Publications by authors named "Lihong Zhang"

338 Publications

Limb-bud and Heart (LBH) mediates proliferation, fibroblast-to-myofibroblast transition and EMT-like processes in cardiac fibroblasts.

Mol Cell Biochem 2021 Mar 5. Epub 2021 Mar 5.

Guangdong Provincial Biomedical Engineering Technology Research, Center for Cardiovascular Disease; Sino-Japanese Cooperation Platform for Translational Research in Heart Failure; Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People's Republic of China.

Cardiac fibrosis is an important pathological change after myocardial infarction (MI). Its progression is essential for post-MI infarct healing, during which transforming growth factor beta1 (TGF-β1) plays a critical role. Limb-bud and Heart (LBH), a newly discovered target gene of TGF-β1, was shown to promote normal cardiogenesis. αB-crystallin (CRYAB), an LBH-interacting protein, was demonstrated to be involved in TGF-β1-induced fibrosis. The roles and molecular mechanisms of LBH and CRYAB during cardiac fibrosis remain largely unexplored. In this study, we investigated the alterations of LBH and CRYAB expression in mouse cardiac tissue after MI. LBH and CRYAB were upregulated in activated cardiac fibroblasts (CFs), while in vitro TGF-β1 stimulation induced the upregulation of LBH, CRYAB, and fibrogenic genes in primary CFs of neonatal rats. The results of the ectopic expression of LBH proved that LBH accelerated CF proliferation under hypoxia, mediated the expression of CRYAB and fibrogenic genes, and promoted epithelial-mesenchymal transition (EMT)-like processes in rat CFs, while subsequent CRYAB silencing reversed the effects induced by elevated LBH expression. We also verified the protein-protein interaction (PPI) between LBH and CRYAB in fibroblasts. In summary, our work demonstrated that LBH promotes the proliferation of CFs, mediates TGF-β1-induced fibroblast-to-myofibroblast transition and EMT-like processes through CRYAB upregulation, jointly functioning in post-MI infarct healing. These findings suggest that LBH could be a promising potential target for the study of cardiac repair and cardiac fibrosis.
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http://dx.doi.org/10.1007/s11010-021-04111-7DOI Listing
March 2021

Cluster of differentiation 147 (CD147) expression is linked with thiram induced chondrocyte's apoptosis via Bcl-2/Bax/Caspase-3 signalling in tibial growth plate under chlorogenic acid repercussion.

Ecotoxicol Environ Saf 2021 Feb 27;213:112059. Epub 2021 Feb 27.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China; College of Animals Husbandry and Veterinary Medicine, Tibet Agricultural and Animal Husbandry University, Linzhi, Tibet 860000, PR China. Electronic address:

Tibial dyschondroplasia (TD) is a metabolic disease of young poultry that affects bone andcartilage's growth. It mostly occurs in broilers due to thiram toxicity in the feed. In this disease, tibial cartilage is not yet ripe for ossification, but it also results in lameness, death, and moral convictions of commercial poultry due to numerous apoptotic changes on cell level. These changes serve a cardinal role in this situation. Many potential problems indicate that chlorogenic acid (CGA) performs an extensive role in controlling apoptosis's perception. However, the actual role of CGA in TD affected chondrocytes in-vitro is still unidentified. The current study investigates the imperceptible insight of CGA on chondrocyte's apoptosis via B-cell lymphoma 2 (Bcl-2), Bcl-2 associated x-protein (Bax), and Caspase-3 with CD147 signalling. The expression of these markers was investigated by Immunofluorescence, western blot analysis, and reverse transcription-quantitative polymerase chain (RT-qPCR). Chondrocytes from the growth plate of tibia were isolated, cultured, and processed. A sub-lethal thiram (2.5 μg/mL) was used to induce cytotoxicity and then treated with an optimum dose (40 μg/ mL) of CGA. According to the results, thiram distorted chondrocyte cells with enhanced apoptotic rate. But, in case of CGA, high expression of CD147 enhanced cell viability of chondrocytes, accompanied by downregulation of Bax/Caspase-3 signalling with the upregulation of Bcl-2. The first possibility has ruled out in the present study by the observation that the cells apoptosis marker, Caspase-3 showed a significant change in CD147 overexpressing cells. Conversely, immunodepletion of CD147 with enhanced cleavage of Caspase-3, indicating the activation of apoptosis in chondrocytes cells. Therefore, these findings suggest a novel insight about CD147 in thiram induced TD about the regulation of Bcl-2/Bax/Caspase-3 apoptosis-signalling axis.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112059DOI Listing
February 2021

Two forms of G protein-coupled estrogen receptor 1 in the ricefield eel: Expression and functional characterization in relation to ovarian follicle development.

Gen Comp Endocrinol 2021 Apr 27;304:113720. Epub 2021 Jan 27.

Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, PR China; Biology Department, School of Life Sciences, Sun Yat-Sen University, Guangzhou, PR China. Electronic address:

G protein-coupled estrogen receptor 1 (Gper1) mediates many rapid, non-genomic estrogenic effects in vertebrates, and plays an important reproductive role in the maintenance of oocyte meiotic arrest in teleost fishes. In the present study, two genes for Gper1, namely gper1a and gper1b, were identified in the genome of a teleost fish, the ricefield eel (Monopterus albus) through Blast and syntenic analysis. Although genes neighboring gper1b are of high synteny, ricefield eel Gper1b shares very low (around 15) percent identities with Gper1 homologues of other vertebrates. In transiently transfected HEK293T cells, both ricefield eel Gper1a and Gper1b responded to estradiol (E) and estradiol-BSA (E-BSA) challenges by activating pCRE but not pSRE luciferase reporters, which were abolished by G-15 and NF-449. The production of cAMP was also increased in HEK293T cells transfected with Gper1a or Gper1b expression construct after E-BSA challenge, which was also abolished by G-15. Surprisingly, both Gper1a and Gper1b showed ligand-independent effects on pCRE luciferase reporters at higher transfected doses (10 ng). RT-PCR analysis showed that the transcript of gper1a is broadly expressed in tissues of both female and male fish while the expression of gper1b in tissues demonstrates obvious sexual dimorphism, with transcripts detected in all tissues examined in female whereas they were barely detectable in some peripheral tissues of male including the testis. In the ovary, the expression of both gper1a and gper1b was detected in the oocyte but not the follicular layer, with the mRNA levels increased during vitellogenesis, peaked at the late vitellogenic stage, and decreased precipitously at the full-grown and germinal vesicle breakdown (GVBD) stages. Moreover, E and E-BSA induced cAMP production in the in vitro incubated follicles at mid-vitellogenic stage but not the GVBD stage, and the induction could be completely abolished by G-15, a Gper1 inhibitor. Taken together, these results suggest that both Gper1a and Gper1b may play important roles in the development and maturation of ovarian follicles in ricefield eels, possibly through inhibition of oocyte meiotic resumption.
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http://dx.doi.org/10.1016/j.ygcen.2021.113720DOI Listing
April 2021

Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis.

