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Metabolic dysfunction-associated steatotic liver disease:Navigating terminological evolution,diagnostic frontiers and therapeutic horizon-an editorial exploration

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World Journal of Gastroenterology 2024年第18期30卷 2387-2390页

作者： Aleksandra Boldys Lukasz Buldak department of Internal medicine and clinical pharmacology School of Medicine in KatowiceMedical University of SilesiaKatowice 40-752Poland

Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within *** redefinition of NAFLD in 2023 marked a significant reposition in terminology,emphasizing a broader understanding of liver steatosis and its associated *** is now recognized as a major risk factor for liver cirrhosis,hepatocellular carcinoma,and systemic complications such as cardiovascular diseases or systemic *** challenges arise,particularly in identifying MASLD in lean individuals,necessitating updated diagnostic protocols and investing in non-invasive diagnostic ***,there is an urgent need for effective treatments targeting MASLD,with emerging pharmacological options focusing on,among others,carbohydrate and lipid ***,understanding the roles of bile acid metabolism,the microbiome,and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic *** is a strong need to emphasize the importance of collaborative efforts in understanding,diagnosing,and managing MASLD to improve physicians’approaches and patient outcomes.

关键词： Metabolic dysfunction-associated steatotic liver disease Diagnostics Pathophysiology of metabolic dysfunction-associated steatotic liver disease Therapy of metabolic dysfunction-associated steatotic liver disease Therapeutic innovations

GRK2 inhibits Flt-1^(+)macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2024年第1期14卷 241-255页

作者： Xuezhi Yang Yingjie Zhao Qi Wei Xuemin Zhu Luping Wang Wankang Zhang Xiaoyi Liu Jiajie Kuai Fengling Wang Wei Wei Institute of clinical pharmacology Anhui Medical UniversityKey Laboratory of Anti-Inflammatory and Immune MedicineAnhui Collaborative Innovation Center of Anti-Inflammatory and Immune MedicineMinistry of EducationHefei 230032China department of clinical pharmacology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China

Rheumatoid arthritis(RA)is an autoimmune disease with a complex ***-derived macrophages(MDMs)infiltration are associated with RA *** have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor ***,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been ***,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)*** inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)*** experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting *** further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγ***,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 ***,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and ***,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular *** GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.

关键词： GRK2 Monocyte-derived macrophages Rheumatoid arthritis PPARg Flt-1

Agmatine ameliorates diabetes type 2-induced nephropathy in rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第1期14卷 8-16页

作者： Fatemah O.Kamel Ohoud Shagroud Mai AAlim A.Sattar Ahmad Gamal S Abd El-Aziz Abdulhadi S.Burzangi Duaa Bakhshwin Maha Jamal Shahid Karim department of clinical pharmacology Faculty of MedicineKing Abdulaziz UniversityJeddah 21589Saudi Arabia department of Anatomy Faculty of MedicineKing Abdulaziz UniversityJeddah 21589Saudi Arabia

Objective:To assess the nephroprotective potential of agmatine in a rat model of streptozotocin-induced diabetic ***:A single dose of streptozotocin(40 mg/kg)coupled with a fructose diet induced diabetes in Wistar ***(40 and 80 mg/kg)was administered to rats for 12 *** body weight and fasting blood glucose were measured *** level,urine output,total protein,albumin,blood urea nitrogen,creatinine,and cystatin-C were also determined at the end of the ***,superoxide dismutase,glutathione,interleukin-1β,interleukin-6,and tumor necrosis factor-alpha were evaluated in kidney *** study was also performed using hematoxylin and eosin ***:Agmatine at both doses significantly increased final body weight,and lowered fasting blood glucose,urine output,insulin,total protein,albumin,blood urea nitrogen,creatinine,and cystatin-C levels compared with the diabetic group(P<0.05).Inflammatory markers and antioxidant effect were significantly improved in agmatine-treated ***,the histopathological changes in renal structure were ameliorated by agmatine ***:Agmatine alleviates diabetic nephropathy by improving renal functions and reducing inflammation and oxidative *** molecular mechanisms of its nephroprotective actions need to be investigated in future study.

关键词： Agmatine Type 2 diabetes Nephropathy Oxidative stress Nephroprotection

Neuroprotective effect of liraglutide and memantine in a rat model of Alzheimer’s disease

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Asian Pacific Journal of Tropical Biomedicine 2024年第5期14卷 207-214页

作者： Duaa M.Bakhshwin Foziya W.Alhalabi Mohamad Omar Barasheed Ahmed M.Bakhshwin Maha H.Jamal Mohammed A.Bazuhair Fatemah O.Kamel Rania M.Magadmi Zoheir A Damanhouri Samar M.Alsaggaf department of clinical pharmacology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia Hera General Hospital MakkahSaudi Arabia department of Pathology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia department of clinical Anatomy Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia

Objective:To assess the effect of memantine combined with liraglutide on aluminum chloride(AlCl_(3))and D-galactose(D-GAL)-induced neurotoxicity in ***:Male Wistar rats were divided into 5 groups of 5 animals each:the positive control,the negative control,the memantine-treated group,the liraglutide-treated group,and the combination group treated with memantine and ***_(3)and D-GAL were used to induce *** tests,brain beta-amyloid protein,and oxidative stress biomarkers were ***:The Morris water maze test indicated an enhanced memory in the combination ***,the combination treatment of liraglutide and memantine resulted in a remarkable reduction in the beta-amyloid protein level in the brain *** inflammation and oxidative stress biomarkers were significantly reduced,and the levels of antioxidant parameters were ***:The combination of liraglutide and memantine exerts neuroprotective effects and enhances memory and cognitive functions in rats with Alzheimer’s disease.

