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Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

Neural Regeneration Research 2024年第3期19卷 529-535页

作者： Sandro Huenchuguala Juan Segura-Aguilar Escuela de Tecnología Médica Facultad de SaludUniversidad Santo TomásLos CarrerasOsornoChile Molecular&clinical pharmacology Instituto de Ciencias Biomedicas(ICBM)Faculty of medicineUniversity of ChileIndependenciaSantiagoChile

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal *** preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical ***,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic *** lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big *** our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic *** exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic *** endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in t

关键词： 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 6-hydroxydopamine aminochrome dopaminergic neurons DT-diaphorase exogenous neurotoxins glutathione transferase M2-2

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Traditional Chinese Medicine Integrated Responsive Microneedles for Systemic Sclerosis Treatment

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Research 2024年第1期2023卷 139-147页

作者： Xi Luan Xiaoxuan Zhang Min Nie Yuanjin Zhao Department of Rheumatology and Immunology Nanjing Drum Tower HospitalSchool of PharmacyClinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China

Traditional Chinese medicine,such as Tripterygium wilfordii and Paeonia lactiflora,has potential values in treating systemic sclerosis(SSc)and other autoimmune diseases,while their toxic side effect elimination and precise tropical drug delivery are still ***,we present multiple traditional Chinese medicine integrated photoresponsive black phosphorus(BP)microneedles(MNs)with the desired features for the SSc *** employing a template-assisted layer-by-layer curing method,such MNs with triptolide(TP)/paeoniflorin(Pae)needle tips and BP-hydrogel needle bottoms could be well *** combined administration of TP and Pae can not only provide anti-inflammatory,detoxification,and immunomodulatory effects to treat skin lesions in the early stage of SSc but also remarkably reduce the toxicity of single drug ***,the additive BPs possess good biocompatibility and near-infrared(NIR)responsiveness,imparting the MN photothermal-controlled drug release *** on these features,we have demonstrated that the traditional Chinese medicine integrated responsive MNs could effectively improve skin fibrosis and telangiectasia,reduce collagen deposition,and reduce epidermal thickness in the SSc mouse *** results indicated that the proposed Chinese medicine integrated responsive MNs had enormous potential in clinical therapy of SSc and other diseases.

关键词： needle precise template

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Avoiding misdiagnosis of multilocular thymic cysts as malignant tumors on computer tomography

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World Journal of clinical Cases 2024年第19期12卷 3671-3675页

作者： Yu-Hong Zhang Yan-Miao Liu Kai-Li Shen Jing-Jing Wu Fu-Shan Tang Key Laboratory of clinical pharmacy in Zunyi City Zunyi Medical UniversityZunyi 563006Guizhou ProvinceChina Department of Traditional Chinese Medicine Central Hospital in Jinchang CityJinchang 737102Gansu ProvinceChina The First clinical Institute Zunyi Medical UniversityZunyi 563006Guizhou ProvinceChina Department of clinical pharmacy Key Laboratory of Basic Pharmacology of Guizhou Province and School of PharmacyZunyi Medical UniversityZunyi 563006Guizhou ProvinceChina

This editorial provides insights from a case report by Sun et al published in the World Journal of clinical *** case report focuses on a case where a multilocular thymic cyst(MTC)was misdiagnosed as a thymic tumor,resulting in an unnecessary surgical *** MTCs and thymic tumors are rare conditions that heavily rely on radiological imaging for accurate ***,the similarity in their imaging presentations can lead to misinterpretation,resulting in unnecessary surgical *** to the ongoing lack of comprehensive knowledge about MTCs and thymic tumors,we offer a summary of diagnostic techniques documented in recent literature and examine potential causes of *** computer tomography(CT)values surpass 20 Hounsfield units and display comparable morphology,there is a risk of misdiagnosing MTCs as thymic *** various differential diagnostic methods like biopsy,molecular biology,multi-slice CT,CT functional imaging,positron emission tomography/CT molecular functional imaging,magnetic resonance imaging and radiomics,proves advantageous in reducing clinical misdiagnosis.A deeper understanding of these conditions requires increased attention and exploration by healthcare ***,the continued advancement and utilization of various diagnostic methods are expected to enhance precise diagnoses,provide appropriate treatment options,and improve the quality of life for patients with thymic tumors and MTCs in the *** advancement and utilization of various diagnostic methods are expected to enhance precise diagnoses,provide appropriate treatment options,and improve the quality of life for patients with thymic tumors and MTCs in the future.

关键词： Thymic tumor Multilocular thymic cyst Misdiagnosis Differential diagnosis Imaging manifestation Computed tomography

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The clinical antiprotozoal drug nitazoxanide and its metabolite tizoxanide extend Caenorhabditis elegans lifespan and healthspan

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3266-3280页

作者： Wenfeng Li Shuming Chen Jing Lang Jing Luo Jiahui Chen Liping Zhang Zhijie Sun Deli Dong Department of pharmacology China Pharmaceutical UniversityNanjing 210009China

The drugs extending healthspan in clinic have always been *** is an FDA-approved clinical antiprotozoal *** is rapidly metabolized to tizoxanide after absorption in *** previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK,oral nitazoxanide protects against experimental hyperlipidemia,hepatic steatosis,and ***,we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 ***,both nitazoxanide and tizoxanide improve high glucose-induced shortening of *** *** has been a clinical drug with a good safety profile,we suggest that it is a novel anti-aging drug.

