Izhodišča: Zastrupitev z ogljikovim monoksidom (CO) močno okrne funkcijo astrocitov in nevronov. Pozne nevropsihološke posledice zastrupitve lahko preprečimo z zdravljenjem s hiperbaričnim kisikom ...(HBO). V raziskavi smo preučevali učinek CO in HBO na zgodnje procese celične smrti v nevronski in mešani kulturi ter ugotavljali, ali se raven glutationa v astrocitih po izpostavljenosti CO in HBO spremeni in ali bi lahko le-ta bil možna nova tarča za zdravljenje zastrupitve s CO.
Metode: Primarne astrocitne, nevronske in mešane celične kulture možganske skorje podgane smo izpostavili 3.000 ppm CO v zraku, nato pa jih v obdobju 24-urne normoksije v različnih časovnih presledkih za 1 uro izpostavili 100-odstotnemu kisiku pri tlaku 3 barov. V celicah mešane in nevronske kulture smo merili aktivnost laktat dehidrogenaze (LDH) in kaspaz 3/7, v astrocitih pa raven glutationa.
Rezultati: CO je povzročil zvišanje aktivnosti LDH in kaspaz 3/7 v nevronskih kulturah, v mešanih pa le zvišanje aktivnosti kaspaz 3/7. Po izpostavitvi CO in HBO se je zvišala aktivnost LDH v nevronskih kulturah in znižala aktivnost kaspaz 3/7 v mešanih kulturah. CO je v astrocitih povzročil znižanje celokupnega glutationa (GSHt), zvišanje glutation disulfida (GSSG) in znižanje GSH/GSSG, po izpostavitvi CO in HBO pa se je zvišala GSHt, znižala GSSG in zvišala GSH/GSSG.
Zaključek: Razlike v citotoksičnem delovanju CO in zaščitni vlogi HBO v nevronski, mešani in astrocitni kulturi kažejo, da so nevroni, ki rastejo brez astrocitov, v primerjavi z mešano kulturo dovzetnejši za škodljive učinke CO ter nakazujejo, da astrociti ob oksidativnem stresu poskušajo ščititi nevrone, ki so pri sintezi glutationa odvisni od njih.
Opstati ili umrijeti – regulacija stanične smrti Miletić, Marina; Murati, Teuta; Slavica, Anita ...
Hrvatski časopis za prehrambenu tehnologiju, biotehnologiju i nutricionizam,
06/2021, Letnik:
16, Številka:
1-2
Journal Article
Odprti dostop
Stanično umiranje je temeljni biološki proces, koji je u fiziološkom smislu embrionalnoga razvoja i obnove tkiva, te kao patološki odgovor na ozljedu
stanica i infekciju patogenima, uključen u ...mehanizme koji kontroliraju razvoj, homeostazu i imunološku regulaciju višestaničnih organizama.
Stanice mogu umrijeti slučajnom (biološki nekontrolirani procesi) ili reguliranom (genetski kontrolirani molekularni procesi) staničnom smrću.
Stanična smrt odvija se različitim mehanizmima koji dovode do pojave različitih morfoloških promjena u stanicama zahvaćenim tim procesima.
Nedavna otkrića u tom području i detekcija sve većeg broja novih oblika regulirane stanične smrti, rezultirala su novom sustavnom klasifikacijom
i nomenklaturom različitih tipova stanične smrti. U ovom preglednom radu dan je uvid u sustav klasifikacije, mehanizme i obilježja glavnih tipova
stanične smrti: nekroze, apoptoze i autofagije.
Cell death is fundamental biological activity involved in mechanisms controlling the development, homeostasis and immune regulation of
multicellular organisms in the physiological context of embryonic development and tissue regeneration, as a pathological response to cell injury
and pathogen infection. Cells can die by accidental (biologically uncontrolled processes) or regulated (genetically controlled molecular processes)
cell death. Cell death occurs by different mechanisms leading to the development of specific morphologies. Recent discoveries in this field and
the increasing number of new forms of regulated cell death have resulted in a novel classification system and nomenclature of different cell death
modalities. This review provides an insight into the system of classification, mechanisms and characteristics of main cell death modalities: necrosis,
apoptosis and autophagy.