Nature 2021 Jan 25. Epub 2021 Jan 25.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-a new coronavirus that has led to a worldwide pandemic-has a furin cleavage site (PRRAR) in its spike protein that is absent in other group-2B coronaviruses. To explore whether the furin cleavage site contributes to infection and pathogenesis in this virus, we generated a mutant SARS-CoV-2 that lacks the furin cleavage site (ΔPRRA). Here we report that replicates of ΔPRRA SARS-CoV-2 had faster kinetics, improved fitness in Vero E6 cells and reduced spike protein processing, as compared to parental SARS-CoV-2. However, the ΔPRRA mutant had reduced replication in a human respiratory cell line and was attenuated in both hamster and K18-hACE2 transgenic mouse models of SARS-CoV-2 pathogenesis. Despite reduced disease, the ΔPRRA mutant conferred protection against rechallenge with the parental SARS-CoV-2. Importantly, the neutralization values of sera from patients with coronavirus disease 2019 (COVID-19) and monoclonal antibodies against the receptor-binding domain of SARS-CoV-2 were lower against the ΔPRRA mutant than against parental SARS-CoV-2, probably owing to an increased ratio of particles to plaque-forming units in infections with the former. Together, our results demonstrate a critical role for the furin cleavage site in infection with SARS-CoV-2 and highlight the importance of this site for evaluating the neutralization activities of antibodies.
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http://dx.doi.org/10.1038/s41586-021-03237-4DOI Listing
January 2021

Targeted disruption of pi-pi stacking in Malaysian banana lectin reduces mitogenicity while preserving antiviral activity.

Sci Rep 2021 Jan 12;11(1):656. Epub 2021 Jan 12.

Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.

Lectins, carbohydrate-binding proteins, have been regarded as potential antiviral agents, as some can bind glycans on viral surface glycoproteins and inactivate their functions. However, clinical development of lectins has been stalled by the mitogenicity of many of these proteins, which is the ability to stimulate deleterious proliferation, especially of immune cells. We previously demonstrated that the mitogenic and antiviral activities of a lectin (banana lectin, BanLec) can be separated via a single amino acid mutation, histidine to threonine at position 84 (H84T), within the third Greek key. The resulting lectin, H84T BanLec, is virtually non-mitogenic but retains antiviral activity. Decreased mitogenicity was associated with disruption of pi-pi stacking between two aromatic amino acids. To examine whether we could provide further proof-of-principle of the ability to separate these two distinct lectin functions, we identified another lectin, Malaysian banana lectin (Malay BanLec), with similar structural features as BanLec, including pi-pi stacking, but with only 63% amino acid identity, and showed that it is both mitogenic and potently antiviral. We then engineered an F84T mutation expected to disrupt pi-pi stacking, analogous to H84T. As predicted, F84T Malay BanLec (F84T) was less mitogenic than wild type. However, F84T maintained strong antiviral activity and inhibited replication of HIV, Ebola, and other viruses. The F84T mutation disrupted pi-pi stacking without disrupting the overall lectin structure. These findings show that pi-pi stacking in the third Greek key is a conserved mitogenic motif in these two jacalin-related lectins BanLec and Malay BanLec, and further highlight the potential to rationally engineer antiviral lectins for therapeutic purposes.
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http://dx.doi.org/10.1038/s41598-020-80577-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804308PMC
January 2021

A Macromolecular Drug for Cancer Therapy via Extracellular Calcification.

Angew Chem Int Ed Engl 2021 Jan 11. Epub 2021 Jan 11.

Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.

Cancer chemotherapy typically relies on drug endocytosis and inhibits tumor cell proliferation via intracellular pathways; however, severe side effects may arise. In this study, we performed a first attempt to develop macromolecular-induced extracellular chemotherapy involving biomineralization by absorbing calcium from the blood through a new type of drug, polysialic acid conjugated with folate (folate-polySia), which selectively induces biogenic mineral formation on tumor cells and results in the pathological calcification of tumors. The macromolecule-initiated extracellular calcification causes cancer cell death mainly by intervening with the glycolysis process in cancer cells. Systemic administration of folate-polySia inhibited cervical and breast tumor growth and dramatically improved survival rates in mice. This study provides an extracellular therapeutic approach for malignant tumor diseases via calcification that is ready for clinical trials and offers new insights into macromolecular anticancer drug discovery.
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http://dx.doi.org/10.1002/anie.202016122DOI Listing
January 2021

Efficacy and safety of paclitaxel-coated balloon angioplasty for dysfunctional arteriovenous fistulas: a multicenter randomized controlled trial.

Am J Kidney Dis 2021 Jan 5. Epub 2021 Jan 5.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China. Electronic address:

Rationale & Objective: Previous studies have illustrated the potential superiority of drug-coated balloons (DCBs) in maintaining patency after initial angioplasty for arteriovenous fistula (AVF) dysfunction due to stenosis. Our trial evaluated the efficacy and safety of DCBs for preventing fistula restenosis in Chinese hemodialysis patients.

Study Design: Multicenter, prospective, randomized, open-label, blinded-endpoint, controlled trial.

Settings & Participants: A total of 161 hemodialysis patients with fistula dysfunction from 10 centers in China.

Intervention: Subjects were randomized 1:1 to treatment with initial dilation following DCB or only plain high-pressure balloon (HPB) angioplasty.

Outcomes: The primary endpoint was target lesion primary patency, defined as target lesion intervention-free survival in conjunction with an ultrasound-measured peak systolic velocity ratio (PSVR) ≤ 2.0 at six months. The secondary endpoints included (1) device, technical, clinical, and procedural success; (2) major adverse events; (3) degree of target lesion stenosis at 6 months; and (4) clinically driven target lesion and target shunt revascularization within 12 months.

