Publications by authors named "Zhigang Zhang"

693 Publications

Reciprocal regulation of LOXL2 and HIF1α drives the Warburg effect to support pancreatic cancer aggressiveness.

Cell Death Dis 2021 Nov 26;12(12):1106. Epub 2021 Nov 26.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.

Hypoxic microenvironment is common in solid tumors, particularly in pancreatic ductal adenocarcinoma (PDAC). The Warburg effect is known to facilitate cancer aggressiveness and has long been linked to hypoxia, yet the underlying mechanism remains largely unknown. In this study, we identify that lysyl oxidase-like 2 (LOXL2) is a hypoxia-responsive gene and is essential for the Warburg effect in PDAC. LOXL2 stabilizes hypoxia-inducible factor 1α (HIF1α) from prolyl hydroxylase (PHD)-dependent hydroxylation via hydrogen peroxide generation, thereby facilitating the transcription of multiple glycolytic genes. Therefore, a positive feedback loop exists between LOXL2 and HIF1α that facilitates glycolytic metabolism under hypoxia. Moreover, LOXL2 couples the Warburg effect to tumor growth and metastasis in PDAC. Hijacking glycolysis largely compromises LOXL2-induced oncogenic activities. Collectively, our results identify a hitherto unknown hypoxia-LOXL2-HIF1α axis in regulating the Warburg effect and provide an intriguing drug target for PDAC therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-04391-3DOI Listing
November 2021

Femtosecond all-polarization-maintaining Nd fiber laser at 920 nm mode locked by a biased NALM.

Opt Express 2021 Nov;29(23):38199-38205

We demonstrate a femtosecond all-polarization-maintaining Nd fiber laser working at 920 nm mode locked by a biased non-linear loop mirror. The broadest spectral width of the pulse is 25.2 nm and the output power is 8 mW with 320 mW pump power. The measured pulse width is 109 fs with extra-cavity compression. The laser configuration of all-polarization-maintaining fiber can directly enhance the environmental stability of generated pulses. The seed pulses of the oscillator were amplified over 400 mW, which served as the light source for a two-photon microscope. To the best of our knowledge, this is the first demonstration of a 920 nm femtosecond Nd polarization-maintaining fiber laser based on a non-linear loop mirror.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.434767DOI Listing
November 2021

Plants and Microbes Mediate the Shift in Ecosystem Multifunctionality From Low to High Patterns Across Alpine Grasslands on the Tibetan Plateau.

Front Plant Sci 2021 15;12:760599. Epub 2021 Oct 15.

State Key Laboratory of Tibetan Plateau Earth System, Resources and Environment (TPESRE), Institute of Tibetan Plateau Research, Chinese Academy of Sciences, Beijing, China.

Both plant communities and soil microbes have been reported to be correlated with ecosystem multifunctionality (EMF) in terrestrial ecosystems. However, the process and mechanism of aboveground and belowground communities on different EMF patterns are not clear. In order to explore different response patterns and mechanisms of EMF, we divided EMF into low (<0) and high patterns (>0). We found that there were contrasting patterns of low and high EMF in the alpine grassland ecosystem on the Tibetan Plateau. Specifically, compared with low EMF, environmental factors showed higher sensitivity to high EMF. Soil properties are critical factors that mediate the impact of community functions on low EMF based on the change of partial correlation coefficients from 0 to 0.24. In addition, plant community functions and microbial biomass may mediate the shift of EMF from low to high patterns through the driving role of climate across the alpine grassland ecosystem. Our findings will be vital to clarify the mechanism for the stability properties of grassland communities and ecosystems under ongoing and future climate change.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2021.760599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554250PMC
October 2021

"γδT Cell-IL17A-Neutrophil" Axis Drives Immunosuppression and Confers Breast Cancer Resistance to High-Dose Anti-VEGFR2 Therapy.

Front Immunol 2021 15;12:699478. Epub 2021 Oct 15.

Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Angiogenesis is an essential physiological process and hallmark of cancer. Currently, antiangiogenic therapy, mostly targeting the vascular endothelial growth factor (VEGF)/VEGFR2 signaling axis, is commonly used in the clinic for solid tumors. However, antiangiogenic therapies for breast cancer patients have produced limited survival benefits since cancer cells rapidly resistant to anti-VEGFR2 therapy. We applied the low-dose and high-dose VEGFR2 mAb or VEGFR2-tyrosine kinase inhibitor (TKI) agents in multiple breast cancer mouse models and found that low-dose VEGFR2 mAb or VEGFR2-TKI achieved good effects in controlling cancer progression, while high-dose treatment was not effective. To further investigate the mechanism involved in regulating the drug resistance, we found that high-dose anti-VEGFR2 treatment elicited IL17A expression in γδ T cells VEGFR1-PI3K-AKT pathway activation and then promoted N2-like neutrophil polarization, thus inducing CD8 T cell exhaustion to shape an immunosuppressive microenvironment. Combining anti-VEGFR2 therapy with immunotherapy such as IL17A, PD-1 or Ly-6G mAb therapy, which targeting the immunomodulatory axis of "γδT17 cells-N2 neutrophils" , showed promising therapeutic effects in breast cancer treatment. This study illustrates the potential mechanism of antiangiogenic therapy resistance in breast cancer and provides synergy treatment for cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.699478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554133PMC
October 2021

Aged neutrophils form mitochondria-dependent vital NETs to promote breast cancer lung metastasis.

J Immunother Cancer 2021 10;9(10)

Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China

Background: Neutrophils-linked premetastatic niche plays a key role in tumor metastasis, but not much is known about the heterogeneity and diverse role of neutrophils in niche formation. Our study focuses on the existence and biological function of a rarely delved subset of neutrophils, named as tumor-associated aged neutrophils (Naged, CXCR4CD62L), involved in premetastatic niche formation during breast cancer metastasis.

