method. This case demonstrated that these regional analgesia techniques had a stable hemodynamic process, satisfactory anesthetic effect, effective postoperative analgesia, and no effect on postoperative cognitive function. Further studies are needed to determine the appropriate doses of local anesthetics in the elderly with multiple organ system failure to reduce delayed local anesthesia systemic toxicity.
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http://dx.doi.org/10.1097/MD.0000000000029478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276141PMC
June 2022

Beneficial effects of dietary capsaicin in gastrointestinal health and disease.

Exp Cell Res 2022 Aug 27;417(2):113227. Epub 2022 May 27.

Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, China; The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China. Electronic address:

Chili pepper and its major active compound capsaicin have long been used not only a daily food additive but also medication worldwide. Like in other human organs and systems, capsaicin has multiple actions in gastrointestinal (GI) physiology and pathology. Numerous studies have revealed that capsaicin acts on GI tract in TRPV1-dependent and -independent manners, mostly depending on its consumption concentrations. In this review, we will focus on the beneficial role of capsaicin in GI tract, a less highlighted aspect, in particular how dietary capsaicin affects GI health, the mechanisms of actions and its preventive/therapeutic potentials to several GI diseases. Dietary capsaicin affects GI tract not only via TRPV1-derpendent and independent manners, but also via acute and chronic effects. Although high dose intake of dietary capsaicin is harmful to human health sometimes, current literatures suggest that appropriate dose intake is likely beneficial to GI health and is preventive/therapeutic to GI disease in most cases as well. With extensive and intensive studies on its GI actions, capsaicin, as a daily consumed food additive, has potential to become a safe drug for the treatment of several GI diseases.
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http://dx.doi.org/10.1016/j.yexcr.2022.113227DOI Listing
August 2022

Research on prediction of daily admissions of respiratory diseases with comorbid diabetes in Beijing based on long short-term memory recurrent neural network.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2022 Feb;51(1):1-9

1. School of Public Health, Capital Medical University, Beijing 100069, China.

To compare the performance of generalized additive model (GAM) and long short-term memory recurrent neural network (LSTM-RNN) on the prediction of daily admissions of respiratory diseases with comorbid diabetes. Daily data on air pollutants, meteorological factors and hospital admissions for respiratory diseases from Jan 1st, 2014 to Dec 31st, 2019 in Beijing were collected. LSTM-RNN was used to predict the daily admissions of respiratory diseases with comorbid diabetes, and the results were compared with those of GAM. The evaluation indexes were calculated by five-fold cross validation. Compared with the GAM, the prediction errors of LSTM-RNN were significantly lower [root mean squared error (RMSE): 21.21±3.30 vs. 46.13±7.60, <0.01; mean absolute error (MAE): 14.64±1.99 vs. 36.08±6.20, <0.01], and the value was significantly higher (0.79±0.06 vs. 0.57±0.12, <0.01). In gender stratification, RMSE, MAE and values of LSTM-RNN were better than those of GAM in predicting female admission (all <0.05), but there were no significant difference in predicting male admission between two models (all >0.05). In seasonal stratification, RMSE and MAE of LSTM-RNN were lower than those of GAM in predicting warm season admission (all <0.05), but there was no significant difference in value (>0.05). There were no significant difference in RMSE, MAE and between the two models in predicting cold season admission (all >0.05). In the stratification of functional areas, the RMSE, MAE and values of LSTM-RNN were better than those of GAM in predicting core area admission (all <0.05). has lower prediction errors and better fitting than the GAM, which can provide scientific basis for precise allocation of medical resources in polluted weather in advance.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109758PMC
February 2022

Predicting the Risk of Microtia From Prenatal Factors: A Hospital-Based Case-Control Study.

Front Pediatr 2022 21;10:851872. Epub 2022 Apr 21.

Center for Clinical Big Data and Analytics, Second Affiliated Hospital and Department of Big Data in Health Science, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.

Background: Although a wide range of risk factors for microtia were identified, the limitation of these studies, however, is that risk factors were not estimated in comparison with one another or from different domains. Our study aimed to uncover which factors should be prioritized for the prevention and intervention of non-syndromic microtia via tranditonal and meachine-learning statistical methods.