关键词： Nitazoxanide Tizoxanide C.elegans Healthspan Lifespan AMPK Akt Mitochondrial uncoupling

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Harnessing endothelial cells and vascularization strategies for nerve regeneration

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Neural Regeneration Research 2024年第11期19卷 2337-2338页

作者： Papon Muangsanit Poppy Smith Virology and Cell Technology Research Team National Center for Genetic Engineering and Biotechnology(BIOTEC)National Science and Technology Development Agency(NSTDA)PathumthaniThailand UCL Centre for Nerve Engineering UCLLondonUK Department of pharmacology UCL School of PharmacyUCLLondonUK

Peripheral nerves are essential components of the human body’s communication system,transmitting signals between the central nervous system and various body *** resulting from trauma or disease can result in debilitating sensory and motor *** injuries,particularly those resulting in significant gaps in the nerve tissue,pose a formidable challenge for clinicians and *** their limitations,including limited availability and donor site morbidity,nerve autografts remain the clinical gold standard for treating nerve injuries.

关键词： injuries nerves donor

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Olfactory dysfunction and its related molecular mechanisms in Parkinson’s disease

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Neural Regeneration Research 2024年第3期19卷 583-590页

作者： Yingying Gu Jiaying Zhang Xinru Zhao Wenyuan Nie Xiaole Xu Mingxuan Liu Xiaoling Zhang College of pharmacy Nantong UniversityNantongJiangsu ProvinceChina

Changes in olfactory function are considered to be early biomarkers of Parkinson’s *** dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients with early-stage Parkinson’s disease,and can often predate the diagnosis by ***,olfactory dysfunction should be considered a reliable marker of the ***,the mechanisms responsible for olfactory dysfunction are currently *** this article,we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s *** the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels,we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s *** findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s ***,therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms,highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.

关键词： biomarker early-stage olfactory disorders olfactory dysfunction Parkinson’s disease

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Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration Research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing Geriatric Medical Research Center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular *** r,the causal relationship between hypertension and cerebral small vessel disease remains *** has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular *** hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and *** is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of *** review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive *** also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

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Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 52-68页

作者： Tingting Yang Jiayu Yuan Yuting Peng Jiale Pang Zhen Qiu Shangxiu Chen Yuhan Huang Zhenzhou Jiang Yilin Fan Junjie Liu Tao Wang Xueyan Zhou Sitong Qian Jinfang Song Yi Xu Qian Lu Xiaoxing Yin Jiangsu Key Laboratory of New Drug Research and clinical pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China Department of pharmacy Affiliated Lianyungang Hospital of Xuzhou Medical UniversityLianyungangJiangsu222061China Department of pharmacy The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China New Drug Screening Center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing210009China School of Life Sciences University of EssexEssex CO43SQUnited Kingdom Department of Urology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China Department of pharmacy Affiliated Hospital of Jiangnan UniversityWuxiJiangsu214000China

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological ***,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains ***,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH *** the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH *** of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)***’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 *** findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

关键词： Metformin Benign prostatic hyperplasia Sex steroid hormones homeostasis Proliferation DHT YAP1-TEAD4 heterodimer

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Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management

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Journal of Pharmaceutical Analysis 2024年第1期14卷 16-38页

作者： Nguyen Quang Thu Nguyen Tran Nam Tien Nguyen Thi Hai Yen Thuc-Huy Duong Nguyen Phuoc Long Huy Truong Nguyen Department of pharmacology and PharmacoGenomics Research Center Inje University College of MedicineBusan47392Republic of Korea Department of Chemistry University of EducationHo Chi Minh City700000Viet Nam Faculty of pharmacy Ton Duc Thang UniversityHo Chi Minh City700000Viet Nam

The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB *** strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and *** chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous *** technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics *** improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target *** on TDM,the dose would be optimized individually to achieve favorable *** is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome *** article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two ***,we discussed the advantages and disadvantages of this technique in practical *** pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was ***,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.

关键词： Tuberculosis Therapeutic drug monitoring LC-MS MIPD Pharmacometabolomics Precision medicine

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Noncanonical pyroptosis pathway: a promising target of traditional Chinese medicine in the treatment of sepsis-related injury

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Integrative Medicine Discovery 2024年第20期8卷 1-4页

作者： Yan-Yan Cen Pan Wang Ting Zhu Ya-Lan Xiong Xi-Chun Pan Department of pharmacology College of PharmacyArmy Medical UniversityChongqing 400038China.

Sepsis is a life-threatening disease of organ failure caused by dysregulated host responses to infection and other infectious ***-organ injury is the leading cause of high mortality and septic shock during *** studies suggest that noncanonical pyroptosis,characterized mainly by the direct activation of caspase-11-gasdermin D-mediated pyroptosis by cytoplastic lipopolysaccharide,is closely related to sepsis-related organ ***,this review summarizes recent advances in the regulatory mechanisms and targeted natural products from traditional Chinese medicine of the noncanonical pyroptosis pathway in sepsis-related injury.

关键词： sepsis-related injury noncanonical pyroptosis caspase-11 gasdermin D

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