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Proton-pump inhibitor use does not affect semen luality in subfertile men

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Asian Journal of Andrology 2018年第3期20卷 290-293页

作者： Sorena Keihani James R Craig Chong Zhang Angela P Presson Jeremy B Myers William O Brant kenneth i aston Benjamin R Emery Timothy G Jenkins Douglas T Carrell James M Hotaling Division of Urology Department of Surgery University of Utah Salt Lake City Utah 84132 USA Division of Epidemiology Department of Internal Medicine University of Utah Salt Lake City Utah 84132 USA Andrology and iVF Laboratory Department of Surgery (Urology) University of Utah Salt Lake City Utah 84108 USA

Proton-pump inhibitors （PPis） are among the most widely used drugs worldwide. PPi use has recently been linked to adverse changes in semen quality in healthy men; however, the effects of PPi use on semen parameters remain largely unknown specifically in cases with male factor infertility. We examined whether PPi use was associated with detrimental effects on semen parameters in a large population of subfertile men. We retrospectively reviewed data from 12 257 subfertile men who had visited our fertility clinic from 2003 to 2013. Patients who reported using any PPis for 〉3 months before semen sample collection were included; 7698 subfertile men taking no medication served as controls. Data were gathered on patient age, medication use, and conventional semen parameters; patients taking any known spermatotoxic medication were excluded. Linear mixed-effect regression models were used to test the effect of PPi use on semen parameters adjusting for age. A total of 248 patients （258 samples） used PPis for at least 3 months before semen collection. in regression models, PPi use （either as the only medication or when used in combination with other nonspermatotoxic medications） was not associated with statistically significant changes in semen parameters. To our knowledge, this is the largest study to compare PPi use with semen parameters in subfertile men. Using PPis was not associated with detrimental effects on semen quality in this retrospective study.

关键词： infertility proton-pump inhibitors semen analysis sperm quality spermatozoa

特发性少精子症和无精子症与Pygo2基因蛋白编码区SNPs的相关性

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遗传 2013年第5期35卷 616-622页

作者：葛少钦 Jeanine Grifin 刘丽华 kenneth i.aston Luke Simon Timothy G.Jenkins Benjamin R.Emery Douglas T.Carrell Andrology and iVF Laboratories Division of UrologyDepartment of SurgeryUniversity of Utah School of MedicineSalt Lake City UT 84108USA 河北大学医学部 Department of Obstetrics and Gynecology University of Utah School of MedicineSalt Lake City UT 84108USA Department of Physiology University of Utah School of MedicineSalt Lake City UT 84108USA

男性不育常伴随精子数量减少。Pygo2基因在染色质重塑的伸长精细胞中表达,其功能受损会导致精子形成阻滞和精子生成减少而引发不育。文章旨在检测引起人特发性少精子症和无精子症的Pygo2基因突变。从77例正常生育力男性和195例特发性少... 详细信息

男性不育常伴随精子数量减少。Pygo2基因在染色质重塑的伸长精细胞中表达,其功能受损会导致精子形成阻滞和精子生成减少而引发不育。文章旨在检测引起人特发性少精子症和无精子症的Pygo2基因突变。从77例正常生育力男性和195例特发性少精子症和无精子症患者静脉血提取DNA,采用聚合酶链式反应-测序方法对Pygo2基因3个蛋白质编码区进行测序对比,非同义单核苷酸多态性(Single nucleotide polymorphisms,SNPs)位点分别用SiFT、Polyphen-2和Mutation Taster软件进行诱发蛋白质结构和表型改变的检测和分析。结果表明,195例患者中,178例(30例轻度或中度少精子症,57例重度少精子症和91例无精子症)基因序列分析报告完好,无精子症中3例患者分别在2个位点(rs61758740,rs141722381)发生了非同义突变SNPs,重度少精子症中1例患者在位点rs61758741发生了非同义突变,3个突变位点在SNPs基因数据库都已有报道,轻度或中度少精子症患者以及正常生育力男性中不存在SNPs。rs61758740可使PYGO2蛋白第141位蛋氨酸(M)变为异亮氨酸(i),rs61758741使PYGO2蛋白第261位碱性赖氨酸(K)变为酸性谷氨酸(E),rs141722381使PYGO2蛋白第240位亲水侧链天冬酰胺(N)变为疏水侧链异亮氨酸(i)。软件分析表明,在所发现的3个SNP非同义突变位点中,rs141722381引起的单个氨基酸改变会导致PYGO2蛋白空间结构破坏和诱发相关疾病。因此,Pygo2基因蛋白质编码序列区SNPs可能是特发性少精子症和无精子症的诱发因素之一,导致男性不育。

关键词：特发性少精子症特发性无精子症 Pygo2基因 SNPs

Pefabloc- A sulfonyl fluoride serine protease inhibitor blocks induction of Diotericin in Drosoohila 1（2）mbn cells

