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Keyword Index for Volume 95

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… regulatory T cell 896, 1202 relative survival 1296 renal cancer 1076, 1167 renal cell carcinoma 298, 374, 1244 reovirus oncolysis 1020 resistance 172, 661 resistance mechanisms 955 response 1174 retinoids 463 retinol 406 risk 363, 393, 914, 934, 1047 risk factors 642 road distance 944 ROS 1497 rosiglitazone …

Pharmacological Strategies for Mitigating Cytarabine-Induced Multi-Organ Toxicity: A Scoping Review on Mechanisms, Efficacy and Clinical Implications.

BACKGROUND: Cytarabine (Ara-C) remains the cornerstone of remission-induction and consolidation chemotherapy for acute myeloid leukemia (AML) and related hematological malignancies. Despite more than six decades of clinical use, its multi-organ toxicity continues to be managed almost exclusively through dose attenuation and supportive care, with no approved upstream pharmacological prevention strategy available. OBJECTIVES: This scoping review aimed to systematically map the breadth and nature of pharmacological agents tested in vivo for their capacity to mitigate cytarabine-induced multi-org

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… . × 7 d | C57BL/6J mice, M, 6–8 wk | Ocular: meibomian gland dysfunction, lacrimal hyposecretion | Rosiglitazone 10 mg/kg/day p.o. × 7 d (PPARγ agonist) | Normalized corneal fluorescein score, tear volume, MG acinar area; restored PPARγ/AWAT2/SOAT1/ELOVL4 and Nrf2/HO-1/SOD1 antioxidant signaling. … Oral rosiglitazone (10 mg/kg/day), a PPARγ agonist, normalized corneal fluorescein score, tear volume, lacrimal-gland α-SMA and AQP5, meibomian-gland acinar area, PCNA/P63/Lrig1 proliferation and progenitor markers, K1/K10 hyperkeratinization, the AKT/FoxO1/FoxO3a axis, and oxidative-stress indices. …

Potential Therapeutic Benefits of Maintaining Mitochondrial Health in Peripheral Neuropathies.

BackgroundPeripheral neuropathies are a group of diseases characterized by malfunctioning of peripheral nervous system. Neuropathic pain, one of the core manifestations of peripheral neuropathy remains as the most severe disabling condition affecting the social and daily routine life of patients suffering from peripheral neuropathy.MethodThe current review is aimed at unfolding the possible role of mitochondrial dysfunction in peripheral nerve damage and to discuss on the probable therapeutic strategies against neuronal mitotoxicity. The article also highlights the therapeutic significance of

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… Rosiglitazone, Pioglitazone). It has been recently observed that PPARγ agonists can effectively prevent the glucose induced neurotoxicity and various deficits in streptozotocin (STZ) induced experimental DN [ 141 ]. … Rosiglitazone treatment reduces diabetic neuropathy in streptozotocin-treated DBA/2J mice. Endocrinology. 2008;149(10):4928–4937. doi: 10.1210/en.2008-0869. [http://dx.doi.org/10.1210/en.2008-0869]. [PMID: 18583417]. 142. Choi J., Chandrasekaran K., Inoue T., Muragundla A., Russell J.W. …

miR-21 regulates osteogenic and adipogenic differentiation of BMSCs by targeting PTEN.

ObjectiveTo explore the effects and mechanism of miR-21 on the osteogenic/adipogenic differentiation of mouse BMSCs.MethodsThe bilateral ovaries of C57BL/6J mice (n=24) were removed to construct an osteoporosis model. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-21, osteogenic/adipogenic genes, and PTEN. ALP and ARS and ORO staining were used to detect the formation of calcium nodules and lipid droplets in BMSCs. Western blot was used to detect the expression of PTEN.ResultsmiR-21 was significantly down-regulated in osteoporotic mice. The

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… When a 70% convergence was reached, the cells were then generated by DMEM consisting of 10% FBS, 10 µmol/L rosiglitazone, and 1 µmol/L dexamethasone. The solution was substituted every three days, and used for subsequent experiments after 20 days. …

Reporting of surrogate endpoints in randomised controlled trial protocols (SPIRIT-Surrogate): extension checklist with explanation and elaboration.

Randomised controlled trials often use surrogate endpoints to substitute for a target outcome (an outcome of direct interest and relevance to trial participants, clinicians, and other stakeholders—eg, all cause mortality) to improve efficiency (through shortened duration of follow-up, reduced sample size, and lower research costs), and for ethical or practical reasons. However, their use has a fundamental limitation in terms of uncertainty of the intervention effect on the target outcome and limited information on potential intervention harms. There have been increasing calls for improved repo

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… harmful on the target outcome. 90 One widely cited example is the case of suppressing arrhythmia (abnormal heart rhythm), where drugs aimed at reducing arrhythmias as a surrogate endpoint for cardiovascular related mortality were later discovered to increase mortality. 91 For diabetes, a drug treatment (rosiglitazone …

Выявляется высокий уровень использования медицинских услуг после операции на шейном позвоночнике с использованием комплексных методов прогнозирования.

