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Cholesterol business:lifeor death byrust

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1247-1248页

作者： Shubhangi Gavalil Francesca Maremonti Andreas Linkermann Division of Nephrology Department of Internal Medicine 3University Hospital Carl Gustav Carus at the Technische Universitat DresdenDresdenGermany Division of Nephrology Department of MedicineAlbert Einstein College of MedicineBronxNYUSA

In two recent manuscripts published in Nature,the cholesterol-synthesis pathway was identified as a master regulator of ferroptosis sensitivity and therefore as a novel therapeutic target.1,2 Ferroptosis does not only represent one way to eliminate cancer cells,but also contributes to acute organ damage in the kidney,heart,brain,and liver,and it kills tissues during the process of organ *** term“ferroptosis”should be defined as a cellular process of iron-catalyzed lipid peroxidation-mediated rupture of the plasma membrane.

关键词： rupture death damage

Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome

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Journal of Pharmaceutical Analysis 2024年第1期14卷 152-155页

作者： Shuyu Zheng Yanlin Xin Jiamin Lin Zejuan Xie Keyu Cheng Shanshan Wang Wenli Lu Hao Yang Tianming Lu Jun Li Ruogu Qi Yuanyuan Guo department of Biochemistry and Molecular Biology School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing210023China department of Neurosurgery The Second Affiliated HospitalZhejiang UniversityHangzhou310009China

The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget *** a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(***)and is used as an expectorant for pulmonary disease in Asia[2].

关键词： NSCLC eIF4E treatment

Individualized Traditional Chinese medicine treatment vs antibiotics for recurrent urinary tract infections: a multicenter, randomized controlled study

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Journal of Traditional Chinese medicine 2024年第3期44卷 524-529页

作者： GU Xiangchen QIU Meisi XIE Lin CHEN Min DENG Yueyi ZHANG Changming JIAN Guihua WANG Chen WANG Yi department of Nephrology Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 200437China department of Nephrology Rizhao Hospital of Traditional Chinese MedicineShanghai 200437China department of Nephrology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai200032China department of Nephrology Shanghai Municipal Traditional Chinese Medicine Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 200071China department of Nephrology the Sixth People's Hospital Affiliated Shanghai Jiaotong UniversityShanghai 200233China department of Nephrology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China

OBJECTIVE: To systematically assess the effects of individualized Chinese medicines on recurrent urinary tract infections(rUTIs).METHODS: This study recruited 230 adult female patients in the remission phase of rUTIs from five hospitals in China. The patients were randomly allocated to two groups: an individualized Chinese medicine group(n = 114) and a control group(n = 116). Patients in the Chinese medicine group received individualized Chinese herbs, which were evaluated for syndrome *** in the control group received antibiotic treatment combined with a Chinese medicine placebo. The duration of treatment was three courses of four weeks each, with a three-month subsequent follow-up. UTI recurrence rate,Traditional Chinese medicine(TCM) syndrome scores,36-item Short Form Survey(SF-36) score, and urine secretory immunoglobulin A(SIgA) were measured and analyzed before and after treatment in each group. RESULTS: Patients from the Chinese medicine group exhibited significant decreases in both short-and longterm UTI recurrence rates compared with the control group(P medicine and control groups were significant(P medicine group were also significantly higher than those in the control group after treatment(P medicine group also demonstrated a significant increase in urine SIg A expression. CONCLUSION: Taken together, compared to the oftenused long-term antimicrobial prophylaxis during the remission stage of r UTIs, treating patients with an individualized Chinese medicine decoction by syndrome differentiation could effectively reduce the recurrence rate, improve the patients' TCM syndrome scores and quality of life, and enhance immunity, which in turn helps to prevent antibiotic resistance.

关键词： urinary tract infections medicine Chinese traditional syndrome differentiation quality of life immunoglobulin A secretory randomized controlled trial

Targeted NGS analysis reveals a complex genetic background of idiopathic erythrocytosis in a large Venetian family

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Genes & Diseases 2024年第2期11卷 561-563页

作者： Bertozzi Irene Benetti Andrea Regazzo Daniela Polese Francesca Biagetti Giacomo Ceolotto Giulio Randi Maria Luigia First Medical Clinic University of Padua Department of Medicine – DIMEDVia Giustiniani 2Padova 35123Italy Transfusion medicine department Ospedale dell'Angelo - Venezia MestreVia Paccagnella 1Venice 30174Italy Emergency medicine University of Padua Department of Medicine – DIMEDVia Giustiniani 2Padova 35123Italy

Absolute erythrocytosis,due to an increased production of red blood cells,becomes manifest with hemoglobin(Hb)levels above 165 or 160 g/L or with a hematocrit(HCT)above 51%and 48%in males and females,respectively.1 A minority of patients have polycythemia vera(PV);acquired secondary erythrocytosis frequently occurs due to appropriate or inappropriate erythropoietin(EPO)excess,while congenital secondary erythrocytosis may derive from genetic defects causing tissue *** erythrocytosis occurs in patients with genetic mutations of the oxygen-sensing pathway(VHL,PHD2,_HIF-1-alpha)or the erythropoietin receptor(EPOR)genes.2 Recently,HFE gene variants have been described in sporadic erythrocytoses.3 In a high proportion(about 70%)of patients with erythrocytosis,a specific etiology remains elusive despite extensive testing,and the diagnosis of idiopathic erythrocytosis(IE)is ruled out.