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insect Science 2012年第4期19卷 472-476页

作者： Karin C. Johansson kenneth Soderhall Maria i. Lind Department of Comparative Physiology Evolutionary Biology Centre Uppsala University Uppsala Sweden

insects protect themselves against microbial infection by an efficient innate immune system that is activated by recognition ofinvariant microbial surface molecules. in the fruit fly Drosophila melanogaster the presence of bacteria is associated with expression of antimicrobial peptides in host immune-competent tissues. Host receptors detect infection and relay the signal to mount the appropriate immune response. in Drosophila hemocyte- like l（2）mbn cells pre-infection treatment with Pefabloc, a commonly used serine protease inhibitor, induced two major effects： it blocked expression of the antibacterial peptide Diptericin in response to live Gram-negative bacteria and bacterial surface molecules （crude lipopolysaccharide contaminated by peptidoglycans） and it induced morphological changes.

关键词： cell morphology diptericin Drosophila iMD pathway immune response,proteinase inhibitor

Charge storage mechanisms of cathode materials in rechargeable aluminum batteries

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Science China Chemistry 2021年第11期64卷 1888-1907页

作者： Jiashen Meng Lujun Zhu Aderemi B.Haruna kenneth i.Ozoemena Quanquan Pang School of Materials Science and Engineering Peking UniversityBeijing100871China Beijing Key Laboratory of Theory and Technology for Advanced Batteries Materials Peking UniversityBeijing100871China Molecular Sciences institute School of ChemistryUniversity of the WitwatersrandPrivate Bag 3PO WitsJohannesburg2050South Africa

Rechargeable aluminum batteries(RABs)have attracted great interest as one of the most promising candidates for large-scale energy storage because of their high volumetric capacity,low cost,high safety and the abundance of ***,compared with the aluminum anodes,the cathode materials face more problems including low specific capacity,relatively sluggish kinetics in most host structures and/or limited cycle lifespan,which pose the major challenge for RABs in further practical *** the past years,intensive efforts have been devoted to developing new cathode materials and/or designing engineered nanostructures to greatly improve RABs’electrochemical *** addition to nanotechnologybased electrode structure designs,the intrinsic chemical structures and charge storage mechanisms of cathode materials play an equally crucial role,if not more,in revolutionizing the battery *** review,here,focuses on current understandings into the charge storage mechanisms of cathode materials in RABs from a chemical reaction point of ***,the fundamental chemistry,charge storage mechanisms and design principles of RAB cathode materials are *** on different ion charge carriers,the current cathode materials are classified into four groups,including Al^(3+)-hosting,Al Cl_(4)^(-)-hosting,Al Cl_(2)^(+)/Al Cl_(2)^(+)-hosting,and Cl^(-)-hosting cathode ***,the respective typical electrode structures,optimization strategies,electrochemical performances and charge storage mechanisms are discussed in detail to establish their chemistry-structure-property *** review on current understandings of the cathode charge storage mechanisms will lay the ground and hopefully set new directions into the rational design of high-performance cathode materials in RABs,and open up new opportunities for designing new electrolyte systems with respect to the targeted cathode systems.

关键词： rechargeable aluminum batteries charge storage mechanisms cathode materials charge carriers large-scale energy storage

Diabetes mellitus and glymphatic dysfunction:Roles for oxidative stress,mitochondria,circadian rhythm,artificial intelligence,and imaging

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World Journal of Diabetes 2025年第1期16卷 39-48页

作者： kenneth Maiese National Heart Lungand Blood InstituteNational Institutes of HealthBethesdaMD 20810United States

Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the *** represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately *** cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm *** pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic *** studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.

关键词： Artificial intelligence Circadian rhythm Clock genes Diabetes mellitus magnetic resonance imaging Glymphatic pathway Mitochondria Oxidative stress Programmed cell death Sleep fragmentation

The uprising of metabolic dysfunction-associated fatty liver disease(MAFLD)in acute-on-chronic liver failure(ACLF)

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Hepatobiliary Surgery and Nutrition 2021年第6期10卷 857-859页

作者： kenneth i.Zheng Ming-Hua Zheng NAFLD Research Center Department of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina institute of Hepatology Wenzhou Medical UniversityWenzhouChina Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province WenzhouChina

Metabolic dysfunction-associated fatty liver disease(MAFLD)(1)is currently the leading cause of chronic liver disease in the United States(US)and Europe,and the second leading cause for liver transplantation(2).Despite advancements in knowledge over the past decade,MAFLD-related cirrhosis is the most rapidly growing etiology for acute-on-chronic liver failure(ACLF)in the US(3-5).ACLF is a syndrome characterized by acute deterioration of cirrhosis and extrahepatic failure of 1 or more *** represents a significant healthcare burden,and is associated with high short-term ***,an epidemiology study showed a 3-fold increase in MAFLD-related ACLF waitlisted patients in the United Network for Organ Sharing(UNOS)database from 2005 to 2017(4),and a similar trend was observed in the European Liver Transplant Registry(ELTR)database(5).This is particularly concerning,as the quick rise in MAFLD-related ACLF has created a major gap between the number of patients requiring a liver transplant and the number of available liver donors.

