MicroRNA mediated therapeutic effects of natural agents in prostate cancer.

BACKGROUND: Several natural products, extensively studied for their anticancer activities, have been found to play an efficient role in preventing prostate cancer (PCa). Recently many natural agents have been reported to modulate microRNAs (miRNAs), that are involved in cancer cell growth. The microRNAs are endogenous small noncoding ribonucleic acid molecules that regulate various biological processes through an elegant mechanism of post-transcriptional control of gene expression. Besides being involved in cancer initiation, progression, angiogenesis, inflammation, they have been reported to be responsible for chemoresistance, and radioresistance of tumors. The dysregulated miRNA expression has been associated with many cancers including PCa. Over the past several years, it has been found that natural agents are good regulators of miRNAs and have a role in PCa also. Understanding the molecular mechanisms involving miRNAs by natural agents could result in developing useful strategies to combat this deadly disease. METHODS: In order to collect research articles, the PubMed search engine was used with keywords 'prostate cancer' and 'natural agents' and 2007 papers were retrieved, further refinement with keywords 'phytochemical' and 'prostate cancer' showed 503 papers. Data was collected from research articles, published from 2010 to 2021. From these, research articles showing miRNA-mediated mechanisms were selected. RESULTS: In this review, we have summarized the information available on the modulation of miRNAs by natural agents, their derivatives, and various combinatorial strategies with chemo/radiation therapy for the mitigation of PCa. CONCLUSIONS: Based on the current review of literature, it has been found that the use of natural agents is a novel approach for altering miRNA expression strongly associated with PCa development, recurrence and resistance.

Galangin induces cell death by modulating the expression of glyoxalase-1 and Nrf-2 in HeLa cells.

The present study was designed to understand the anticancer property and molecular mechanisms associated with chemo preventive effects of galangin. The anticancer effect was evaluated in vitro using human cervical cancer cell line (HeLa). Galangin was found to be effective in inducing cell death and inhibiting proliferation & migration significantly. The inhibitory effect of galangin could be correlated with the increase in ROS production & induction of apoptosis. Besides this the activity of glyoxalase-1, an enzyme important for the detoxification of cytotoxic metabolite methy glyoxal and Nrf-2 (a trascription factor), involved in redox signalling were found to be decreased. We concluded that galangin exerts its chemo preventive effect via redox signalling by inhibiting glyoxalase-1 & increasing oxidative & carbonyl stress.

Antioxidant and antimicrobial properties of the essential oil and extracts of Zanthoxylum alatum grown in north-western Himalaya.

The essential oil obtained from the fresh leaves of Zanthoxylum alatum was analysed by gas chromatography/mass spectrometry (GC/MS). Fourteen components were identified, and linalool (30.58%), 2-decanone (20.85%), ß -fenchol (9.43%), 2-tridecanone (8.86%), ß -phellandrene (5.99%), Sabinene (4.82%), and α -pinene (4.11%) were the main components. The EO and methanolic extract of Z. alatum exhibited potent antifungal activity against Alternaria alternata, Alternaria brassicae, and Curvularia lunata. The EO also showed significant antibacterial activity against Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, and Escherichia coli. Further, antimicrobial constituents of the EO were isolated by bioautography and preparative thin layer chromatography (PTLC) and identified as ß -fenchol and linalool using GC/MS analysis. In addition to this, the free radical scavenging activity and antioxidant potential of EO and methanolic extract/fractions of Z. alatum were also investigated using in vitro assays including scavenging ability against DPPH(•), reducing power and chelating ability on Fe(2+) ions. Our results demonstrate that Z. alatum could be used as a resource of antioxidant and antimicrobial compounds which may find applications in food and pesticide industries.

Antioxidant activity and protective effect against plasmid DNA strand scission of leaf, bark, and heartwood extracts from Acacia catechu.