Methods: 293 pairs of 1:1 matched non-syndromic microtia cases and controls who visited Shanghai Ninth People's Hospital were enrolled in the current study during 2017-2019. Thirty-nine risk factors across four domains were measured (i.e., parental sociodemographic characteristics, maternal pregnancy history, parental health conditions and lifestyles, and parental environmental and occupational exposures). Lasso regression model and multivariate conditional logistic regression model were performed to identify the leading predictors of microtia across the four domains. The area under the curve (AUC) was used to calculate the predictive probabilities.

Results: Eight predictors were identified by the lasso regression, including abnormal pregnancy history, genital system infection, teratogenic drugs usage, folic acid supplementation, paternal chronic conditions history, parental exposure to indoor decoration, paternal occupational exposure to noise and maternal acute respiratory infection. The additional predictors identified by the multivariate conditional logistic regression model were maternal age and maternal occupational exposure to heavy metal. Predictors selected from the conditional logistic regression and lasso regression both yielded AUCs (95% CIs) of 0.83 (0.79-0.86).

Conclusion: The findings from this study suggest some factors across multiple domains are key drivers of non-syndromic microtia regardless of the applied statistical methods. These factors could be used to generate hypotheses for further observational and clinical studies on microtia and guide the prevention and intervention strategies for microtia.
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http://dx.doi.org/10.3389/fped.2022.851872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070100PMC
April 2022

mPEG-PDLLA Micelles Potentiate Docetaxel for Intraperitoneal Chemotherapy in Ovarian Cancer Peritoneal Metastasis.

Front Pharmacol 2022 6;13:861938. Epub 2022 Apr 6.

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

Ovarian cancer is the second most common cause of gynecological cancer death in women. It is usually diagnosed late and accompanied by peritoneal metastasis. For ovarian cancer with peritoneal metastasis, intraperitoneal (IP) chemotherapy can maintain a high drug concentration in the abdominal cavity and reduce local and systemic toxicity. Recently, docetaxel (DTX) has shown broad-spectrum antitumor activity against various malignant tumors, including ovarian cancer with peritoneal metastasis. However, DTX has limited clinical applications due to its poor water solubility, predisposition to hypersensitivity, fluid retention, and varying degrees of neurotoxicity. In this study, we prepared methoxy-poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA) micelles loaded with DTX and developed an alternative, less toxic, more effective DTX formulation, without Tween 80, and evaluated its pharmacokinetics in the abdominal cavity and its efficacy in ovarian cancer with peritoneal metastasis. The mean diameter of DTX-mPEG-PDLLA was about 25 nm, and the pharmacokinetics of BALB/c mice IP showed that the plasma exposure of DTX-mPEG-PDLLA was about four times lower than that of DTX. Importantly, DTX-mPEG-PDLLA was significantly more effective than DTX and prolonged the survival period in a SKOV-3 ovarian cancer peritoneal metastasis model. Moreover, the apoptosis rate was significantly increased . Based on these findings, it is expected that DTX-mPEG-PDLLA can enhance efficacy against ovarian cancer peritoneal metastasis, while reducing toxic side effects, and has the potential to be used in the clinical treatment of peritoneal metastatic cancer.
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http://dx.doi.org/10.3389/fphar.2022.861938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019464PMC
April 2022

Trends and influencing factors of perinatal birth defects in Huai'an from 2008 to 2020.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Mar 25;50(7):1-9. Epub 2021 Mar 25.

2. School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China.

: To analyze the incidence, trends and related factors of birth defects in Huai'an from 2008 to 2020. : The surveillance data from maternal and child health system of Huai'an from 2008 to 2020 and Huai'an Statistical Yearbook were used for analysis. Taking the annual change percentage and average annual change percentage (AAPC) as the main outcome indicators, the JoinPoint regression analysis was performed to estimate the changing trend of birth defects from 2008 to 2020. Spearman correlation analysis was used to examine the association between birth defects and birth rate, marriage rate, proportion of women with advanced maternal age. : During 2008 to 2020, a total of 3414 cases of neonatal birth defects occurred in Huai'an, with an incidence of 4.6‰ (3414/736 608). The rate of perinatal birth defects in Huai'an showed an increasing trend (AAPC=8.8%, =3.2, <0.01), and the year of 2016 was a significant changing point. Among 24 types of birth defects, the incidence of congenital heart disease rose and became the most prevalent defect, while the incidence of neural tube malformations such as anencephaly, encephalocele and spina bifida was declined. The incidence of birth defect was negatively correlated with the birth rate (=-0.751, <0.01), not correlated with marriage rate (=-0.516, >0.05), and positively correlated with the proportion of women with advanced maternal age (=0.726, <0.01). : The incidence of birth defects in Huai'an shows an increasing trend from 2008 to 2020 with congenital heart disease as the most common type of birth defect, and the increase of birth defects incidence is closely related with the increase of the proportion of women with advanced maternal age.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109768PMC
March 2021