关键词： Alzheimer’s disease Cognitive function Glucagonlike peptide-1 Liraglutide Memantine

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

Modern View on Potentials of Forensic Pharmaceutical and Pharmacological Expertise

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Journal of Forensic Science and medicine 2024年第1期10卷 62-67页

作者： Elena M.Vazhnichaya Nataliia M.Deviatkina department of pharmacology Clinical Pharmacology and PharmacyPoltava State Medical UniversityPoltavaUkraine

The great number of drugs and their variety have increased the potential of therapy but increased the risks of crimes related to the production,sale,and use of *** prosecution of such crimes requires pharmaceutical or pharmacological *** development of forensic pharmacy and forensic pharmacology is relevant and needs consideration of their modern *** purpose of the work is to analyze literature data on the scientific basis of forensic pharmaceutical and pharmacological expertise and their modern *** texts of articles,book chapters,and websites were studied using keywords relevant to the purpose of the *** is shown,that modern forensic pharmaceutical expertise is a separate type of expertise that focuses on the study of drugs and documents that regulate the production,distribution,and quality of *** uses the latest analytical methods of pharmacy.A pharmacologist analyzes body fluids and tissues and interprets the resulting data to help courts and investigators assess the role of a drug in the person’s behavior,illness,injury,or *** range of issues included in the pharmacological examination is fully within the competence of the forensic medical examination,which can be appointed in civil cases or criminal proceedings connected with harm to health or *** pharmacology is not the same as forensic toxicology or pharmacovigilance and requires a separate approach based on purely pharmacological knowledge.

关键词： drug expertise forensic pharmacology forensic pharmacy

Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1677-1692页

作者： Dongsheng Bai Jiawei Zhao Runde Wang Jiaying Du Chen Zhou Chunyang Gu Yuxiang Wang Lulu Zhang Yue Zhao Na Lu State Key Laboratory of Natural medicines Jiangsu Key Laboratory of Carcinogenesis and InterventionDepartment of PhysiologySchool of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing 210009China department of clinical pharmacology School of PharmacyNanjing Medical UniversityNanjing 211166China

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal *** identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is *** our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus *** enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory ***,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy ***,*** up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet *** espe-cially significant finding is that *** activates the AhR pathway,thereby promoting the expression of *** summary,our results strongly indicate that *** enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.

关键词： Chemotherapy Mucositis Eubacterium coprostanoligenes MUC2 AUF1

Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension

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Chronic Diseases and Translational medicine 2024年第2期10卷 102-117页

作者： Nicholas R.Powell Tyler Shugg Jacob Leighty Matthew Martin Rolf P.Kreutz Michael T.Eadon Dongbing Lai Tao Lu Todd C.Skaar Division of clinical pharmacology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA department of pharmacology and Toxicology School of MedicineIndiana UniversityIndianapolisIndianaUSA department of Cardiology School of MedicineKrannert Institute of CardiologyIndiana UniversityIndianapolisIndianaUSA Division of Nephrology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA department of Medical and Molecular Genetics School of MedicineIndiana UniversityIndianapolisIndianaUSA

Background Hypertension(HTN)involves genetic variability in the renin-angiotensin system and influences antihypertensive *** previously reported that angiotensinogen(AGT)messenger RNA(mRNA)is endogenously bound by miR-122-5p and rs699 A>G decreases reporter mRNA in the microRNA functional-assay *** AGT promoter variant rs5051 C>T is in linkage disequilibrium(LD)with rs699 A>G and increases AGT *** independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C>T counterbalances AGT decreased by rs699 A>G,and when these variants occur independently,it translates to HTN-related *** We used in silico,in vitro,in vivo,and retrospective models to test this *** In silico,rs699 A>G is predicted to increase miR-122-5p binding affinity by 3%.Mir-eCLIP results show rs699 is 40–45 nucleotides from the strongest microRNA-binding site in the AGT ***,rs699 A>G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression ***-Tissue Expression(GTEx)and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A>G occurs independently from rs5051 C>***,GTEx and the in vitro experiments suggest rs699 A>G confers cell-type-specific effects on AGT mRNA abundance,and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A>G associations with *** We found that rs5051 C>T and rs699 A>G significantly associate with systolic blood pressure in Black participants in the UK Biobank,demonstrating a fourfold larger effect than in White *** studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C>T or rs699 A>*** like this will help clinicians move beyond the use of race as a surrogate for genotype.

关键词： angiotensinogen genetic and genomic medicine hypertension rs699

Expect the unexpected:Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism

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World Journal of clinical Cases 2024年第7期12卷 1200-1204页

作者： Ana Majic Tengg Maja Cigrovski Berkovic Ivan Zajc Ivan Salaric Danko Müller Iva Markota department of Endocrinology DiabetesMetabolic Diseases and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia department for Sport and Exercise medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia department of Oral Surgery Clinical Hospital DubravaZagreb 10000Croatia University of Zagreb School of Dental medicine Zagreb 10000Croatia clinical department of Pathology and Cytology Clinical Hospital DubravaZagreb 10000Croatia

Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium *** commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and *** tumors are rare,benign,tumor-like bone lesions,occurring in 1.5%to 4.5%of patients with HPT,as a complication of an uncontrolled disease pathway,and are nowadays rarely seen in clinical *** tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic ***,it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone *** diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium,phosphorus,and *** when present,brown tumor is quite pathognomonic for HPT,the histologic finding often suggests a giant cell tumor,while clinical presentation might suggest other more frequent pathologies such as metastatic *** of brown tumors frequently focuses on managing the underlying HPT,which can often lead to regression and resolution of the lesion,without the need for surgical ***,in refractory cases or when dealing with large symptomatic lesions,surgical treatment may be necessary.

关键词： Brown tumor Hyperparathyroidism Lytic bone lesions Giant cell tumor