UNLABELLED: The antioxidant activity of methanol extract/fractions of leaf, bark, and heartwood of Acacia catechu was evaluated by various antioxidant assays, including free radical, superoxide and hydroxyl radical, reducing power, metal ion chelation, as well as hydroxyl radical induced DNA strand scission. The leaf, bark, and heartwood powder was extracted in methanol and the lyophilized methanol extract was fractionated with different solvents in the order of increasing polarity. The results indicate that ethyl acetate fraction of heartwood has the highest antioxidant capacities, presenting lower EC(50) values particularly in free radical scavenging activity, including DPPH radicals (4.76 ± 0.14 µg/mL), superoxide anions (26.21 ± 0.79 µg/mL), and hydroxyl radicals (33.69 ± 1.42 µg/mL), in direct assay systems. Reducing power was also highest in ethyl acetate fraction of heartwood (EC(50) of 79.05 ± 1.02 µg/mL). As for the chelating power on ferrous ions, leaf extract was more effective than bark and heartwood extracts. Furthermore, the ethyl acetate and acetone fractions of heartwood significantly protected pBR322 supercoiled plasmid DNA against strand scission induced by hydroxyl radicals in a Fenton's reaction mixture. PRACTICAL APPLICATION: The present investigation suggests that the three organs of A. catechu differ significantly in their antioxidant potential as seen in the DPPH radical scavenging assay, reducing power assay, metal ion chelating assay, superoxide radical scavenging assay and hydroxyl radical scavenging assay. Further, our results showed that crude methanol extract and ethyl acetate fraction of heartwood of A. catechu might have a good potential as a source for natural health products due to its antioxidant and DNA protective activities.

Antioxidant activity of acetone extract/fractions of Terminalia bellerica Roxb. fruit.

Terminalia bellerica Roxb. (Family: Combretaceae) has been valued in Indian system of medicine for treatment of wide range of diseases and reported to have antioxidant properties. In the present study, the free radical scavenging activity and antioxidant potential of acetone extract/fractions of its fruit was investigated using in vitro assays, including scavenging ability against 2,2'-diphenyl-2-picrylhydrazyl (DPPH), beta-carotene bleaching inhibition, reducing power and chelating ability on Fe2+ ions. The fruit powder was extracted at room temperature with different solvents in the order of increasing and decreasing polarity to obtain crude acetone extract which was further partitioned with ethyl acetate and water (1:1). It was found that ethyl acetate fraction was more effective than crude acetone extract in all antioxidant assays, except chelating power which was highest in water fraction. Maximum antioxidant activities (expressed as EC50 values) observed were 14.56 microg/ml, 27.81 microg/ml and 67.8 microg/ml in DPPH, beta-carotene bleaching and reducing power assays, respectively. The antioxidant potential was compared with known antioxidant (butylated hydroxyl toluene) and correlated with total phenolic and flavonoid content in crude extract and fractions. Fractions rich in polyphenolic content were more effective than the crude extract.

Dentigerous cysts of anterior maxilla in a young child: a case report.

Dentigerous cysts are the most common bony lesions of the jaws in children. It is one of the most prevalent types of odontogenic cysts associated with an erupted or developing tooth, particularly the mandibular third molars; the other teeth that are commonly affected are, in order of frequency, the maxillary canines, the maxillary third molars and, rarely, the central incisor. Radiographically, the cyst appears as ovoid well-demarcated unilocular radiolucency with a sclerotic border. The present case report describes the surgical enucleation of a dentigerous cyst involving the permanent maxillary right central incisor; the surgery was followed by oral rehabilitation. Careful evaluation of the history and the clinical and radiographical findings help clinicians to correctly diagnose the condition, identify the etiological factors, and administer the appropriate treatment.

An unusual presentation of all the mandibular anterior teeth with two root canals--a case report.

A rare case of two root canals in all mandibular anterior teeth is presented. The patient initially reported for the treatment of mandibular right central and lateral incisors. However, radiographic evaluation revealed variant root canal and apical foramen patterns.

Management of two unusual cases of dens invaginatus and talon cusp associated with other dental anomalies.