Results: The percentage with target lesion primary patency as defined by a PSVR ≤ 2.0 was higher in the DCB group than in the control group (DCB 65% vs. control 37%, rate difference 28%, 95% CI 13%-43%, P<0.001) at 6 months. The target lesion and target shunt intervention-free survival of the DCB group were not superior to those of the control group at 6 months (P=0.3 and P= 0.2, respectively) but were superior at 12 months (target lesion, DCB 73% vs. control 58%, P=0.04; target shunt, DCB 73% vs. control 57%, P=0.04). Average degree of target lesion stenoses at 6 months was not significantly different between the two groups (DCB 44% ± 16% vs. control 49% ± 18%, P=0.09). There were no significant differences in major adverse events or in device, technical, clinical, or procedural success rates between the groups.

Limitations: Small sample size; short follow-up period; procedural differences between the two groups such as unequal inflation times, and balloon lengths.

Conclusions: Compared to conventional HPB angioplasty, DCB treatment achieved superior primary patency defined using PSVR measured at 6 months and superior intervention-free survival of both the target lesion and the target shunt at 12 months without evidence for greater adverse events.
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http://dx.doi.org/10.1053/j.ajkd.2020.11.022DOI Listing
January 2021

Associations Between Delivery Mode and Early Childhood Body Mass Index Z-Score Trajectories: A Retrospective Analysis of 2,685 Children From Mothers Aged 18 to 35 Years at Delivery.

Front Pediatr 2020 17;8:598016. Epub 2020 Dec 17.

Department of Traditional Chinese Medicine, The Huangdao Maternal and Child Health Care Hospital, Qingdao, China.

To investigate the association between cesarean delivery (CD) and trajectory patterns of age- and sex-specific body mass index (BMI) z-score in early childhood. A retrospective cohort study was conducted among 2,685 children whose maternal age at the time of birth was between 18 and 35 years, and birth data and anthropometric measurement data during their ages 3-60 months were collected. A group-based trajectory modeling approach was used to identify distinct BMI z-score trajectories, and multinomial logistic regressions were applied to estimate the associations among CD (both elective and non-elective combined), elective and non-selective CD, and BMI z-score trajectory classes. Of the 2,685 participants, 46.5% ( = 1,248) were born by vaginal delivery (VD), 20.7% ( = 556) by elective CD, and 32.8% ( = 881) by non-elective CD. Five BMI z-score trajectory patterns were identified, and they were "increasing from moderate to high" (10.1%, = 270), "increasing from mild to moderate" (34.2%, = 919), "increasing from low to high" (10.5%, = 283), "stable mild" (30.1%, = 808), and "stable low" (15.1%, = 405) groups. Compared with children delivered by VD, those who delivered by CD (both elective and non-elective combined), elective CD, and non-elective CD were associated with the "increasing from moderate to high" trajectory [odds ratio (OR) = 1.61, 95% confidence interval (CI): 1.13-2.29; OR = 1.64, 95%CI: 1.06-2.54; and OR = 1.59, 95%CI: 1.05-2.39, respectively] and were also associated with the "increasing from low to high" trajectory (OR = 1.60, 95%CI: 1.17-2.19, OR = 1.75, 95%CI: 1.16-2.63; and OR = 1.53, 95%CI: 1.00-2.34, respectively). Both elective and non-elective CD were associated with the risk of accelerated weight gain in early childhood.
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http://dx.doi.org/10.3389/fped.2020.598016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774081PMC
December 2020

Posterior reversible encephalopathy syndrome coexists with acute cerebral infarction: challenges of blood pressure management.

Quant Imaging Med Surg 2020 Dec;10(12):2356-2365

Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Hypertension is the most common cause of posterior reversible encephalopathy syndrome (PRES) and acute cerebral infarction. Due to the lack of randomized controlled clinical trials (RCTs), early antihypertensive methods are diverse, even contradictory. So far, there is no consensus on the method of blood pressure (BP) management when the 2 diseases coexist. Generally, antihypertensive therapy should be initiated quickly in the acute phase of PRES, as most patients have elevated BP. However, various factors must be considered before the administration of early antihypertensive therapy in acute cerebral infarction. The coexistence of PRES and acute cerebral infarction is uncommon clinically, and more complicated subsequent BP management. This article reports a case of PRES coexisting with acute lacunar cerebral infarction, which was caused by hypertension. We have analyzed and summarized the antihypertensive principles in PRES and different phases of acute cerebral ischemic injury. We assert that when PRES and acute cerebral infarction coexist, the antihypertensive treatment should be individualized, and careful consideration should be given to the various influencing factors.
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http://dx.doi.org/10.21037/qims-20-392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596407PMC
December 2020

Bioinformatic investigation for candidate genes and molecular mechanism in the pathogenesis of membranous nephropathy.

Nephrology (Carlton) 2021 Mar 26;26(3):262-269. Epub 2020 Nov 26.

Renal Division, Shanghai Fifth People's Hospital, Fudan University, Shanghai, P.R. China.

Aim: We aimed to explore the detailed molecular mechanism of immune-associated genes in membranous nephropathy (MN).

Methods: A microarray data set (GSE133288) was retrieved from the Gene Expression Omnibus database. Differentially expressed mRNAs (DEMs) in MN vs control groups were identified, and MN-related DEMs (MN-DEMs) were further verified and screened using the comparative toxicogenomics database (CTD) database. The publicly available database, InnateDB was used to investigate immune genes, and the overlapped genes between MN-DEMs and the immune genes were considered as MN-related immune genes (iDEMs). A protein-protein interaction network (PPI) was constructed based on these iDEMs, followed by function and pathway enrichment analysis. Finally, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) associated with iDEMs were predicted, followed by a lncRNA-miRNA-mRNA (competing endogenous RNAs, ceRNA) network construction.

Results: A total of 327 DEMs and 48 iDEMs were revealed; a PPI network was constructed with 100 PPI pairs and 37 iDEMs. iDEMs including JUN and FOS were mainly enriched in pathways such as osteoclast differentiation and function including response to immobilization stress, respectively. Based on mRNA-associated miRNA and lncRNA prediction, 30 ceRNA interactions including KCNQ1OT1-miR-204-5p-SRY-Box Transcription Factor 4 (SOX4) were explored.