Расходы на медицинское обслуживание пациентов с хроническими заболеваниями позвоночника и пациентов, проходящих хирургическую операцию, продолжают расти заметными темпами. Таким образом, выявление пациентов, подверженных риску в плане более широкого использования послеоперационного медицинского обслуживания, имеет решающее значение для оптимизации результатов медицинского обслуживания и распределения ресурсов. Цель нашего исследования заключается в использовании целого ряда предоперабельных характеристик пациентов, включая всеобъемлющую медицинскую, хирургическую и социальную историю, для разр

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… “acarbose”, “miglitol”, “metformin”, “alogliptin”, “linagliptin”, “saxagliptin”, “sitagliptin”, “nateglinide”, “repaglinide”, “canagliflozin”, “dapagliflozin”, “empagliflozin”, “ertugliflozin”, “bexagliflozin”, “glimepiride”, “glipizide”, “tolazamide”, “tolbutamide”, “glyburide”, “chlorpropamide”, “rosiglitazone …

CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology.

The acronym for the CCN family was recently revised to represent "cellular communication network". These six, small, cysteine-enriched and evolutionarily conserved proteins are secreted matricellular proteins, that convey and modulate intercellular communication by interacting with structural proteins, signalling factors and cell surface receptors. Their role in the development and physiology of musculoskeletal system, constituted by connective tissues where cells are interspersed in the cellular matrix, has been broadly studied. Previous research has highlighted a crucial balance of CCN prote

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… Targeted gene editing (lentishCCN1, AdshCCN1) and administration of anti-CCN1 monoclonal antibodies, or drugs (rosiglitazone) in collagen-induced (CIA) murine models of RA invariably led to an amelioration of RA symptoms with decreased inflammatory scores and monocyte infiltration, decreased production … PPARγ agonist rosiglitazone inhibits migration and invasion by downregulating Cyr61 in rheumatoid arthritis fibroblast-like synoviocytes. Int J Rheum Dis. 2017;20:1499–1509. doi: 10.1111/1756-185X.12913. Lafont J, Thibout H, Dubois C, Laurent M, Martinerie C. …

Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs.

The severe acute respiratory syndrome coronavirus 2 (SARS-COv-2) is the etiologic agent of the 2019 coronavirus disease (COVID19). The majority of infected people presents flu like symptoms and among them 15-20% develops a severe interstitial pneumonitis (IP) that may eventually evolve in acute respiratory distress syndrome (ARDS). IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes. The virus is recognized by the "pattern recognition receptors" (PRR) of the immune cells that release cytokines a

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… PPARγ Agonists Peroxisome proliferator-activated receptor gamma (PPARγ- agonists, rosiglitazone and pioglitazone, are drugs in clinical use for diabetes ( 61 ). …

Chemotherapy-induced acute kidney injury: epidemiology, pathophysiology, and therapeutic approaches.

Despite significant advancements in oncology, conventional chemotherapy remains the primary treatment for diverse malignancies. Acute kidney injury (AKI) stands out as one of the most prevalent and severe adverse effects associated with these cytotoxic agents. While platinum compounds are well-known for their nephrotoxic potential, other drugs including antimetabolites, alkylating agents, and antitumor antibiotics are also associated. The onset of AKI poses substantial risks, including heightened morbidity and mortality rates, prolonged hospital stays, treatment interruptions, and the need for

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… Furthermore, IL-10, TNF-alpha inhibitors such as salicylates, and the PPAR agonists fibrate and rosiglitazone, have shown promise against cisplatin nephrotoxicity through their anti-inflammatory effects ( 106 – 109 ). … Rosiglitazone synergizes anticancer activity of cisplatin and reduces its nephrotoxicity in 7, 12-dimethyl benz{a}anthracene (DMBA) induced breast cancer rats. BMC Cancer. (2009) 9:107. doi: 10.1186/1471-2407-9-107 110. …

Роль микроглии в синаптогенезе, синаптической и синаптической пластичности в физиологических условиях и в нарушениях центральной нервной системы.

