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Drug resistance mechanisms in cancers:Execution of prosurvival strategies

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Journal of Biomedical Research 2024年第2期38卷 95-121页

作者： Pavan Kumar Dhanyamraju Fels Cancer Institute of Personalized medicine Lewis-Katz School of MedicineTemple UniversityPhiladelphiaPA 19140USA

One of the quintessential challenges in cancer treatment is drug *** mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be *** phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug *** significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer ***,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment *** the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic ***,I highlight available treatment options and conclude with future directions.

关键词： cancer drug resistance mechanisms microRNAs treatment strategies

Lin28 as a therapeutic target for central nervous system regeneration and repair

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Neural Regeneration Research 2024年第2期19卷 397-398页

作者： Shuo Wang Shuxin Li Shriners Hospitals Pediatric Research Center Department of Neural SciencesLewis Katz School of Medicine at Temple UniversityPhiladelphiaPAUSA

Axon disconnection in the central nervous system(CNS) usually causes signal transduction failure and severe functional deficits in patients with neurological disorders. Currently, there is no cure for patients with CNS axon injury and they usually suffer from life-long neurological defects(e.g., paralysis, loss of sensory function, and autonomic dysfunction) and life-threatening complications(e.g., autonomic dysreflexia).

关键词： paralysis therapeutic system

Challenges with non-descriptive compliance labeling of end-stage renal disease patients in accessibility for renal transplantation

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World Journal of Nephrology 2024年第1期13卷 9-13页

作者： Benjamin Peticca Tomas M Prudencio Samuel G Robinson Sunil S Karhadkar Department of Surgery Lewis Katz School of Medicine at Temple University HospitalPhiladelphiaPA 19140United States

Non-descriptive and convenient labels are uninformative and unfairly project blame onto *** language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent behaviors of all providers involved in the enterprise of *** such as noncompliant and nonadherent serve as a reason for waitlist inactivation and limit access to life-saving *** labels fail to capture all the circum-stances surrounding a patient’s inability to follow their care regimen,trivialize social determinants of health variables,and bring unsubstantiated subjectivity into decisions regarding organ ***,insufficient Medicare coverage has forced patients to ration or stop taking medication,leading to allograft failure and their subsequent diagnosis of *** argue that perpetuating non-descriptive language adds little substantive information,in-creases subjectivity to the organ allocation process,and plays a major role in reduced access to *** patients with existing barriers to care,such as racial/ethnic minorities,these effects may be even more *** committees must ensure thorough documentation to correctly encapsulate the entirety of a patient’s position and give voice to an already vulnerable population.

关键词： End-stage renal disease Compliance Labeling Social determinants

Psychiatric Sequelae of Chronic Pruritic Dermatoses

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Open Journal of Medical Psychology 2024年第2期13卷 25-38页

作者： Kelly Frasier Vivian Li Kathleen Click Christina Dudzik Michelle Sobotka Evadne Rodriguez Karina Stech Nuvance Health/Vassar Brothers Medical Center Poughkeepsie NY USA school of Osteopathic medicine Kansas City University Kansas City MO USA Touro College of Osteopathic medicine Middleton Campus Middletown NY USA Abrazo Health Network Goodyear AZ USA school of medicine University of Missouri-Columbia Columbia MO USA lewis katz school of medicine at Temple University Philadelphia PA USA

This comprehensive review investigates the significant psychological impact and profound psychological comorbidities found in individuals suffering from chronic pruritic dermatoses, including atopic dermatitis, chronic urticaria, and prurigo nodularis. Highlighting the complex, reciprocal relationship between pruritus and psychiatric conditions such as depression, anxiety, and sleep disturbances, this paper elucidates the comprehensive impact of dermatological disorders on the skin in addition to the far-reaching effects on an individual’s psychological well-being. By evaluating the efficacy of integrated psychodermatological interventions, including cognitive behavioral therapy, mindfulness practices, pharmacological treatments, and innovative telepsychiatry and digital health solutions, this review aims to lay the foundation for a more holistic approach to treatment of concurrent dermatological and psychiatric conditions. Future research endeavors should delve deeper into the mechanistic foundation of the pruritus-psychiatry interface, the refinement of tailored treatment strategies, and the evaluation of long-term patient outcomes. In doing so, this review seeks to contribute to the optimization of patient care and well-being, underscoring the pivotal role of addressing both dermatological and psychological needs in achieving comprehensive health outcomes.

