Xi-Kun Yuan Pin-Shi Ni Zhen-Hao Yan Zhi Yu Zhuang-Zhi Wang Chen-Kai Zhang Fang-Hui Li Xiao-Ming Yu 1Sports Department, Nanjing University of Science and Technology ZiJin College, Nanjing, China, 2School of Sport Sciences, Nanjing Normal University, Nanjing, China, 3Shanghai Seventh People's Hospital, Shanghai, China To investigate the effects of life-long exercise (LLE) on age-related inflammatory cytokines, apoptosis, oxidative stress, ferroptosis markers, and the NRF2/KAEP 1/Klotho pathway in rats. Eight-month-old female Sprague-Dawley rats were divided into four groups: 1) LLE: 18-month LLE training starting at 8 months of age, 2) Old moderate-intensity continuous training (OMICT): 8 months of moderate-intensity continuous training starting at 18 months of age, 3) Adult sedentary (ASED): 8 month-old adult sedentary control group, and 4) Old sedentary (OSED): a 26-month-old sedentary control group. Hematoxylin eosin staining was performed to observe the pathological changes of kidney tissue injury in rats; Masson's staining to observe the deposition of collagen fibers in rat kidney tissues; and western blotting to detect the expression levels of IL-6, IL 1beta, p53, p21, TNF-alpha, GPX4, KAEP 1, NRF2, SLC7A11, and other proteins in kidney tissues. Results: Compared with the ASED group, the OSED group showed significant morphological changes in renal tubules and glomeruli, which were swollen and deformed, with a small number of inflammatory cells infiltrated in the tubules. Compared with the OSED group, the expression levels of inflammation-related proteins such as IL-1beta, IL-6, TNF alpha, and MMP3 were significantly lower in the LLE group. Quantitative immunofluorescence analysis and western blotting revealed that compared with the ASED group, KAEP 1 protein fluorescence intensity and protein expression levels were significantly enhanced, while Klotho and NRF2 protein fluorescence intensity and protein expression levels were reduced in the OSED group. Compared with the OSED group, KAEP 1 protein fluorescence intensity and protein expression levels were reduced in the LLE and OMICT groups. Klotho and KAEP 1 protein expression levels and immunofluorescence intensity were higher in the LLE group than in the OSED group. The expression levels of GPX4 and SLC7A11, two negative marker proteins associated with ferroptosis, were significantly higher in the LLE group than in the OSED group, while the expression of p53 a cellular senescence-associated protein that negatively regulates SLC7A11, and the downstream protein p21 were significantly decreased. LLE may ameliorated aging-induced oxidative stress, inflammatory response, apoptosis, and ferroptosis by regulating Klotho and synergistically activating the NRF2/KAEP 1 pathway. Keywords: Life-long exercise, Moderate intensity continuous training, Aging, Kidney tissue, Ferroptosis.

• MeSH
• apoptóza * fyziologie   MeSH
• biologické markery metabolismus   MeSH
• faktor 2 související s NF-E2 * metabolismus   MeSH
• ferroptóza * fyziologie   MeSH
• glukuronidasa metabolismus   MeSH
• kondiční příprava zvířat * fyziologie   MeSH
• krysa rodu Rattus MeSH
• ledviny * metabolismus   patologie   MeSH
• oxidační stres * fyziologie   MeSH
• potkani Sprague-Dawley * MeSH
• proteiny Klotho * MeSH
• signální transdukce fyziologie   MeSH
• stárnutí metabolismus   patologie   MeSH
• zánět metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• faktor 2 související s NF-E2 * MeSH
• glukuronidasa MeSH
• Klotho Protein, rat MeSH Prohlížeč
• Nfe2l2 protein, rat MeSH Prohlížeč
• proteiny Klotho * MeSH

The protease caspase-3 is a key mediator of apoptotic programmed cell death. But weak or transient caspase activity can contribute to neuronal differentiation, axonal pathfinding, and synaptic long-term depression. Despite the importance of sublethal, or nonapoptotic, caspase activity in neurodevelopment and neural plasticity, there has been no simple method for mapping and quantifying nonapoptotic caspase activity (NACA) in rodent brains. We therefore generated a transgenic mouse expressing a highly sensitive and specific fluorescent reporter of caspase activity, with peak signal localized to the nucleus. As a proof of concept, we first obtained evidence that NACA influences neurophysiology in an amygdalar circuit. Then focusing on the amygdala, we were able to quantify a sex-specific persistent elevation in caspase activity in females after restraint stress. This simple in vivo caspase activity reporter will facilitate systems-level studies of apoptotic and nonapoptotic phenomena in behavioral and pathologic models.

