MT-RNR2 plays its anti-apoptotic role partly by avoiding deploying energy from complete oxidation of organic compounds to inorganic wastes. Thus MT-RNR2 can potentially serve as a new biomarker in the diagnosis of bladder carcinoma especially that it is present in blood circulation.
Human exposure to radio-therapeutic doses of gamma rays can produce late effects, which negatively affect cancer patients’ quality of life, work prospects, and general health. This study was performed to explore the role of Piceatannol (PIC) in the process of “mitochondrial biogenesis” signaling pathway as possible management of disturbances induced in stressed animal model(s) either by gamma-irradiation (IR) or administration of reserpine (RES); as a mitochondrial complex-I inhibitor. PIC (10 mg/kg BW/day; orally) were given to rats for 7 days, after exposure to an acute dose of γ-radiation (6 Gy), or after a single reserpine injection (1 g/kg BW; sc). Compared to reserpine or γ-radiation, PIC has attenuated hepatic and renal mitochondrial oxidative stress denoted by the significant reduction in the content of lipid peroxides and NO with significant induction of SOD, CAT, GSH-PX, and GR activities. PIC has also significantly alleviated the increase of the inflammatory markers, TNF-α and IL-6 and apoptotic markers, cytochrome c, and caspase-3. The decrease of oxidative stress, inflammation, and apoptotic responses were linked to a significant amelioration in mitochondrial biogenesis demonstrated by the increased expression and proteins’ tissue contents of SIRT1/p38-AMPK, PGC-1α signaling pathway. The results are substantiated by the significant amelioration in mitochondrial function verified by the higher levels of ATP content, and complex I activity, besides the improvement of hepatic and renal functions. Additionally, histopathological examinations of hepatic and renal tissues showed that PIC has modulated tissue architecture after reserpine or gamma-radiation-induced tissue damage. Piceatannol improves mitochondrial functions by regulating the oxidant/antioxidant disequilibrium, the inflammatory and apoptotic responses, suggesting its possible use as adjuvant therapy in radio-therapeutic protocols to attenuate hepatic and renal injuries.
Histone deacetylase 6 (HDAC6) is an attractive target for cancer therapeutic intervention. Selective HDAC6 inhibitors is important to minimise the side effects of pan inhibition. Thus, new class of hydroxamic acid-based derivatives were designed on structural basis to perform preferential activity against HDAC6 targeting solid tumours. Interestingly, 1-benzylbenzimidazole-2-thio-
N
-hydroxybutanamide
10a
showed impressive preference with submicromolar potency against HDAC6 (IC
50
= 510 nM).
10a
showed cytotoxic activity with interesting profile against CCHE-45 at (IC
50
= 112.76 µM) when compared to standard inhibitor Tubacin (IC
50
= 20 µM). Western blot analysis of acetylated-α-tubulin verified the HDAC6 inhibiting activity of
10a
. Moreover, the insignificant difference in acetylated-α-tubulin induced by
10a
and Tubacin implied the on-target cytotoxic activity of
10a
. Docking of
10a
in the binding site of HDAC6 attributed the activity of
10a
to π-π stacking with the amino acids of the hydrophobic channel of HDAC6 and capture of zinc metal in bidentate fashion. The therapeutic usefulness besides the on-target activity may define
10a
as an interesting safe-lead inhibitor for future development.
The treatment failure recorded among patients and animals infected with diarrheagenic Escherichia coli (DEC) was increased due to the presence of specific virulence markers among these strains. These markers were used to classify DEC into several pathotypes. We analyzed the correlations between DEC pathotypes and antimicrobial resistances, the existence of virulence genes, serotypes, and hosts. The ETEC pathotype was detected with a high prevalence rate (25%). Moreover, the ETEC and EPEC pathotypes were highly associated with human infections in contrast to the EIEC and EAEC phenotypes, which were commonly recognized among animal isolates. Interestingly, the antimicrobial resistance was affected by E. coli pathotypes. With the exception of EIEC and STEC, imipenem represented the most effective antibiotic against the other pathotypes. There were fixed correlations between the DEC pathotypes and the presence of virulence markers and hosts; meanwhile, their correlation with serotypes was variable. Additionally, the vast majority of our isolates were highly diverse, based on both phenotypic and ERIC molecular typing techniques. Our promising results gave a clear indication for the heterogeneity and weak clonality of DEC pathotypes in Egypt, which can be utilized in the evaluation of the current therapeutic protocols and infection control guidelines.
Cataract is the principal cause of blindness. The enzyme, aldose reductase (AR) is a key player in polyol pathway. Buildup of polyols and oxidative stress are the main causes of cataractogenesis. This study investigated the cytoprotective properties of esculetin and idebenone in galactose‐induced cataract. Rats were partitioned into four groups each of ten rats. Control group was fed with normal diet; group 2 rats were fed with galactose diet (50%); groups 3, 4 rats were fed with galactose diet concurrently with either esculetin (50 mg/kg BW) or idebenone (100 mg/kg BW), for 20 days. The study revealed that esculetin and idebenone significantly reduced the elevated levels of Bax/Bcl‐2 ratio, malondialdehyde, and DNA fragmentation and increased total antioxidant capacity level in lenses compared to the cataract‐induced group. Only esculetin decreased AR, galactitol, and advanced glycated end products levels in lenses. Histopathological examinations supported the biochemical findings. Esculetin and idebenone may have chemopreventive effects for sugar cataract.
Practical applications
Cataract is an age‐related disease that might cause blindness in older adult people. Presently, no absolute pharmacological treatment is accessible for cataract. The use of natural products or their derivatives attract particular attention in modern medicines as they are believed to be safer with few or no side effects. Esculetin is a polyphenolic compound found in many medicinal plants. Idebenone is a synthetic analogue of coenzyme Q10. The current study is an approach to explore the anticataract effects of esculetin and idebenone in galactose‐induced cataract in rats. Our study proved that both agents have anticataractogenic potentials due to their antioxidant and antiapoptotic properties.
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