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RNA–DNA hybrid is a part of the R‐loop which is an important non‐standard nucleic acid structure. RNA–DNA hybrid/R‐loop causes genomic instability by inducing DNA damages or inhibiting DNA replication. It also plays biologically important roles in regulation of transcription, replication, recombination and repair. Here, we have employed catalytically inactive human RNase H1 mutant (D145N) to visualize RNA–DNA hybrids and map their genomic locations in fission yeast cells. The RNA–DNA hybrids appear as multiple nuclear foci in rnh1∆rnh201∆ cells lacking cellular RNase H activity, but not in the wild‐type. The majority of RNA–DNA hybrid loci are detected at the protein coding regions and tRNA. In rnh1∆rnh201∆ cells, cells with multiple Rad52 foci increase during S‐phase and about 20% of the RNA–DNA hybrids overlap with Rad52 loci. During S‐phase, more robust association of Rad52 with RNA–DNA hybrids was observed in the protein coding region than in M‐phase. These results suggest that persistent RNA–DNA hybrids in the protein coding region in rnh1∆rnh201∆ cells generate DNA damages during S‐phase, potentially through collision with DNA replication forks. [ABSTRACT FROM AUTHOR]

Abstract Exposure to ionizing radiation can induce genetic aberrations via unrepaired DNA strand breaks. To investigate quantitatively the dose–effect relationship at the molecular level, we irradiated dry pBR322 plasmid DNA with 3 MeV protons and assessed fragmentation yields at different radiation doses using long-read sequencing from Oxford Nanopore Technologies. This technology applied to a reference DNA model revealed dose-dependent fragmentation, as evidenced by read length distributions, showing no discernible radiation sensitivity in specific genetic sequences. In addition, we propose a method for directly measuring the single-strand break (SSB) yield. Furthermore, through a comparative study with a collection of previous works on dry DNA irradiation, we show that the irradiation protocol leads to biases in the definition of ionizing sources. We support this scenario by discussing the size distributions of nanopore sequencing reads in the light of Geant4 and Geant4-DNA simulation toolkit predictions. We show that integrating long-read sequencing technologies with advanced Monte Carlo simulations paves a promising path toward advancing our comprehension and prediction of radiation-induced DNA fragmentation.

Chondrosarcoma is a rare malignant tumor that forms in bone and cartilage. The primary treatment involves surgical removal of the tumor with a margin of healthy tissue. Especially if complete surgical removal is not possible, radiation therapy and chemotherapy are used in conjunction with surgery, but with a generally low efficiency. Ongoing researches are focused on understanding the genetic and molecular basis of chondrosarcoma following high linear energy transfer (LET) irradiation, which may lead to treatments that are more effective. The goal of this study is to evaluate the differential effects of DNA damage repair inhibitors and high LET irradiation on chondrosarcoma versus chondrocyte cells and the LET-dependency of the effects. Two chondrosarcoma cell lines with different IDH mutation status and one chondrocyte cell line were exposed to low LET (X-ray) and high LET (carbon ion) irradiation in combination with an Olaparib PARP inhibitor. Cell survival and DNA repair mechanisms were investigated. High LET irradiation drastically reduced cell survival, with a biological efficiency three times that of low LET. Olaparib significantly inhibited PARylation in all the tested cells. A significant reduction in cell survival of both chondrosarcoma and chondrocyte cells was observed following the treatment combining Olaparib and X-ray. PARP inhibition induced an increase in PARP-1 expression and a reduced effect on the cell survival of WT IDH chondrosarcoma cells. No radiosensitizing effect was observed in cells exposed to Olaparib paired with high LET irradiation. NHEJ was activated in response to high LET irradiation, neutralizing the PARP inhibition effect in both chondrosarcoma cell lines. When high LET irradiation is not available, PARP inhibition could be used in combination with low LET irradiation, with significant radiosensitizing effects on chondrosarcoma cells. Chondrocytes may be affected by the treatment combination too, showing the need to preserve normal tissues from radiation fields when this kind of treatment is suggested. [ABSTRACT FROM AUTHOR]

