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Glycolysis and glucose metabolism as a target for bioenergetic and neuronal protection in glaucoma

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Neural Regeneration Research 2024年第8期19卷 1637-1638页

作者： Pete A.Williams Robert J.Casson Department of Clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden Ophthalmic Research Laboratories Discipline of Ophthalmology and Visual SciencesUniversity of AdelaideAdelaideAustralia

Vision is arguably our most valued sense,yet approximately 340 million people globally suffer blindness or moderate visual impairment,highlighting the need to further develop and advance treatments for ophthalmic *** refers to a group of ocular disorders united by a clinically characteristic optic neuropathy with associated retinal ganglion cell loss.

关键词： metabolism glaucoma globally

Small molecular decoys in Alzheimer's disease

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Neural Regeneration Research 2024年第8期19卷 1658-1659页

作者： Sho Oasa Valentina L.Kouznetsova Igor F.Tsigelny Lars Terenius Department of Clinical Neuroscience Center for Molecular MedicineKarolinska InstitutetStockholmSweden San Diego Supercomputer Center University of California San DiegoLa JollaCAUSA Department of Neurosciences University of California San DiegoLa JollaCAUSA Department of Clinical Neuroscience Karolinska University HospitalKarolinska InstitutetStockholmSweden

Recent progress in the treatment of Alzheimer’s disease(AD)using antibodies against amyloid sustains amyloid generation as a key process in *** formation starts with two amyloidbeta(Aβ)molecules interacting(dimer formation)followed by an accelerating build-up of socalled protofibrils,which turn into fibrils,which accumulate in the characteristic plaques.

关键词： Alzheimer decoy Aβ

Is convenience really king? Comparative evaluation of catastrophic costs due to tuberculosis in the public and private healthcare sectors of Viet Nam: a longitudinal patient cost study

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贫困所致传染病(英文) 2024年第2期13卷 17-28页

作者： Nguyen Hoa Binh Quang Vo Luan Nguyen Forse Rachel Jeanette Wiemers Anja Maria Christine Huynh Huy Ba Dong Thuy Thi Thu Phan Yen Thi Hoang Creswell Jacob Dang Thi Minh Ha Nguyen Lan Huu Shedrawy Jad L?nnroth Knut Nguyen Tuan Dinh Van Dinh Luong Annerstedt Kristi Sidney Codlin Andrew James National Lung hospital Ha Noi Viet Nam Friends for International TB Relief Ha Noi Viet Nam Department of Global Public Health WHO Collaboration Centre On Tuberculosis and Social Medicine Karolinska Institute Stockholm Sweden Stop TB Partnership Geneva Switzerland Pham Ngoc Thach hospital Ho Chi Minh City Viet Nam

Background In Viet Nam, tuberculosis (TB) represents a devastating life-event with an exorbitant price tag, partly due to lost income from daily directly observed therapy in public sector care. Thus, persons with TB may seek care in the private sector for its flexibility, convenience, and privacy. Our study aimed to measure income changes, costs and catastrophic cost incurrence among TB-affected households in the public and private *** Between October 2020 and March 2022, we conducted 110 longitudinal patient cost interviews, among 50 patients privately treated for TB and 60 TB patients treated by the National TB Program (NTP) in Ha Noi, Hai Phong and Ho Chi Minh City, Viet Nam. Using a local adaptation of the WHO TB patient cost survey tool, participants were interviewed during the intensive phase, continuation phase and post-treatment. We compared income levels, direct and indirect treatment costs, catastrophic costs using Wilcoxon rank-sum and chi-squared tests and associated risk factors between the two cohorts using multivariate *** The pre-treatment median monthly household income was significantly higher in the private sector versus NTP cohort (USD 868 vs USD 578;P=0.010). However, private sector treatment was also significantly costlier (USD 2075 vs USD 1313;P=0.005), driven by direct medical costs which were 4.6 times higher than costs reported by NTP participants (USD 754 vs USD 164;P<0.001). This resulted in no significant difference in catastrophic costs between the two cohorts (Private: 55% vs NTP: 52%;P=0.675). Factors associated with catastrophic cost included being a single-person household [adjusted odds ratio [(aOR=13.71; 95% confidence interval (CI): 1.36–138.14;P=0.026], unemployment during treatment (aOR=10.86; 95%CI: 2.64–44.60;P<0.001) and experiencing TB-related stigma (aOR=37.90; 95%CI: 1.72–831.73;P=0.021).Conclusions Persons with TB in Viet Nam face similarly high risk of catastrophic costs whether treated in the

关键词： Tuberculosis Patient cost Catastrophic cost Private sector Comparative analysis Viet Nam

Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

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Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li Department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden Department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Physiology and Pharmacology Karolinska InstitutetStockholmSweden Department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA Department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

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Neural Regeneration Research 2025年第1期20卷 41-53页