A cross-sectional analysis about bacterial vaginosis, high-risk human papillomavirus infection, and cervical intraepithelial neoplasia in Chinese women.

Sci Rep 2022 04 22;12(1):6609. Epub 2022 Apr 22.

Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.

Bacterial vaginosis (BV) is a genital infection that frequently presents in women infected with human papillomavirus (HPV), but the correlation between BV, HPV and cervical intraepithelial neoplasia (CIN) development is still elusive. We organized a cross-sectional analysis which enrolled 624 participants and obtained 423 samples of vaginal secretions from them, including 193 HPV-negative samples and 230 HR-HPV-positive samples. We used 16S rRNA sequencing to measure the vaginal microbiota diversity in women with different BV, HPV and CIN status, and then calculated risk factors for CIN by logistic regression. We found that the diversity of vaginal microbiota was significantly increased after BV, HPV and BV-infected CIN group. The Observed species and Chao1 index of H.C group showed little difference with normal group, while its Shannon index was considerable higher than normal group. L. iners enriched in HPV infection group compared with others significantly. BV (OR = 0.358; 95% CI = 0.195-0.656; P < .05) and HR-HPV infection (OR = 0.016; 95% CI = 0.004-0.072; P < .001) were risk factors for CIN. In conclusion, we consider BV as a risk factor for CIN. The enrichment of L. iners under HPV infection state may contribute to maintenance of vaginal dysbiosis, and BV infection could facilitate the disturb.
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http://dx.doi.org/10.1038/s41598-022-10532-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033840PMC
April 2022

Surgical Resection of Intraocular Tumors (Partial Transscleral Sclerouvectomy Combined With Mircoinvasive Vitrectomy and Reconstruction of the Eyeball) in Asian Patients: Twenty-Five Years Results.

Front Oncol 2022 15;12:768635. Epub 2022 Mar 15.

Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Medical Artificial Intelligence Research and Verification Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Objective: To describe the outcome of intraocular tumor resection by partial transscleral sclerouvectomy (PTSU) combined with micro-invasive vitrectomy and reconstruction of the eyeball (MVRE) in Asian patients.

Design Methods And Participants: This retrospective, interventional cohort study included 366 patients who underwent PTSU combined with MVRE for intraocular tumors both in adult and pediatric age groups. The medical records of these patients were reviewed for clinical, operative, and histopathological features.

Main Outcome Measures: Globe salvage, best corrected visual acuity (BCVA), surgical side effects, tumor control, and tumor-related metastasis and death.