Exposure to ionizing radiation can induce genetic aberrations via unrepaired DNA strand breaks. To investigate quantitatively the dose–effect relationship at the molecular level, we irradiated dry pBR322 plasmid DNA with 3 MeV protons and assessed fragmentation yields at different radiation doses using long-read sequencing from Oxford Nanopore Technologies. This technology applied to a reference DNA model revealed dose-dependent fragmentation, as evidenced by read length distributions, showing no discernible radiation sensitivity in specific genetic sequences. In addition, we propose a method for directly measuring the single-strand break (SSB) yield. Furthermore, through a comparative study with a collection of previous works on dry DNA irradiation, we show that the irradiation protocol leads to biases in the definition of ionizing sources. We support this scenario by discussing the size distributions of nanopore sequencing reads in the light of Geant4 and Geant4-DNA simulation toolkit predictions. We show that integrating long-read sequencing technologies with advanced Monte Carlo simulations paves a promising path toward advancing our comprehension and prediction of radiation-induced DNA fragmentation. [ABSTRACT FROM AUTHOR]

In clinics, chemotherapy is often combined with surgery and radiation to increase the chances of curing cancers. In the case of glioblastoma (GBM), patients are treated with a combination of radiotherapy and TMZ over several weeks. Despite its common use, the mechanism of action of the alkylating agent TMZ has not been well understood when it comes to its cytotoxic effects in tumor cells that are mostly non-dividing. The cellular response to alkylating DNA damage is operated by an intricate protein network involving multiple DNA repair pathways and numerous checkpoint proteins that are dependent on the type of DNA lesion, the cell type, and the cellular proliferation state. Among the various alkylating damages, researchers have placed a special on O6-methylguanine (O6-mG). Indeed, this lesion is efficiently removed via direct reversal by O6-methylguanine-DNA methyltransferase (MGMT). As the level of MGMT expression was found to be directly correlated with TMZ efficiency, O6-mG was identified as the critical lesion for TMZ mode of action. Initially, the mode of action of TMZ was proposed as follows: when left on the genome, O6-mG lesions form O6-mG: T mispairs during replication as T is preferentially mis-inserted across O6-mG. These O6-mG: T mispairs are recognized and tentatively repaired by a post-replicative mismatched DNA correction system (i.e., the MMR system). There are two models (futile cycle and direct signaling models) to account for the cytotoxic effects of the O6-mG lesions, both depending upon the functional MMR system in replicating cells. Alternatively, to explain the cytotoxic effects of alkylating agents in non-replicating cells, we have proposed a "repair accident model" whose molecular mechanism is dependent upon crosstalk between the MMR and the base excision repair (BER) systems. The accidental encounter between these two repair systems will cause the formation of cytotoxic DNA double-strand breaks (DSBs). In this review, we summarize these non-exclusive models to explain the cytotoxic effects of alkylating agents and discuss potential strategies to improve the clinical use of alkylating agents. [ABSTRACT FROM AUTHOR]

The present investigation dealt with harmful effects of hexavalent chromium (Cr [VI]) on liver of Swiss albino mice. This variant exhibited cytotoxicity, mutagenicity, and carcinogenicity. Our study focused on elucidating the hepatotoxic effects of chronic low‐dose exposure to Cr (VI) (2, 5, and 10 ppm) administered via drinking water for 4 and 8 months. The observed elevation in SGPT, ALP, and SGOT and increased oxidative stress markers unequivocally confirmed the severe disruption of liver homeostasis at these low treatment doses. Noteworthy alterations in histoarchitecture, body weight, and water intake provided further evidences of the harmful effects of Cr (VI). Production of reactive oxygen species (ROS) during metabolism led to DNA damages. Immunohistochemistry and qRT‐PCR analyses revealed that chronic low‐dose exposure of Cr (VI) induced apoptosis in liver tissue. Our study exhibited alterations in the expression pattern of DNA repair genes (Rad51, Mutyh, Mlh1, and Ogg1), coupled with promoter hypermethylation of Mutyh and Rad51, leading to transcriptional inhibition. Our findings underscored the potential of low‐dose Cr (VI) exposure on hepatotoxicity by the intricate interplay between apoptosis induction and epigenetic alterations of DNA repair genes. The study investigated the hepatotoxic effects of chronic low‐dose hexavalent chromium (Cr VI) exposure on Swiss albino mice. Administered through drinking water at 2, 5, and 10 ppm for 4 and 8 months, it resulted in elevated liver enzymes, oxidative stress, altered histoarchitecture, and disruptions in body weight and water intake. Reactive oxygen species production induced DNA damage, leading to apoptosis in liver tissue. DNA repair gene expression alterations and promoter hypermethylation of Rad51 and Mutyh were observed. [ABSTRACT FROM AUTHOR]