关键词： diagnosis patients congenital

Effect and Safety of Herbal medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy:A Multicenter Double-Blind Randomized Controlled Trial

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Chinese Journal of Integrative medicine 2024年第3期30卷 195-202页

作者： HUANG Hao-yue LIN Yu-ping WEI Hua FU Yu ZHOU Yue-hong FANG Zhao-hui QIU Xiao-tang WANG Mei LI Qing-bo LI Shan-shan WANG Shi-dong DAI Fang LIU Zhen-jie ZHAO Ling WEN Jian-xuan WU Li-yan ZENG Hui-yan ZHANG Jin-ming LU Qi-yun HE Liu SONG Wei SUN Lu LUO Lu-lu HE Jia-li XIE Wen-wen LIANG Qing-shun HUANG Yuan ZHU Sheng-ling LONG Jie-er GAO Zhi-juan WEN Ze-huai LI Chun-ji OUYANG Wen-wei LI Geng WU Ming-hui LI An-xiang HUANG Jin-zhu Sanjoy K Paul TANG Xian-yu FAN Guan-jie department of Endocrinology Guangdong Provincial Hospital of Chinese MedicineGuangzhou510120China The Second Clinical College of Guangzhou University of Chinese medicine Guangzhou510120China department of Endocrinology The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou510120China Guangdong Provincial Academy of Chinese Medical Sciences Guangzhou510120China department of Endocrinology The First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China department of Endocrinology Liuyang Hospital of Chinese MedicineChangsha410000China department of Endocrinology The First Affiliated Hospital of Anhui University of Chinese MedicineHefei230000China department of Endocrinology Hainan Provincial Hospital of Traditional Chinese MedicineHaikou570100China department of Endocrinology The Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang110000China department of Geriatric Luoyang No.1 Hospital of Traditional Chinese MedicineLuoyangHenan Province471000China department of Endocrinology The Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550000China department of Endocrinology Beijing University of Chinese Medicine Affiliated Dongzhimen HospitalBeijing100000China department of Endocrinology The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550000China Melbourne EpiCentre The University of Melbourne and Melbourne HealthMelbourne3013Australia

Objective:To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction(TW)in treating patients with diabetic peripheral neuropathy(DPN).Methods:It is a multicenter double-blinded randomized controlled *** with DPN were recruited between November 18,2016 and May 30,2018 from 8 hospitals in *** patients received basic treatments for glycemic *** received foot baths with TW herbal granules either 66.9 g(intervention group)or 6.69 g(control group)for 30 min once a day for 2 weeks and followed by a 2-week rest,as a therapeutic *** the Toronto Clinical Scoring System total score(TCSS-TS)6 points,the patients received a total of 3 therapeutic courses(for 12 weeks)and were followed up for 12 *** primary outcome was change in TCSS-TS score at 12 and 24 *** outcomes included changes in bilateral motor nerve conduction velocity(MNCV)and sensory nerve conduction velocity(SNCV)of the median and common peroneal *** was also ***:Totally 632 patients were enrolled,and 317 and 315 were randomized to the intervention and control groups,*** the 12-week intervention,patients in both groups showed significant declines in TCSSTS scores,and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment(P0.05),and no serious adverse event was related with ***:Treatment of TW foot baths was safe and significantly benefitted patients with DPN.A low dose of TW appeared to be more effective than a high dose.(Registry *** CTR-IOR-16009331)

关键词： diabetic peripheral neuropathy herbal medicine foot baths Chinese medicine randomized controlled trial Tangbi Waixi Decoction

The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy

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Genes & Diseases 2024年第1期11卷 321-334页

作者： Md Rakibul Alam Md Mizanur Rahman Zhiguo Li department of Toxicology and Cancer Biology College of MedicineUniversity of KentuckyLexingtonKY 40506USA department of medicine(Nephrology) Faculty of Medicine and DentistryUniversity of AlbertaEdmontonAlberta T6E2H7Canada

Exosomes are small membrane vesicles containing microRNA,RNA,DNA fragments,and proteins that are transferred from donor cells to recipient *** cells release exo-somes to reprogram the factors associated with the tumor microenvironment(TME)causing tu-mor metastasis and immune *** evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1(PD-L1)that binds with re-ceptor program death protein 1(PD-1)and promote tumor progression by escaping immune ***,some FDA-approved monoclonal antibodies are clinicallyused for cancer treatment by blocking PD-1/PD-L1 *** notable treatment outcomes,some pa-tients show poor drug *** PD-L1 plays a vital role in lowering the treatment response,showing resistance to PD-1/PD-L1 blockage therapy through recapitulating the ef-fect of cell surface *** enhance therapeutic response,inhibition of exosomal PD-L1 is *** signaling is the central regulator of tumorigenesis and can regulate exosome biogenesis and secretion by modulating Rab GTPase family and membrane fusion ***-mune checkpoints are also connected with calcium signaling and calcium channel blockers like amlodipine,nifedipine,lercanidipine,diltiazem,and verapamil were also reported to suppress cellular PD-L1 ***,to enhance the PD-1/PD-L1 blockage therapy response,the reduction of exosomal PD-L1 secretion from cancer cells is in our therapeutic *** this review,we proposed a therapeutic strategy by targeting calcium signaling to inhibit the expression of PD-L1-containing exosome levels that could reduce the anti-PD-1/PD-L1 therapy resistance and increase the patient's drug response rate.