The management of two unusual cases of dens invaginatus and talon cusp is presented. The first concerns talon cusp in maxillary primary and permanent lateral incisors, a supplemental tooth with dens invaginatus hampering eruption of the permanent incisors. The other present with bizarre crown morphology of a lateral incisor with talon cusp, dens invaginatus and a palatal accessory cusp-like structure. Early diagnosis and management are important to avoid complications.

Periapical repair and apical closure of a pulpless tooth using calcium hydroxide--a case report.

A case with a open apex and a large periapical lesion in a 10 year old boy is presented. The lesion formed as a result of necrosis from trauma to a maxillary right central incisor 1 year ago. Apical closure and complete healing of periapical lesion was observed after non-surgical endodontic treatment using calcium hydroxide paste. This report suggests that even large periapical lesions could respond favourably to non-surgical treatment.

Hypertaurodontism in molars and premolars: management of two rare cases.

The management of two cases of hypertaurodontism, is presented. The first case shows this uncommon dental anomaly in all the four permanent first molars. The second case is concerned with endodontic management of a hypertaurodontic mandibular second premolar. The authors wish to highlight the importance of careful radiographic examination in diagnosing this rare dental anomaly in view of the difficulties encountered in performing endodontic treatment.

Radiomodification of glyoxalase I in the liver and spleen of mice: adaptive response and split-dose effect.

Glyoxalase system, particularly glyoxalase I (Gly I) plays an important role in regulation of cell division and is considered to be a metabolic indicator of cell proliferation. The glyoxalase system is likely to have a close link with cellular radiosensitivity. Therefore, we have examined the effect of adaptive and split-dose of y-rays on the activity of Gly I in the liver and spleen of mice. For the adaptive response studies, mice pre-treated with a conditioning dose of 0.5 Gy were given a challenging dose of 4 Gy at varying time intervals. In the split-dose studies, a dose of 4 Gy was delivered into two equal fractions and spaced at different time intervals. The results show that pre-exposure to a conditioning dose or the fractionation of total dose decreased the specific activity of Gly I in the liver and spleen of mice. The decreased activity of Gly I was suggestive of protective action induced by the conditioning dose and fractionation of dose. The similar pattern of radiation response of Gly I probably supported the possibility of involvement of a common pathway in the radiation-induced adaptive and split-dose effect. From these observations a close link between the Gly I and the adaptive-response as well as the split-dose effect is speculated. Since, the glyoxalase system is vital for a variety of biological functions including cell division and repair, the present findings may have relevance in understanding the dose-fractionation as well as the biological defence induced by low doses of radiations.

Post-exposure radioprotection by Chlorella vulgaris (E-25) in mice.

Oral administration of an algal mutant C. vulgaris E-25, 1 hr before or immediately after exposure to sublethal gamma-rays increased the number of endogenous spleen colony forming units (E-CFU). The magnitude of radioprotection was dependent on both, the dose of C. vulgaris fed and the time of administration. An optimal E-CFU was observed when 500 mg/kg body wt. of C. vulgaris was fed 1 hr before or immediately after irradiation. Significant recovery was observed in the number of bone marrow cells and the spleen weight. LD50/30 for Chlorella pre- and post-treated mice were 8.66 and 9.0 Gy, respectively compared to the control value of 7.8 Gy. The dose reduction factor (DRF) was 1.11 and 1.15 for pre-treated and post-treated mice respectively.

Evaluation of radioprotective action of a mutant (E-25) form of Chlorella vulgaris in mice.

The possible role of orally fed Chlorella vulgaris (E-25) in modulating the gamma-ray induced chromosomal damage in whole-body irradiated mice was evaluated using a micronucleus test. Different doses of E-25 were administered either chronically (once, twice or thrice a day for 28 days) or as single acute doses before/after irradiation. A significant radioprotective effect was observed in both acute and chronic pretreatments, but only at doses above 400 mg/kg body weight. However, in mice that received E-25 (500 mg/kg) three times a day for 28 days, there was no protective effect, and a significant loss in their body weight was observed. Interestingly, E-25 afforded significant radioprotection even when it was administered within 0.4 hr after irradiation.