Air pollution is a severe problem in the modern world. Urbanization, industrialization, and traffic emit air pollutants such as carbon monoxide (CO), nitrous oxides (NOx), hydrocarbons (HCs), and particulate matter into the environment. Plants can absorb air pollutants through stomata. They adversely affect the various metabolic and physiological processes of plant species. This review describes the impact of air pollution on plant health, morphologically, physiologically, and genetically, and the tolerance ability of plants located along roadside areas. Many morphological effects, like chlorosis, necrosis, leaf area, stomatal clogging, plant productivity, leaf falling, and reduction in flower yield, are observed due to the influence of air pollution. Air pollutants also damage the DNA and affect the biochemicals of the plants, as well as pH, relative water content (RWC), simple sugar, ascorbic acid (AA), total chlorophyll content (TCH), proline, and polyamines. Some plants located under pollution stress can mitigate air pollution. Plants with higher APTI values are more tolerant of air pollution, while those with the lowest APTI values can be used as an indicator of the rate of air pollution. There is much morphological, biochemical, and DNA damage noted in this review. Different strategies can be used to diagnose the effects of air pollution in the future and develop green belts to mitigate air pollution in pollution-stressed areas. [ABSTRACT FROM AUTHOR]

Many studies have indicated that tumor growth factor‐beta (TGF‐β) signaling mediates radiation‐induced bystander effects (RIBEs). The primary cilium (PC) coordinates several signaling pathways including TGF‐β signaling to regulate diverse cellular processes. But whether the PC participates in TGF‐β induced RIBEs remains unclear. The cellular levels of TGF‐β1 were detected by western blot analysis and the secretion of TGF‐β1 was measured by ELISA kit. The ciliogenesis was altered by CytoD treatment, STIL siRNA transfection, IFT88 siRNA transfection, or KIF3a siRNA transfection, separately, and was detected by western blot analysis and immunofluorescence staining. G0/G1 phase cells were arrested by serum starvation and S phase cells were induced by double thymidine block. The TGF‐β1 signaling was interfered by LY2109761, a TGF‐β receptor 1 (TβR1) inhibitor, or TGF‐β1 neutral antibody. The DNA damages were induced by TGF‐β1 or radiated conditional medium (RCM) from irradiated cells and were reflected by p21 expression, 53BP1 foci, and γH2AX foci. Compared with unirradiated control, both A549 and Beas‐2B cells expressed and secreted more TGF‐β1 after carbon ion beam or X‐ray irradiation. RCM collected from irradiated cells or TGF‐β1 treatment caused an increase of DNA damage in cocultured unirradiated Beas‐2B cells while blockage of TGF‐β signaling by TβR1 inhibitor or TGF‐β1 neutral antibody alleviates this phenomenon. IFT88 siRNA or KIF3a siRNA impaired PC formation resulted in an aggravated DNA damage in bystander cells, while elevated PC formation by CytoD or STIL siRNA resulted in a decrease of DNA damage. Furthermore, TGF‐β1 induced more DNA damages in S phases cells which showed lower PC formation rate and less DNA damages in G0/G1 phase cells which showed higher PC formation rate. This study demonstrates the particular role of primary cilia during RCM induced DNA damages through TGF‐β1 signaling restriction and thereby provides a functional link between primary cilia and RIBEs. [ABSTRACT FROM AUTHOR]

