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Anti-EGFR antibody monotherapy for colorectal cancer with severe hyperbilirubinemia: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 557-562页

作者： Toshiaki Tsurui Yuya Hirasawa Yutaro Kubota Kiyoshi Yoshimura Takuya Tsunoda Department of Medical Oncology Showa UniversityTokyo 1428555Japan Department of Clinical Immuno Oncology Clinical Research Institute of Clinical Pharmacology and TherapeuticsShowa UniversityTokyo 1578577Japan

BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic ***,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently *** SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe *** tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated *** RAS or BRAF mutations were *** Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was *** drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly ***,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse *** Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.

关键词： Colorectal neoplasms Panitumumab Chemotherapy Hyperbilirubinemia Jaundice Case report

Sexual dimorphism of G protein-coupled receptor signaling in the brain

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Neural Regeneration Research 2024年第8期19卷 1635-1636页

作者： Sara Aljoudi Hamdan Hamdan Khaled S.Abd-Elrahman Department of Physiology and Immunology College of Medicine and Health SciencesKhalifa UniversityAbu DhabiUnited Arab Emirates Healthcare Engineering Innovation Center(HEIC) Khalifa UniversityAbu DhabiUnited Arab Emirates Department of Anesthesiology Pharmacology and Therapeuticsand Djavad Mowafaghian Center for Brain HealthUniversity of British ColumbiaVancouverBCCanada Department of pharmacology and therapeutics College of Medicine and Health ScienceKhalifa UniversityAbu DhabiUnited Arab Emirates Department of pharmacology and Toxicology Faculty of PharmacyAlexandria UniversityAlexandriaEgypt

G protein-coupled receptors(GPCRs)represent the most substantial family of membrane receptors that are targeted by *** and Drug Administration-approved *** of the preclinical research to understand the pharmacology of... 详细信息

关键词： drugs clinical targeted

Glial response in the midcingulate cortex in Huntington’s disease

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Neural Regeneration Research 2025年第1期20卷 207-208页

作者： Thulani H.Palpagama Andrea Kwakowsky Center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand pharmacology and therapeutics School of MedicineGalway Neuroscience CenterUniversity of GalwayGalwayIreland

Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and *** can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive *** causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

关键词： Huntington degeneration cortex

Neuroinflammation as a therapeutic target in Huntington's disease

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Neural Regeneration Research 2025年第3期20卷 817-818页

作者： Andrea Kwakowsky Thulani H.Palpagama Center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand pharmacology and therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： Huntington inflammation Medicine

Severe aconite poisoning successfully treated with veno-arterial extracorporeal membrane oxygenation:A case report

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World Journal of Clinical Cases 2024年第2期12卷 399-404页

作者： Saeko Kohara Yoshito Kamijo Ryoko Kyan Ichiro Okada Eiju Hasegawa Soichiro Yamada Koichi Imai Asuka Kaizaki-Mitsumoto Satoshi Numazawa Department of Critical Care Medicine and Trauma National Hospital Organization Disaster Medical CenterTokyo 1900014Japan Department of Clinical Toxicology Saitama Medical UniversitySaitama 3500495Japan Saitama Prefectural Institute of Public Health Saitama Prefectural Institute of Public HealthSaitama 3550133Japan Division of Toxicology Department of PharmacologyToxicology and TherapeuticsShowa University School of PharmacyTokyo 1428555Japan

BACKGROUND Most species of aconite contain highly toxic aconitines,the oral ingestion of which can be fatal,primarily because they cause ventricular *** describe a case of severe aconite poisoning that was successfully treated through venoarterial extracorporeal membrane oxygenation(VA-ECMO)and in which detailed toxicological analyses of the aconite roots and biological samples were performed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).CASE SUMMARY A 23-year-old male presented to the emergency room with circulatory collapse and ventricular arrhythmia after ingesting approximately half of a root labeled,“Aconitum japonicum Thunb”.Two hours after arrival,VA-ECMO was initiated as circulatory collapse became refractory to antiarrhythmics and *** hours after arrival,an electrocardiogram revealed a return to sinus *** patient was weaned off VA-ECMO and the ventilator on hospital days 3 and 5,*** hospital day 15,he was transferred to a psychiatric *** other half of the root and his biological samples were toxicologically analyzed using LC-MS/MS,revealing 244.3 mg/kg of aconitine and 24.7 mg/kg of mesaconitine in the *** on admission contained 1.50 ng/mL of *** hospital day 2,neither were *** on admission showed 149.09 ng/mL of aconitine and 3.59 ng/mL of mesaconitine,but these rapidly decreased after hospital day *** The key to saving the life of a patient with severe aconite poisoning is to introduce VA-ECMO as soon as possible.