Methods: We explored the distributions of Naged in 206 patients and mice models (4T1 and MMTV-PyMT) by flow cytometry. The ability of Naged to form neutrophil extracellular traps (NETs) and promote tumor metastasis in patients and mice was determined by polychromatic immunohistochemistry, scanning electron microscopy and real-time video detection. Furthermore, the differences among tumor-associated Naged, Non-Naged and inflammation-associated aged neutrophils were compared by transcriptome, the biological characteristics of Naged were comprehensively analyzed from the perspectives of morphology, the metabolic capacity and mitochondrial function were investigated by Seahorse, co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP) and transmission electron microscopy (TEM). Finally, 120 patients' sample were applied to confirm the acceleration of Naged formation through secreted NAMPT, and the importance of blocking this pathway in mice was evaluated.

Results: We find that Naged accumulate in the lung premetastatic niche at early stage of breast tumorigenesis in multiple mice models and also exist in peripheral blood and metastatic lung of patients with breast cancer. Naged exhibit distinct cell marker and morphological feature of oversegmented nuclei. Further transcriptome reveals that Naged are completely different from those of Non-Aged or inflammation-associated aged neutrophils and illustrates that the key transcription factor SIRT1 in Naged is the core to maintain their lifespan via mitophagy for their function. The responsible mechanism is that SIRT1 can induce the opening of mitochondrial permeability transition pore channels to release mitochondrial DNA and lead to the mitochondria-dependent vital NETs formation, rather than traditional Cit-Histone H3 dependent fatal-NETs. Further mechanically investigation found tumor derived NAMPT could induce Naged formation. Additionally, therapeutic interventions of Naged and its formation-linked pathways could effectively decrease breast cancer lung metastasis.

Conclusions: Naged exerts a vital role in breast cancer lung metastasis, and strategies targeting SIRT1-Naged-NETs axis show promise for translational application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2021-002875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559246PMC
October 2021

Global Diversification and Distribution of Coronaviruses With Furin Cleavage Sites.

Front Microbiol 2021 7;12:649314. Epub 2021 Oct 7.

State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, China.

Knowledge about coronaviruses (CoVs) with furin cleavage sites is extremely limited, although these sites mediate the hydrolysis of glycoproteins in plasma membranes required for MERS-CoV or SARS-CoV-2 to enter cells and infect humans. Thus, we have examined the global epidemiology and evolutionary history of SARS-CoV-2 and 248 other CoVs with 86 diversified furin cleavage sites that have been detected in 24 animal hosts in 28 countries since 1954. Besides MERS-CoV and SARS-CoV-2, two of five other CoVs known to infect humans (HCoV-OC43 and HCoV-HKU1) also have furin cleavage sites. In addition, human enteric coronavirus (HECV-4408) has a furin cleavage site and has been detected in humans (first in Germany in 1988), probably spillover events from bovine sources. In conclusion, the presence of furin cleavage sites might explain the polytropic nature of SARS-CoV-2- and SARS-CoV-2-like CoVs, which would be helpful for ending the COVID-19 pandemic and preventing outbreaks of novel CoVs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.649314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529245PMC
October 2021

Reinforcement learning based robust control algorithms for coherent pulse stacking.

Opt Express 2021 Aug;29(16):26068-26081

For the fast and robust control of the delay lines for coherent pulse stacking, we combined the stochastic parallel gradient descent with momentum (SPGDM) and the soft actor-critic (SAC) into a powerful algorithm, SAC-SPGDM. The simulation shows that the algorithm can find the optimal delay-line positions to ensure the 128 pulses are coherently stacked for 7-stage pulses stacking within 25 steps.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.426906DOI Listing
August 2021

New insights into Li distribution in the superionic argyrodite LiPSCl.

Chem Commun (Camb) 2021 Oct 14;57(82):10787-10790. Epub 2021 Oct 14.

Department of NanoEngineering, University of California San Diego, La Jolla, CA 92093, USA.

By using temperature-dependent neutron powder diffraction combined with maximum entropy method analysis, a previously unreported Li lattice site was discovered in the argyrodite LiPSCl solid-state electrolyte. This new finding enables a more complete description of the Li diffusion model in argyrodites, providing structural guidance for designing novel high-conductivity solid-state electrolytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cc03083cDOI Listing
October 2021

Should Postoperative Radiation for Long Bone Metastases Cover Part or All of the Orthopedic Hardware? Results of a Large Retrospective Analysis.

Adv Radiat Oncol 2021 Nov-Dec;6(6):100756. Epub 2021 Jul 28.

Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.

Purpose: For patients with long bone metastases who undergo orthopedic stabilization surgery followed by radiotherapy (RT), it is unclear what extent of hardware coverage by the radiation field is needed for optimal tumor control.

Methods And Materials: Long bone metastases treated with surgical intervention followed by radiation between August 2011 to May 2019 from a single institution were reviewed. Local recurrence, defined as any in-bone recurrence, was identified by chart review. Accompanying demographic and treatment characteristics were recorded. Statistical analysis to evaluate factors associated with tumor recurrence included univariate analysis, multivariate analysis, and propensity score matching.

Results: Among 138 patients with 145 long bone metastases undergoing postoperative RT with a median follow-up of 29.5 months, 36 bone metastases experienced a local recurrence. Most patients (92%) were treated with conventional RT and the median delivered dose was 30 Gy (interquarile range, 20-30 Gy). On univariate analysis, whole hardware RT field coverage and higher dose (biologically effective dose 10 ≥39 Gy) were associated with reduced local recurrence (0.44 hazard ratio [HR]; 95% confidence interval [CI], 0.22%-0.86%;  = .017; 0.5 HR; 95% CI, 0.26%-0.96%;  = .038, respectively). Covariates of time from surgery to RT start, histology of primary tumor (categorized as resistant vs sensitive), intramedullary hardware placement, reaming procedure, and margin status did not reach statistical significance. To adjust for confounding effects, we also conducted a propensity score matched analysis which confirmed that whole hardware coverage was statistically associated with a decreased risk of recurrence on the matched dataset (0.24 HR; 95% CI, 0.07%-0.84%;  = .026).