作者： Alessio Canovai Pete A.Williams Department of Biology University of PisaPisaItaly Department of Clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

Impact of low-intensity extracorporeal shockwave therapy on vascular parameters and sexual function in patients with arteriogenic erectile dysfunction

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Asian Journal of Andrology 2024年第4期26卷 344-348页

作者： Matteo Rubino Anna Ricapito Marco Finati Ugo G Falagario Pasquale Annese Vito Mancini Gian Maria Busetto Luigi Cormio Giuseppe Carrieri Carlo Bettocchi Andrology Unit Department of Urology and Renal TransplantationUniversity of FoggiaFoggia 71122Italy Department of Molecular Medicine and Surgery Karolinska InstitutetStockholm 17177Sweden Department of Urology Bonomo Teaching HospitalUniversity of FoggiaAndria 76123Italy.

Previous published studies have shown an improvement of penile hemodynamic parameters after low-intensity extracorporeal shockwave therapy(Li-ESWT).However,the clinical significance of these findings remains unclear,and definitive selection criteria for Li-ESWT based on preexisting comorbidities have yet to be *** was an observational study of 113 patients with ED,evaluated between January 2019 and December 2021 in Andrology Unit at the Department of Urology and Renal Transplantation,University of Foggia(Foggia,Italy).Penile dynamic Doppler was performed to evaluate vascular parameters and 5-item version of the International Index of Erectile Dysfunction(IIEF-5)questionnaire was administered to assess the severity of *** was repeated 1 month after *** with a peak systolic velocity(PSV)30 cm s−1 at posttherapeutic penile dynamic Doppler.A clinically significant IIEF-5 score improvement was observed in 7 patients,21 patients,and 2 patients with mild-to-moderate,moderate,and severe pretreatment ED,*** different outcomes were assessed based on smoking habits,previous pelvic surgery,or use of oral phosphodiesterase-5 inhibitor(PDE5i).On the other side,only 1(6.7%)in 15 patients with diabetes mellitus showed an IIEF-5 score improvement after *** treatment determined a significant increase in PSV and correlated IIEF-5 improvement in ED *** advantage seemed particularly evident for moderate ED and was not affected by smoking habits,previous pelvic surgery,and use of ***,diabetic patients did not benefit from the treatment.

关键词： arteriogenic erectile dysfunction International Index of Erectile Function low-intensity extracorporeal shockwave therapy peak systolic velocity

Bidirectional relationship between type 2 diabetes mellitus and coronary artery disease:Prospective cohort study and genetic analyses

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Chinese Medical Journal 2024年第5期137卷 577-587页

作者： Wenqiang Zhang Li Zhang Chenghan Xiao Xueyao Wu Huijie Cui Chao Yang Peijing Yan Mingshuang Tang Yutong Wang Lin Chen Yunjie Liu Yanqiu Zou Ling Zhang Chunxia Yang Yuqin Yao Jiayuan Li Zhenmi Liu Xia Jiang Ben Zhang Department of Epidemiology and Biostatistics Institute of Systems EpidemiologyWest China-Peking Union Medical College C.C.Chen Institute of HealthWest China School of Public Health and West China Fourth HospitalSichuan UniversityChengduSichuan 610041China Department of Maternal Child and Adolescent HealthWest China School of Public Health and West China Fourth HospitalSichuan UniversityChengduSichuan 610041China Department of Iatrical Polymer Material and Artificial Apparatus School of Polymer Science and EngineeringSichuan UniversityChengduSichuan 610041China Department of Occupational and Environmental Health West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduSichuan 610041China Department of Nutrition and Food Hygiene West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduSichuan 610041China Department of Clinical Neuroscience Karolinska InstitutetStockholm 17177Sweden

Background:While type 2 diabetes mellitus(T2DM)is considered a putative causal risk factor for coronary artery disease(CAD),the intrinsic link underlying T2DM and CAD is not fully *** aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and ***:We evaluated phenotypic associations using data from the United Kingdom Biobank(N=472,050).We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM,with and without adjustment for body mass index(BMI)(T2DM:N_(case)/N_(control)=74,124/824,006;T2DM adjusted for BMI[T2DM_(adj)BMI]:N_(case)/N_(control)=50,409/523,897)and for CAD(N_(case)/N_(control)=181,522/984,168).We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM(N_(case)/N_(control)=180,834/1,159,055).Results:Observational analysis suggested a bidirectional relationship between T2DM and CAD(T2DM→CAD:hazard ratio[HR]=2.12,95%confidence interval[CI]:2.01–2.24;CAD→T2DM:HR=1.72,95%CI:1.63–1.81).A positive overall genetic correlation between T2DM and CAD was observed(r_(g)=0.39,P=1.43×10^(-75)),which was largely independent of BMI(T2DM_(adj)BMI–CAD:r_(g)=0.31,P=1.20×10^(–36)).This was corroborated by six local signals,among which 9p21.3 showed the strongest genetic ***-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic *** randomization analysis supported a bidirectional causal relationship(T2DM→CAD:odds ratio[OR]=1.13,95%CI:1.11-1.16;CAD→T2DM:OR=1.12,95%CI:1.07-1.18),which was confirmed in multiancestry individuals(T2DM→CAD:OR=1.13,95%CI:1.10-1.16;CAD→T2DM:OR=1.08,95%CI:1.04-1.13).This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors,with mediation proportions of 54.1%(95%CI:24.9-83.4%)and 90.4%(95%CI

