PURPOSE: The study sought to understand the experiences of working age adults with myeloma and their partner/family members, living in Czechia, Germany, and Poland. METHODS: Qualitative interviews were conducted with 36 working age adults living with myeloma, and three family members. Data were collected from May to October 2022. Thematic analysis was applied to the data. RESULTS: Healthcare and state support within each country are described. The degree of work engagement was informed by patients' symptom burden, treatment needs, state financial aid, and family/financial obligations. Many did not conceptualise their status as involving 'return to work' as they had continued to be engaged with their jobs throughout. For some, remote working enabled them to manage treatments/side-effects and their job, while avoiding infection. In some cases, patients did not tell their employer or colleagues about their illness, for fear of discrimination. CONCLUSION: While experiences varied between countries, common across accounts was a struggle to balance ongoing treatments with employment, at a time when participants were expected to finance their own households and maintain their income and roles. Implications for Cancer Survivors To improve quality of life, clinical discussions around treatment decision-making should take into account patients' attitudes/approach to work, type of work engaged in, and other activities considered important to them. European Union and national cancer plans should set out optimum standards for employers, to ensure an equitable benchmark for how employees are supported. Such approaches would improve legal protections and better enforcement of employer policies to accommodate patients' limitations in the workplace.

• MeSH
• dospělí MeSH
• kvalita života * MeSH
• kvalitativní výzkum MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * psychologie   terapie   epidemiologie   mortalita   MeSH
• přežívající onkologičtí pacienti * psychologie   statistika a číselné údaje   MeSH
• rozhovory jako téma MeSH
• zaměstnanost * statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Německo MeSH
• Polsko MeSH

OBJECTIVES: To determine the safety and oncological advantages of en bloc resection of bladder tumour (ERBT) vs conventional transurethral resection of bladder tumour (cTURBT) in terms of resection quality, staging quality, and safety. PATIENTS AND METHODS: We conducted a single-blinded randomised controlled trial at seven European hospitals with the following inclusion criteria: first diagnosis of non-muscle-invasive bladder cancer, no singular carcinoma in situ, and tumour size >4.3 mm. Patients were randomised intraoperatively in a 1:1 ratio to either the ERBT or cTURBT group. Outcome analysis was performed using the chi-square test, t-test, and multivariate regression analysis. RESULTS: A total of 97 patients were randomised into the study (cTURBT = 40, ERBT = 57). A switch to cTURBT was necessary in two patients (3.5%) and 11.5% of the screened patients were preoperatively excluded for ERBT. There was no difference in the specimen presence of detrusor muscle with 73.7% in cTURBT and 67.3% in ERBT specimens (P = 0.69). There were no significant differences in mean operative time (ERBT 27.6 vs cTURBT 25.4 min, P = 0.450) or mean resection time (ERBT 16.3 vs cTURBT 15.5 min, P = 0.732). Overall the complication rate did not differ significantly (ERBT 18.2% vs cTURBT 7.5%, P = 0.142). Bladder perforations occurred significantly more often in the ERBT group (ERBT seven vs cTURBT none, P = 0.020). R0 status was reported more often after ERBT, whilst a second resection was significantly less frequent after ERBT (P = 0.018). Recurrence rates were comparable for both techniques after 6 months of follow-up. CONCLUSION: The feasibility of ERBT is higher than previously reported. Whereas other perioperative and safety parameters are comparable to cTURBT, bladder perforations occurred significantly more often in the ERBT group and raised safety concerns. This is why this trial was terminated.