关键词： Aconite poisoning Fatal arrhythmia Veno-arterial extracorporeal membrane oxygenation Aconitine Mesaconitine Case report

The potential mechanism of Isodon suzhouensis against COVID-19 via EGFR/TLR4 pathways

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Food Science and Human Wellness 2024年

作者： Hong Duan Wei Wang Shu Li Han Li Ghulam Jilany Khan Fawang Liu Kefeng Zhai Lili Li Zhaojun Wei General Clinical Research Center Anhui Wanbei Coal-Electricity Group General Hospital Department of pharmacology and therapeutics Faculty of Pharmacy University of Central Punjab College of Biological and Food Engineering Anhui Polytechnic University School of Biological and Food Engineering Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province Suzhou University School of Food and Biological Engineering Hefei University of Technology

Corona Virus Disease 2019 (COVID-19) has brought the new challenges to scientific research. Isodon suzhouensis has good anti-inflammatory and antioxidant stress effects， which is considered as a potential treatment for COVID-19. The possibility for the treatment of COVID-19 with suzhouensis and its potential mechanism of action were explored by employing molecular docking and network pharmacology. Network pharmacology and molecular docking were used to screen drug targets， and Lipopolysaccharide (LPS) induced RAW264.7 and NR8383 cells inflammation model was used for experimental verification. Collectively a total of 209 possible linkages against 18 chemical components from suzhouensis and 1194 COVID-19 related targets were selected. Among these， 164 common targets were obtained from the intersection of suzhouensis and COVID-19. GO and KEGG enriched 582 function targets and 87 target proteins pathways， respectively. The results from molecular docking studies revealed that rutin， vitexin， isoquercitrin and quercetin had significant binding ability with SARS-CoV-23CLpro and ACE2. In vitro studies showed that Isodon suzhouensis extract (ISE) may inhibit the activation of PI3K/Akt pathway and the expression level of downstream pro-inflammatory factors by inhibiting the activation of EGFR in RAW264.7 cells induced by LPS. In addition， ISE was able to inhibit the activation of TLR4/NF-κB signaling pathway in NR8383 cells exposed to LPS. Overall， the network pharmacology and in vitro studies conclude that active components from suzhouensis have strong therapeutic potential against COVID-19 through multi-target， multi-pathway dimensions and can be a promising candidate against COVID-19.

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Correlations between serum kidney injury molecule-1,cystatin C and immunosuppressants:A cross-sectional study of renal transplant patients in Bahrain

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Journal of Biomedical Research 2024年第3期38卷 269-277页

作者： Kannan Sridharan Shamik Shah Mona Al Hammad Fatima Ali Mohammed Sindhan Veeramuthu Mona Abdulla Taher Mustafa Mohamed Hammad Lamees Jawad Eman Farid Department of pharmacology and therapeutics College of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain Department of Nephrology Salmaniya Medical ComplexManamaKingdom of Bahrain Department of Internal Medicine College of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain Salmaniya Medical Complex ManamaKingdom of Bahrain Department of Laboratory Medicine Salmaniya Medical ComplexManamaKingdom of Bahrain Department of Microbiology Immunologyand Infectious DiseasesCollege of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for *** creatinine is the standard for monitoring kidney function;however,cystatin C(Cys C)and kidney injury molecule-1(KIM-1)have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney ***,we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil,tacrolimus,sirolimus,everolimus,or cyclosporine to evaluate kidney *** used both the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)2021 equation,which is based on creatinine and combined creatinine with Cys C,and the CKD-EPI 2012 equation,which is based on Cys C alone,to estimate glomerular filtration rate(GFR).Then,we assessed the association between serum KIM-1 and GFR<90 mL per minute per 1.73 *** observed significantly higher serum Cys C levels in patients with the elevated serum creatinine,compared with those with normal serum *** estimated GFRs based on creatinine were significantly higher than those based on the other equations,while a significant positive correlation was observed among all *** KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations.A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR<90 mL per minute per 1.73 *** observed a significant correlation between serum creatinine and Cys C in our renal transplant ***,serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

关键词： KIM-1 cystatin C mycophenolate mofetil tacrolimus everolimus sirolimus cyclosporine

Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-López Iva Tic David Valle-García Marta Ribalta-Vilella Luis Labrador Deb Ranjan Banerjee Ana Guerrero Gemma Casadesus Coralie Poulard Mercè Pallàs Christian Grinán-Ferré Department of pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of pharmacology and therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer Lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UMR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAMP8

Small molecule conjugates with selective estrogen receptor β agonism promote anti-aging benefits in metabolism and skin recovery

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2137-2152页

作者： Tarik Zahr Vijay K.Boda Jian Ge Lexiang Yu Zhongzhi Wu Jianwen Que Wei Li Li Qiang Naomi Berrie Diabetes Center Columbia UniversityNew YorkNY 10032USA Department of Molecular pharmacology and therapeutics Columbia UniversityNew YorkNY 10032USA Department of Pharmaceutical Sciences College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Drug Discovery Center College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Division of Digestive and Liver Diseases Columbia UniversityNew YorkNY 10032USA Center for Human Development Columbia UniversityNew YorkNY 10027USA Department of Pathology and Cell Biology Columbia UniversityNew YorkNY 10032USA Department of Medicine Columbia UniversityNew YorkNY 10032USA

Estrogen is imperative to mammalian reproductivity,metabolism,and ***,the hormone activating estrogen receptor(ERs)αcan cause major safety concerns due to the enrichment of ERαin female tissues and certain *** contrast,ERβis more broadly expressed in metabolic tissues and the ***,it is desirable to generate selective ERβagonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERα***,we report the design and production of small molecule conjugates containing selective non-steroid ERβagonists Gtx878 or *** of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity,visceral adipose integrity,skeletal muscle function,and skin health,with validation in *** further uncovered the benefits of ERβconjugates in the skin using two inducible skin injury mouse models,showing increased skin basal cell proliferation,epidermal thickness,and wound ***,our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.

关键词： Estrogen receptorβ Aging Metabolism Skin injury Muscle metabolism Small molecule conjugates Regeneration Adiposity