Noise and toluene can have significant adverse effects on different systems in the human body, but little is known about their combination. The aim of this study was to see how their combined action ...reflects on serum levels of inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β), body weight, and pathological changes in the heart, lung, stomach, and spleen tissues. To do that we exposed New Zealand rabbits to 1000 mg/L toluene and 100 dB of white noise in a chamber specifically designed for the purpose over two consecutive weeks. Serum levels of TNF-α and IL-1β were measured with the enzyme-linked immunosorbent assay (ELISA), whereas Bax and Bcl-2 expressions in tissues were determined with real-time polymerase chain reaction (PCR). Noise and toluene changed TNF-α and IL-1β serum levels on different days following the end of exposure and significantly increased the Bax/Bcl-2 ratio in the lung and spleen. In addition, they induced different pathological changes in the heart, lung, spleen, and stomach tissues. This study has confirmed that exposure to noise and toluene can induce a range of toxicopathological changes, probably by inducing inflammatory pathways and apoptosis, but their combined effects look weaker than those of its components, although histopathological findings suggest the opposite.
Herbal medicines have played an important role in treating different diseases since ancient times. Bioactive components of medicinal plants are a good starting point for discovering new drugs such as ...chemotherapeutics. Currently, there are four classes of plant-derived chemotherapeutic drugs used in clinical practice. However, to discover new potential cytotoxic molecules, the research effort on herbal extracts has not diminished. The aim of this review was to evaluate the chemical constituents of plants that possess cytotoxicity, the signalling pathways responsible for this effect, and the influence of solvent polarity on potential cytotoxic effect and to present the cytotoxic activity of selected herbal extracts. The polyphenolic, anthraquinon, diterpneoid, triterpenoid, flavonoid, betulinic acid and berberine content contributes to cytotoxicity of herbal extracts. The inhibitory effect on cancer cells viability could be a consequence of the non-apoptotic processes, such as cell cycle arrestment, and the apoptotic process in tumour cells through different signalling pathways. The influence of solvent polarity on potential cytotoxic effect of herbal extracts should not be ignored. In general, the best cytotoxic activity was found in nonpolar and moderately polar herbal extracts. The herbal extract with IC
below 30 μg/ml could be considered a very strong cytotoxic agent. Considering that many antitumor drugs have been discovered from natural products, further research on plants and plant-derived chemicals may result in the discovery of potent anticancer agents.
Chronic lymphocytic leukaemia (CLL) manifests as clonal expansion of mature B lymphocytes, whose accumulation is primarily attributed to the dysregulation of apoptosis. Aberrant expression, as well ...as genetic alterations within various Bcl2 family members and central regulators of the intrinsic, mitochondria-mediated apoptotic pathway all hasve been observed in CLL. Here, we report the expression analysis of the anti-apoptotic Bcl2 gene in a cohort of 58 CLL patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed a significant overexpression of Bcl2 mRNA in CLL samples compared to control samples (p=<0.001). Receiver operating characteristic (ROC) analysis showed that the level of Bcl2 expression exerts a high discriminatory power between patients and healthy subjects (A=0.98, 95% CI=0.95-1.009, p<0.0001).