Conclusion: mRNAs including FOS and JUN might participate in MN development via response to immobilization stress function and the osteoclast differentiation pathway. The mRNA SOX4 might contribute to MN progression via sponging KCNQ1OT1-miR-204-5p interaction.
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http://dx.doi.org/10.1111/nep.13833DOI Listing
March 2021

Oxytocin-like signal regulates Lh cells directly but not Fsh cells in the ricefield eel Monopterus albus†.

Biol Reprod 2021 Feb;104(2):399-409

Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, P.R. China.

The synthesis and release of LH and FSH in the pituitary of vertebrates are differentially regulated during gonadal development and maturation. However, the underlying neuroendocrine mechanisms remain to be fully elucidated. The present study examined the possible involvement of isotocin (Ist), an oxytocin-like neuropeptide, in the regulation of Lh and Fsh in a teleost, the ricefield eel Monopterus albus. The immunoreactive isotocin receptor 2 (Istr2) was shown to be localized to Lh but not Fsh cells. In contrast, immunoreactive isotocin receptor 1 (Istr1) was not observed in either Lh or Fsh cells in the pituitary. Interestingly, Lh cells in female ricefield eels expressed Istr2 and secreted Lh in response to Ist challenge stage-dependently and in correlation with ovarian vitellogenesis. Moreover, Ist decreased Lh contents in the pituitary of female fish, indicating its stimulatory roles on Lh release in vivo. The induction of Lh release by Ist in dispersed pituitary cells was blocked by a PLC or IP3R inhibitor but not by a PKA or PKC inhibitor, indicating the involvement of the IP3/Ca2+ pathway. Collectively, the above results indicate that isotocin may bind to Istr2 to stimulate Lh release via the IP3/Ca2+ pathway, and play important roles in the ovarian maturation in ricefield eels. Furthermore, the present study suggests a novel neuroendocrine mechanism underlying the differential regulation of Lh and Fsh in vertebrates.
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http://dx.doi.org/10.1093/biolre/ioaa202DOI Listing
February 2021

Gene duplication drives genome expansion in a major lineage of Thaumarchaeota.

Nat Commun 2020 10 30;11(1):5494. Epub 2020 Oct 30.

School of Biological Sciences, University of Aberdeen, Aberdeen, UK.

Ammonia-oxidising archaea of the phylum Thaumarchaeota are important organisms in the nitrogen cycle, but the mechanisms driving their radiation into diverse ecosystems remain underexplored. Here, existing thaumarchaeotal genomes are complemented with 12 genomes belonging to the previously under-sampled Nitrososphaerales to investigate the impact of lateral gene transfer (LGT), gene duplication and loss across thaumarchaeotal evolution. We reveal a major role for gene duplication in driving genome expansion subsequent to early LGT. In particular, two large LGT events are identified into Nitrososphaerales and the fate of these gene families is highly lineage-specific, being lost in some descendant lineages, but undergoing extensive duplication in others, suggesting niche-specific roles. Notably, some genes involved in carbohydrate transport or coenzyme metabolism were duplicated, likely facilitating niche specialisation in soils and sediments. Overall, our results suggest that LGT followed by gene duplication drives Nitrososphaerales evolution, highlighting a previously under-appreciated mechanism of genome expansion in archaea.
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http://dx.doi.org/10.1038/s41467-020-19132-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603488PMC
October 2020

Detection of interleukin-8 on microgapped dual electrodes for measuring asthma complication.

Biotechnol Appl Biochem 2020 Oct 30. Epub 2020 Oct 30.

Faculty of Chemical Engineering Technology, Universiti Malaysia Perlis (UniMAP), Perlis, Malaysia.

Detection of asthma by a suitable biomarker is mandatory for the early identification, which helps in providing a right medication for the complete cure. Interleukins (ILs) have played a major role in asthma; in particular IL-8 is highly correlated with severe asthma. This research was focused on to detect IL-8 level by its partner antibody on a microgapped dual electrodes sensor. The sensing surface was modified into graphene oxide (GO), and an antibody was fixed by using the amine-aldehyde linker. GO enhanced the antibody immobilization and the consequence electric current flow upon interacting with IL-8. The detection limit of IL-8 was reached to 10 pg/mL in a linear range from 1 to 10,000 pg/mL with the regression of y = 0.7246x - 0.906 (R² = 0.9758); further, the sensitivity falls at 1 pg/mL. The surface does not show the antifouling effect with control antibody, and proteins, indicating the specific IL-8 detection. The detection of IL-8 helps in diagnosing and solving the related problems of asthmatic patients.
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http://dx.doi.org/10.1002/bab.2056DOI Listing
October 2020

The 'SELection End points in Communities of bacTeria' (SELECT) Method: A Novel Experimental Assay to Facilitate Risk Assessment of Selection for Antimicrobial Resistance in the Environment.

Environ Health Perspect 2020 10 21;128(10):107007. Epub 2020 Oct 21.

European Centre for Environment and Human Health, University of Exeter Medical School, Cornwall, UK.

Background: Antimicrobial resistance (AMR) is one of the most significant health threats to society. A growing body of research demonstrates selection for AMR likely occurs at environmental concentrations of antibiotics. However, no standardized experimental approaches for determining selective concentrations of antimicrobials currently exist, preventing appropriate environmental and human health risk assessment of AMR.

Objectives: We aimed to design a rapid, simple, and cost-effective novel experimental assay to determine selective effect concentrations of antibiotics and to generate the largest experimental data set of selective effect concentrations of antibiotics to date.

Methods: Previously published methods and data were used to validate the assay, which determines the effect concentration based on reduction of bacterial community (wastewater) growth. Risk quotients for test antibiotics were generated to quantify risk.

Results: The assay (SELection End points in Communities of bacTeria, or the SELECT method) was used to rapidly determine selective effect concentrations of antibiotics. These were in good agreement with quantitative polymerase chain reaction effect concentrations determined within the same experimental system. The SELECT method predicted no effect concentrations were minimally affected by changes in the assay temperature, growth media, or microbial community used as the inoculum. The predicted no effect concentrations for antibiotics tested ranged from for ciprofloxacin to for erythromycin.