关键词： Type 2 diabetes mellitus Coronary artery disease Phenotypic association Genetic correlation Mendelian randomization

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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Journal of Pharmaceutical Analysis 2024年第1期14卷 100-114页

作者： Sze Wan Hung Massimiliano Gaetani Yiran Li Zhouyurong Tan Xu Zheng Ruizhe Zhang Yang Ding Gene Chi Wai Man Tao Zhang Yi Song Yao Wang Jacqueline Pui Wah Chung Tak Hang Chan Roman A.Zubarev Chi Chiu Wang Department of Obstetrics&Gynaecology The Chinese University of Hong KongHong KongChina Division of Physiological Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Chemical Proteomics Core Facility Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Unit of Chemical Proteomics Science for Life Laboratory(SciLifeLab)StockholmSE 17177Sweden Center for Reproductive Medicine Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450003China Department of Chemistry McGill UniversityMontrealH3A2K6Canada Department of Pharmacological&Technological Chemistry I.M.Sechenov First Moscow State Medical UniversityMoscow119146Russia Reproduction and Development Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine The Chinese University of Hong KongHong KongChina

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the *** is a major pathophysiology in *** previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain *** this study,we demonstrated that oral ProEGCG can be effective in preventing and treating ***,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,*** simulation and BioLayer interferometry were used to confirm their binding *** results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)*** vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling ***,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

关键词： Molecular targets ProEGCG EGCG Angiogenesis Treatment Endometriosis

Reduced efficacy of single-dose albendazole against Ascaris lumbricoides, and Trichuris trichiura, and high reinfection rate after cure among school children in southern Ethiopia: a prospective cohort study

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Infectious Diseases of Poverty 2024年第1期13卷 95-96页

作者： Tigist Dires Gebreyesus Eyasu Makonnen Tafesse Tadele Kalkidan Mekete Habtamu Gashaw Heran Gerba Eleni Aklillu Department of Global Public Health Karolinska Institutet Karolinska University Hospital Stockholm Sweden Ethiopian Food and Drug Authority Addis Ababa Ethiopia Center for Innovative Drug Development and Therapeutic Trials for Africa College of Health Sciences Addis Ababa University Addis Ababa Ethiopia Departments of Pharmacology and Clinical Pharmacy College of Health Sciences Addis Ababa University Addis Ababa Ethiopia College of Medicine and Health Sciences Hawassa University Hawassa Ethiopia Ethiopian Public Health Institute Addis Ababa Ethiopia

Background Mass drug administration(MDA)program of albendazole to at-risk populations as preventive chemo-therapy is the core public health intervention to control soil-transmitted helminths(STHs).Achieving this goal relies on drug effectiveness in reducing the parasite reservoirs in the community and preventing *** assessed the effcacy of albendazole against STH parasite infection and reinfection status after *** A total of 984 schoolchildren infected with at least one type of STH parasite(hookworm,Ascaris lumbri-coides,Trichuris trichiura)in southern Ethiopia were enrolled and received albendazole and praziquantel in MDA campaign conducted from January to March *** exams at week-4 and at week-8 of post-MDA were done using Kato Katz *** primary outcome was effcacy assessed by cure rate(CR)and fecal egg reduction rates(ERRs)at four weeks of *** secondary outcome was reinfection status defined as parasite egg positivity at eight weeks among those who were cured at 4 weeks of *** comparisons in CR and related factors were assessed with chi-square or Fisher's exact *** of CR were examined through univariate and multi-variate regression *** The overall CR and ERR for hookworm infection were 97.2%(95%CI:94.6-99.4)and 97.02%,*** overall CR and ERR for *** were 71.5%(95%CI:68.3-74.6)and 84.5% *** overall CR and ERR and for *** were 49.5%(95%CI:44.8-54.2)and 68.3%,*** CR among moderate *** infec-tion intensity was 28.6%.Among children cured of hookworm,*** and *** at week 4 post-MDA,4.6%,18.3% and 52.4% became reinfected at week-8 post-MDA,*** lower CR(36.6%)and higher reinfection after cure(60.6%)among *** and *** coinfected children than *** only(CR=69.6%,reinfection rate=15.1%)or *** only infected children(CR=55.6%,reinfection rate=47.1%)was obse

关键词： Soil transmitted helminths Neglected tropical diseases Preventive chemotherapy Albendazole School age children Ethiopia