Conclusions: In this analysis of mostly patients undergoing conventional radiation, coverage of the whole hardware was associated with reduced local recurrence for patients with long bone metastases, consistent with prior reports. Investigation of approaches to further reduce local recurrence, such as preoperative stereotactic radiation, may be warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.adro.2021.100756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450200PMC
July 2021

Effect of inorganic mercury exposure on reproductive system of male mice: Immunosuppression and fibrosis in testis.

Environ Toxicol 2021 Sep 27. Epub 2021 Sep 27.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Mercury as a toxic heavy metal will accumulate in the body and induce various diseases through the food chain. However, it is unknown that the detailed mechanism of reproductive disorder induced by inorganic mercury in male mice to date. This study investigated the toxicological effect of mercuric chloride (HgCl ) exposure on reproductive system in male mice. Male Kunming mice received normal saline daily or HgCl (3 mg/kg bodyweight) by intraperitoneal injection for a week. The reproductive function was evaluated, and the HgCl exposure induced the decline of sperm quality, pregnancy rate, mean litter size, and survival rate. Notably, we firstly found the HgCl -induced immunosuppression and fibrosis in mice testis according to the results of RNA sequencing. Collectively, these findings demonstrate that HgCl exposure disrupts the reproductive system and induces testicular immunosuppression and fibrosis via inhibition of the CD74 signaling pathway in male mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/tox.23378DOI Listing
September 2021

Prevalence of Suboptimal Health Status and Its Influencing Factors among Chinese Software Programmers.

Iran J Public Health 2021 Jul;50(7):1361-1371

Department of Toxicology, School of Public Health, Shaanxi University of Chinese Medicine, Shaanxi, China.

Background: There is a lack of specific study of the suboptimal health status (SHS) in software programmers. The aims of the present study were to investigate the prevalence of SHS and analyze the influencing factors among Chinese software programmers.

Methods: A cross-sectional survey using a programmer SHS scale was conducted to evaluate the prevalence of SHS, as well chi-square test and multi-factor logistic regression were applied to analyze the relationship between suboptimal health and personal basic information, living and work habits in software programmers.

Results: The prevalence of SHS was 18.67% in software programmers. Single factor analysis found that there were differences in suboptimal health prevalence among different work cities ( = 0.031), hours of sleep per day ( = 0.046), overtime days per month ( = 0.010) and exercise frequency per week ( = 0.015). The factors for suboptimal health such as hours of sleep per day (OR = 0.307, 95% CI = 0.096∼0.984) and exercise frequency per week (OR = 0.190, 95% CI = 0.054∼0.671) significantly affected subjects of SHS via multi-factor logistic regression analysis, indicating that adequate sleep and exercise decreased the chance of SHS up to 30.70% and 19.00%, respectively.

Conclusion: Suboptimal health had become a serious public health challenge in Chinese software programmers. Whilst, the health status of the programmers could be effectively elevated by improving lifestyles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18502/ijph.v50i7.6625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426766PMC
July 2021

Autophagy in Alzheimer's disease pathogenesis: Therapeutic potential and future perspectives.

Ageing Res Rev 2021 Dec 20;72:101464. Epub 2021 Sep 20.

The Brain Cognition and Brain Disease Institute (BCBDI), CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, China. Electronic address:

Alzheimer's disease (AD) is a complex neurodegenerative disease in the elderly and the most common cause of human dementia. AD is characterized by accumulation of abnormal protein aggregates including amyloid plaques (composed of beta-amyloid (Aβ) peptides) and neurofibrillary tangles (formed by hyper-phosphorylated tau protein). Synaptic plasticity, neuroinflammation, calcium signaling etc. also show dysfunction in AD patients. Autophagy is an evolutionarily conserved lysosome-dependent cellular event in eukaryotes. It is closely linked to modulation of protein metabolism, through which damaged organelles and mis-folded proteins are degraded and then recycled to maintain protein homeostasis. Accumulating evidence has shown that impaired autophagy also contributes to AD pathogenesis. In the present review, we highlight the role of autophagy, including bulk and selective autophagy, in regulating metabolic circuits in AD pathogenesis. We also discuss the potential and future perspectives of autophagy-inducing strategies in AD therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arr.2021.101464DOI Listing
December 2021

Ablative radiation therapy for hepatocellular carcinoma is associated with reduced treatment- and tumor-related liver failure and improved survival.

J Gastrointest Oncol 2021 Aug;12(4):1743-1752

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: More than 70% of patients with hepatocellular carcinoma (HCC) are not candidates for curative therapy or recur after curative-intent therapy. There is growing evidence on the use of ablative radiation therapy (RT) for liver tumors. We aimed to analyze outcomes of HCC patients treated with conventional versus ablative RT.

Methods: We retrospectively analyzed medical records of HCC patients treated with liver RT from 2001 to 2019. We defined ablative RT as biologically effective dose (BED) ≥80 Gy. RECIST 1.1 was used to define early responses at 3-6 months after RT, and local control (LC) at last follow-up (FU). Data was analyzed using Fisher exact test, Kaplan-Meier, cumulative incidence rates, Cox proportional hazards model and Fine-Gray competing risks.

Results: Forty-five patients were identified, of whom 14 (31.1%) received ablative RT using a stereotactic technique. With median FU of survivors of 10.1 months, 1-year cumulative incidence of LC was 91.7% for ablative and 75.2% for BED <80 Gy. At early FU, patients treated with ablative RT had better responses compared to BED <80 Gy, with 7% progressing versus 19%, and 21.4% with complete response versus none (P=0.038). On univariate analysis (UVA), Child-Pugh (CP) score [hazard ratio (HR): 3 for CP-B, HR: 16 for CP-C] and BED (HR: 7.69 for BED <80 Gy) correlated with deterioration of liver function, leading to liver failure. Most liver failure cases were due to disease progression. No RT-related liver failure occurred in the ablative RT group. On UVA, only BED ≥80 Gy was associated with improved overall survival (OS) (HR: 0.4; P=0.044). Median OS (mOS) and 1-year OS were 7 months and 35% respectively for BED <80 Gy compared to 28 months and 66% for BED ≥80 Gy. No grade 3+ bowel toxicity was reported in either group.