• MeSH
• cystektomie * metody   škodlivé účinky   MeSH
• jednoduchá slepá metoda MeSH
• karcinom z přechodných buněk chirurgie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory močového měchýře * chirurgie   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transuretrální resekce močového měchýře MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

BACKGROUND: Effective end-of-life care requires transitioning pharmacotherapy from chronic disease management to symptom relief. Patients in pre-terminal and terminal palliative care may be at risk of receiving potentially inappropriate drugs regarding indication, dosage, route of administration, and polypharmacy, which can increase the risk of deteriorating quality of life. However, data on this process in Home Hospice Care (HHC) is limited. This pilot retrospective study evaluated the pharmacotherapy of 50 patients during their final days under HHC, focusing on changes in treatment and preferred administration routes to optimize symptomatic care. METHODS: Anonymised medical records data were analysed retrospectively to assess the shift from chronic disease pharmacotherapy to symptom and quality-of-life-focused treatment. Statistical methods were applied to identify trends in drug utilisation and administration routes. RESULTS: The study group qualified the most common drugs associated with potential drug-related problems: antidepressants (26%), sedatives/hypnotics (32%), gastroprotection (34%), antihypertensives (46%), coanalgesics (50%), and analgesics (84%). On the final day, the mean was 2.64 systemic medication (standard deviation 1.27), with a minimum number of drugs and a maximum of 6. The most common symptom addressed was pain, which occurred in 28 patients in the group (56%). Therefore, terminal analgosedation was mapped in more detail when, at the end of life, 26 patients (52%) were terminally transferred to continuous medication administered subcutaneously. Continuous subcutaneous linear driver for analgosedation containing two components was used in 12 patients (46.2%) or three components in 14 patients (53.8%). CONCLUSIONS: This retrospective study highlights the importance of targeted pharmacotherapy adjustments in terminal care, including multidisciplinary HHC teams. Pharmacotherapy is simplified and targeted to prevalent symptoms, using the widely used subcutaneous drug administration.

• MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• paliativní péče * MeSH
• péče o umírající * metody   MeSH
• péče v hospici * metody   MeSH
• pilotní projekty MeSH
• polypharmacy MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• služby domácí péče * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND AIMS: Anti-tumor necrosis factor-α inhibitors (anti-TNFs) are the established treatment for perianal Crohn's disease (pCD), but relapse and non-response are common. Data on second- and third-line biologics are limited. We present the first direct comparison of second- and third-line biologics in pCD patients with active perianal disease previously treated with first-line anti-TNFs. METHODS: A multicenter retrospective cohort study included adult patients with pCD who failed first-line anti-TNF. The primary outcome was clinical perianal response, with secondary outcomes of radiological response (magnetic resonance imaging or transrectal ultrasound) and healing, and clinical remission. Propensity score matching (PSM) was used to adjust for baseline differences. RESULTS: A total of 486 pCD patients from 23 IBD centers were included, with 333/486 (68.5%) and 216/263 (82.1%) matched by PSM in the second and third-line treatment groups, respectively. In the second-line group, 62/78 (79.5%) of ustekinumab (UST)-treated patients achieved clinical perianal response, compared to 46/78 (58.9%) with vedolizumab (VDZ) (OR 4.47, 95% CI, 1.94-10.28, P < .001) and 38/78 (48.7%) with anti-TNFs (OR 5.29, 95% CI, 2.39-11.71, P < .001). In the third-line group, 38/49 (77.6%) of UST-treated patients achieved clinical perianal response, compared to 29/49 (59.2%) with VDZ (OR 9.96, 95% CI, 2.6-38.4, P < .001) and 27/49 (55.1%) with anti-TNFs (OR 12.03, 95% CI, 2.99-48.47, P < .001). UST-treated patients also had higher radiological response rates than VDZ (OR 3.28, 95% CI, 1.07-10.07, P = .038). CONCLUSION: In pCD patients failing anti-TNFs as first-line treatment, ustekinumab may be more effective than vedolizumab or another anti-TNF as second or third-line therapy.