DNA damage induced by the ultraviolet (UV) light, which affects adversely on genome stability, causes many kinds of diseases. Thus, a biochemical or biomechanical method in DNA damage protection is well required. In the present study, we investigated the effects of mechanical factors, such as deformation of cell nucleus using polydimethylsiloxane (PDMS)-based microfabricated array of micropillars, on UV radiation resistance of DNA in cultured cells. The epithelial-like cells spread normally in the spaces between micropillars and their nuclei showed remarkable deformation and appeared to be "trapped" mechanically on the array of pillars. We found that the UV radiation-induced DNA damage estimated by the fluorescent intensity of the phospho-histone γ-H2AX, was significantly inhibited with the nucleus deformation on the pillars. The result indicates that the inhibition of UV radiation-induced DNA damages might be resulted from structural change of DNA caused by the mechanical stress of the cell nucleus on the micropillars. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the cytotoxicity of chromium(III) oxide micro particles (Cr2O3-Ps) in rainbow trout (Oncorhynchus mykiss) spermatozoa. Firstly, Cr2O3-Ps were synthesized and structurally characterized the surface, morphological for particle size and thermal properties. In addition, its structural and elemental purity was determined using energy-dispersive X-ray (EDX) spectrum and elemental maps. Structural purity, thermal properties, and stability of Cr2O3-Ps were also examined in detail by performing thermal analysis techniques. The cytotoxicity of Cr2O3-Ps was measured by the observation of velocities, antioxidant activities, and DNA damages in rainbow trout spermatozoa after exposure during 3 h in vitro incubation. The straight line velocity (VSL), the curvilinear velocity (VCL), and the angular path velocity (VAP) of spermatozoa decreased after exposure to Cr2O3-Ps. While the superoxide dismutase (SOD) and the catalase (CAT) decreased, the lipid peroxidation increased in a dose-dependent manner. However, the total glutathione (tGSH) was not affected in this period. DNA damages were also determined in spermatozoa using Comet assay. According to DNA in tail (%) data, DNA damages have been detected with gradually increasing concentrations of Cr2O3-Ps. Furthermore, all of class types which are categorized as the intensity of DNA fragmentation has been observed between 50 and 500 µg/L concentrations of Cr2O3-Ps exposed to rainbow trout spermatozoa. At the end of this study, we determined that the effective concentrations (EC50) were 76.67 µg/L for VSL and 87.77 µg/L for VCL. Finally, these results about Cr2O3-Ps may say to be major risk concentrations over 70 µg/L for fish reproduction in aquatic environments. [ABSTRACT FROM AUTHOR]

Simple Summary: The roughscale sole, Clidoderma asperrimum, is found in the East and West Seas of Korea, waters north of Hokkaido in Japan, as well as the East China Sea, the East Pacific, and the Canadian Maritimes. In 2021, this fish was categorized as an endangered species. Thus, there is a need to maintain gametes by freezing sperm. This study investigated the impacts of the cryoprotective agent, diluent, dilution ratio, and thawing temperature on the cryopreservation of fish sperm. In this investigation, sperm dilution 1:1 with a mixture of 10% dimethyl sulfoxide + Stein's solution and thawing at 10 °C provided the most effective DNA damage prevention. These results support the development of a roughscale sole sperm cryopreservation procedure. The roughscale sole, Clidoderma asperrimum is categorized as an endangered species. Sperm freezing is essential for preserving gametes. This study examined the CPA concentration, diluent, dilution ratio, and thawing temperature to design a sperm cryopreservation protocol for roughscale sole. The variables examined included sperm motility and kinematics, cell survival, fertilization, and DNA fragmentation. Sperm motility parameters were assessed via computer-assisted sperm analysis using a CEROS II instrument. Cell survival rate and DNA damage were assessed using the Cell Counting Kit-8 and single-cell gel electrophoresis assay, respectively. Sperm preservation was tested using several CPAs, including ethylene glycol, dimethyl sulfoxide (DMSO), glycerol, propylene glycol, and methanol. The diluents tested were 300 mM sucrose, 300 mM glucose, Stein's solution, Ringer's solution, and Hank's solution. The optimal conditions for sperm cryopreservation were 10% DMSO + Stein's solution. After thawing, sperm motility was highest with a 1:1 dilution ratio (sperm to CPA + diluent), at 69.20 ± 0.32%; thawing at 10 °C was optimal for post-thaw motility (72.03 ± 0.95%). The highest fertilization rate (40.00 ± 1.22%) was obtained using DMSO. The fresh sperm had the lowest tail DNA, followed by 10% DMSO + Stein's solution. The developed cryopreservation methods can be used in roughscale sole hatcheries. [ABSTRACT FROM AUTHOR]