Conclusions: Greater than 90% LC was achieved after stereotactic ablative RT, which was associated with minimized tumor- and treatment-related liver failure and improved survival for highly selected inoperable HCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jgo-21-116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421883PMC
August 2021

Excellent response to very-low-dose radiation (4 Gy) for indolent B-cell lymphomas: is 4 Gy suitable for curable patients?

Blood Adv 2021 10;5(20):4185-4197

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.

Radiotherapy plays an important role in managing highly radiosensitive, indolent non-Hodgkin lymphomas, such as follicular lymphoma and marginal zone lymphoma. Although the standard of care for localized indolent non-Hodgkin lymphomas remains 24 Gy, de-escalation to very-low-dose radiotherapy (VLDRT) of 4 Gy further reduces toxicities and duration of treatment. Use of VLDRT outside palliative indications remains controversial; however, we hypothesize that it may be sufficient for most lesions. We present the largest single-institution VLDRT experience of adult patients with follicular lymphoma or marginal zone lymphoma treated between 2005 and 2018 (299 lesions; 250 patients) using modern principles including positron emission tomography staging and involved site radiotherapy. Outcomes include best clinical or radiographic response between 1.5 and 6 months after VLDRT and cumulative incidence of local progression (LP) with death as the only competing risk. After VLDRT, the overall response rate was 90% for all treated sites, with 68% achieving complete response (CR). With a median follow-up of 2.4 years, the 2-year cumulative incidence of LP was 25% for the entire cohort and 9% after first-line treatment with VLDRT for potentially curable, localized disease. Lesion size >6 cm was associated with lower odds of attaining a CR and greater risk of LP. There was no suggestion of inferior outcomes for potentially curable lesions. Given the clinical versatility of VLDRT, we propose to implement a novel, incremental, adaptive involved site radiotherapy strategy in which patients will be treated initially with VLDRT, reserving full-dose treatment for those who are unable to attain a CR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2021004939DOI Listing
October 2021

Investigation of the pectin grafting with gallic acid and propyl gallate and their antioxidant activities, antibacterial activities and fresh keeping performance.

Int J Biol Macromol 2021 Nov 4;190:343-350. Epub 2021 Sep 4.

Key Laboratory of Characteristics Garden Plants Resource in Fujian and Taiwan, School of Biological Science and Biotechnology, Minnan Normal University, Zhangzhou 363000, PR China. Electronic address:

In this paper, a method for the enzymatic modification of pectin, in which gallic acid (GA) and propyl gallate (PG) were grafted onto pectin molecules in an aqueous/organic two-phase system catalyzed by lipase, was proposed. The potential reaction mechanism was explored through UV-Vis, FTIR and H NMR spectroscopic methods and density functional theory. Results suggested that the lipase played a dual role during the modification by catalyzing the hydrolysis of methyl ester bonds of pectin in the aqueous phase and the esterification between the 4-OH of GA and PG and the -COOH of pectin in the organic phase. Moreover, the effects of GA and PG on the antioxidant and the antibacterial activities of pectin were evaluated, and results showed that the antioxidant and the antibacterial activities of modified pectin were better than those of native pectin. The effect of modified pectin on the quality of fresh bass (Lateolabrax maculatus) was further studied. Results suggested that, compared to control group, the total viable count, histamine level, malondialdehyde content and acid value of bass fillets treated with modified pectin were significantly reduced, whereas the sensory score was significantly increased.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.08.219DOI Listing
November 2021

Comparative study of gut microbiota from captive and confiscated-rescued wild pangolins.

J Genet Genomics 2021 09 5;48(9):825-835. Epub 2021 Aug 5.

State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China. Electronic address:

Pangolins are among the most critically endangered animals due to widespread poaching and worldwide trafficking. Captive breeding is considered to be one way to protect them and increase the sizes of their populations. However, comparative studies of captive and wild pangolins in the context of gut microbiota are rare. Here, the gut microbiome of captive and confiscated-rescued wild pangolins is compared, and the effects of different periods of captivity and captivity with and without antibiotic treatment are considered. We show that different diets and periods of captivity, as well as the application of antibiotic therapy, can alter gut community composition and abundance in pangolins. Compared to wild pangolins, captive pangolins have an increased capacity for chitin and cellulose/hemicellulose degradation, fatty acid metabolism, and short-chain fatty acid synthesis, but a reduced ability to metabolize exogenous substances. In addition to increasing the ability of the gut microbiota to metabolize nutrients in captivity, captive breeding imposes some risks for survival by resulting in a greater abundance of antibiotic resistance genes and virulence factors in captive pangolins than in wild pangolins. Our study is important for the development of guidelines for pangolin conservation, including health assessment, disease prevention, and rehabilitation of wild pangolin populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgg.2021.07.009DOI Listing
September 2021

Luteolin alleviates inorganic mercury-induced kidney injury via activation of the AMPK/mTOR autophagy pathway.

J Inorg Biochem 2021 Nov 19;224:111583. Epub 2021 Aug 19.