• MeSH
• biologické přípravky * terapeutické užití   MeSH
• Crohnova nemoc * farmakoterapie   diagnostické zobrazování   MeSH
• dospělí MeSH
• gastrointestinální látky * terapeutické užití   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• indukce remise MeSH
• inhibitory TNF terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• nemoci anu * farmakoterapie   MeSH
• retrospektivní studie MeSH
• tendenční skóre MeSH
• ustekinumab * terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Chem. Listy 2022; 116: 101−109. doi: 10.54779/ chl20220101 vladimir.pliska@biol.ethz.ch, parizek@porodnice.cz Došlo 12. 10. 2021, přijato 1. 11. 2021.

Abstract: Licence agreements between the Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague (IOCB), and the pharmaceutical company Ferring AB Malmö enabled the Swedish company to produce and commercialize worldwide a number of neurohypophyseal peptides designed at the IOCB. Several of them found therapeutic applications. dDAVP: 1-deamino-8-D-arginine-vasopressin was designed in one of the IOCB peptide laboratories (M. Zaoral and F. Šorm) in 1967. It displayed an extremely high antidiuretic activity (various tests indicate a 2- to 50-fold increase, as compared to arginine vasopressin) and a very low pressor activity. The peptide (covered by the U.S. Patent No. 3,497,491, 1970) has been used as a preferred drug in the substitution therapy of the central form of diabetes insipidus (Minirin®, today as Desmopressin INN). Besides, as later discovered (Mannucci et al. 1977), dDAVP increases the plasma concentration of the blood clottiing factor VIII. This fact extended its clinical use as haemostatics in cases of milder forms of haemophilia A, von Willebrand-Jürgens syndrome and some thrombocyte dysfunctions. Despite of the clinical success of dDAVP, a closer look reveals certain inadequacies in the presently available pharmacological data: several reports declare activity values and the prolongation effect (index of persistence) in very broad ranges. Triglycyl-8- -lysine-vasopressin (Terlipressin), a peptide with lysine vasopressin chain extended at the N-terminal by a triglycine residue, acts mainly as a prodrug (releasing lysine vasopressin after aminopeptidase splitting at the Na group). The analogue belongs to the so-called „synthetic hormonogens“; individual peptides carrying various acylating groups were synthesized in the midsixties at the IOCB and legally protected by U.S. Patent No. 3,558,590 (1968). It was a part of the licence agreements mentioned above. The activities of triglycyl-8-lysine-vasopressin (both antidiuretic and vasopressor) are about 100 times lower than those of lysine vasopressin, but its persistence is 5 times longer. As such, it is occasionally used in emergency medicine in cases of esophageal (and other gastroenteral) bleeding, traumatic or septic shock, in cirrhotic patients and patients with portal hypertension. Its use as an early abortion drug was discussed but not pursued. Carbetocin (deaminocarba1-2-O-methyltyrosin-oxytocin) was synthetized in the laboratory of Karel Jošt at the IOCB before 1971; its synthesis was covered by a Czechoslovak patent (CS-149,028 B1) in June 1973 (at that time, Czechoslovak patent law did not provide for the patentability of substances as such) and first published in a biophysical communication by Frič et al., 1974). As a part of the licence agreement, it was included in the production program of Ferring AB, but marketed later also by several other pharmaceutical companies due to an incomplete patent protection. The peptide is a moderately active uterotonic partial agonist and as such has been utilized in veterinary obstetrics for delivery induction in cows and (multiparous) pigs: its milder and better--controlled uterotonic action was found preferential as compared to oxytocin so far used for these purposes. In the last two decades, carbetocin has been commonly used also in the human obstetrics, especially to prevent the peri- and post-partum haemorrhage, from the maternal side the most frequent and most severe delivery complication. It became a life-saving drug in emergency obstetrics.