• Klíčová slova
• amygdala, caspases, in vivo reporter, mapping, nonapoptotic, sex differences, stress,
• MeSH
• apoptóza * fyziologie   MeSH
• kaspasa 9 MeSH
• mozek * MeSH
• myši transgenní MeSH
• myši MeSH
• neuroplasticita MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• kaspasa 9 MeSH

Reports of programmed cell death (PCD) in phytoplankton raise questions about the ecological evolutionary role of cell death in these organisms. We induced PCD by nitrogen deprivation and unregulated cell death (non-PCD) in one strain of the green microalga Ankistrodesmus densus and investigated the effects of the cell death supernatants on phylogenetically related co-occurring organisms using growth rates and maximum biomass as proxies of fitness. PCD-released materials from A. densus CCMA-UFSCar-3 significantly increased growth rates of two conspecific strains compared to healthy culture (HC) supernatants and improved the maximum biomass of all A. densus strains compared to related species. Although growth rates of non-A. densus with PCD supernatants were not statistically different from HC treatment, biomass gain was significantly reduced. Thus, the organic substances released by PCD, possibly nitrogenous compounds, could promote conspecific growth. These results support the argument that PCD may differentiate species or subtypes and increases inclusive fitness in this model unicellular chlorophyte. Further research, however, is needed to identify the responsible molecules and how they interact with cells to provide the PCD benefits.

• Klíčová slova
• Ankistrodesmus, inclusive fitness, kin selection, phytoplankton, programmed cell death,
• MeSH
• apoptóza fyziologie   MeSH
• druhová specificita MeSH
• dusík MeSH
• fytoplankton MeSH
• mikrořasy * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dusík MeSH

Apoptosis signal-regulating kinase (ASK) 1, a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, modulates diverse responses to oxidative and endoplasmic reticulum (ER) stress and calcium influx. As a crucial cellular stress sensor, ASK1 activates c-Jun N-terminal kinases (JNKs) and p38 MAPKs. Their excessive and sustained activation leads to cell death, inflammation and fibrosis in various tissues and is implicated in the development of many neurological disorders, such as Alzheimer's, Parkinson's and Huntington disease and amyotrophic lateral sclerosis, in addition to cardiovascular diseases, diabetes and cancer. However, currently available inhibitors of JNK and p38 kinases either lack efficacy or have undesirable side effects. Therefore, targeted inhibition of their upstream activator, ASK1, stands out as a promising therapeutic strategy for treating such severe pathological conditions. This review summarizes recent structural findings on ASK1 regulation and its role in various diseases, highlighting prospects for ASK1 inhibition in the treatment of these pathologies.

• Klíčová slova
• 14-3-3, ASK1, MAP kinase, kinase, phosphorylation, protein–protein interaction,
• MeSH
• apoptóza fyziologie   MeSH
• fosforylace MeSH
• JNK mitogenem aktivované proteinkinasy metabolismus   MeSH
• lidé MeSH
• MAP kinasa-kinasa-kinasa 5 genetika   metabolismus   fyziologie   ultrastruktura   MeSH
• MAP kinasový signální systém MeSH
• MAP kinasy kinas (kinas) genetika   metabolismus   MeSH
• mapy interakcí proteinů genetika   fyziologie   MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• oxidace-redukce MeSH
• oxidační stres MeSH
• proteiny 14-3-3 metabolismus   MeSH
• proteiny regulující apoptózu metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• stres endoplazmatického retikula MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• JNK mitogenem aktivované proteinkinasy MeSH
• MAP kinasa-kinasa-kinasa 5 MeSH
• MAP kinasy kinas (kinas) MeSH
• MAP3K5 protein, human MeSH Prohlížeč
• mitogenem aktivované proteinkinasy p38 MeSH
• proteiny 14-3-3 MeSH
• proteiny regulující apoptózu MeSH