Discussion: The lack of evidence demonstrating environmental selection for AMR, and of associated human health risks, is a primary reason for the lack of action in the mitigation of release of antibiotics into the aquatic environment. We present a novel method that can reliably and rapidly fill this data gap to enable regulation and subsequent mitigation (where required) to lower the risk of selection for, and human exposure to, AMR in aquatic environments. In particular, ciprofloxacin and, to a lesser extent, azithromycin, cefotaxime, and trimethoprim all pose a significant risk for selection of AMR in the environment. https://doi.org/10.1289/EHP6635.
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http://dx.doi.org/10.1289/EHP6635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577113PMC
October 2020

α-enolase is highly expressed in liver cancer and promotes cancer cell invasion and metastasis.

Oncol Lett 2020 Nov 24;20(5):152. Epub 2020 Aug 24.

Department of Clinical Laboratory Center, Shaoxing People's Hospital, Shaoxing, Zhejiang 312000, P.R. China.

The expression levels of α-enolase, also known as enolase 1 (ENO1), in liver cancer tissues and the autoantibody levels of ENO1 in the sera of patients with liver cancer were detected to investigate the function of ENO1 in the invasion and metastasis of liver cancer, as well as its clinical diagnostic value. Small interfering RNA (siRNA) was used to disrupt ENO1 gene expression in HepG2 and Huh7 liver cancer cells. The proliferation ability of liver cancer cells was assessed using Cell Counting Kit-8 (CCK-8); the migration ability of liver cancer cells was assessed using scratch tests; and the migration and invasion abilities of liver cancer cells were assessed using Transwell assays. ENO1 expression in liver cancer tissues (43.8%) was significantly higher than that in benign liver lesions (15.2%) (P=0.005). The serum anti-ENO1 antibody levels in the liver cancer group were significantly higher than those in the control and benign liver lesion groups (P<0.001). After ENO1 gene interference, the proliferation, migration and invasion abilities of HepG2 and Huh7 liver cancer cells exhibited different degrees of suppression. The results revealed that ENO1 promotes liver cancer invasion and metastasis; ENO1 plays an important role in liver cancer and can be used as a potential liver cancer-associated marker.
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http://dx.doi.org/10.3892/ol.2020.12003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471668PMC
November 2020

MicroRNA-27b targets CBFB to inhibit differentiation of human bone marrow mesenchymal stem cells into hypertrophic chondrocytes.

Stem Cell Res Ther 2020 09 11;11(1):392. Epub 2020 Sep 11.

The Key Laboratory of Pathobiology, Ministry of Education, Department of Pathology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China.

Background: Human bone marrow-derived mesenchymal stem cells (hBMSCs) have chondrocyte differentiation potential and are considered to be a cell source for cell-transplantation-mediated repair of cartilage defects, including those associated with osteoarthritis (OA). However, chondrocyte hypertrophic differentiation is a major obstacle for the application of hBMSCs in articular cartilage defect treatment. We have previously shown that microRNA-27b (miR-27b) inhibits hypertrophy of chondrocytes from rat knee cartilage. In this study, we investigated the role of miR-27b in chondrocyte hypertrophic differentiation of hBMSCs.

Methods: Chondrogenic marker and microRNA expression in hBMSC chondrogenic pellets were evaluated using RT-qPCR and immunohistochemistry. The hBMSCs were transfected with miR-27b before inducing differentiation. Gene and protein expression levels were analyzed using RT-qPCR and western blot. Coimmunoprecipitation was used to confirm interaction between CBFB and RUNX2. Luciferase reporter assays were used to demonstrate that CBFB is a miR-27b target. Chondrogenic differentiation was evaluated in hBMSCs treated with shRNA targeting CBFB. Chondrogenic hBMSC pellets overexpressing miR-27b were implanted into cartilage lesions in model rats; therapeutic effects were assessed based on histology and immunohistochemistry.

Results: The hBMSCs showed typical MSC differentiation potentials. During chondrogenic differentiation, collagen 2 and 10 (COL2 and COL10), SOX9, and RUNX2 expression was upregulated. Expression of miR-140, miR-143, and miR-181a increased over time, whereas miR-27b and miR-221 were downregulated. Cartilage derived from hBMSC and overexpressing miR-27b exhibited higher expression of COL2 and SOX9, but lower expression of COL10, RUNX2, and CBFB than did the control cartilage. CBFB and RUNX2 formed a complex, and CBFB was identified as a novel miR-27b target. CBFB knockdown by shRNA during hBMSC chondrogenic differentiation led to significantly increased COL2 and SOX9 expression and decreased COL10 expression. Finally, miR-27b-overexpressing hBMSC chondrogenic pellets had better hyaline cartilage morphology and reduced expression of hypertrophic markers and tend to increase repair efficacy in vivo.

Conclusion: MiR-27b plays an important role in preventing hypertrophic chondrogenesis of hBMSCs by targeting CBFB and is essential for maintaining a hyaline cartilage state. This study provides new insights into the mechanism of hBMSC chondrocyte differentiation and will aid in the development of strategies for treating cartilage injury based on hBMSC transplantation.
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http://dx.doi.org/10.1186/s13287-020-01909-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488425PMC
September 2020

Evolution of antibiotic resistance at low antibiotic concentrations including selection below the minimal selective concentration.

Commun Biol 2020 Sep 3;3(1):467. Epub 2020 Sep 3.

European Centre for Environment and Human Health, University of Exeter Medical School, ESI, University of Exeter, Penyrn Campus, Penryn, Cornwall, TR10 9EF, UK.

Determining the selective potential of antibiotics at environmental concentrations is critical for designing effective strategies to limit selection for antibiotic resistance. This study determined the minimal selective concentrations (MSCs) for macrolide and fluoroquinolone antibiotics included on the European Commission's Water Framework Directive's priority hazardous substances Watch List. The macrolides demonstrated positive selection for ermF at concentrations 1-2 orders of magnitude greater (>500 and <750 µg/L) than measured environmental concentrations (MECs). Ciprofloxacin illustrated positive selection for intI1 at concentrations similar to current MECs (>7.8 and <15.6 µg/L). This highlights the need for compound specific assessment of selective potential. In addition, a sub-MSC selective window defined by the minimal increased persistence concentration (MIPC) is described. Differential rates of negative selection (or persistence) were associated with elevated prevalence relative to the no antibiotic control below the MSC. This increased persistence leads to opportunities for further selection over time and risk of human exposure and environmental transmission.
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http://dx.doi.org/10.1038/s42003-020-01176-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471295PMC
September 2020

Furin Cleavage Site Is Key to SARS-CoV-2 Pathogenesis.

bioRxiv 2020 Aug 26. Epub 2020 Aug 26.