• Klíčová slova
• carbetocin,
• MeSH
• desmopresin aplikace a dávkování   dějiny   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• neurohypofyzární hormony * dějiny   farmakologie   klasifikace   MeSH
• oxytocin antagonisté a inhibitory   dějiny   farmakologie   MeSH
• poporodní krvácení farmakoterapie   MeSH
• terlipresin aplikace a dávkování   dějiny   farmakologie   terapeutické užití   MeSH
• uterotonika aplikace a dávkování   dějiny   farmakologie   klasifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH
• Švédsko MeSH

CONTEXT: SB16 is a proposed biosimilar to reference denosumab (DEN; brand name: Prolia). OBJECTIVE: This phase 3 randomized, double-blind, multicenter study evaluated the biosimilarity of SB16 to DEN in women with postmenopausal osteoporosis (NCT04664959). DESIGN: The study included 457 postmenopausal osteoporosis patients who had a lumbar spine or total hip T-score between -2.5 and -4. Patients were randomized in a 1:1 ratio to receive either 60 mg of SB16 or DEN subcutaneously at month 0 and month 6. At month 12, patients were rerandomized to continue with the assigned treatment or switch from DEN to SB16 up to month 18. This report includes results up to month 12. METHODS: The primary endpoint was the percent change from baseline in lumbar spine bone mineral density (BMD) at month 12. Secondary endpoints including the percent change from baseline in BMD of the lumbar spine (except for month 12), total hip, and femoral neck; pharmacokinetic, pharmacodynamic (serum C-telopeptide of type I collagen, and procollagen type I N-terminal propeptide), safety, and immunogenicity profiles were measured up to month 12. RESULTS: The least-squares mean differences in percent change from baseline in lumbar spine BMD at month 12 were 0.33% (90% CI, -0.25 to 0.91) in the full analysis set and 0.39% (95% CI, -0.36 to 1.13) in the per-protocol set; both within the predefined equivalence margin. The secondary endpoints were comparable between the 2 treatment groups. CONCLUSION: The reported efficacy, pharmacokinetic, pharmacodynamic, safety, and immunogenicity data support the biosimilarity of SB16 to DEN.

• MeSH
• bederní obratle účinky léků   diagnostické zobrazování   MeSH
• biosimilární léčivé přípravky * terapeutické užití   farmakokinetika   aplikace a dávkování   škodlivé účinky   MeSH
• denosumab * terapeutické užití   farmakokinetika   škodlivé účinky   aplikace a dávkování   MeSH
• dvojitá slepá metoda MeSH
• inhibitory kostní resorpce * terapeutické užití   farmakokinetika   aplikace a dávkování   škodlivé účinky   MeSH
• kostní denzita účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• postmenopauzální osteoporóza * farmakoterapie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Cíl: Těhotenství se nepovažuje za stav zvyšující náchylnost organismu k infekci SARS-CoV-2 (severe-acute-respiratory-syndrome-related coronavirus 2), avšak v případě nákazy v graviditě se zvyšuje riziko závažnějšího průběhu nemoci covid-19. Ve většině případů ovšem bývá průběh infekce v graviditě mírný nebo bezpříznakový. Hlavním cílem studie u těhotných žen s covidem-19 (coronavirové onemocnění) bylo dokázat, že způsob porodu se nemění a závažné komplikace jak porodnické, tak neonatologické se kvůli tomuto onemocnění nevyskytují častěji. Metody: Do retrospektivní, observační, multicentrické studie byly zařazeny pacientky s pozitivním testem na covid-19, které byly přijaty a následně porodily v období od 15. března 2020 do 15. března 2021. Data z porodnických oddělení pěti center v České republice během pandemie covidu-19 byla analyzována ve vztahu k metodě a době porodu, symptomům covidu-19 a potenciálním komplikacím s ohledem na demografii a komorbidity těhotných žen. Infekce koronavirem byla u pacientek potvrzena pomocí PCR (polymerázové řetězové reakce). Statistická analýza byla hodnocena pomocí programu Excel. Výsledky: Během sledovaného období bylo ve studijních centrech detekováno 236 těhotných žen s covidem-19. Většina pacientek byla asymptomatická (59,7 %). U symptomatických pacientek byly nejčastějšími příznaky kašel (52,6 %), nachlazení (43,2 %) a horečka (37,9 %) a covidová pneumonie byla diagnostikována u 8 pacientek. Porod byl proveden vaginálně u 52,5 % pacientek, těhotenství bylo ukončeno císařským řezem v 44,5 %, per VEX (vakuumextrakce) v 2,1 % a per forcipem v 0,8 % případů. Průměrný týden gravidity v době porodu byl 38 a předčasný porod byl proveden u 19,1 % pacientek. Výsledky tyto studie u těhotných žen s covidem-19 prokázaly, že způsob porodu se nezměnil a výskyt větších komplikací jak porodnických, tak neonatologických nebyl ve většině případů zaznamenán. Dva prezentované závažné průběhy covidu-19 u těhotných žen však vedly k předčasnému ukončení těhotenství. Jediným přidruženým rizikovým faktorem byla obezita pacientky. Závěry: Ačkoli je covid-19 onemocnění, které je u těhotných žen většinou asymptomatické nebo má pouze mírné příznaky podobné chřipce, je spojeno se zvýšenou nemocností a úmrtností ve srovnání s těhotnými ženami bez covidu-19. Výzvou do budoucna je možnost segregace pacientek do nízko a vysoce rizikových skupin na základě prokázaných rizikových faktorů a důsledné očkování těhotných žen nebo žen plánujících početí. V kritických případech je nutné správné načasování předčasného ukončení těhotenství a včasná indikace počátku zrání plic plodu.