Hematologic malignancies (HM) comprise diverse cancers of lymphoid and myeloid origin, including lymphomas (approx. 40%), chronic lymphocytic leukemia (CLL, approx. 15%), multiple myeloma (MM, approx. 15%), acute myeloid leukemia (AML, approx. 10%), and many other diseases. Despite considerable improvement in treatment options and survival parameters in the new millennium, many patients with HM still develop chemotherapy‑refractory diseases and require re-treatment. Because frontline therapies for the majority of HM (except for CLL) are still largely based on classical cytostatics, the relapses are often associated with defects in DNA damage response (DDR) pathways and anti-apoptotic blocks exemplified, respectively, by mutations or deletion of the TP53 tumor suppressor, and overexpression of anti-apoptotic proteins of the B-cell lymphoma 2 (BCL2) family. BCL2 homology 3 (BH3) mimetics represent a novel class of pro-apoptotic anti-cancer agents with a unique mode of action-direct targeting of mitochondria independently of TP53 gene aberrations. Consequently, BH3 mimetics can effectively eliminate even non-dividing malignant cells with adverse molecular cytogenetic alterations. Venetoclax, the nanomolar inhibitor of BCL2 anti-apoptotic protein has been approved for the therapy of CLL and AML. Numerous venetoclax-based combinatorial treatment regimens, next-generation BCL2 inhibitors, and myeloid cell leukemia 1 (MCL1) protein inhibitors, which are another class of BH3 mimetics with promising preclinical results, are currently being tested in several clinical trials in patients with diverse HM. These pivotal trials will soon answer critical questions and concerns about these innovative agents regarding not only their anti-tumor efficacy but also potential side effects, recommended dosages, and the optimal length of therapy as well as identification of reliable biomarkers of sensitivity or resistance. Effective harnessing of the full therapeutic potential of BH3 mimetics is a critical mission as it may directly translate into better management of the aggressive forms of HM and could lead to significantly improved survival parameters and quality of life in patients with urgent medical needs.

• Klíčová slova
• BH3 mimetics, apoptosis, biomarkers, hematologic malignancies, resistance, targeted therapy, venetoclax,
• MeSH
• apoptóza fyziologie   MeSH
• bicyklické sloučeniny heterocyklické terapeutické užití   MeSH
• biologické markery metabolismus   MeSH
• hematologické nádory farmakoterapie   metabolismus   MeSH
• lidé MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• poškození DNA účinky léků   genetika   MeSH
• sulfonamidy terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• bicyklické sloučeniny heterocyklické MeSH
• biologické markery MeSH
• nádorový supresorový protein p53 MeSH
• sulfonamidy MeSH
• venetoclax MeSH Prohlížeč

Iron is essential for a healthy pregnancy, and iron supplementation is nearly universally recommended, regardless of maternal iron status. A signal of potential harm is the U-shaped association between maternal ferritin, a marker of iron stores, and risk of adverse pregnancy outcomes. However, ferritin is also induced by inflammation and may overestimate iron stores during inflammation or infection. In this study, we use mouse models to determine whether maternal iron loading, inflammation, or their interaction cause poor pregnancy outcomes. Only maternal exposure to both iron excess and inflammation, but not either condition alone, causes embryo malformations and demise. Maternal iron excess potentiates embryo injury during both LPS-induced acute inflammation and obesity-induced chronic mild inflammation. The adverse interaction depends on TNFα signaling, causes apoptosis of placental and embryo endothelium, and is prevented by anti-TNFα or antioxidant treatment. Our findings raise important questions about the safety of indiscriminate iron supplementation during pregnancy.