College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin 150030, China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 600 Changjiang Road, Harbin 150030, China. Electronic address:

Inorganic mercury is a ubiquitous toxic pollutant in the environment. Exposure to inorganic mercury can cause various poisonous effects, including kidney injury. However, no safe and effective treatment for kidney injury caused by inorganic mercury has been found and used. Luteolin (Lut) possesses various beneficial bioactivities. Here, our research aims to investigate the protective effect of Lut on renal injury induced by mercury chloride (HgCl) and identify the underlying autophagy regulation mechanism. Twenty-eight 6-8 weeks old Wistar rats were randomly assigned to four groups: control, HgCl, HgCl + Lut, and Lut. We performed the determination of oxidative stress and renal function indicators, histopathological analysis, the terminal deoxynucleotidyl transferase-mediated deoxyuracil nucleoside triphosphate nick-end labeling assay to detect apoptosis, western blot detection of autophagy-related protein levels, and atomic absorption method to detect mercury content. Our results showed that Lut ameliorated oxidative stress, apoptosis and restored the autophagy and renal function caused by HgCl in rats. Concretely, the level of nuclear factor E2-related factor, renal adenosine monophosphate-activated protein kinase (AMPK) expression, and autophagy regulation-related proteins levels were down-regulated, and the mammalian target of rapamycin (mTOR) expression was up-regulated by HgCl treatment. However, Lut treatment reversed the above changes. Notably, Lut reduced the accumulation of HgCl in the kidneys and promoted the excretion of HgCl through urine. Collectively, our results demonstrate that Lut can attenuate inorganic mercury-induced renal injury via activating the AMPK/mTOR autophagy pathway. Therefore, Lut may be a potential biological medicine to protect against renal damage induced by HgCl.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinorgbio.2021.111583DOI Listing
November 2021

Amyloid-β toxicity modulates tau phosphorylation through the PAX6 signalling pathway.

Brain 2021 Oct;144(9):2759-2770

School of Biomedical Sciences, University of Hong Kong, Hong Kong, China.

The molecular link between amyloid-β plaques and neurofibrillary tangles, the two pathological hallmarks of Alzheimer's disease, is still unclear. Increasing evidence suggests that amyloid-β peptide activates multiple regulators of cell cycle pathways, including transcription factors CDKs and E2F1, leading to hyperphosphorylation of tau protein. However, the exact pathways downstream of amyloid-β-induced cell cycle imbalance are unknown. Here, we show that PAX6, a transcription factor essential for eye and brain development which is quiescent in adults, is increased in the brains of patients with Alzheimer's disease and in APP transgenic mice, and plays a key role between amyloid-β and tau hyperphosphorylation. Downregulation of PAX6 protects against amyloid-β peptide-induced neuronal death, suggesting that PAX6 is a key executor of the amyloid-β toxicity pathway. Mechanistically, amyloid-β upregulates E2F1, followed by the induction of PAX6 and c-Myb, while Pax6 is a direct target for both E2F1 and its downstream target c-Myb. Furthermore, PAX6 directly regulates transcription of GSK-3β, a kinase involved in tau hyperphosphorylation and neurofibrillary tangles formation, and its phosphorylation of tau at Ser356, Ser396 and Ser404. In conclusion, we show that signalling pathways that include CDK/pRB/E2F1 modulate neuronal death signals by activating downstream transcription factors c-Myb and PAX6, leading to GSK-3β activation and tau pathology, providing novel potential targets for pharmaceutical intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awab134DOI Listing
October 2021

Source analysis and influencing factors of historical changes in PAHs in the sediment core of Fuxian Lake, China.

Environ Pollut 2021 Nov 16;288:117935. Epub 2021 Aug 16.

School of Geography Science, Nanjing Normal University, Nanjing, 210023, PR China; Jiangsu Center for Collaborative Innovation in Geographical Information Resource Development and Application, Nanjing Normal University, Nanjing, 210023, PR China; Key Laboratory of Virtual Geographic Environment (Nanjing Normal University), Ministry of Education, Nanjing, 210023, PR China; State Key Laboratory Cultivation Base of Geographical Environment Evolution (Jiangsu Province), Nanjing, 210023, PR China.

In this study, the influencing factors and sources of historical changes in polycyclic aromatic hydrocarbons (PAHs) in the sediment core of Fuxian Lake were analyzed. Before 1970, the ΣPAH concentration fluctuated widely, with one or more maximum values. During 1971-2004, the ΣPAH concentration showed a slow growth trend, while during 2005-2017, the concentration increased sharply, reaching a peak value of 821 ng g. dw in 2017. The results of a positive matrix factorization (PMF) model demonstrated that before 1970, PAHs were mainly derived from biomass burning in the Fuxian Lake sediment core, with an overall contribution of 40 %. During 1971-2004, the source of PAHs was mainly coal combustion, with an overall contribution of 34 %. During 2005-2017, PAHs primarily originated from traffic, with an overall contribution of 33 %. Population, coal, GDP, motor, and petroleum had a significant influence on low molecular weight (LMW) PAHs in 1980-2004 and 2005-2017. Motor, coal, population, and GDP had a greater impact on high molecular weight (HMW) PAHs. Before 1970 and in 1971-2004, meteorological factors had little effect on PAHs in the sediment core in Fuxian Lake. During 2005-2017, day and rainfall were significantly negatively correlated with HMW PAHs, while temperature and wind were not correlated with PAH concentrations. During 2005-2017, total organic carbon (TOC) and total nitrogen (TN) had greater adsorption effects on HMW PAHs than on LMW PAHs. Before 1970 and in 1971-2004, the adsorption effects of TOC and TN on 3-4-ring PAHs were greater than those of 2-ring and 5-6-ring PAHs. Total phosphorus (TP) had no adsorption effect on PAHs in the entire sedimentary column.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2021.117935DOI Listing
November 2021

Influence of hydrogel spacer placement with prostate brachytherapy on rectal and urinary toxicity.

BJU Int 2021 Aug 13. Epub 2021 Aug 13.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Objective: To determine the influence of rectal hydrogel spacer placement (HSP) on late rectal toxicity outcomes in prostate cancer patients treated with low-dose-rate (LDR) brachytherapy, with or without supplemental external beam radiotherapy (EBRT).

