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Воздействие лечения на стероидом у женщин с множественным склерозом.

Множественный склероз (MS) — хроническое воспалительное нейродегенеративное заболевание центральной нервной системы. Происхождение MS связано с стероидными изменениями во время менструального цикла и беременности. Поскольку данных о воздействии лечения противомоскитных препаратов на стероидом недостаточно, мы провели оценку стерейдомичных изменений (79 стероидов) у 61 женщины-психолога репродуктивного возраста 39 лет (29, 47 лет) после лечения с помощью антимиосных препаратов на платформе GC-MS/MS и иммуномассы (кортизол и эстрадиол). Эти изменения были оценены с использованием уровней стероид

Gut microbiota and microbial metabolites for osteoporosis.

Osteoporosis is an age-related bone metabolic disease. As an essential endocrine organ, the skeletal system is intricately connected with extraosseous organs. The crosstalk between bones and other organs supports this view. In recent years, the link between the gut microecology and bone metabolism has become an important research topic, both in preclinical studies and in clinical trials. Many studies have shown that skeletal changes are accompanied by changes in the composition and structure of the gut microbiota (GM). At the same time, natural or artificial interventions targeting the GM can

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… By inhibiting the ubiquitination and subsequent degradation of pregnane X receptor (PXR) induced by RANKL, osteoclast differentiation and function are inhibited. 34 VDR is a widely expressed nuclear receptor with multiple physiological effects. … Gut Clostridium sporogenes-derived indole propionic acid suppresses osteoclast formation by activating pregnane X receptor. Pharmacol Res. 2024;202:107121. doi: 10.1016/j.phrs.2024.107121. 35. Song C, Ma Y, Wang Y, Li P, Chen Y, Liu H, Zhang Z. …

Induction of CYP3A activity by dexamethasone may not be strong, even at high doses: insights from a case of tacrolimus co-administration.

BackgroundDexamethasone (DEX) induces CYP3A activity in a concentration-dependent manner. However, no study has examined changes in the blood concentration of CYP3A substrate drugs when DEX is administered at high doses. Herein, we present a case in which tacrolimus (TAC), a typical CYP3A substrate drug, was co-administered with a chemotherapy regimen that included high-dose DEX.Case presentationA 71-year-old woman underwent liver transplantation for hepatocellular carcinoma 18 years prior to her inclusion in this case study. She was receiving TAC orally at 2 mg/day and had a stable trough blo

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… Induction of CYP activity by DEX is mediated by the pregnane X receptor (PXR/NR1I2), whereas PXR / NR1I2 polymorphisms have been reported to affect DDIs of steroids and TAC [ 17 ]. Additionally, CYP3A5 polymorphisms are known to influence the pharmacokinetics of TAC [ 10 , 18 ]. … Stifft F van Kuijk SMJ Bekers O Christiaans MHL Increase in tacrolimus exposure after steroid tapering is influenced by CYP3A5 and pregnane X receptor genetic polymorphisms in renal transplant recipients Nephrol Dial Transplant 2018 33 1668 1675 10.1093/ndt/gfy096 29733390 18. …

Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare.

Vitamin D has received a lot of attention recently as a result of a meteoric rise in the number of publications showing that vitamin D plays a crucial role in a plethora of physiological functions and associating vitamin D deficiency with many acute and chronic illnesses including disorders of calcium metabolism, autoimmune diseases, some cancers, type 2 diabetes mellitus, infectious diseases and cardiovascular disease. The recent data on vitamin D from experimental, ecological, case-control, retrospective and prospective observational studies, as well as smaller intervention studies, are sign

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… This could mean: drugs that can stimulate the pregnane X receptor can potentially trigger all of the negative consequences of a vitamin D deficiency. … Prescription and over the counter drugs that can activate the pregnane X receptor (PXR) (selection) PXR ligands | Examples Androgen receptor antagonists | Cyproterone acetate Antiepileptics | Phenytoin, carbamazepine Antiestrogens | Tamoxifen Antihypertensives | Nifedipine, spironolactone Antimycotics …

Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

Drug-Drug Interaction Study to Assess the Effect of Cytochrome P450 Inhibition and Induction on the Pharmacokinetics of the Novel Cereblon Modulator Avadomide (CC-122) in Healthy Adult Subjects.