Abstract Background Degenerative kidney diseases are mostly associated with oxidative stress. Natural products are considered as the antioxidants enrich food that can restrict the progress of oxidative stress induced disorders. Therefore, the present study was aimed to evaluate the renal protective effect of Ajuga parviflora leaf extract in carbon tetrachloride intoxicated rats. Methods The hydromethanolic extract of A. parviflora leaves was obtained by extracting twice in 60% methanol. The principal bioactive constituents were detected by LC/MS analysis. Toxicity of plant extract was assessed using brine shrimp lethal toxicity test and acute toxicity model on healthy Sprague-Dawley male rats. Nephroprotective effects of plant extract were also evaluated on rats by inducing CCl4 renal toxicity in comparison with positive control and naïve groups. The dose of A. parviflora administered to animal was 100, 200 and 300 mg/kg. All administrations were given orally on an alternate day basis for 30 days. Urine and serum biomarkers were analyzed, along with antioxidant enzymes. Finally, the DNA damages, lipid peroxides, hydrogen peroxides and nitrites were assessed in rat’s renal tissue. The histopathology alterations in renal tissues were further studied for kidney damages. Results The LC/MS analysis confirmed the presence of different important pharmacological compounds in A. parviflora methanolic leaf extract. The key bioactive compounds include pyocyanin, zonisamide, D Saccharic acid, altretamine, carbocyclic thromboxane A2, Sinapyl alcohol, and vitamin C. The important polypeptides identified include Lys-Tyr-Lys, His-His-Lys, Met-Asp-Arg, Phe-Val-Arg, and PyroGlu-Val-Arg. The LD50 of A. parviflora was found to be > 1000 μg/mL. A. parviflora administration significantly subsides CCl4 toxicity in rats, reduced the elevated level of RBCs, pus and epithelial cells. The abnormal elevated level of specific gravity, creatinine, urobilinogen, urea and albumin were also reduced to normal physiological level. The reduced urinary protein and pH were also normalized. The serum urobilinogen, urea and total bilirubin levels were also reversed to normal levels while the diminished albumin and total protein levels also came to normal. The important phase I and II enzyme levels were also reversed in A. parviflora administered rats. The H2O2, thiobarbituric acid reactive substance (TBARS) and nitrite levels were significantly decreased. Furthermore, the damaged DNA and histopathological changes in CCl4 exposed rats were also highly significantly reversed after the administration of A. parviflora. All effects were significant (P

Abstract Background Recently, a next-generation sequencing (NGS)-based method has been used for the successful detection of circulating tumor DNA (ctDNA) in various cancer types. Thus, the use of NGS on liquid biopsies will improve cancer diagnosis and prognosis. However, the low-allelic fraction of ctDNA poses a challenge for the sensitive and specific detection of tumor variants in cell-free DNA (cfDNA). To distinguish true variants from false positives, the characteristics of errors that occur during sample preparation and sequencing need to be elucidated. Methods We generated capture-based targeted deep sequencing data from plasma cfDNA and peripheral blood leucocyte (PBL) gDNA to profile background errors. To reveal cfDNA-associated DNA lesions, background error profiles from two sample types were compared in each nucleotide substitution class. Results In this study, we determined the prevalence of single nucleotide substitutions in cfDNA sequencing data to identify DNA damage preferentially associated with cfDNA. On comparing sequencing errors between cfDNA and cellular genomic DNA (gDNA), we observed that the total substitution error rates in cfDNA were significantly higher than those in gDNA. When the substitution errors were divided into 12 substitution error classes, C:G>T:A substitution errors constituted the largest difference between cfDNA and gDNA samples. When the substitution error rates were estimated based on the location of DNA-fragment substitutions, the differences in error rates of most substitution classes between cfDNA and gDNA samples were observed only at the ends of the DNA fragments. In contrast, C:G>T:A substitution errors in the cfDNA samples were not particularly associated with DNA-fragment ends. All observations were verified in an independent dataset. Conclusions Our data suggested that cytosine deamination increased in cfDNA compared to that in cellular gDNA. Such an observation might be due to the attenuation of DNA damage repair before the release of cfDNA and/or the accumulation of cytosine deamination after it. These findings can contribute to a better understanding of cfDNA-associated DNA damage, which will enable the accurate analysis of somatic variants present in cfDNA at an extremely low frequency.

Red light has been shown to increase sperm swimming speeds, but there is little characterization of its effect on DNA or swimming force. In this study 633nm laser light irradiation did not induce significant levels of oxidative DNA damage.