Results: The mean follow-up duration was 87 months (median, 66; range, 1-303 months). Among the 366 patients, the mean age was 8.5 years (median, 7; range, 1-19 years) in the 37 pediatric patients, and was 43 years (median, 42; range, 20-51) in 329 adult patients. The tumor mainly involved the ciliary body (n=136; 37.2%) and choroid (n=86; 23.5%). The common pathologic diagnosis of the 366 patients was as follows. In the pediatric age group, histopathologic examination revealed positive tumor margins in 37 patients mainly including ciliary body medulloepithelioma (8/37), ciliary body melanocytoma (13/37) and uveal melanoma (5/37). In the adult group, the pathological diagnosis mainly included melanoma (195/329), RPE adenoma (21/329), amelanotic melanoma (13/329), ciliary body adenoma of nonpigmented epithelium (19/329), schwannoma/neurilemmoma (11/329), melanocytoma (24/329), and leiomyoma (9/329). The globe salvage rate was 81.1% in the pediatric age groups (<20 years), and 93.6% in the adult group (≥20 years), respectively. Of the 338 salvaged eyes, final BCVA was 20/20 to 20/40 in 16 (4.7%), 20/40 to 20/80 in 58 (17.2%), 20/80 to 20/200 in 160 (47.3%), and ≤ 20/200 in 104 (30.8%). Early side effects included corneal edema in 28 (7.7%) patients, hyphema in 46 (12.6%), and vitreous hemorrhage in 76 (21%) patients. Postoperative side effects included proliferative vitreoretinopathy (PVR) in 67 (18.3%), late cataract in 42 (11.5%), and glaucoma in 18 (5%) patients. Local tumor recurrence was detected in 20 patients (5.5%) at a mean interval of 23.6 months, including melanoma (n=19) and medulloepithelioma (n=1). Enucleation was necessary in 28 (7.7%) cases owing to recurrence in 15 (53.6%), eye prophylaxis with high-grade malignancy in 5 (17.8%), and blind painful eye in 8 (28.6%) cases. Kaplan-Meier estimated for 5, 10-year metastasis rate and metastasis-related death rate (95%CI) in 213 UM patients were 3.2% (1.4%-7.0%), 6.9% (3.8%-12.3%); and 3.5% (1.6%-7.6%), 7.6% (4.2%-13.5%), respectively.

Conclusions: As a surgically challenging procedure, PTSU combined with MVRE offers several theoretical advantages over enucleation and radiotherapy. It can achieve control of most intraocular tumors, preserve useful vision, and maintain a cosmetically normal eye.
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http://dx.doi.org/10.3389/fonc.2022.768635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965069PMC
March 2022

Correction to: Effect of EMD on the orthodontically induced root resorption repair process in rats.

J Orofac Orthop 2022 May;83(3):221

Department of Orthodontics, College of Stomatology, Chongqing Medical University, Chongqing, China.

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http://dx.doi.org/10.1007/s00056-022-00390-xDOI Listing
May 2022

Role of cytokine storm in coronavirus infections: culprit or accomplice?

Front Biosci (Landmark Ed) 2022 03;27(3):102

Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China.

At present, there are seven known types of human coronaviruses (HCoVs), which can be further divided into two categories: low pathogenic and highly pathogenic. The low pathogenic HCoVs infect the upper respiratory tract, mainly causing mild, cold-like respiratory diseases. By contrast, highly pathogenic HCoVs mainly infect the lower respiratory tract and cause fatal types of pneumonia, which include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as the recent outbreak of coronavirus disease 2019 (COVID-19). Highly pathogenic HCoV infection has a high morbidity and mortality, which is usually related to the strong immune response induced by highly proinflammatory cytokines, which is also known as "cytokine storm". Therefore, it is particularly important to explore the role of cytokine storm in the process of highly pathogenic HCoV infection. We review the epidemiological and clinical manifestations of highly pathogenic HCoV infection, and reveal the pathology of cytokine storm and its role in the process of highly pathogenic HCoV infection.
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http://dx.doi.org/10.31083/j.fbl2703102DOI Listing
March 2022

Can Digital Transformation Promote the Rapid Recovery of Cities from the COVID-19 Epidemic? An Empirical Analysis from Chinese Cities.

Int J Environ Res Public Health 2022 03 17;19(6). Epub 2022 Mar 17.

Non-Traditional Security Institute, Huazhong University of Science and Technology, Wuhan 430074, China.

Background: Digital transformation has become a key intervention strategy for the global response to the COVID-19 epidemic, and digital technology is helping cities recover from the COVID-19 epidemic. However, the effects of urban digital transformation on the recovery from the COVID-19 epidemic still lack mechanism analyses and empirical testing. This study aimed to explain the theoretical mechanism of urban digital transformation on the recovery from the COVID-19 epidemic and to test its effectiveness using an empirical analysis.

Methods: This study, using a theoretical and literature-based analysis, summarizes the impact mechanisms of urban digital transformation on the recovery of cities from the COVID-19 epidemic. A total of 83 large- and medium-sized cities from China are included in the empirical research sample, covering most major cities in China. The ordinary least squares (OLS) method is adopted to estimate the effect of China's urban digitalization level on population attraction in the second quarter of 2020.