Patients And Methods: A total of 224 patients underwent LDR brachytherapy with HSP, as monotherapy or combined with EBRT, between January 2016 and December 2019. Dosimetric variables reflecting the extent of rectal sparing and late rectal toxicity outcomes were evaluated. This spacer cohort was retrospectively compared to a similar patient group (n = 139) in whom HSP was not used.

Results: Hydrogel spacer placement was associated with significantly reduced rectal doses for all dosimetric variables; the median percentage rectal dose to 1 cc of rectum and rectal dose to 2 cc of rectum of the spacer cohort were all significantly lower compared to the non-spacer cohort. The incidence rates of overall (any grade) and grade ≥2 rectal toxicity were lower in patients with HSP compared to patients who did not undergo HSP: 12% and 1.8% vs 31% and 5.8%, respectively. The 3-year cumulative incidence of overall rectal toxicity was significantly lower with HSP than without (15% vs 33%; P < 0.001), corresponding to an overall rectal toxicity reduction on univariable analysis (hazard ratio 0.45, 95% confidence interval 0.28-0.73; P = 0.001). In this patient cohort treated with prostate brachytherapy, none of the urethral dosimetric variables or the presence or absence of HSP was associated with late urinary toxicity.

Conclusion: Hydrogel rectal spacer placement is a safe procedure, associated with significantly reduced rectal dose. HSP translates to a decrease in overall late rectal toxicity in patients receiving dose-escalated brachytherapy-based procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bju.15572DOI Listing
August 2021

Hippo-YAP/MCP-1 mediated tubular maladaptive repair promote inflammation in renal failed recovery after ischemic AKI.

Cell Death Dis 2021 07 30;12(8):754. Epub 2021 Jul 30.

Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Acute kidney injury (AKI) is associated with significant morbidity and its chronic inflammation contributes to subsequent chronic kidney disease (CKD) development. Yes-associated protein (YAP), the major transcriptional coactivator of the Hippo pathway, has been shown associated with chronic inflammation, but its role and mechanism in AKI-CKD transition remain unclear. Here we aimed to investigate the role of YAP in AKI-induced chronic inflammation. Renal ischemia/reperfusion (I/R) was used to induce a mouse model of AKI-CKD transition. We used verteporfin (VP), a pharmacological inhibitor of YAP, to treat post-IRI mice for a period, and evaluated the influence of YAP inhibition on long-term outcomes of AKI. In our results, severe IRI led to maladaptive tubular repair, macrophages infiltration, and progressive fibrosis. Following AKI, the Hippo pathway was found significantly altered with YAP persistent activation. Besides, tubular YAP activation was associated with the maladaptive repair, also correlated with interstitial macrophage infiltration. Monocyte chemoattractant protein 1 (MCP-1) was found notably upregulated with YAP activation. Of note, pharmacological inhibition of YAP in vivo attenuated renal inflammation, including macrophage infiltration and MCP-1 overexpression. Consistently, in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) induced YAP activation and MCP-1 overproduction whereas these could be inhibited by VP. In addition, we modulated YAP activity by RNA interference, which further confirmed YAP activation enhances MCP-1 expression. Together, we concluded tubular YAP activation with maladaptive repair exacerbates renal inflammation probably via promoting MCP-1 production, which contributes to AKI-CKD transition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-04041-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324794PMC
July 2021

Single-cell transcriptomics reveals heterogeneous progression and EGFR activation in pancreatic adenosquamous carcinoma.

Int J Biol Sci 2021 22;17(10):2590-2605. Epub 2021 Jun 22.

Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing 100020, China.

Pancreatic adenosquamous carcinoma (PASC) - a rare pathological pancreatic cancer (PC) type - has a poor prognosis due to high malignancy. To examine the heterogeneity of PASC, we performed single-cell RNA sequencing (scRNA-seq) profiling with sample tissues from a healthy donor pancreas, an intraductal papillary mucinous neoplasm, and a patient with PASC. Of 9,887 individual cells, ten cell subpopulations were identified, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and cancer cells. Cancer cells were divided into five clusters. Notably, cluster 1 exhibited stem-like phenotypes expressing UBE2C, ASPM, and TOP2A. We found that S100A2 is a potential biomarker for cancer cells. LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells. Furthermore, the copy number variations in ductal and cancer cells were greater than in the reference cells. The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC. The gene sets expressed by cancer-associated fibroblasts were enriched in the immunosuppressive pathways. We demonstrate that EGFR-associated ligand-receptor pairs are activated in ductal-stromal cell communications. Hence, this study revealed the heterogeneous variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered intercellular interactions following PASC progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijbs.58886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315026PMC
June 2021

Antiangiogenic therapy reverses the immunosuppressive breast cancer microenvironment.

Biomark Res 2021 Jul 22;9(1):59. Epub 2021 Jul 22.

Department of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310000, Zhejiang Province, China.

Tumor angiogenesis induces local hypoxia and recruits immunosuppressive cells, whereas hypoxia subsequently promotes tumor angiogenesis. Immunotherapy efficacy depends on the accumulation and activity of tumor-infiltrating immune cells (TIICs). Antangiogenic therapy could improve local perfusion, relieve tumor microenvironment (TME) hypoxia, and reverse the immunosuppressive state. Combining antiangiogenic therapy with immunotherapy might represent a promising option for the treatment of breast cancer. This article discusses the immunosuppressive characteristics of the breast cancer TME and outlines the interaction between the tumor vasculature and the immune system. Combining antiangiogenic therapy with immunotherapy could interrupt abnormal tumor vasculature-immunosuppression crosstalk, increase effector immune cell infiltration, improve immunotherapy effectiveness, and reduce the risk of immune-related adverse events. In addition, we summarize the preclinical research and ongoing clinical research related to the combination of antiangiogenic therapy with immunotherapy, discuss the underlying mechanisms, and provide a view for future developments. The combination of antiangiogenic therapy and immunotherapy could be a potential therapeutic strategy for treatment of breast cancer to promote tumor vasculature normalization and increase the efficiency of immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40364-021-00312-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296533PMC
July 2021

Intensity-modulated radiation therapy and doxorubicin in thyroid cancer: A prospective phase 2 trial.