关键词： acute epidemiology organs

Targeting the core of neurodegeneration:FoxO,mTOR,and SiRT1

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Neural Regeneration Research 2021年第3期16卷 448-455页

作者： kenneth Maiese Cellular and Molecular Signaling New York New YorkNYUSA

The global increase in lifespan noted not only in developed nations,but also in large developing countries parallels an observed increase in a significant number of noncommunicable diseases,most notable neurodegenerative *** disorders present a number of challenges for treatment options that do not resolve disease ***,it is believed by the year 2030,the services required to treat cognitive disorders in the United States alone will exceed$2 trillion *** forkhead transcription factors,silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae),the mechanistic target of rapamycin,and the pathways of autophagy and apoptosis offer exciting avenues to address these challenges by focusing upon core cellular mechanisms that may significantly impact nervous system *** pathways are intimately linked such as through cell signaling pathways involving protein kinase B and can foster,sometimes in conjunction with trophic factors,enhanced neuronal survival,reduction in toxic intracellular accumulations,and mitochondrial *** mechanisms among these pathways also exist that can oversee reparative processes in the nervous ***,mammalian forkhead transcription factors,silent mating type information regulation 2 homolog 1,mechanistic target of rapamycin,and autophagy can lead to cellular demise under some scenarios that may be dependent upon the precise cellular environment,warranting future studies to effectively translate these core pathways into successful clinical treatment strategies for neurodegenerative disorders.

关键词： Alzheimer's disease apoptosis autophagy erythropoietin forkhead FoxO mechanistic target of rapamycin silent mating type information regulation 2 homolog 1

Novel applications of trophic factors,Wnt and WiSP for neuronal repair and regeneration in metabolic disease

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Neural Regeneration Research 2015年第4期10卷 518-528页

作者： kenneth Maiese Cellular and Molecular Signaling

Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in sig-niifcant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but are susceptible to the detrimental outcomes of this disorder. Dia-betes mellitus leads to multiple complications in the central and peripheral nervous systems that include cognitive impairment, retinal disease, neuropsychiatric disease, cerebral ischemia, and peripheral nerve degeneration. Although multiple strategies are being considered, novel target-ing of trophic factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1, and stem cell tissue regeneration are considered to be exciting prospects to overcome the cellular mechanisms that lead to neuronal injury in diabetes mellitus involving oxidative stress, apoptosis, and au-tophagy. Pathways that involve insulin-like growth factor-1, ifbroblast growth factor, epidermal growth factor, and erythropoietin can govern glucose homeostasis and are intimately tied to Wnt signaling that involves Wnt1 and Wnt1 inducible signaling pathway protein 1 （CCN4） to foster control over stem cell proliferation, wound repair, cognitive decline,β-cell proliferation, vascular regeneration, and programmed cell death. Ultimately, cellular metabolism through Wnt signal-ing is driven by primary metabolic pathways of the mechanistic target of rapamycin and AMP activated protein kinase. These pathways offer precise biological control of cellular metabolism, but are exquisitely sensitive to the different components of Wnt signaling. As a result, unexpected clinical outcomes can ensue and therefore demand careful translation of the mechanisms that govern neural repair and regeneration in diabetes mellitus.

关键词： Alzheimer’s disease AMPK apoptosis autophagy central nervous system CCN4 EGF diabetes mellitus erythropoietin EPO FGF iGF-1 mTOR neuron neuropathy oxidative stress psychiatric stem cells WiSP1 Wnt

Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

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Neural Regeneration Research 2016年第3期11卷 372-385页

作者： kenneth Maiese Cellular and Molecular Signaling Newark NJ USA

Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this *** impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic *** mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（Pi 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SiRT1）,Wnt1 inducible signaling pathway protein 1（WiSP1）,and growth *** a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this *** studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.

关键词： Akt AMP activated protein kinase(AMPK) apoptosis Alzheimer’s disease autophagy β-cell cancer cardiovascular disease caspase CCN family diabetes mellitus epidermal growth factor erythropoietin fibroblast growth factor forkhead transcription factors Fox O FRAP1 hamartin(tuberous sclerosis 1)/tuberin(tuberous sclerosis 2)(TSC1/TSC2) insulin mechanistic target of rapamycin(mTOR) m TOR Complex 1(m T ORC1) m TOR Complex 2(m TORC2) nicotinamide nicotinamide adenine dinucleotide(NAD+) non-communicable diseases oxidative stress phosphoinositide 3-kinase(Pi 3-K) programmed cell death silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae)(SiRT1) sirtuin stem cells wingless Wnt Wnt1 inducible signaling pathway protein 1(WiSP1)