• MeSH
• apoptóza fyziologie   MeSH
• embryo savčí patologie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) MeSH
• ferritin analýza   MeSH
• hepcidiny genetika   MeSH
• komplikace těhotenství MeSH
• kultivované buňky MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• obezita patologie   MeSH
• placenta patologie   MeSH
• těhotenství MeSH
• TNF-alfa metabolismus   MeSH
• železo metabolismus   toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• ferritin MeSH
• hepcidiny MeSH
• TNF-alfa MeSH
• železo MeSH

Aflatoxin B1 (AFB1) is a mycotoxin often found in food and livestock feed. It can affect human and animal health and is especially damaging to the liver. This study aims to evaluate whether Bacillus amyloliquefaciens (hereafter referred to as B. amyloliquefaciens) B10 can alleviate the toxic effects of AFB1 and, if so, what mechanism is responsible for its action. Specific pathogen-free (SPF) Kunming mice (5-6 weeks old) were divided into four groups (Control, AFB1, B10 strain, and AFB1 + B10 strain) and conducted continuously via gavage for 28 days. Oxidation indices (MDA, T-AOC, SOD, GSH-Px, and CAT) were then measured using their liver tissues and liver coefficient were calculated. Apoptosis was determined using the TUNEL method. Gene expression was determined for Bax, Bcl-2, BIP, CHOP, JNK, Caspase-12, Caspase-9, and Caspase-3, and protein expression was detected for Bax, Bcl-2, and Caspase-3. Our results showed that AFB1 induced the oxidative damage and apoptosis in the livers of mice. However, for mice given B. amyloliquefaciens B10, the biochemical indices, pathological changes, the expressions of genes and proteins related to oxidative stress and apoptosis were significantly reversed. The results indicate that B. amyloliquefaciens B10 antagonizes oxidative damage and apoptosis induced by AFB1 in the livers of mice. The results of this study are of significance for the future use of this strain to reduce the harm of AFB1 to human health and animal reproductive performance.

• Klíčová slova
• Aflatoxin B1, Apoptosis, Bacillus amyloliquefaciens B10, Liver, Oxidative stress,
• MeSH
• aflatoxin B1 toxicita   MeSH
• apoptóza fyziologie   MeSH
• Bacillus amyloliquefaciens růst a vývoj   fyziologie   MeSH
• játra účinky léků   patologie   MeSH
• myši MeSH
• oxidační stres účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• tělesná hmotnost účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aflatoxin B1 MeSH

Acute respiratory distress syndrome (ARDS) is characterized by diffuse lung damage, inflammation, oedema formation, and surfactant dysfunction leading to hypoxemia. Severe ARDS can accelerate the injury of other organs, worsening the patient´s status. There is an evidence that the lung tissue injury affects the right heart function causing cor pulmonale. However, heart tissue changes associated with ARDS are still poorly known. Therefore, this study evaluated oxidative and inflammatory modifications of the heart tissue in two experimental models of ARDS induced in New Zealand rabbits by intratracheal instillation of neonatal meconium (100 mg/kg) or by repetitive lung lavages with saline (30 ml/kg). Since induction of the respiratory insufficiency, all animals were oxygen-ventilated for next 5 h. Total and differential counts of leukocytes were measured in the arterial blood, markers of myocardial injury [(troponin, creatine kinase - myocardial band (CK-MB), lactate dehydrogenase (LD)] in the plasma, and markers of inflammation [tumour necrosis factor (TNF)alpha, interleukin (IL)-6], cardiovascular risk [galectin-3 (Gal-3)], oxidative changes [thiobarbituric acid reactive substances (TBARS), 3-nitrotyrosine (3NT)], and vascular damage [receptor for advanced glycation end products (RAGE)] in the heart tissue. Apoptosis of heart cells was investigated immunohistochemically. In both ARDS models, counts of total leukocytes and neutrophils in the blood, markers of myocardial injury, inflammation, oxidative and vascular damage in the plasma and heart tissue, and heart cell apoptosis increased compared to controls. This study indicates that changes associated with ARDS may contribute to early heart damage what can potentially deteriorate the cardiac function and contribute to its failure.