The contribution of Ionizing Radiation (IoR) in diagnosis and therapy increases every day. Therefore it is considered one of the most popular genotoxic exogenous agent. Hence the estimation of DNA damages due to the applied IoR dose is a must. There are many techniques used for the detection of DNA damage that depend on different measurable parameters. In this work, Comet and Cytochalasin-B Blocked Micronucleus (CBMN) assays were applied in order to detect the extent of DNA damage due to the exposure to different doses of gamma rays. Peripheral blood lymphocytes were exposed to doses of 2, 4, 6, and 8 Gy from 137Cs gamma-radiation source. Measured Comet assay dose parameters (tail DNA, tail length and tail moment) exhibit a significantly high correlation (p < 0.01) with the exposure dose. However, micronuclei (MNi) (CBMN parameter) showed a p-value greater than 0.05. Thus we can conclude that Comet assay is evidently more reliable than CBMN in the estimation of the magnitude of DNA damage in peripheral blood lymphocytes due to exposure to gamma radiation.

Abstract Background Myrin®-p Forte is an anti-tuberclosis agent that can cause hepatic injuries in clinical settings. Maytenus royleanus (Celastraceae) is a medicinal plant, possesses antioxidant and anticancer activities. The hepatoprotective effect of the methanol extract of Maytenus royleanus leaves (MEM) against Myrin®-p Forte induced hepatotoxicity in mice was investigated. Methods Mice were randomly parted into six groups (n = 6). Fixed-dose combination of Myrin®-p Forte (13.5 mg/kg Rifampicin, 6.75 mg/kg Isoniazid, 36.0 mg/kg Pyrazinamide and 24.8 mg/kg Ethambutol; RIPE] was administered for 15 days to induce liver injury. In treatment groups MEM (200 mg/kg and 400 mg/kg doses) and Vitamin B6 (180mg/kg) were administered prior to RIPE. Control group received 2% DMSO. Serum liver function tests, DNA damage, tissue antioxidant enzymes and histopathological alterations were studied. HPLC analysis was performed to determine the chemical composition using standard compounds. Results The quercitin, gallic acid, luteolin, viteixin, apigenin, kaempherol, hyperoside and myricetin contents of all samples were determined by reverse-phase HPLC. Quercetin (0.217 mg/g dry weight) and luteolin (0.141 mg/g dry weight) were the major flavonoids identified in MEM. Myrin®-p Forte markedly (p

Background: Recently, a next-generation sequencing (NGS)-based method has been used for the successful detection of circulating tumor DNA (ctDNA) in various cancer types. Thus, the use of NGS on liquid biopsies will improve cancer diagnosis and prognosis. However, the low-allelic fraction of ctDNA poses a challenge for the sensitive and specific detection of tumor variants in cell-free DNA (cfDNA). To distinguish true variants from false positives, the characteristics of errors that occur during sample preparation and sequencing need to be elucidated. Methods: We generated capture-based targeted deep sequencing data from plasma cfDNA and peripheral blood leucocyte (PBL) gDNA to profile background errors. To reveal cfDNA-associated DNA lesions, background error profiles from two sample types were compared in each nucleotide substitution class. Results: In this study, we determined the prevalence of single nucleotide substitutions in cfDNA sequencing data to identify DNA damage preferentially associated with cfDNA. On comparing sequencing errors between cfDNA and cellular genomic DNA (gDNA), we observed that the total substitution error rates in cfDNA were significantly higher than those in gDNA. When the substitution errors were divided into 12 substitution error classes, C:G>T:A substitution errors constituted the largest difference between cfDNA and gDNA samples. When the substitution error rates were estimated based on the location of DNA-fragment substitutions, the differences in error rates of most substitution classes between cfDNA and gDNA samples were observed only at the ends of the DNA fragments. In contrast, C:G>T:A substitution errors in the cfDNA samples were not particularly associated with DNA-fragment ends. All observations were verified in an independent dataset. Conclusions: Our data suggested that cytosine deamination increased in cfDNA compared to that in cellular gDNA. Such an observation might be due to the attenuation of DNA damage repair before the release of cfDNA and/or the accumulation of cytosine deamination after it. These findings can contribute to a better understanding of cfDNA-associated DNA damage, which will enable the accurate analysis of somatic variants present in cfDNA at an extremely low frequency. [ABSTRACT FROM AUTHOR]