SARS-CoV-2 has resulted in a global pandemic and shutdown economies around the world. Sequence analysis indicates that the novel coronavirus (CoV) has an insertion of a furin cleavage site (PRRAR) in its spike protein. Absent in other group 2B CoVs, the insertion may be a key factor in the replication and virulence of SARS-CoV-2. To explore this question, we generated a SARS-CoV-2 mutant lacking the furin cleavage site (ΔPRRA) in the spike protein. This mutant virus replicated with faster kinetics and improved fitness in Vero E6 cells. The mutant virus also had reduced spike protein processing as compared to wild-type SARS-CoV-2. In contrast, the ΔPRRA had reduced replication in Calu3 cells, a human respiratory cell line, and had attenuated disease in a hamster pathogenesis model. Despite the reduced disease, the ΔPRRA mutant offered robust protection from SARS-CoV-2 rechallenge. Importantly, plaque reduction neutralization tests (PRNT ) with COVID-19 patient sera and monoclonal antibodies against the receptor-binding domain found a shift, with the mutant virus resulting in consistently reduced PRNT titers. Together, these results demonstrate a critical role for the furin cleavage site insertion in SARS-CoV-2 replication and pathogenesis. In addition, these findings illustrate the importance of this insertion in evaluating neutralization and other downstream SARS-CoV-2 assays.

Importance: As COVID-19 has impacted the world, understanding how SARS-CoV-2 replicates and causes virulence offers potential pathways to disrupt its disease. By removing the furin cleavage site, we demonstrate the importance of this insertion to SARS-CoV-2 replication and pathogenesis. In addition, the findings with Vero cells indicate the likelihood of cell culture adaptations in virus stocks that can influence reagent generation and interpretation of a wide range of data including neutralization and drug efficacy. Overall, our work highlights the importance of this key motif in SARS-CoV-2 infection and pathogenesis.

Article Summary: A deletion of the furin cleavage site in SARS-CoV-2 amplifies replication in Vero cells, but attenuates replication in respiratory cells and pathogenesis in vivo. Loss of the furin site also reduces susceptibility to neutralization .
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http://dx.doi.org/10.1101/2020.08.26.268854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457603PMC
August 2020

MicroRNA-200c Inhibits the Metastasis of Triple-Negative Breast Cancer by Targeting ZEB2, an Epithelial-Mesenchymal Transition Regulator.

Ann Clin Lab Sci 2020 Jul;50(4):519-527

Department of Clinical Laboratory, Taizhou Central Hospital (Taizhou University Hospital), Taizhou

Objective: Triple-negative breast cancer (TNBC) is one of the most common malignant, highly heterogeneous tumors in women. MicroRNAs (miRNAs), such as miR-200c, play an important role in various types of malignant cancer, including TNBC. However, the biological role of miRNA-200c in TNBC is not well understood. In this study, we investigated the mechanism of miR-200c in the growth of TNBC.

Methods: Reverse transcription quantitative polymerase chain reaction was used to detect the expression of miR-200c in TNBC tissues and TNBC cells. Cell Counting Kit-8 (CCK-8) assays, wound healing, and transwell assays were used to observe the effects of miR-200c on TNBC cell proliferation, migration, and invasion, respectively. The expression of epithelial-mesenchymal transition (EMT) markers were detected by Western blotting. Dual luciferase reporter assays were used to test whether ZEB2 is a novel target of miR-200c.

Result: Our results show that ZEB2 is a novel target of miR-200c and that ZEB2 mediates the metastasis of triple-negative breast cancer via EMT.

Conclusion: miR-200c attenuates TNBC cell invasion and EMT by targeting ZEB2. Our data therefore suggest that miR-200c may be used to develop novel early-stage diagnostic and therapeutic strategies for TNBC.
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July 2020

Distinguishing between COVID-19 and influenza during the early stages by measurement of peripheral blood parameters.

J Med Virol 2021 02 13;93(2):1029-1037. Epub 2020 Aug 13.

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 infection. This study aims to examine the changes in peripheral blood parameters during the early stages of COVID-19 and influenza. We analyzed the peripheral blood parameters of 169 COVID-19 patients and 131 influenza patients during the early-onset stage. Results from the patients with COVID-19 were compared with those from healthy controls and influenza patients. In addition, results from patients with common and severe COVID-19 were further compared. There were significant differences between COVID-19 and influenza patients in terms of age, white blood cell count, platelet count, percentage of neutrophils, percentage of lymphocytes, percentage of monocytes, percentage of eosinophils, percentage of basophils, neutrophil, count and monocyte count. Two parameters (monocyte count and percentage of basophils) were combined to clarify the diagnostic efficacy of COVID-19 and influenza and the area under the curve was found to be 0.772. Comparison of peripheral blood parameters from common COVID-19, severe COVID-19, and influenza patients revealed many differences during the early disease stages. The diagnostic formula developed by this study will be of benefit for physicians in the differentiation of COVID-19 and influenza.
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http://dx.doi.org/10.1002/jmv.26384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436548PMC
February 2021

Assessing the analgesic efficacy of oral epigallocatechin-3-gallate on epidural catheter analgesia in patients after surgical stabilisation of multiple rib fractures: a prospective double-blind, placebo-controlled clinical trial.

Pharm Biol 2020 Dec;58(1):741-744

Department of Anesthesiology, Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.

Context: Thoracic trauma results in multiple rib fractures (MRF), and surgical stabilisation of rib fractures (SSRF) can relieve fracture pain. Epigallocatechin-3-gallate (EGCG) is reported to exhibit beneficial effects in bone-related metabolic and differentiation processes.

Objective: To study the clinical effect of EGCG on regional analgesia for pain relief in MRF patients after SSRF.

Materials And Methods: Ninety-seven MRF patients (61 males, 36 females) who were on epidural catheter analgesia after SSRF were recruited. They were randomly divided into: oral EGCG 100 mg (oral grade) twice daily for 10 days and placebo groups. Pain scores, incentive spirometry (IS) volumes, respiratory rate and oxygen saturation (SpO) were assessed day 10 after SSRF.