关键词： Psychodermatology Chronic Pruritic Dermatoses Psychological Comorbidities Integrated Interventions Pruritus-Psychiatry Interface

The Impact of Psychosocial Influences on Chronic Wound Healing

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Open Journal of Medical Psychology 2024年第3期13卷 39-57页

作者： Kelly Frasier Vivian Li Sara Christoforides Kathleen Daly Alexandra Loperfito Karina Stech Milena Dragovic Nuvance Health/Vassar Brothers Medical Center Poughkeepsie NY USA Lake Erie College of Osteopathic medicine New York NY USA Medical College of Georgia Augusta University Augusta GA USA Edward Via College of Osteopathic medicine Blacksburg VA USA lewis katz school of medicine Temple University Philadelphia PA USA College of Osteopathic medicine California Health Sciences University Clovis CA USA

This comprehensive review explores the intricate dynamics between psychosocial factors and chronic wound healing processes, specifically focusing on prevalent conditions such as pressure ulcers, diabetic foot ulcers, and venous leg ulcers. By examining the roles of psychiatric conditions, including depression, anxiety, and post-traumatic stress disorder (PTSD), this paper illuminates how these factors intricately influence wound healing dynamics, including mechanisms of pain perception and inflammatory responses. Furthermore, we evaluate the effectiveness of integrated biopsychosocial interventions, which encompass a holistic approach to wound care, thereby enhancing healing outcomes for dermatology patients. Future studies should focus on investigating the specific psychosocial determinants that significantly influence wound healing, exploring novel therapeutic strategies, and implementing personalized interventions to meet the unique needs of each patient. Such endeavors hold promise in advancing the fields of psychodermatology and wound management, fostering a deeper understanding and application of psychosocial considerations in dermatological care.

关键词： Psychosocial Factors Chronic Wound Healing Biopsychosocial Interventions Psychiatric Conditions Dermatology Patients

Optical redox imaging of ANT1-de-cient muscles

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 135-140页

作者： He N.Xu Ryan M.Morrow Min Feng Huaqing Zhao Douglas Wallace Lin Z.Li Britton Chance Laboratory of Redox Imaging Department of Radiology Perelman School of Medicine University of Pennsylvania PhiladelphiaPA 19104USA Center for Mitochondrial and Epigenomic medicine Children's Hospital of Philadelphia Research Institute Philadelphia PA 19104USA Center for Biostatistics and Epidemiology lewis katz school of medicine at Temple University Philadelphia PA 19140USA

Adenine nucleotide translocator(ANT)is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner *** plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the *** isoform ANT1 predominately expresses in cardiac and skeletal *** or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular *** aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-de-cient *** and quadriceps resected from age-matched wild type(WT)and ANT1-de-cient mice were snap-frozen in liquid *** Chance redox scanner was utilized to perform 3D optical redox *** sample underwent scanning across 3–5 *** averaging analysis showed no signi-cant differences in the redox indices(NADH,flavin adenine dinucleotide containing-flavoproteins Fp,and the redox ratio Fp/(NADH+Fp)between WT and ANT1-de-cient ***,quadriceps had higher Fp than hearts in both groups(p¼0:0004 and 0.01,respectively).Furthermore,the quadriceps were also more oxidized(a higher redox ratio)than hearts in WT group(p¼0:004).NADH levels were similar in all *** data suggest that under non-stressful physical condition,the ANT1-de-cient muscle cells were in the same mitochondrial state as WT ones and that the signi-cant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-de-cient *** imaging of muscles under physical stress can be conducted in future.