Results: The theoretical analysis found that urban digital transformation improves the ability of cities to recover from the COVID-19 epidemic by promoting social communication, collaborative governance, and resilience. The main findings of the empirical analysis show that the digital level of a city has a significant positive effect on urban population attraction ( < 0.001).

Conclusions: A positive relationship was found between urban digital transformation and the rapid recovery of cities from the COVID-19 epidemic. Digital inventions for social communication, collaborative governance, and urban resilience are an effective way of fighting the COVID-19 emergency.
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http://dx.doi.org/10.3390/ijerph19063567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949457PMC
March 2022

Effect of Wuzhi capsules on cyclosporine A concentration in children with aplastic anemia immunotherapy: a single-center observational study.

Expert Rev Clin Pharmacol 2022 Mar 4;15(3):365-369. Epub 2022 Mar 4.

Department of Hematology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Objective: This research aimed to assess the effect of Wuzhi capsules (WZC) on the blood concentration of cyclosporine A (CsA) in renal aplastic anemia recipients.

Methods: This observational study was carried out at the Hematology Oncology Center, Beijing Children's Hospital between November 2019 and February 2020. A total of 102 Chinese AA recipients receiving CsA (6 mg/kg/d) with or without WZC were included in this study. Baseline data, such as age, therapeutic drug monitoring data, and follow-up information were collected. The promotion concentration of CsA was calculated, and the pharmaceutical economics evaluation with combination of two drugs was also carried out.

Results: Dose- and body weight-adjusted trough concentrations (C/D/W) of CsA in the WZC group were found to be significantly higher than that in the non-WZC group (). The average C of CsA increased by (63.27 ± 45.81) ng/mL. The incidence of adverse events was also not statistically significant between the two groups ( > 0.05).

Conclusion: WZC can increase CsA concentration without increasing adverse drug reactions. Efficient and convenient immunosuppressive effects on AA recipients can be achieved via immunosuppressant therapy in combination with WZC.
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http://dx.doi.org/10.1080/17512433.2022.2045193DOI Listing
March 2022

Gut microbiota and its role in stress-induced hyperalgesia: Gender-specific responses linked to different changes in serum metabolites.

Pharmacol Res 2022 03 10;177:106129. Epub 2022 Feb 10.

Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Long-term stress causes hyperalgesia; and there are gender differences in the mechanism of pain in male and female individuals. The role of gut microbiota in pain has also been verified. However, whether gut microbiota plays a role in hyperalgesia caused by chronic restraint stress (CRS) with gender differences has not been explored. This study investigated the role of gut microbiota in CRS-induced hyperalgesia gender-specifically through 16 S ribosomal RNA (16 S rRNA) gene sequencing and untargeted metabolomic analysis using liquid chromatography-mass spectrometry (LC-MS). The study found that both male and female mice experienced hyperalgesia after CRS and antibiotic treatment. 16 S rRNA gene sequencing reveals gender differences in the fecal microbiota induced by CRS. The pain threshold decreased after transplanting the fecal microbiota from the male and female CRS group to the corresponding pseudo-germ-free mice. In addition, this study detected gender differences in the host gut microbiota and serum metabolism induced by fecal microbiota transplantation (FMT). Specifically, the different serum metabolites between the pseudo-germ-free mice receiving FMT from the CRS group and those from the control group were mainly involved in bile secretion and steroid hormone biosynthesis for male mice, and in taurine and hypotaurine metabolism and tryptophan metabolism for female mice. In summary, the gut microbiota participates in stress-induced hyperalgesia (SIH) with gender differences by influencing the host's gut microbiota composition and serum metabolism. Therefore, our findings provided insights into developing novel gut microbiota-associated drugs for the management of gender-specific SIH.
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http://dx.doi.org/10.1016/j.phrs.2022.106129DOI Listing
March 2022

Association of plasma uric acid levels with cognitive function among non-hyperuricemia adults: A prospective study.

Clin Nutr 2022 03 1;41(3):645-652. Epub 2022 Jan 1.

School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address:

Background & Aims: The neuroprotective roles of uric acid are still controversial. One possible explanation is that previous studies included participants with hyperuricemia, which might interfere with clarifying the association. Therefore, this study aimed to investigate the prospective association between plasma uric acid levels and cognitive function among non-hyperuricemia adults.