关键词： Calcium signaling CD8^(+)T cells Exosomal PD-L1 Exosomes biogenesis Immunosuppression Immunotherapy

The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

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International Journal of Oral Science 2024年第1期16卷 154-162页

作者： Yutaro Ando Masayuki Tsukasaki Nam Cong-Nhat Huynh Shizao Zang Minglu Yan Ryunosuke Muro Kazutaka Nakamura Masatsugu Komagamine Noriko Komatsu Kazuo Okamoto Kenta Nakano Tadashi Okamura Akira Yamaguchi Kazuyuki Ishihara Hiroshi Takayanagi department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan department of Microbiology Tokyo Dental College2-1-14 Kanda-Misaki-choChiyoda-kuTokyoJapan Oral Health Science Center Tokyo Dental College2-9-18Kanda-Misaki-choChiyodakuTokyoJapan department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Unit of Prosthodontics Laboratory of Oral-Maxillofacial Biology Faculty of Odonto-StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam department of Oral and Maxillofacial Surgery Department of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Division of Rheumatology Department of Internal MedicineKeio University School of MedicineTokyoJapan department of Laboratory Animal medicine Research InstituteNational Center for Global Health and MedicineTokyoJapan

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

关键词： period neutrophil destruction

Multiparametric ultrasound as a new concept of assessment of liver tissue damage

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World Journal of Gastroenterology 2024年第12期30卷 1663-1669页

作者： Angela Peltec Ioan Sporea department of Internal medicine Discipline of GastroenterologyState University of Medicine and Pharmacy"Nicolae Testemitanu"Chishinev 2019Moldova department of Gastroenterology and Hepatology "Victor Babes"University of Medicine and PharmacyTimisoara 300736Romania

Liver disease accounts for approximately 2 million deaths per year *** chronic liver diseases(CLDs),whether of toxic,genetic,autoimmune,or infectious origin,undergo typical histological changes in the structure of the *** changes may include the accumulation of extracellular matrix material,fats,triglycerides,or tissue *** methods for diagnosing CLD,such as conventional B-mode ultrasound(US),play a significant role in *** US,when coupled with B-mode US,can be helpful in evaluating the hemodynamics of hepatic vessels and detecting US findings associated with hepatic *** elastography can assess liver stiffness,serving as a surrogate marker for liver *** is important to note that interpreting these values should not rely solely on a histological ***-enhanced US(CEUS)provides valuable information on tissue perfusion and enables excellent differentiation between benign and malignant focal liver *** evaluation,the etiology of liver disease,and the patient current comorbidities all influence the interpretation of liver stiffness *** measurements are most clinically relevant when interpreted as a probability of compensated advanced CLD.B-mode US offers a subjective estimation of fatty infiltration and has limited sensitivity for mild *** controlled attenuation parameter requires a dedicated device,and cutoff values are not clearly ***-titative US parameters for liver fat estimation include the attenuation coefficient,backscatter coefficient,and speed of *** parameters offer the advantage of providing fat quantification alongside B-mode evaluation and other US *** US(MPUS)of the liver introduces a new concept for complete noninvasive *** encourages examiners to utilize the latest features of an US machine,including conventional B-mode,liver stiffness evaluation,fat quantification,dispersion imaging,

关键词： Multiparametric ultrasound Ultrasound-based elastography Liver stiffness Noninvasive diagnostic test for chronic liver disease Liver steatosis assessment Portal hypertension evaluation

Promising use of metformin in treating neurological disorders:biomarker-guided therapies

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Neural Regeneration Research 2024年第5期19卷 1045-1055页

作者： Allison Loan Charvi Syal Margarita Lui Ling He Jing Wang Regenerative medicine Program Ottawa Hospital Research InstituteOttawaONCanada department of Biology Faculty of ScienceUniversity of OttawaOttawaONCanada department of Pediatrics and medicine Johns Hopkins Medical SchoolBaltimoreMDUSA department of Cellular and Molecular medicine Faculty of MedicineUniversity of OttawaOttawaONCanada University of Ottawa Brain and Mind Research Institute OttawaONCanada

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available *** most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy ***,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological *** that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological *** molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted *** this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

关键词： Alzheimer’s disease Huntington’s disease metformin mitochondrial perturbation multiple sclerosis neural degenerative diseases Parkinson’s disease stroke targeted therapy