Poglądy na rolę neutrofilów w procesie zapalnym na przestrzeniostatnich lat uległy fundamentalnym zmianom. Neutrofile sąkrótko żyjącymi, finalnie zróżnicowanymi fagocytami. Ponieważw wyniku kontaktu ...z patogenem ulegają szybkiej aktywacji, nazywanesą często pierwszą linią obrony organizmu. Zaktywowaneneutrofile żyją już bardzo krótko, ulegając apoptozie (kamikazecells). W reumatoidalnym zapaleniu stawów neutrofile mogą byćfagocytowane przez makrofagi, tworząc charakterystyczne komórkiReitera. Ostatnio wykazano, że migracja neutrofilów do tkanekhamuje proces apoptozy, a tym samym ich przedłużająca się aktywnośćmoże skutkować znacznym wydłużeniem czasu trwania procesuzapalnego. Ponadto wykazano, że neutrofile nie są komórkamijedynie biernie odpowiadającymi na zewnętrzne sygnały, aleodgrywają aktywną rolę w inicjacji i regulacji procesu zapalnegopoprzez wydzielanie prozapalnych cytokin, ekspresję receptorówMHC klasy II, a tym samym biorą udział w aktywacji i kontroli aktywnościlimfocytów T. Wykazano istotne znaczenie neutrofilóww patogenezie takich chorób, jak przewlekła obturacyjna chorobapłuc, choroba Behçeta czy zapalenia stawów. Komórki te, w kontekścienajnowszej wiedzy o ich roli, powinny w przyszłości staćsię ważnym celem nowych terapii reumatoidalnego zapaleniastawów.
In this study we analyzed selected parameters of apoptosis in leukemic cells from peripheral blood and bone marrow of patients with chronic lymphocytic leukemia (CLL). The percentage of apoptotic ...leukemic B cells (Δψmlow/CD19+) was significantly lower in peripheral blood (median: 0.99%) than in bone marrow (median: 1.41%) (p<0.0001). These data can support the idea that these two compartments might have different proliferative statuses. There was an inverse correlation between the ex vivo percentage of apoptotic cells and lymphocytosis (R=-0.34; p<0.01), and a direct correlation between the percentage of PB apoptotic B cells and the Rai stage (R=0.42; p<0.05). The percentage of Δψmlow/CD19+ cells was significantly higher in ZAP-70-positive patients than from ZAP-70-negative patients (p<0.01). There was also a significant difference in the median percentage of apoptotic leukemic B cells between the patients carrying del(11q22.3) or/and del(17p13.1) (2.7%) and the patients without these unfavorable genetic aberrations (1.6%) (p<0.01). The B cells from ZAP-70-positive patients with more aggressive disease seem to be more susceptible to spontaneous apoptosis than those from ZAP-70-negative patients. We conclude that the evaluation of ex vivo apoptosis might provide new important information concerning the biology and prognosis of CLL.
W badaniach przeprowadzono analizę wybranych parametrów apoptozy komórek białaczkowych krwi obwodowej i szpiku chorych na przewlekłą białaczkę limfocytową (PBL). Odsetek białaczkowych limfocytów B ulegających spontanicznej apoptozie ex vivo (Δψmlow/CD19+) był większy w szpiku (mediana: 1.41%) w porównaniu z krwią obwodową (mediana: 0.99%) (p<0.0001), co może sugerować związek większej apoptozy spontanicznej ze zwiększoną proliferacją komórek białaczkowych w szpiku. Stwierdzono ponadto ujemną korelację pomiędzy odsetkiem komórek apoptotycznych ex vivo a limfocytozą chorych na PBL (R=-0.34; p<0.01) oraz dodatnią korelację pomiędzy odsetkiem komórek apoptotycznych a stadium zaawansowania klinicznego choroby (wg Rai’a) (R=0.42; p<0.05). Białaczkowe limfocyty B z dodatnią ekspresją ZAP-70 wydają się być bardziej podatne na apoptozę niż limfocyty B pacjentów ZAP-70-negatywnych (p<0.01). Na uwagę zasługuje również istotnie wyższy odsetek komórek Δψmlow/CD19+ u pacjentów z del(11q22.3) i/lub del(17p13.1) (2.7%) w porównaniu z chorymi bez tych niekorzystnych zmian cytogenetycznych (1.6%) (p<0.01). Obserwacje te sugerują, że ocena apoptozy ex vivo może dostarczyć nowych ważnych informacji dotyczących biologii i rokowania PBL
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