Methods: A total of 7828 participants from the China Health and Retirement Longitudinal Study (CHARLS) who were free from hyperuricemia, brain damage, mental retardation, or memory-related diseases at baseline were included. According to the baseline plasma uric acid levels, participants were classified into low (<3.5 mg/dL for men and <2.5 mg/dL for women), low-normal (3.5-4.9 mg/dL for men and 2.5-3.9 mg/dL for women), and high-normal groups (4.9-7.0 mg/dL for men and 3.9-6.0 mg/dL for women). Cognitive function tests covered the domains of executive function (time orientation, numerical ability, and drawing) and episodic memory (immediate and delayed word recall). We used generalized estimating equation models to evaluate the average difference in cognitive function within 4-years' follow-up across different uric acid groups.

Results: Compared with the high-normal group, participants with lower uric acid levels were associated with poorer cognitive performance during 4-years' follow-up. The corresponding level of difference was -0.24 (95% CI: -0.47, -0.01) for low group, and -0.13 (95% CI: -0.26, -0.01) for low-normal group. The associations were significant and similar for the specific domain of executive function (P < 0.001). In addition, a stronger association was observed among participants with baseline age ≥60 years (P < 0.05 for interaction).

Conclusions: Our study supports a potential detrimental role of low levels of plasma uric acid on cognitive function among Chinese adults without hyperuricemia. More research is warranted to confirm this finding and identify the optimal plasma uric acid level for cognitive benefits.
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http://dx.doi.org/10.1016/j.clnu.2021.12.039DOI Listing
March 2022

ICAM-1 Targeted Drug Combination Nanoparticles Enhanced Gemcitabine-Paclitaxel Exposure and Breast Cancer Suppression in Mouse Models.

Pharmaceutics 2021 Dec 31;14(1). Epub 2021 Dec 31.

Department of Pharmaceutics, University of Washington, Seattle, WA 98195, USA.

Despite the availability of molecularly targeted treatments such as antibodies and small molecules for human epidermal growth factor receptor 2 (HER2), hormone receptor (HR), and programmed death-ligand 1 (PD-L1), limited treatment options are available for advanced metastatic breast cancer (MBC), which constitutes ~90% mortality. Many of these monotherapies often lead to drug resistance. Novel MBC-targeted drug-combination therapeutic approaches that may reduce resistance are urgently needed. We investigated intercellular adhesion molecule-1 (ICAM-1), which is abundant in MBC, as a potential target to co-localize two current drug combinations, gemcitabine (G) and paclitaxel (T), assembled in a novel drug-combination nanoparticle (GT DcNP) form. With an ICAM-1-binding peptide (referred to as LFA1-P) coated on GT DcNPs, we evaluated the role of the LFA1-P density in breast cancer cell localization in vitro and in vivo. We found that 1-2% LFA1-P peptide incorporated on GT DcNPs provided optimal cancer cell binding in vitro with ~4× enhancement compared to non-peptide GT DcNPs. The in vivo probing of GT DcNPs labeled with a near-infrared marker, indocyanine green, in mice by bio-imaging and G and T analyses indicated LFA1-P enhanced drug and GT DcNP localization in breast cancer cells. The target/healthy tissue (lung/gastrointestinal (GI)) ratio of particles increased by ~60× compared to the non-ligand control. Collectively, these data indicated that LFA1 on GT DcNPs may provide ICAM-1-targeted G and T drug combination delivery to advancing MBC cells found in lung tissues. As ICAM-1 is generally expressed even in breast cancers that are triple-negative phenotypes, which are unresponsive to inhibitors of nuclear receptors or HER2/estrogen receptor (ER) agents, ICAM-1-targeted LFA1-P-coated GT DcNPs should be considered for clinical development to improve therapeutic outcomes of MBCs.
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http://dx.doi.org/10.3390/pharmaceutics14010089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779833PMC
December 2021

Sulforaphane improves cognitive dysfunction after surgery and anesthesia in mice: The role of Keap1-Nrf2 signaling.

Brain Res Bull 2022 04 15;181:1-11. Epub 2022 Jan 15.

Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address:

Anesthesia and surgery are likely causing cognitive dysfunction in patients, especially the elderly. However, the underlying pathogenic mechanisms largely remain unclear. Accumulating evidence suggest that signaling between Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) plays an important role in the pathogenesis and treatment of brain dysfunction, while sulforaphane (SFN), a natural compound acting as an Nrf2 agonist, can improve brain function. In the present study, we used 9-month-old mice to perform tibial fracture surgery under isoflurane general anesthesia. Hierarchical cluster analysis of Morris water maze test (MWMT) analysis was performed to classify mice into post-operative cognitive dysfunction (POCD) versus non-POCD phenotypes. Expression levels of Keap1 and Nrf2 were significantly decreased in the medial prefrontal cortex (mPFC), hippocampus and liver, but not in the nucleus accumbens, muscle and gut of POCD mice compared to control and non-POCD mice. Interestingly, both pretreatment and posttreatment with SFN significantly improved the abnormal behaviors of mice in the MWMT, in parallel with the up-regulated levels of Keap1-Nrf2 signaling in the mPFC, hippocampus and liver. In conclusion, these results suggest that decreased Keap1-Nrf2 signaling in the mPFC, hippocampus and liver may contribute to the onset of POCD, and that SFN exerts facilitating effects on POCD symptoms by increasing Keap1-Nrf2 signaling.
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http://dx.doi.org/10.1016/j.brainresbull.2022.01.005DOI Listing
April 2022

Targeting PI3Kγ/AKT Pathway Remodels LC3-Associated Phagocytosis Induced Immunosuppression After Radiofrequency Ablation.

Adv Sci (Weinh) 2022 03 17;9(7):e2102182. Epub 2022 Jan 17.

Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.

Residual tumors after insufficient radiofrequency ablation (IRFA) shows accelerated progression and anti-PD-1 resistance. It is also reported that macrophages infiltrating into residual tumors leads to anti-PD-1 resistance. Elements of autophagy have been detected to conjugate LC3 to be increasingly expressed in residual tumors. The underlying mechanisms between LC3 and macrophages are aimed to be investigated, and explore further ways to enhance immunotherapy in treating residual tumors. In mice models and patients, macrophages demonstrate increased infiltration into residual tumors, especially surrounding the ablated zone. Single-cell transcriptome demonstrates enhancement of immunosuppression function in macrophages after IRFA. It is shown that macrophages engulf heat-treated cells through LC3-associated phagocytosis (LAP), enhance IL-4 mediated macrophage programming through the PI3Kγ/AKT pathway, and suppress T cell proliferation. Blockade of the PI3Kγ/AKT pathway enhances the antitumor activity of PD-1 blockades, inhibits malignant growth, and enhances survival in post-IRFA models. In conclusion, in mice models and patients, macrophages demonstrate increased infiltration around ablated zones in residual tumors. Blockade of the PI3Kγ/AKT pathway suppresses the growth of residual tumors in subcutaneous and orthotopic models. The results illustrate the translational potential of PI3Kγ inhibitors to enhance anti-PD-1 therapy for the treatment of residual tumors after IRFA.
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http://dx.doi.org/10.1002/advs.202102182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8895133PMC
March 2022

The impact of invisible-spreaders on COVID-19 transmission and work resumption.

PLoS One 2022 12;17(1):e0252994. Epub 2022 Jan 12.

College of Media and International Culture, Zhejiang University, Hangzhou, China.

The global impact of coronavirus disease 2019 (COVID-19) is unprecedented, and many control and prevention measures have been implemented to test for and trace COVID-19. However, invisible-spreaders, who are associated with nucleic acid detection and asymptomatic infections, have received insufficient attention in the current COVID-19 control efforts. In this paper, we analyze the time series infection data for Italy, Germany, Brazil, India and Sweden since the first wave outbreak to address the following issues through a series of experiments. We conclude that: 1) As of June 1, 2020, the proportion of invisible-spreaders is close to 0.4% in Sweden, 0.8% in early Italy and Germany, and 0.4% in the middle and late stages. However, in Brazil and India, the proportion still shows a gradual upward trend; 2) During the spread of this pandemic, even a slight increase in the proportion of invisible-spreaders could have large implications for the health of the community; and 3) On resuming work, the pandemic intervention measures will be relaxed, and invisible-spreaders will cause a new round of outbreaks.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252994PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754335PMC
January 2022
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