Objective: Pregnancy is not considered a condition that increases the body‘s susceptibility to SARS-CoV-2 (severe-acute-respiratory-syndrome-related coronavirus-2) infection, but in the case of infection in pregnancy, there is an increased risk of a more severe course of COVID-19 (coronavirus disease-19). However, the course of infection in pregnancy is mild or asymptomatic in most cases. The main objective of the study in pregnant women with COVID-19 was to prove that the delivery method is not changed, and serious complications do not occur more frequently due to this disease. Methods: In a retrospective, observational, multicentric study, the pregnant women positively tested to COVID-19 were admitted and subsequently gave birth in the period from 15 March 2020 to 15 March 2021. Data from the delivery departments of five centers in the Czech Republic during COVID-19 pandemic were analyzed in relation to the delivery method and time, COVID-19 symptoms and potential complications with respect to demographics and comorbidities of pregnant women. COVID-19 positivity was confirmed with PCR (polymerase-chain reaction). The Excel program was used during statistical analysis. Results: During the observed study period, 236 pregnant women with COVID-19 were detected at study centers. Most of the patients were asymptomatic (59.7%). In symptomatic patients, most common symptoms were cough (52.6 %), cold (43.2%) and fever (37.9%), and COVID-19 pneumonia was diagnosed in 8 patients. The delivery was performed vaginally in 52.5% patients, the pregnancy was terminated by C-section (cesarean section) in 44.5%, per VEX (vacuum extractor) in 2.1% and per forcipem in 0.8% cases. The average week of pregnancy at the time of delivery was 38 (29–41) and preterm delivery was performed in 19.1% patients. The study results in pregnant women with COVID-19 demonstrated that the method of delivery was not changed and major delivery and neonatological complications did not develop in most cases. However, two presented serious courses of COVID-19 in pregnant women led to premature terminations of pregnancies. The only associated risk factor was the patient‘s obesity. Conclusions: Although COVID-19 is a disease that is mostly asymptomatic in pregnant women or with only mild flu-like symptoms, it is associated with increased morbidity and mortality compared to pregnant women without COVID-19. The challenge for the future is the possibility of segregating patients into lowand high-risk groups based on proven risk factors, and consistent vaccination of pregnant women or women planning conception. In critical cases, the correct timing of premature termination of pregnancy and early indication of the beginning of fetal lung maturation is necessary.