Cancer 2021 Nov 22;127(22):4161-4170. Epub 2021 Jul 22.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: The use of external-beam radiotherapy for locally advanced nonanaplastic thyroid cancer remains controversial. This prospective study evaluated the efficacy and tolerability of intensity-modulated radiation therapy (IMRT) with or without concurrent chemotherapy in patients with locally advanced thyroid cancer.

Methods: The authors conducted a nonrandomized phase 2 trial of IMRT with or without concurrent doxorubicin in patients with gross residual or unresectable nonanaplastic thyroid carcinoma (ClinicalTrials.gov identifier NCT01882816). The primary end point was 2-year locoregional progression-free survival (PFS). Secondary end points included overall survival (OS), safety, patient-reported outcomes, and functional outcomes.

Results: Twenty-seven patients were enrolled: 12 (44.4%) with unresectable disease and 15 (55.6%) with gross residual disease. The median follow-up was 45.6 months (interquartile range, 42.0-51.6 months); the 2-year cumulative incidences of locoregional PFS and OS were 79.7% and 77.3%, respectively. The rate of grade 3 or higher acute and late toxicities was 33.4%. There were no significant functional differences 12 months after treatment (assessed objectively by the modified barium swallow study). Patient-reported quality of life in the experimental group was initially lower but returned to the baseline after 6 months and improved thereafter. In a post hoc analysis, concurrent chemotherapy with intensity-modulated radiation therapy (CC-IMRT) resulted in significantly less locoregional failure at 2 years (no failure vs 50%; P = .001), with higher rates of grade 2 or higher acute dermatitis, mucositis, and dysphagia but no difference in long-term toxicity, functionality, or patient-reported quality of life.

Conclusions: In light of the excellent locoregional control rates achieved with CC-IMRT and its acceptable toxicity profile as confirmed by functional assessments and patient-reported outcomes, CC-IMRT may be preferred over IMRT alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.33804DOI Listing
November 2021

A recombinant spike protein subunit vaccine confers protective immunity against SARS-CoV-2 infection and transmission in hamsters.

Sci Transl Med 2021 08 20;13(606). Epub 2021 Jul 20.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences & School of Public Health, Xiamen University, Xiamen 361102, P. R. China.

Multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary to respond to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a protein subunit vaccine composed of spike ectodomain protein (StriFK) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C). StriFK-FH002C generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus monkeys than those observed in plasma isolated from COVID-19 convalescent individuals. StriFK-FH002C also induced both T1- and T2-polarized helper T cell responses in mice. In hamsters, StriFK-FH002C immunization protected animals against SARS-CoV-2 challenge, as shown by the absence of virus-induced weight loss, fewer symptoms of disease, and reduced lung pathology. Vaccination of hamsters with StriFK-FH002C also reduced within-cage virus transmission to unvaccinated, cohoused hamsters. In summary, StriFK-FH002C represents an effective, protein subunit-based SARS-CoV-2 vaccine candidate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.abg1143DOI Listing
August 2021

Tolerability of Breast Radiotherapy Among Carriers of Germline Variants.

JCO Precis Oncol 2021 19;5. Epub 2021 Jan 19.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.

, a gene that controls repair of DNA double-strand breaks, confers an excess lifetime risk of breast cancer among carriers of germline pathogenic variants (PV). PV homozygotes are particularly sensitive to DNA damage caused by ionizing radiation. Consequently, there is concern that adjuvant radiotherapy (RT) may cause excess morbidity among heterozygous carriers of PV. We evaluated the tolerability of breast RT among carriers of germline variants.

Methods: Of 167 patients with germline variants presenting to our institution with breast cancer, 91 received RT. Treatment-related toxicity was ascertained from medical records and graded across organ systems. Toxicities grade > 2 were recorded from the end of treatment to last evaluable follow-up and were analyzed according to variant pathogenicity.

Results: Of 91 evaluable carriers of variants, with a median follow-up of 32 months following RT, 25% (n = 23) harbored a PV, whereas 75% (n = 68) harbored a variant of uncertain significance (VUS). Prevalence of grade ≥ 2 toxicity unrelated to post-mastectomy reconstruction among patients with PV was: 32% at the end of treatment ( 34% for VUS carriers), 11% at 1 year of follow-up ( 4% for VUS carriers), and 8% at the last follow-up ( 13% for VUS carriers), consistent with previous studies of RT among unselected populations. No grade 4 or 5 toxicities were observed. variant pathogenicity was not associated with local toxicity, contralateral breast cancer, or secondary malignancy in this limited cohort of patients who received breast RT.

Conclusion: We found no evidence of excess RT-associated toxicity among carriers of pathogenic germline variants. Breast-conserving therapy and adjuvant RT may be safely considered among appropriately selected carriers of germline variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/PO.20.00334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232182PMC
January 2021

Incidence and influencing factors of post-intensive care cognitive impairment.

Intensive Crit Care Nurs 2021 Dec 7;67:103106. Epub 2021 Jul 7.

School of Nursing, Lanzhou University, Lanzhou, Gansu Province 730000, China; Department of Intensive Care Unit, The First Hospital of Lanzhou University, Lanzhou, Gansu Province 730000, China. Electronic address:

Objective: To evaluate the incidence and risks factors of short-term post-intensive care (ICU) cognitive impairment.

Design: Prospective, observational study.

Setting: Closed university-affiliated intensive care unit.

Patients: We enrolled consecutive patients >18 yrs of age expected to be in intensive care unit for ≥24 hours.

Interventions: None.