Avadomide (CC-122) is a novel immunomodulatory drug that binds to cereblon, a member of the Cullin 4-RING E3 ubiquitin ligase complex. Avadomide has multiple pharmacologic activities including potent immune modulation, antiangiogenic, antitumor, and antiproliferative activity and is being evaluated as an oncology treatment for hematologic malignancies and advanced solid tumors. In vitro study has indicated that cytochrome P450 (CYP) 3A and CYP1A2 appear to be the major enzymes involved in the oxidative metabolism of avadomide. The effects of CYP3A inhibition/induction and CYP1A2 inhibition on

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… In the case of vandetabib such a regime was confirmed by direct measurement of large increases in plasma concentrations of CYP3A4‐related metabolites under conditions of induction. 19 Second, rifampin could induce other pregnane X receptor‐dependent drug‐metabolizing enzymes and transporters. 20 , 21 … Roles of rifampicin in drug‐drug interactions: underlying molecular mechanisms involving the nuclear pregnane X receptor. Ann Clin Microbiol Antimicrob. 2006;5:3. 21. Niemi M, Backman JT, Fromm MF, Neuvonen PJ, Kivisto KT. Pharmacokinetic interactions with rifampicin: clinical relevance. …

The SUMO Family: Mechanisms and Implications in Thyroid Cancer Pathogenesis and Therapy.

(1) Background: Small ubiquitin-like modifiers (SUMOs) are pivotal in post-translational modifications, influencing various cellular processes, such as protein localization, stability, and genome integrity. (2) Methods: This review explores the SUMO family, including its isoforms and catalytic cycle, highlighting their significance in regulating key biological functions in thyroid cancer. We discuss the multifaceted roles of SUMOylation in DNA repair mechanisms, protein stability, and the modulation of receptor activities, particularly in the context of thyroid cancer. (3) Results: The aberran

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… Among these, peroxisome-proliferator-activated receptor γ (PPARγ) and pregnane X receptor (PXR) are pivotal players in lipid metabolism and xenobiotic responses, respectively. … In the liver, SUMOylation and ubiquitination of the nuclear receptor pregnane X receptor (PXR/NR1I2) regulate its biological functions, particularly in response to xenobiotic or inflammatory stimuli. …

Proteasome inhibition protects blood-brain barrier P-glycoprotein and lowers Aβ brain levels in an Alzheimer's disease model.

BackgroundLoss of P-glycoprotein (P-gp) at the blood-brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer's disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin-proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor

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… In this regard, we previously showed in transgenic human amyloid precursor protein (hAPP)-overexpressing mice that activating the pregnane X receptor with pregnenolone-16-carbonitrile induces P-gp protein expression and transport activity levels, which restores Aβ clearance and reduces brain Aβ levels … Bauer B Hartz AM Fricker G Miller DS Pregnane X receptor up-regulation of P-glycoprotein expression and transport function at the blood-brain barrier Mol Pharmacol 2004 66 3 413 419 15322232 10.1124/mol.66.3. 41. …

How to calculate the dose of chemotherapy.

Body surface area-dosing does not account for the complex processes of cytotoxic drug elimination. This leads to an unpredictable variation in effect. Overdosing is easily recognised but it is possible that unrecognised underdosing is more common and may occur in 30% or more of patients receiving standard regimen. Those patients who are inadvertently underdosed are at risk of a significantly reduced anticancer effect. Using published data, it can be calculated that there is an almost 20% relative reduction in survival for women receiving adjuvant chemotherapy for breast cancer as a result of u

Pathophysiology and treatment of osteoporosis: challenges for clinical practice in older people.

Osteoporosis, a common chronic metabolic bone disease is associated with considerable morbidity and mortality. As the prevalence of osteoporosis increases with age, a paralleled elevation in the rate of incident fragility fractures will be observed. This narrative review explores the origins of bone and considers physiological mechanisms involved in bone homeostasis relevant to management and treatment. Secondary causes of osteoporosis, as well as osteosarcopenia are discussed followed by an overview of the commonly used pharmacological treatments for osteoporosis in older people.

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… Predominantly, AED activate the orphan nuclear and pregnane-X receptors (PXR—expressed in the gut, kidneys and liver) and induce the cytochrome P450 enzyme system (CYP2, CYP3) leading to increased metabolism of vitamin D to inactive metabolites. … Pascussi JM Robert A Nguyen M Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia J Clin Invest 2005 115 177 186 15630458 10.1172/JCI21867 PMC539191 41. …

Pruritus in Systemic Diseases: A Review of Etiological Factors and New Treatment Modalities.

Pruritus is the most frequently described symptom in dermatology and can significantly impair the patient's quality of life. In 10-50% of adults with persistent pruritus, it can be an important dermatologic clue for the presence of a significant underlying systemic disease such as renal insufficiency, cholestasis, hematologic disorder, or malignancy (Etter and Myers, 2002; Zirwas and Seraly, 2001). This review describes the presence of pruritus in different systemic diseases. It is quite important to discover the cause of pruritus for providing relief for the patients experiencing substantial

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… The mechanism of the reported antipruritic effect of rifampicin which is a P450 cytochrome enzyme inducer may be explained, at least partly, by the Pregnane X receptor- (PXR-) dependent transcriptional inhibition of ATX expression. Rifampicin can be hepatotoxic and liver tests should be monitored. …

The role and mechanisms of action of microRNAs in cancer drug resistance.

MicroRNAs (miRNAs) are small non-coding RNAs with a length of about 19-25 nt, which can regulate various target genes and are thus involved in the regulation of a variety of biological and pathological processes, including the formation and development of cancer. Drug resistance in cancer chemotherapy is one of the main obstacles to curing this malignant disease. Statistical data indicate that over 90% of the mortality of patients with cancer is related to drug resistance. Drug resistance of cancer chemotherapy can be caused by many mechanisms, such as decreased antitumor drug uptake, modified

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… In colon cancer cells, miRNA-148a targets transcription factor pregnane X receptor ( PXR ), which regulates CYP3A4 [ 177 ]. Overexpression of miRNA-148a diminished the protein levels of PXR, and this attenuates the induction of CYP3A4. … X receptor RAS-related protein 1a Retinoblastoma Ras homolog gene RNA-induced silencing complex Raf kinase inhibitory protein RNA polymerase II Ribonuclease/angiogenin inhibitor 1 Runt related transcription factor 3 Small cell lung cancer Sirtuin 1 Solute carrier family 7 member 11 Mothers …

IL-6 in the Ecosystem of Head and Neck Cancer: Possible Therapeutic Perspectives.

Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways are substantial players in orchestrating the cancer microenvironment. Thus, they appear to be potential targets in anti-tumor therapy. The aim of this article is to elucidate the role of IL-6 in the tumor ecosystem and to review the possible therapeutic approaches in head and neck cancer.

Googling the Guggul (Commiphora and Boswellia) for Prevention of Chronic Diseases.

Extensive research during last 2 decades has revealed that most drugs discovered today, although costs billions of dollars for discovery, and yet they are highly ineffective in their clinical response. For instance, the European Medicines Agency has approved 68 anti-cancer drugs, and out of which 39 has reached the market level with no indication of increased survival nor betterment of quality of life. Even when drugs did improve survival rate compared to available treatment strategies, most of these were found to be clinically insignificant. This is a fundamental problem with modern drug disc

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… Oswley and Chiang reported that GS antagonizes FXR induction of BSEP but activates pregnane X receptor to inhibit CYP7A1 gene (Owsley and Chiang, 2003 ). In addition, Commiphora and Boswellia showed potent cardioprotective as well as thyroid-stimulatory effects (Singh et al., 1982 ; Deng, 2007 ). … Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7alpha-hydroxylase gene. Biochem. Biophys. Res. Commun. 304, 191–195. 10.1016/S0006-291X(03)00551-5 Panda S., Kar A. (2005). …

Treatment of Psoriasis with Secukinumab in Challenging Patient Scenarios: A Review of the Available Evidence.

Psoriasis (PsO) is a common, systemic, chronic, inflammatory disease characterized by key clinical symptoms, including itching, pain, and scaling. PsO is associated with a high prevalence of comorbidities, including other autoimmune diseases and malignancies. Furthermore, special populations, such as pregnant, pediatric, and elderly patients, and those with erythrodermic PsO, are challenging to treat and require tightly monitored disease and treatment management. Because certain populations have demographic or clinical characteristics that can affect the presentation of PsO and complicate trea

Potential therapeutic targets of Guggulsterone in cancer.

Natural compounds capable of inducing apoptosis in cancer cells have always been of considerable interest as potential anti-cancer agents. Many such compounds are under screening and development with their potential evolution as a clinical drug benefiting many of the cancer patients. Guggulsterone (GS), a phytosterol isolated gum resin of the tree Commiphora mukul has been widely used in Indian traditional medicine as a remedy for various diseses. GS has been shown to possess cancer chemopreventive and therapeutic potential as established by in vitro and in vivo studies. GS has been shown to t

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… Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7alpha-hydroxylase gene. Biochem Biophys Res Commun. 2003;304:191–195. doi: 10.1016/S0006-291X(03)00551-5. 11. …

Изучение связи между ядерными рецепторами в гематологических галереях.

Гематологические магнации (ГМ) представляют собой подмножество новообразований, затрагивающих кровь, костный мозг и лимфатические системы, которые в основном подразделяются на лейкемию, лимфому и множественную миелому. Их прогнозы значительно отличаются друг от друга, причем, несмотря на текущее лечение, часто возникает опасность рецидива. Несмотря на то, что современные терапевтические стратегии расширили общее выживание пациентов, они не предлагают лечения на продвинутых этапах и часто приводят к таким проблемам, как приобретение лекарственной устойчивости, рецидивы и серьезные побочные эффе

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… The first subfamily encompasses thyroid hormone receptor-like members, including vitamin D receptor (VDR), thyroid hormone receptor (THR), retinoic acid receptors (RARs), all peroxisome proliferator-activated receptors (PPARs), and orphan receptors like RORs, Rev-Erb receptor, pregnane X receptor (PXR … X receptor Retinoic acid Retinoic acid receptor Retinoic acid response elements Retinoid X receptor Selective estrogen receptor modulators Small heterodimer partner Transcription factor Transglutaminase 2 Vitamin D receptor Z-ligustilide Author contributions MKM: writing—original draft preparation …

Micronutrients in Oncological Intervention.

Nutritional supplements are widely used among patients with cancer who perceive them to be anticancer and antitoxicity agents. Depending on the type of malignancy and the gender 30%-90% of the cancer patients supplement their diets with antioxidant and immuno-stabilizing micronutrients, such as selenium, vitamin C, and vitamin D, often without the knowledge of the treating physician. From the oncological viewpoint, there are justifiable concerns that dietary supplements decrease the effectiveness of chemotherapy and radiotherapy. Recent studies, however, have provided increasing evidence that

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… Some cytostatics (e.g., cyclophosphamide, paclitaxel) are ligands of the pregnane X receptor (PCR) and can, therefore, increase the enzymatic degradation of 25(OH)D and 1α,25(OH)2D via the induction of 24-hydroxylase in the course of chemotherapy [ 106 , 107 , 108 ]. …

Dietary Polyphenols and Their Biological Significance

Dietary polyphenols represent a wide variety of compounds that occur in fruits, vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products. They are mostly derivatives and/or isomers of flavones, isoflavones, flavonols, catechins and phenolic acids, and possess diverse biological properties such as antioxidant, antiapoptosis, anti-aging, anticarcinogen, anti-inflammation, anti-atherosclerosis, cardiovascular protection, improvement of the endothelial function, as well as inhibition of angiogenesis and cell proliferation activity. Most of these biological actions have bee

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… Modulation of pregnane X receptor-and electrophile responsive element-mediated gene expression by dietary polyphenolic compounds Free Radic. Biol. Med 2007 42 315 325 17210444 10.1016/j.freeradbiomed.2006.09.028 128 Meeran S.M. Katiyar S.K. …

Monitoring residues of pesticides in food in Brazil: A multiscale analysis of the main contaminants, dietary cancer risk estimative and mechanisms associated.

IntroductionPesticides pose a risk for cancer development and progression. People are continuously exposed to such substances by several routes, including daily intake of contaminated food and water, especially in countries that are highly pesticide consumers and have very permissive legislation about pesticide contamination as Brazil. This work investigated the relationship among pesticides, food contamination, and dietary cancer risk.MethodsAnalyzed two social reports from the Brazilian Government: the Program for Analysis of Residues of Pesticides in Food (PARA) and The National Program for

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… These increase hepatocyte proliferation; imazalil, by increasing the expression of transforming growth factor alpha (TGF-α) and genes of the cytochrome p450 family, such as Cyp3a11, a target of the pregnane X receptor (PXR), which has its expression increased in liver carcinogenesis or other adverse …