Background: Degenerative kidney diseases are mostly associated with oxidative stress. Natural products are considered as the antioxidants enrich food that can restrict the progress of oxidative stress induced disorders. Therefore, the present study was aimed to evaluate the renal protective effect of Ajuga parviflora leaf extract in carbon tetrachloride intoxicated rats. Methods: The hydromethanolic extract of A. parviflora leaves was obtained by extracting twice in 60% methanol. The principal bioactive constituents were detected by LC/MS analysis. Toxicity of plant extract was assessed using brine shrimp lethal toxicity test and acute toxicity model on healthy Sprague-Dawley male rats. Nephroprotective effects of plant extract were also evaluated on rats by inducing CCl4 renal toxicity in comparison with positive control and naïve groups. The dose of A. parviflora administered to animal was 100, 200 and 300 mg/kg. All administrations were given orally on an alternate day basis for 30 days. Urine and serum biomarkers were analyzed, along with antioxidant enzymes. Finally, the DNA damages, lipid peroxides, hydrogen peroxides and nitrites were assessed in rat's renal tissue. The histopathology alterations in renal tissues were further studied for kidney damages. Results: The LC/MS analysis confirmed the presence of different important pharmacological compounds in A. parviflora methanolic leaf extract. The key bioactive compounds include pyocyanin, zonisamide, D Saccharic acid, altretamine, carbocyclic thromboxane A2, Sinapyl alcohol, and vitamin C. The important polypeptides identified include Lys-Tyr-Lys, His-His-Lys, Met-Asp-Arg, Phe-Val-Arg, and PyroGlu-Val-Arg. The LD50 of A. parviflora was found to be > 1000 μg/mL. A. parviflora administration significantly subsides CCl4 toxicity in rats, reduced the elevated level of RBCs, pus and epithelial cells. The abnormal elevated level of specific gravity, creatinine, urobilinogen, urea and albumin were also reduced to normal physiological level. The reduced urinary protein and pH were also normalized. The serum urobilinogen, urea and total bilirubin levels were also reversed to normal levels while the diminished albumin and total protein levels also came to normal. The important phase I and II enzyme levels were also reversed in A. parviflora administered rats. The H2O2, thiobarbituric acid reactive substance (TBARS) and nitrite levels were significantly decreased. Furthermore, the damaged DNA and histopathological changes in CCl4 exposed rats were also highly significantly reversed after the administration of A. parviflora. All effects were significant (P < 0.05) and highly significant (P < 0.005) at 100 and 300 mg/kg respectively. Conclusion: The restored urine and serum profile of various parameters to normal physiological levels suggests that the A. parviflora has potential antioxidant and repairing potential in renal disorders. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the leading cancers nowadays. The genetical mechanism behind breast cancer development is an intricate one. In this review, the genetical background of breast cancer, particularly BRCA 1 and BRCA 2 had been included. Moreover, to summarize the genetics of breast cancer, the recent and ongoing preclinical and clinical studies on the treatment of BRCA-associated breast cancer had also been included. A prime knowledge is that the BRCA gene is the basis of breast cancer risk. How it mediates cell proliferation and associated mechanisms are reviewed here. BRCA 1 gene can influence all phases of the cell cycle and regulate cell cycle progression. BRCA 1 gene can also respond to DNA damages and induce responsive mechanisms. The action of the BRCA gene on associated protein has a wide consideration in breast cancer development. Heterogeneity in breast cancer makes them a fascinating and challenging stream to diagnose and treat. Several clinical therapies are available for breast cancer treatments. Chemotherapy, endocrine therapy, radiation therapy and immunotherapy are the milestones in the cancer treatments. Ral binding protein 1 is a promising target for breast cancer treatment and the platinum-based chemotherapies are the other remarkable fields. In immunotherapy, the usage of anti-programmed death (PD)-1 antibody is a new class of cancer immunotherapy that hinders immune effecter inhibition and potentially expanding preexisting anticancer immune responses. Breast cancer genetics and treatment strategies are crucial in escalating survival rates. [ABSTRACT FROM AUTHOR]