Measurements And Main Results: The score of Montreal Cognitive Assessment (MoCA) less than 26 was defined as cognitive impairment at hospital discharge and short-term post-ICU cognitive impairment was diagnosed in 185 of 409 assessed patients (45.2%). According to univariate analysis, age, years of education, occupation, past medical history, main ICU diagnosis, Acute Physiology and Chronic Evaluation Scoring System (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, Charlson comorbidity index, ICU length-of-stay (LOS), total hospital LOS, sedation, vasoactive agents, muscle relaxants, mechanical ventilation and duration of mechanical ventilation, constraints, early active mobilisation, hypoxemia, frequency and severity of delirium, blood pressure, rescue experience, and infection were significant predictors of post-ICU cognitive impairment. Multivariate analysis results showed that the frequency and severity of delirium, and advanced age were risk factors of post-ICU cognitive impairment; high years of education and early active mobilisation were protective factors.

Conclusions: Incidence of post-ICU cognitive impairment is at a high level, which is similar to former researches' results; the frequency and severity of delirium, and advanced age were risk factors of post-ICU cognitive impairment; high years of education and early active mobilisation were protective factors of post-ICU cognitive impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.iccn.2021.103106DOI Listing
December 2021

Progressive deterioration of the upper respiratory tract and the gut microbiomes in children during the early infection stages of COVID-19.

J Genet Genomics 2021 09 29;48(9):803-814. Epub 2021 May 29.

Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China. Electronic address:

Children are less susceptible to coronavirus disease 2019 (COVID-19), and they have manifested lower morbidity and mortality after infection, for which a multitude of mechanisms may be considered. Whether the normal development of the gut-airway microbiome in children is affected by COVID-19 has not been evaluated. Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the upper respiratory tract and the gut microbiomes in nine children. The alteration of the microbiome is dominated by the genus Pseudomonas, and it sustains for up to 25-58 days in different individuals. Moreover, the patterns of alternation are different between the upper respiratory tract and the gut. Longitudinal investigation shows that the upper respiratory tract and the gut microbiomes are extremely variable among children during the course of COVID-19. The dysbiosis of microbiome persists in 7 of 8 children for at least 19-24 days after discharge from the hospital. Disturbed development of both the gut and the upper respiratory microbiomes and prolonged dysbiosis in these nine children imply possible long-term complications after clinical recovery from COVID-19, such as predisposition to the increased health risk in the post-COVID-19 era.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgg.2021.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163695PMC
September 2021

Inhibition of the Nrf2/p38MAPK pathway involved in deltamethrin-induced apoptosis and fibrosis in quail kidney.

Food Chem Toxicol 2021 Sep 30;155:112382. Epub 2021 Jun 30.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin, 150030, China. Electronic address:

Deltamethrin (DLM) is a broad-spectrum and effective pyrethroid insecticide. However, DLM has good residual activity on most surfaces and many insects, so it poses a threat to the environment and health of animals and human. Exposure to DLM can cause kidney injury, but the mechanism is not well understood. Therefore, we investigated the possible mechanism of quail kidney injury induced by chronic exposure to different doses of DLM for 12 weeks. The results showed that chronic exposure to DLM induced apoptosis and fibrosis of quail kidney through the promotion of oxidative stress by down-regulating nuclear factor erythroid 2 related factor 2 (Nrf2), up-regulating the phosphorylation of p38 mitogen-activated protein kinases (p38MAPK). Furthermore, DLM-induced kidney apoptosis in quails as evidenced by increased expression of B-cell lymphoma gene 2-associated X while decreased expression of B-cell lymphoma-extra large. Simultaneously, DLM-induced kidney fibrosis in quails as evidenced by increased expression of fibrosis maker proteins. Overall, the results demonstrate that chronic DLM exposure induces kidney apoptosis and fibrosis via inhibition of the Nrf2/p38MAPK pathway. This study provides a new understanding for the mechanism of DLM-induced quail kidney injury and also provides a theoretical basis for treatment of the DLM poisoning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2021.112382DOI Listing
September 2021

Cultural Adaptation and Validation of Questionnaires for Evaluation of Health-Related Quality of Life with Dysphagia in Different Countries: A Systematic Review.

Dysphagia 2021 Jun 28. Epub 2021 Jun 28.

Evidence-Based Medicine Center, Lanzhou University, Lanzhou, China.

Dysphagia can have devastating and long-lasting effects on the patient's health-related quality of life (HRQoL). In recent years, a number of questionnaires for the evaluation of the HRQoL of patients with dysphagia have been developed and have been adapted for use in different countries and cultures. However, problems may arise in the process of cultural adaptation and validation, which can affect the quality of the questionnaires and their measurements. This study was conducted to systematically summarize the cultural adaptation and validation of questionnaires for the evaluation of dysphagia-related HRQoL in different countries, assessing the varieties, measurement properties, and qualities of these questionnaires, with the aim of identifying the status of their adaptation and validation and ways in which they might be improved. Four databases were searched, and relevant articles were screened, with data from eligible reports extracted and reviewed. The methodological quality of the included articles was evaluated using the QualSyst critical appraisal tool. The HRQoL questionnaires for patients with dysphagia were assessed using the quality criteria for the measurement properties of health status questionnaires proposed by Terwee et al. and Timmerman et al. 29 studies published between 2008 and 2020 were included. The questionnaires described in these 29 studies were translated into 19 languages and culturally adapted to 21 countries. The adapted questionnaires were based on the Swallowing quality of life questionnaire (SWAL-QOL) by Mchorney et al., the Dysphagia Handicap Index (DHI) by Silbergleit et al., the M.D. Anderson Dysphagia Inventory (MDADI) by Chen et al., and the Eating Assessment Tool-10 (EAT-10) by Belafsky et al. It was found that the questionnaires were reliable and valid instruments for the assessment of dysphagia-related HRQoL, but the quality criteria for cultural adaptation and validation were not strictly followed, especially in the categories of criterion validity, agreement, responsiveness, and interpretability. In conclusion, although the questionnaires were found to be both reliable and valid, the quality criteria should be considered and strictly followed in the cultural adaptation and validation process in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00455-021-10330-3DOI Listing
June 2021
-->