关键词： ANT1 redox ratio flavoproteins

Inhibition of central axon regeneration: perspective from chondroitin sulfate proteoglycans in lamprey spinal cord injury

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Neural Regeneration Research 2022年第9期17卷 1955-1956页

作者： Jianli Hu Li-Qing Jin Michael E.Selzer Shriners Hospitals Pediatric Research Center(Center for Neural Repair and Rehabilitation) Lewis Katz School of Medicine at Temple UniversityPhiladelphiaPAUSA Department of Neurology Lewis Katz School of Medicine at Temple UniversityPhiladelphiaPAUSA

Background:Failure of axon regeneration after spinal cord injury(SCI)underlies the paralysis that so profoundly affects patients’quality of *** factors are involved in the regeneration *** sulfate proteoglycans(CSPGs),normal constituents of the perineuronal nets in central nervous system(CNS),are secreted at the injury site and initially were thought to act as a purely physical *** the past decade,the receptor-like protein tyrosine phosphatases,protein tyrosine phosphatase sigma(PTPσ),and leukocyte common antigen-related phosphatase(LAR),have been identified as transmembrane receptors for *** two receptors for myelin-associated growth inhibitors,Nogo receptors 1 and 3(NgR1 and NgR3)also have been found to bind with CSPGs(Sharma et al.,2012).These findings suggest that CSPGs inhibit regeneration by interacting with these receptors,initiating downstream inhibitory signaling(Figure 1).

关键词： paralysis injury leukocyte

Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-Chuan He lewis L.Shi Chicago Medical school Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory medicine Shanghai Jiaotong University School of MedicineShanghai 200000China school of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

Oligodendrocyte pathology in fetal alcohol spectrum disorders

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Neural Regeneration Research 2022年第3期17卷 497-502页

作者： Nune Darbinian Michael E.Selzer Center for Neural Repair and Rehabilitation(Shriners Hospitals Pediatric Research Center) Lewis Katz School of Medicine at Temple UniversityPhiladelphiaPAUSA

The pathology of fetal alcohol syndrome and the less severe fetal alcohol spectrum disorders includes brain *** studies have shed light on the molecular mechanisms underlying these white matter *** models of fetal alcohol syndrome and human studies have shown suppressed oligodendrocyte differentiation and apoptosis of oligodendrocyte precursor *** exposure led to reduced expression of myelin basic protein and delayed myelin basic protein expression in rat and mouse models of fetal alcohol syndrome and in human histopathological *** studies have reported increased expression of many chemokines in dysmyelinating disorders in central nervous system,including multiple sclerosis and fetal alcohol *** ethanol exposure reduced levels of the neuroprotective insulin-like growth factor-1 in fetal and maternal sheep and in human fetal brain tissues,while ethanol increased the expression of tumor necrosis factor α in mouse and human *** matter lesions have been induced in the developing sheep brain by alcohol exposure in early *** fetal alcohol syndrome models have shown reduced axon diameters,with thinner myelin sheaths,as well as reduced numbers of oligodendrocytes,which were also morphologically aberrant *** of markers for mature myelination,including myelin basic protein,also were *** accumulating knowledge concerning the mechanisms of ethanol-induced dysmyelination could lead to the development of strategies to prevent dysmyelination in children exposed to ethanol during fetal *** studies using fetal oligodendrocyte-and oligodendrocyte precursor cell-derived exosomes isolated from the mother's blood may identify biomarkers for fetal alcohol syndrome and even implicate epigenetic changes in early development that affect oligodendrocyte precursor cell and oligodendrocyte function in *** combining various imaging modalities with mo

关键词： alcohol development dysmyelination ethanol fetal alcohol syndrome fetal brain myelin basic protein neurodegeneration oligodendrocyte injury oligodendrocyte precursor cells