The effects of plasma‐activated water (PAW) generated by nonthermal air plasmas of transient spark with water electrospray or atmospheric glow discharge were investigated on maize (Zea mays L. var Saccharata) and barley (Hordeum vulgare L.) seedlings. PAW is characterized by measuring concentrations of reactive oxygen and nitrogen species (H2O2, NO2‐, NO3‐). After 4 weeks of plants growth, the effects of PAW are analyzed by measuring plant growth and physiological parameters: plant length and fresh weight, photosynthetic pigments concentration and photosynthesis rate, total soluble proteins, antioxidant enzyme activity, and DNA damage. The results suggest that PAW, depending on chemical composition, has the potential to improve the plant growth and influence the physiological parameters, while causing no harmful DNA damage. [ABSTRACT FROM AUTHOR]

Background: Myrin®-p Forte is an anti-tuberclosis agent that can cause hepatic injuries in clinical settings. Maytenus royleanus (Celastraceae) is a medicinal plant, possesses antioxidant and anticancer activities. The hepatoprotective effect of the methanol extract of Maytenus royleanus leaves (MEM) against Myrin®-p Forte induced hepatotoxicity in mice was investigated. Methods: Mice were randomly parted into six groups (n = 6). Fixed-dose combination of Myrin®-p Forte (13.5 mg/kg Rifampicin, 6.75 mg/kg Isoniazid, 36.0 mg/kg Pyrazinamide and 24.8 mg/kg Ethambutol; RIPE] was administered for 15 days to induce liver injury. In treatment groups MEM (200 mg/kg and 400 mg/kg doses) and Vitamin B6 (180mg/kg) were administered prior to RIPE. Control group received 2% DMSO. Serum liver function tests, DNA damage, tissue antioxidant enzymes and histopathological alterations were studied. HPLC analysis was performed to determine the chemical composition using standard compounds. Results: The quercitin, gallic acid, luteolin, viteixin, apigenin, kaempherol, hyperoside and myricetin contents of all samples were determined by reverse-phase HPLC. Quercetin (0.217 mg/g dry weight) and luteolin (0.141 mg/g dry weight) were the major flavonoids identified in MEM. Myrin®-p Forte markedly (p < 0.05) deteriorated lipid profile and upregulated the concentration of LDH, AST, ALP, ALT and γ-GT in serum along with DNA fragmentation (37.13 ± 0.47%) and histopathological injuries in hepatic tissues of mice compared with the control group. Myrin®-p Forte increased (p < 0.001) lipid peroxidation and H2O2 while decreased (p < 0.001) the activity level of CAT, SOD, POD, GPx, GST, GSR, γ-GT and GSH. Co-administration of MEM (200 mg/kg; 400 mg/kg) or the vitamin B6 (180 mg/kg) to Myrin®-p Forte administered mice significantly ameliorated LDL, cholesterol, HDL and triglyceride content. Furthermore, MEM dose dependently corrected serum liver function tests, decrease % DNA fragmentation (17.82 ± 0.35 and 7.21 ± 0.32 respectively), DNA damage. MEM treated protect RIPE induced oxidative damage by enhancing antioxidants to oxidants balance. Histological examination comprehends biochemical findings. Conclusion: The antioxidant effects of MEM exerted the hepatoprotective potential against the Myrin®-p Forte induced hepatotoxicity in mice. [ABSTRACT FROM AUTHOR]

The increased use of pesticides is the origin of multiple damages to the environment and to humans; thus, the search for new strategies to reduce or even protect the toxic effects caused by these synthetic products became a necessity. In this context, our study attempted to evaluate the protective effects of fennel essential oil (FEO), the main essential oil extracted from Faeniculum vulgare Mill., a plant with aromatic, flavorful, and medicinal uses, against toxicity induced by an insecticide—triflumuron (TFM)—in human carcinoma cells (HCT116). Our methodological approach consists of the cytotoxicity assay starting with the cell viability test, the ROS generation, the malondialdehyde (MDA) production, the DNA fragmentation, and the measurement of some antioxidant enzymes activities such as catalase (CAT) and superoxide dismutase (SOD). Also, we measured the mitochondrial transmembrane potential. The outcome of the current study showed clearly that after 2 h of HCT 116 cell pretreatment with FEO, there were increase in cell viability, reduction in ROS generation, and modulation in CAT and SOD activities induced by TFM. In the same manner, significant decreases in MDA levels were found. Mainly, the results indicated a perceptible decrease in DNA damages and a significant reduction in the mitochondrial membrane potential loss. Our work demonstrates that FEO can be an important protector against toxic effects induced by TFM in HCT 116 cells. [ABSTRACT FROM AUTHOR]