Микроглии являются постоянными иммунными клетками мозга, которые были широко изучены для их иммунного наблюдения и фагоцитоза. В последние годы постепенно признается важная роль микроглии в синапсовом образовании, ликвидации и пластичности. Синапсы являются основным режимом связи между нейронами. Они постоянно меняются в количестве и пластичности на протяжении всего жизненного цикла, который является основой обучения и памяти. Микроглии являются сильно мотилированными, ветковыми формами, которые осуществляют мониторинг микроокружающей среды центральной нервной системы (КНС) и поощряют синапсов

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… Drug candidates such as pioglitazone and rosiglitazone target peroxisome proliferator-activated receptor gamma (PPAR-γ) to inhibit the pro-inflammatory effects of microglia [ 352 , 353 ]. …

Reporting of surrogate endpoints in randomised controlled trial reports (CONSORT-Surrogate): extension checklist with explanation and elaboration.

Randomised controlled trials commonly use surrogate endpoints to substitute for a target outcome (outcome of direct interest and relevance to trial participants, clinicians, and other stakeholders—eg, all cause mortality) to improve their efficiency (through shorter trial duration, reduced sample size, and thus lower research costs), or for ethical or practical reasons. But reliance on surrogate endpoints can increase the uncertainty of an intervention’s treatment effect and potential failure to provide adequate information on intervention harms, which has led to calls for improved reporting o

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… patients and the public. 88 This example included suppression of arrhythmia (abnormal heart rhythm), where drugs to reduce arrhythmias (considered to be a surrogate endpoint for cardiovascular related mortality) were later found to increase mortality. 88 More recent examples include a diabetes treatment (rosiglitazone … Rosiglitazone: what went wrong? BMJ 2010 ; 341 : c4848 . 10.1136/bmj.c4848 20819889 90 Kumar S Rajkumar SV . Surrogate endpoints in randomised controlled trials: a reality check . Lancet 2019 ; 394 : 281 - 3 . 10.1016/S0140-6736(19)31711-8 . 31354129 91 Kumar SK Harrison SJ Cavo M . …

A review of mitochondrial dysfunction in diabetic sarcopenia: Mechanisms, diagnosis, and treatment approaches.

Diabetic sarcopenia is a common complication of diabetes, substantially impacting patients' quality of life and prognosis. Its pathogenesis is closely related to energy metabolism, with mitochondria-often referred to as the cellular "powerhouse"-playing a central role in this process. This review focuses on the role of mitochondrial dysfunction in diabetic sarcopenia, emphasizing mechanisms such as energy metabolism imbalance, oxidative stress-induced damage, and abnormalities in mitochondrial biogenesis and dynamics. Additionally, we discussed current research on diagnostic and therapeutic st

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… Additionally, AMPK activation enhances insulin sensitivity, regulates muscle protein metabolism, and reduces muscle protein degradation. 45 Thiazolidinediones such as rosiglitazone modulate peroxisome proliferator-activated receptor gamma (PPARγ) activity, influencing the expression of mitochondrial-related …

Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.

Endoplasmic reticulum (ER) stress is a key cellular mechanism that is important in the development of many diseases, including cancer. Since the discovery of the unfolded protein response (UPR), research has greatly improved our understanding of how ER stress affects cellular functions, especially protein folding and adaptation to stress. The UPR consists of three main branches: IRE1, ATF6, and PERK, each of which is crucial for regulating stress responses, protein homeostasis, and apoptosis. These pathways normally help cells handle stress effectively; however, excessive or prolonged activati

Связь между окисляющим стрессом, митохондриальной дисфункцией, железным метаболизмом и микроглией в множестве склерозов: обзор нарации.

В последние годы в патогенезе множественного склероза особое внимание уделяется митохондриальным процессам, влияющим на начало заболевания. Окисляющий стресс будет одним из последствий митохондриальной дисфункции, и его воздействие на ткани мозга хорошо описано. Микроглия, как макрофаж мозга, имеет важную функцию в удалении нежелательных метаболитов, а также железа, который является усилителем окислительного стресса. Существуют новшества с точки зрения связи между этими процессами, которые в большей степени перенаправляют исследования на сам процесс нейродегенерации, с тем чтобы больше не дела

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… As inhibitors of ferroptosis, deferoxamine, vitamins C and E, ferrostatin 1, lipostatin 1, ebselen (has the function of the enzyme GSHPx), and idebenone (synthetic coenzyme Q), as well as rosiglitazone, troglitazone and pioglitazone are proposed. …

Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expre

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… ESE3/EHF, a promising target of rosiglitazone, suppresses pancreatic cancer stemness by downregulating CXCR4. Gut. 2022;71(2):357–371. doi: 10.1136/gutjnl-2020-321952. 52. Liu J, Jiang W, Zhao K, et al. Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma. …

Docosahexaenoic Acid Modulates a HER2-Associated Lipogenic Phenotype, Induces Apoptosis, and Increases Trastuzumab Action in HER2-Overexpressing Breast Carcinoma Cells.

In breast cancer, lipid metabolic alterations have been recognized as potential oncogenic stimuli that may promote malignancy. To investigate whether the oncogenic nature of lipogenesis closely depends on the overexpression of HER2 protooncogene, the normal breast cell line, HB4a, was transfected with HER2 cDNA to obtain HER2-overexpressing HB4aC5.2 cells. Both cell lines were treated with trastuzumab and docosahexaenoic acid. HER2 overexpression was accompanied by an increase in the expression of lipogenic genes involved in uptake (CD36), transport (FABP4), and storage (DGAT) of exogenous fat

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… GW9662, a potenteantagonista of PPAR gamma, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPAR gamma agonist rosiglitazone, independently of PPAR gamma activation British Journal of Pharmacology 2004 143 8 933 937 10.1038/sj.bjp.0705973 2-s2.0-11244253710 15533890 …

Adipocyte-Tumor Interactions in the Bone Marrow Niche: Implications for Metastasis and Therapy.

Bone metastases continue to be a major cause of morbidity and mortality in patients with advanced cancers, driven by the dynamic remodeling of the bone marrow niche. Traditionally viewed as passive space-fillers, bone marrow adipocytes (BMAs) are now recognized as active regulators of tumor growth, therapeutic resistance, and skeletal pathology. BMAs comprise a significant portion of the adult marrow space, particularly in aging and obesity, and facilitate metastatic colonization through various mechanisms. These include metabolic coupling, where adipocyte-derived fatty acids fuel tumor oxidat

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… The researchers administered rosiglitazone and pioglitazone, both PPARγ agonists, to adult mice and observed a significant transformation of unilocular adipocytes into multilocular ones. … Another study demonstrates that treatment with TZDs, such as rosiglitazone, induces deacetylation of PPARγ at specific lysine residues (K268 and K293). This modification promotes the browning of WAT, characterized by increased mitochondrial content and thermogenic gene expression [ 173 ]. …

Роль альфа-рецептора, активированного пероксидисом, в нейродегенеративных заболеваниях и других неврологических расстройствах: перспективы клинического применения.

Альфа-рецептор, активированный с помощью пероксисом, является членом сверхсемейства суперрецептора ядерного гормона и функционирует в качестве коэффициента транскрипции, связанного с регулированием клеточного метаболизма. Предыдущие исследования показали, что PPARα играет ключевую роль в возникновении и развитии нейродегенеративных заболеваний. Таким образом, альфа-агонисты, работающие на рецепторах, привлекают все большее внимание в качестве потенциальных средств лечения неврологических расстройств. Цель этого обзора состоит в том, чтобы прояснить прогресс в области исследований, касающихся п

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… Additionally, the administration of rosiglitazone in rat primary cortical neurons has been found to increase PPARγ expression and induce neurite growth (Lezana et al., 2016). …

Перекресток между диабетом и болезнью Альцгеймера: Молекулярная перспектива.

Общемировая распространенность видов 2 Заболевание сахарным диабетом (T2DM) и болезнью Альцгеймера (AD) значительно возрастает в зависимости от возраста. Растущие данные подтверждают концептуализацию АД как типа 3 диабет, термин, предлагаемый для описания метаболического заболевания, вызванного главным образом поврежденной инсулиновой сигнализацией и инсулиновой резистентностью в мозге. В рамках этого обзора изучаются общие молекулярные механизмы, лежащие в основе как T2DM, так и AD, включая хроническую нейроинфламму, окислительный стресс, митохондриальную дисфункцию и поврежденный метаболизм

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… Observational: ↓ dementia risk (no RCT; some conflicting reports) Moderate (observational); suggestive, unconfirmed by RCT [ 207 , 208 , 209 ] Thiazolidinediones (glitazones) Pioglitazone; rosiglitazone PPARγ agonists; ↑ peripheral insulin sensitivity Human: Phase 3 RCT (TOMMORROW) + meta‐analysis …

Micro- and Macrovascular Complications in Early-Onset Type 2 Diabetes in Indians: Prevalence and Predictors in a Prospective Cross-Sectional Study.

Introductionand Aims: The prevalence of T2DM is rising among young people, placing them at greater risk for complications. We studied the prevalence and predictors of micro- and macrovascular complications in early-onset diabetes subjects (EOD, MethodsA total of 800 subjects (400 EOD, 400 LOD), matched for gender and diabetes duration, were prospectively recruited and assessed for the prevalence of peripheral neuropathy, retinopathy, nephropathy, and ASCVD. Multivariate logistic regression analyzed predictors of diabetes complications.ResultsThe median age at diagnosis of diabetes was 35 years

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… Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and -βcell function in TODAY. Diabetes Care 2013. 36 1749–1757. ( 10.2337/dc12-2393) 8. Al-Saeed AH, Constantino MI, Molyneaux L, et al. …