• MeSH
• apoptóza fyziologie   MeSH
• biologické markery metabolismus   MeSH
• králíci MeSH
• modely nemocí na zvířatech MeSH
• oxidační stres fyziologie   MeSH
• poranění srdce metabolismus   patologie   MeSH
• poškození plic metabolismus   patologie   MeSH
• syndrom aspirace mekonia metabolismus   patologie   MeSH
• syndrom dechové tísně metabolismus   patologie   MeSH
• zánět metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH

The aim of this study was to investigate the use of a standardized animal model subjected to antibiotic treatment, and the effects of this treatment on the course of dextran sodium sulphate (DSS)-induced colitis in mice. By decontamination with selective antibiotics and observation of pathogenesis of ulcerative colitis (UC) induced chemically by exposure of mice to various concentrations of DSS, we obtained an optimum animal PGF model of acute UC manifested by mucin depletion, epithelial degeneration and necrosis, leading to the disappearance of epithelial cells, infiltration of lamina propria and submucosa with neutrophils, cryptitis, and accompanied by decreased viability of intestinal microbiota, loss of body weight, dehydration, moderate rectal bleeding, and a decrease in the selected markers of cellular proliferation and apoptosis. The obtained PGF model did not exhibit changes that could contribute to inflammation by means of alteration of the metabolic status and the induced dysbiosis did not serve as a bearer of pathogenic microorganisms participating in development of ulcerative colitis. The inflammatory process was induced particularly by exposure to DSS and its toxic action on compactness and integrity of mucosal barrier in the large intestine. This offers new possibilities of the use of this animal model in studies with or without participation of pathogenic microbiota in IBD pathogenesis.

• Klíčová slova
• DSS-induced colitis, antibiotics, gut microbiota, histopathology, pseudo germ-free model,
• MeSH
• antibakteriální látky farmakologie   MeSH
• apoptóza fyziologie   MeSH
• epitelové buňky patologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• proliferace buněk fyziologie   MeSH
• síran dextranu farmakologie   MeSH
• střevní mikroflóra účinky léků   fyziologie   MeSH
• střevní sliznice mikrobiologie   patologie   MeSH
• ulcerózní kolitida chemicky indukované   farmakoterapie   patologie   MeSH
• zánět farmakoterapie   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• síran dextranu MeSH

The Bcl-2 protein family comprises both pro- and antiapoptotic members that control the permeabilization of the mitochondrial outer membrane, a crucial step in the modulation of apoptosis. Recent research has demonstrated that the carboxyl-terminal transmembrane domain (TMD) of some Bcl-2 protein family members can modulate apoptosis; however, the transmembrane interactome of the antiapoptotic protein Mcl-1 remains largely unexplored. Here, we demonstrate that the Mcl-1 TMD forms homooligomers in the mitochondrial membrane, competes with full-length Mcl-1 protein with regards to its antiapoptotic function, and induces cell death in a Bok-dependent manner. While the Bok TMD oligomers locate preferentially to the endoplasmic reticulum (ER), heterooligomerization between the TMDs of Mcl-1 and Bok predominantly takes place at the mitochondrial membrane. Strikingly, the coexpression of Mcl-1 and Bok TMDs produces an increase in ER mitochondrial-associated membranes, suggesting an active role of Mcl-1 in the induced mitochondrial targeting of Bok. Finally, the introduction of Mcl-1 TMD somatic mutations detected in cancer patients alters the TMD interaction pattern to provide the Mcl-1 protein with enhanced antiapoptotic activity, thereby highlighting the clinical relevance of Mcl-1 TMD interactions.

• Klíčová slova
• Bcl-2, Bok, Mcl-1, apoptosis, transmembrane,
• MeSH
• apoptóza fyziologie   MeSH
• buněčná smrt fyziologie   MeSH
• endoplazmatické retikulum metabolismus   MeSH
• HeLa buňky MeSH
• lidé MeSH
• mitochondriální membrány metabolismus   MeSH
• mitochondrie metabolismus   MeSH
• protein MCL-1 metabolismus   MeSH
• proteinové domény MeSH
• protoonkogenní proteiny c-bcl-2 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• BOK protein, human MeSH Prohlížeč
• MCL1 protein, human MeSH Prohlížeč
• protein MCL-1 MeSH
• protoonkogenní proteiny c-bcl-2 MeSH