Results: Comparing results from the placebo and EGCG group, in the 10-day intervention course, oral EGCG reduced pain score (8 at base line vs. 4 at end of intervention in EGCG group,  < 0.05; 4 in EGCG group vs. 6 in placebo group at end of intervention,  < 0.05), improved IS volume (713 at base line vs. 1072 at end of intervention in EGCG group,  < 0.05; 1072 in EGCG group vs. 953 in placebo group at end of intervention,  < 0.05) and respiratory rate (24 at base line vs. 15 at end of intervention in EGCG group,  < 0.05; 15 in EGCG group vs. 19 in placebo group at end of intervention,  < 0.05). However, no further enhancing effect on SpO was observed in the EGCG group (0.98 in EGCG group vs. 0.98 in placebo group at end of intervention,  > 0.05).

Discussion And Conclusions: Although the study is limited by a relatively small sample size and lack of serum factor analysis, the key results and the study design, for the first time, nevertheless pave the way for trials with larger number of patients to understand the effect of EGCG in MRF patients that are undergoing SSRF.
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http://dx.doi.org/10.1080/13880209.2020.1797123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470119PMC
December 2020

Differential distribution and potential regulatory roles of estrogen receptor 2a and 2b in the pituitary of ricefield eel Monopterus albus.

Gen Comp Endocrinol 2020 11 18;298:113554. Epub 2020 Jul 18.

Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, PR China; Biology Department, School of Life Sciences, Sun Yat-Sen University, Guangzhou, PR China. Electronic address:

Estrogens play important regulatory roles in the pituitary of vertebrates. Two forms of estrogen receptor 2 (Esr2), namely Esr2a and Esr2b, are identified in teleosts, but their differential roles remain to be fully elucidated. In the present study, expression and potential functional roles of Esr2a and Esr2b were characterized in ricefield eels. esr2a and esr2b mRNA were broadly distributed in tissues, with high levels observed in the brain, pituitary, and gonads. In order to examine the cellular localization of Esr2a and Esr2b in the pituitary, specific antisera against ricefield eel Esr2a and Esr2b were generated, respectively. Interestingly, immunohistochemistry and Western blot analysis revealed that Esr2a and Esr2b were differentially distributed in the pituitary, with the former localized to the adenohypophysis while the latter to the neurohypophysis. Dual fluorescent immunostaining showed that immunoreactive Esr2a was present in Gh and Prl cells, but not in Lh and Fsh cells. Estradiol (E) stimulated lhb and prl gene expression in dispersed pituitary cells of intersexual ricefield eels, but had no effects on gh, fshb, and gnrhr2 gene expression and Gh release. Results of the present study are helpful for further understanding the roles and mechanisms of estrogen signals in the pituitary.
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http://dx.doi.org/10.1016/j.ygcen.2020.113554DOI Listing
November 2020

Pleural effusion and acute right heart failure due to a ruptured right sinus of Valsalva aneurysm and correction by surgical intervention.

J Cardiovasc Thorac Res 2020 12;12(2):150-151. Epub 2020 May 12.

Department of ICU, the Fuwai Yunnan Cardiovascular Hospital, Kunming, China.

In the study, we present the case of a 65-year-old male with rupture of right SVA into the right atrium that caused pleural effusion and acute right-sided heart failure (ARHF), which corrected by surgical intervention.
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http://dx.doi.org/10.34172/jcvtr.2020.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321002PMC
May 2020

Detection of human papillomavirus distinguishes second primary tumors from lung metastases in patients with squamous cell carcinoma of the cervix.

Thorac Cancer 2020 08 3;11(8):2297-2305. Epub 2020 Jul 3.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: In patients with squamous cell carcinoma of the cervix (SCCC), a squamous cell carcinoma (SqCC) in the lung represents either a second primary tumor or metastasis. This distinction between second primary tumors and lung metastases in patients with SCCC significantly influences patient prognosis and therapy. Here, we aimed to differentiate second primary tumors from lung metastases in patients with SCCC by exploring the HPV status in SqCCs involving the lung within a large cohort.

Methods: P16 expression was assessed using immunohistochemistry on tissue microarrays including a total of 415 primary lung SqCCs and 21 lung SqCCs with prior SCCC. Following this, we performed HPV DNA typing and the sensitive RNAscope in situ method to screen all the cases for HPV E6/E7 expression, which is a more reliable indicator of transcriptively active HPV in tumor cells.

Results: The p16 positive expression rate was 13.7% (57/415) in primary lung SqCCs, but HPV DNA was not detected in any of the 57 primary lung SqCC cases that positively expressed p16. In contrast, HPV DNA was detected in all cases (21/21) with prior SCCC. Consistently, all 21 lung SqCCs with prior SCCC (21/21) showed extensive HPV16 E6/E7 expression. In striking contrast, none of the primary lung SqCCs (0/415) had a detectable RNAscope signal.

Conclusions: HPV does not seem to play a role in the development of primary lung SqCCs. HPV detection may be helpful in distinguishing second primary tumors from lung metastases in patients with SCCC.
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http://dx.doi.org/10.1111/1759-7714.13544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396378PMC
August 2020

Discovery of Adamantane Carboxamides as Ebola Virus Cell Entry and Glycoprotein Inhibitors.

ACS Med Chem Lett 2020 Jun 1;11(6):1160-1167. Epub 2020 May 1.

Arisan Therapeutics, 11189 Sorrento Valley Road, Suite 104, San Diego, California 92121, United States.

We identified and explored the structure-activity-relationship (SAR) of an adamantane carboxamide chemical series of Ebola virus (EBOV) inhibitors. Selected analogs exhibited half-maximal inhibitory concentrations (EC values) of ∼10-15 nM in (VSV) pseudotyped EBOV (pEBOV) infectivity assays, low hundred nanomolar EC activity against wild type EBOV, aqueous solubility >20 mg/mL, and attractive metabolic stability in human and nonhuman liver microsomes. X-ray cocrystallographic characterizations of a lead compound with the EBOV glycoprotein (GP) established the EBOV GP as a target for direct compound inhibitory activity and further provided relevant structural models that may assist in identifying optimized therapeutic candidates.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294737PMC
June 2020

Upregulation of programmed death ligand 1 by liver kinase B1 and its implication in programmed death 1 blockade therapy in non-small cell lung cancer.

Life Sci 2020 Sep 6;256:117923. Epub 2020 Jun 6.

Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin Province, China; School of Life Sciences, Henan University, Kaifeng, Henan Province, China. Electronic address:

Aims: Liver kinase B1 (LKB1) deficiency is associated with reduced expression of programmed death ligand 1 (PD-L1) and inferior clinical outcomes of PD-1/PD-L1 blockade in non-small cell lung cancer (NSCLC). This study aimed to investigate the mechanism by which LKB1 regulates PD-L1 expression and its role in programmed death 1 (PD-1) blockade therapy in NSCLC.

Main Methods: The impact of LKB1 on PD-L1 was assessed by western blot, qRT-PCR and immunohistochemistry in NSCLC. Activators/inhibitors of AMPK and NRF2 were applied to explore the mechanisms underlying the regulation of PD-L1 by LKB1. Efficiency of combined application of metformin and PD-1 blockade was evaluated in immunocompetent C57BL/6 mice.

Key Findings: A remarkable positive correlation between LKB1 and PD-L1 expression was demonstrated in NSCLC tissues. Knockdown of LKB1 decreased PD-L1 in TC-1 cells, whereas overexpression of LKB1 increased PD-L1 in A549 cells. We further characterized that AMPK mediated the upregulation of PD-L1 by LKB1. Inhibition of AMPK or NRF2 markedly reduced PD-L1 in LKB1-intact NSCLC cells. In contrast, activation of AMPK or NRF2 reversed PD-L1 expression in LKB1-deficient NSCLC cells. Combined administration of metformin and anti-PD-1 antibody efficiently inhibited the growth of LKB1-intact tumors, whereas no obvious suppression was observed in LKB1-deficient tumors.

Significance: These findings demonstrated that LKB1 upregulates PD-L1 expression in NSCLC by activating the AMPK and KEAP1/NRF2 signaling. Activation of LKB1-AMPK with metformin improves the therapeutic effect of PD-1 blockade in NSCLC with wild-type LKB1.
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http://dx.doi.org/10.1016/j.lfs.2020.117923DOI Listing
September 2020

Discovery of 6-Phenylhexanamide Derivatives as Potent Stereoselective Mitofusin Activators for the Treatment of Mitochondrial Diseases.

J Med Chem 2020 07 18;63(13):7033-7051. Epub 2020 Jun 18.

Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, Missouri 63110, United States.

Mutations in the mitochondrial fusion protein mitofusin (MFN) 2 cause the chronic neurodegenerative condition Charcot-Marie-Tooth disease type 2A (CMT2A), for which there is currently no treatment. Small-molecule activators of MFN1 and MFN2 enhance mitochondrial fusion and offer promise as therapy for this condition, but prototype compounds have poor pharmacokinetic properties. Herein, we describe a rational design of a series of 6-phenylhexanamide derivatives whose pharmacokinetic optimization yielded a 4-hydroxycyclohexyl analogue, , with the potency, selectivity, and oral bioavailability of a preclinical candidate. Studies of - and -4-hydroxycyclohexyl isostereomers unexpectedly revealed functionality and protein engagement exclusively for the trans form, . Preclinical absorption, distribution, metabolism, and excretion (ADME) and target engagement studies of support further development of 6-phenylhexanamide derivatives as therapeutic agents for human CMT2A.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731667PMC
July 2020

An epidemiological survey of laryngopharyngeal reflux disease at the otorhinolaryngology-head and neck surgery clinics in China.

Eur Arch Otorhinolaryngol 2020 Oct 25;277(10):2829-2838. Epub 2020 May 25.

Department of Otorhinolaryngology, Head and Neck Surgery, Fenyang Hospital, Shanxi Province, Fenyang, Shanxi, China.

Purpose: Using the Reflux Symptom Index (RSI), this nationwide study aimed to investigate the incidence, diagnostic status, risk factors, and common symptoms of adult laryngopharyngeal reflux disease (LPRD) at otorhinolaryngology-head and neck surgery (OHNS) clinics in China.

Methods: This multicenter cross-sectional survey began at the different institutions ranged from July to October 2017, and the duration was 12 months. A total of 90,440 eligible patients were finally enrolled from 72 medical institutions in China. All these patients completed the questionnaire based on RSI. In this study, LPRD was defined as RSI > 13.

Results: There were 9182 with LPRD among the 90,440 eligible participants (10.15%). However, only 1294 had a history of LPRD diagnosis among those with LPRD (14.09%). There were regional differences in the frequency of LPRD (P < 0.001). The proportions of patients with LPRD in males (vs. females), middle- and old-aged patients (vs. young), with current smoking history (vs. no smoking), and current drinking history (vs. no drinking) were significantly higher (all P < 0.001). Middle and old age, current smoking, and drinking history were independent predictors of LPRD (all P < 0.001, OR 1.240, 1.261, and 1.481, respectively). "Sensations of something stuck in throat or a lump in throat", "clearing throat", and "excess throat mucus or postnasal drip" were the most frequent clinical symptoms in patients with LPRD.

Conclusions: LPRD has a high incidence at the OHNS clinics in China. However, the diagnostic status of this disease is not optimistic. Older age, smoking, and drinking history were risk factors for LPRD.
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http://dx.doi.org/10.1007/s00405-020-06045-0DOI Listing
October 2020

Jatrorrhizine Hydrochloride alleviates tert-butyl hydroperoxide-induced endothelial cell injury through its anti-inflammatory activity and PPAR-γ activation.

Cell Mol Biol (Noisy-le-grand) 2020 May 15;66(2):125-129. Epub 2020 May 15.

Department of Nephrology, Xi'an Central Hospital Affiliated to Xi'an Jiaotong University, Xi'an, PR China.

The aim of this study was to investigate whether Jatrorrhizine hydrochloride (JAH) can attenuate oxidative damage of endothelial cells by regulating mitochondrial function and inflammatory response. It was found that JAH inhibited tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in mouse brain endothelial cells (MBECs) by increasing cell viability and inhibiting cell apoptosis. Moreover, JAH significantly inhibited the production of reactive oxygen species (ROS) and lipid peroxidation. It enhanced mitochondrial membrane potential (MMP) and maintained ATP synthesis. In addition, JAH regulated the expressions of inflammatory cytokines and increased the activation of endothelial nitric oxide synthase (eNOS). The protective effect of JAH was related to the protein expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) gene. In conclusion, these results suggest that JAH may have therapeutic potential for ischemic stroke associated with endothelial dysfunction through its antioxidant and anti-inflammatory properties.
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May 2020