• MeSH
• COVID-19 * komplikace   mortalita   MeSH
• diagnostické zobrazování metody   MeSH
• komplikace porodu * mikrobiologie   MeSH
• komplikace těhotenství * mikrobiologie   MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Česká republika MeSH

AIMS: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. New treatments are needed to cardiovert recent-onset paroxysmal AF quickly and safely. RESTORE-1 was a multicentre, randomized, double-blind, placebo-controlled trial of a 120 mg orally inhaled solution of flecainide acetate (FlecIH-103) for cardioversion of symptomatic, recent-onset (≤48 h) paroxysmal AF. The study aim was to evaluate the efficacy and safety of FlecIH-103 administered via oral inhalation. METHODS AND RESULTS: Patients experiencing a recent-onset paroxysmal AF episode were randomized to receive a single dose of FlecIH-103 or placebo delivered over two 3.5 min inhalation periods, while patients were monitored using 12-lead electrocardiograms and Holter. The trial was stopped prematurely after treating 55 patients, due to lower-than-expected conversion rates and plasma levels. Mean age was 59.6 years, 31.5% of patients were female, and 59.2% were having their first AF episode. Conversion rate was 30.8% (95% confidence interval: 14.7-43.8) for the active group (n = 39) and 0.0% for the placebo group (n = 12) (P = 0.04). Median time to conversion was 12.8 min (IQR: 17.2). In the active group, the mean flecainide plasma level was 198 ng/mL (SD: 156), which is ∼50% lower than in the previous studies. The most common adverse events (AEs) were dysgeusia, dyspnoea, and cough. All AEs were short-lasting and of mild or moderate intensity. CONCLUSION: Despite early termination of the trial, FlecIH-103 was significantly more effective than placebo in cardioverting AF. Safety data did not show any serious AEs. Further studies of FlecIH-103 are needed to optimize the combination of drug formulation and inhalation delivery platform. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov, unique identifier: NCT05039359.

• MeSH
• antiarytmika * aplikace a dávkování   škodlivé účinky   MeSH
• aplikace inhalační MeSH
• časové faktory MeSH
• dvojitá slepá metoda MeSH
• elektrokardiografie ambulantní MeSH
• fibrilace síní * farmakoterapie   diagnóza   patofyziologie   MeSH
• flekainid * aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• předčasné ukončení klinických zkoušek MeSH
• senioři MeSH
• srdeční frekvence * účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Oxidative stress and chronic inflammation are important drivers in the pathogenesis and progression of many chronic diseases, such as cancers of the breast, kidney, lung, and others, autoimmune diseases (rheumatoid arthritis), cardiovascular diseases (hypertension, atherosclerosis, arrhythmia), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease), mental disorders (depression, schizophrenia, bipolar disorder), gastrointestinal disorders (inflammatory bowel disease, colorectal cancer), and other disorders. With the increasing demand for less toxic and more tolerable therapies, flavonoids have the potential to effectively modulate the responsiveness to conventional therapy and radiotherapy. Flavonoids are polyphenolic compounds found in fruits, vegetables, grains, and plant-derived beverages. Six of the twelve structurally different flavonoid subgroups are of dietary significance and include anthocyanidins (e.g. pelargonidin, cyanidin), flavan-3-ols (e.g. epicatechin, epigallocatechin), flavonols (e.g. quercetin, kaempferol), flavones (e.g. luteolin, baicalein), flavanones (e.g. hesperetin, naringenin), and isoflavones (daidzein, genistein). The health benefits of flavonoids are related to their structural characteristics, such as the number and position of hydroxyl groups and the presence of C2C3 double bonds, which predetermine their ability to chelate metal ions, terminate ROS (e.g. hydroxyl radicals formed by the Fenton reaction), and interact with biological targets to trigger a biological response. Based on these structural characteristics, flavonoids can exert both antioxidant or prooxidant properties, modulate the activity of ROS-scavenging enzymes and the expression and activation of proinflammatory cytokines (e.g., interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)), induce apoptosis and autophagy, and target key signaling pathways, such as the nuclear factor erythroid 2-related factor 2 (Nrf2) and Bcl-2 family of proteins. This review aims to briefly discuss the mutually interconnected aspects of oxidative and inflammatory mechanisms, such as lipid peroxidation, protein oxidation, DNA damage, and the mechanism and resolution of inflammation. The major part of this article discusses the role of flavonoids in alleviating oxidative stress and inflammation, two common components of many human diseases. The results of epidemiological studies on flavonoids are also presented.

• MeSH
• flavonoidy * farmakologie   chemie   terapeutické užití   metabolismus   MeSH
• lidé MeSH
• nádory farmakoterapie   metabolismus   patologie   MeSH
• neurodegenerativní nemoci farmakoterapie   metabolismus   MeSH
• oxidační stres * účinky léků   MeSH
• zánět * farmakoterapie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

To explore the effects and underlying mechanisms of Mdivi-1 on three common clinical models of acute kidney injury (AKI). Three common AKI cell models were constructed, classified into the control group (human renal tubular epithelial cells [HK-2] cells), the Iohexol group (HK-2 cells treated with Iohexol), the Genta group (HK-2 cells treated with Gentamicin), and the Cis group (HK-2 cells treated with Cisplatin). To explore the optimal protective concentration of Mdivi-1 for each AKI cell model, the experimental design consisted of the following seven groups: the control group (HK-2 cells cultured in medium), three injury groups (HK-2 cells subjected to Iohexol, Gentamicin, or Cisplatin), and the corresponding protection groups (with a certain concentration of Mdivi-1 added to each injury group). Cellular survival and apoptosis, reactive oxygen species (ROS) levels, and the expression of recombinant Sirtuin 3 (SIRT3) in each group were measured. Mitochondrial fission and fusion dynamics in cells were observed under an electron microscope. To explore relevant pathways, the changes in relevant pathway proteins were analyzed through Western blotting. The half maximal inhibitory concentration (IC50) values were 150.06 mgI/ml at 6 h in the Iohexol group, 37.88 mg/ml at 24 h in the Gentamicin group, and 13.48 microM at 24 h in the Cisplatin group. Compared with the control group, the three injury groups showed increased cell apoptosis rates and higher expressions of apoptotic proteins in HK-2 cells, with an accompanying decrease in cell migration. After the addition of corresponding concentrations of Mdivi-1, the optimal concentrations were 3 μM in the Iohexo-3 group, 1 microM in the Genta-1 group, and 5 μM in the Cis-5 group, HK-2 cells showed the highest survival rate, reduced apoptosis, decreased mitochondrial ROS and SIRT3 expression, and reduced mitochondrial fission and autophagy when compared with each injury group. Further verification with Western blot analysis after the addition of Mdivi-1 revealed a reduction in the expressions of mitochondrial fission proteins DRP1, Nrf2, SIRT3, Caspase-3, Jun N-terminal Kinase (JNK)/P-JNK, NF-kappaB, Bcl2, and autophagic protein P62, as well as reduced ROS levels. Mdivi-1 had protective effects on the three common AKI cell models by potentially reducing mitochondrial fission in cells and inhibiting the production of ROS through the mediation of the NF- B/JNK/SIRT3 signaling pathway, thereby exerting protective effects. Key words AKI, Cisplatin, Gentamicin, Iohexol, Mdivi-1.

• MeSH
• akutní poškození ledvin * metabolismus   patologie   farmakoterapie   MeSH
• apoptóza účinky léků   MeSH
• buněčné linie MeSH
• lidé MeSH
• MAP kinasový signální systém účinky léků   fyziologie   MeSH
• mitochondriální dynamika * účinky léků   fyziologie   MeSH
• NF-kappa B * metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• signální transdukce * účinky léků   MeSH
• sirtuin 3 * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH