miRNA-221: A Potential Biomarker of Progressive Liver Injury in Chronic Liver Disease (CLD) due to Hepatitis B Virus (HBV) and Nonalcoholic Fatty Liver Disease (NAFLD).

Background: Early detection of progressive liver damage in chronic liver disease (CLD) patients is crucial for better treatment response. Several studies have shown the association of microRNA (miRNA) in the progression of CLD in regulating cell proliferation, fibrosis, and apoptosis as well as in carcinogenesis. Objectives: The study was aimed at determining the expression of miRNA-221 among different stages of fibrosis in CLD patients due to hepatitis B virus (HBV) and nonalcoholic fatty liver disease (NAFLD) and thus evaluate its role as an early biomarker in CLD. Methods: A total of 100 participants (75 CLD patients and 25 healthy control) were recruited in this cross-sectional study and divided into four groups, of which 25 as healthy control, 25 in CLD without fibrosis, 25 were CLD with fibrosis, and 25 were CLD with cirrhosis. Total RNA was extracted from plasma followed by cDNA synthesis, and finally, the expression of miRNA-221 was analyzed for its diagnostic potential as a single biomarker using the qRT-PCR method. Results: The plasma level of miRNA-221 was significantly upregulated in different fibrosis stages of CLD (p < 0.05), and this upregulation was positively correlated with the progression of fibrosis (p < 0.05). Significantly increased expression of miRNA-221 was found in NAFLD patients compared to HBV patients in the CLD without fibrosis patient group (p < 0.05), while expression of miRNA-221 was significantly upregulated among HBV patients in the CLD with the fibrosis group. miRNA-221 showed high diagnostic accuracy in discriminating different stages of fibrosis from healthy control (p < 0.05). Conclusion: miRNA-221 may be used as a potential plasma biomarker for early prediction of fibrosis progression in CLD patients.

Biological Functions of Dillenia pentagyna Roxb. Against Pain, Inflammation, Fever, Diarrhea, and Thrombosis: Evidenced From in vitro, in vivo, and Molecular Docking Study.

Dillenia pentagyna Roxb. is traditionally used to treat cancer, wound healing, diabetes, and diarrhea in local tribes. This study was designed to evaluate the pharmacological potentiality of this plant. In vivo analgesic, anti-inflammatory, and antipyretic studies of the methanol extracts of D. pentagyna (MEDP) leaves were performed by using acetic acid-induced nociception, formalin-induced paw licking, and yeast-induced pyrexia assay methods, respectively. In vivo antidiarrheal activity was carried out in mice by following castor oil-induced diarrhea and gastrointestinal transit manner. In vitro thrombolytic experiment was performed employing the clot lysis activity. Besides, a molecular docking study was performed by executing the software (PyRx, Discovery Studio, and UCSF Chimera). In the acetic acid-induced writhing study, MEDP possesses significant writhing inhibition in a dose-dependent manner. It showed 50.86% of maximum inhibition of pain in the case of MEDP at a dose of 400 mg/kg body weight. In the anti-inflammatory study, maximum inhibition rate was observed at a value of 59.98 and 41.29% in early and late phases, respectively, at the dose of 400 mg/kg body weight. In the case of yeast-induced hyperpyrexia, MEDP reduced hyperpyrexia in a dose-dependent manner. In the antidiarrheal assay, MEDP moderately inhibited the occurrence of diarrhea in all the experiments. In the thrombolytic study, a moderate (17.76%) clot lysis potency has been yielded by MEDP. Again, the molecular docking simulation revealed strong binding affinities with almost all the targeted proteins. The present study suggests that the MEDP possesses remarkable pharmacological activity and this finding validated the ethnobotanical significance of D. pentagyna as the source of pain, fever, and diarrhea management agent.

Extracts of Musa basjoo induce growth inhibition and changes in the protein expression of cell cycle control molecules in human colorectal cancer cell lines.

Musa basjoo (MB) is a species of the banana plant belonging to the genus Musa that has been used as a folk medicine. However, evidence-based biological activities and the molecular mechanism of action of MB are unknown. Thus, the aim of the present study was to examine whether the crude dried leaf extracts of MB inhibit the growth of colorectal (HT29 and HCT116) and other types (HepG2, MCF-7 and PC-3) of human cancer cell lines. Crude extracts of MB inhibited the growth of cells with IC50 values of 136 µg/ml (acetone extract, HT29), 51 µg/ml (acetone extract, HCT116), 45 µg/ml (acetone extract, HepG2), 40 µg/ml (acetone extract, MCF-7), 29 µg/ml (acetone extract, PC-3), 175 µg/ml (methanol extract, HT29), 137 µg/ml (methanol extract, HCT116), 102 µg/ml (methanol extract, HepG2), 85 µg/ml (methanol extract, MCF-7), and 85 µg/ml (methanol extract, PC-3) in colony formation assays, and 126 µg/ml (acetone extract, HT29), 68 µg/ml (acetone extract, HCT116), 260 µg/ml (methanol extract, HT29), and 216 µg/ml (methanol extract, HCT116) in MTT assays. Thin layer chromatography analysis revealed the potential existence of aromatic compounds in the acetone extract of MB. Flow cytometric analysis indicated that the percentage of cells in G1 increased, and this was associated with a concomitant decrease of cells in the S and/or G2-M phases of the cell cycle. When colorectal cancer cells were treated with acetone extract of MB, there was a marked decrease in the levels of expression of the cyclin D1, cyclin E, cdk2 and cdk4 proteins and a marked increase in the levels of the expression of the p21CIP1, p27KIP1, and p53 proteins, but those of apoptosis-associated protein PARP did not change. There was a tendency for acetone extract of MB to inhibit xenograft tumor growth in mice. Collectively, the crude extracts of MB contain active components that exert growth inhibition of human cancer cells. This is the first systematic study of the anticancer activity of MB and may broaden insights into the possible clinical approach of specific herbal medicines.

Reduced High-Dose Radiation-Induced Residual Genotoxic Damage by Induction of Radioadaptive Response and Prophylactic Mild Dietary Restriction in Mice.

Radioadaptive response (RAR) describes a phenomenon in a variety of in vitro and in vivo systems that a low-dose of priming ionizing radiation (IR) reduces detrimental effects of a subsequent challenge IR at higher doses. Among in vivo investigations, studies using the mouse RAR model (Yonezawa Effect) showed that RAR could significantly extenuate high-dose IR-induced detrimental effects such as decrease of hematopoietic stem cells and progenitor cells, acute radiation hematopoietic syndrome, genotoxicity and genomic instability. Meanwhile, it has been demonstrated that diet intervention has a great impact on health, and dietary restriction shows beneficial effects on numerous diseases in animal models. In this work, by using the mouse RAR model and mild dietary restriction (MDR), we confirmed that combination of RAR and MDR could more efficiently reduce radiogenotoxic damage without significant change of the RAR phenotype. These findings suggested that MDR may share some common pathways with RAR to activate mechanisms consequently resulting in suppression of genotoxicity. As MDR could also increase resistance to chemotherapy and radiotherapy in normal cells, we propose that combination of MDR, RAR, and other cancer treatments (i.e., chemotherapy and radiotherapy) represent a potential strategy to increase the treatment efficacy and prevent IR risk in humans.

Biomarkers of Brain Damage Induced by Radiotherapy.

Radiotherapy remains currently a critical component for both primary and metastatic brain tumors either alone or in combination with surgery, chemotherapy, and molecularly targeted agents, while it could cause simultaneously normal brain tissue injury leading to serious health consequences, that is, development of cognitive impairments following cranial radiotherapy is considered as a critical clinical disadvantage especially for the whole brain radiotherapy. Biomarkers can help to detect the accurate physiology or conditions of patients with brain tumor and develop effective treatment procedures for these patients. In the near future, biomarkers will become one of the prime driving forces of cancer treatment. In this minireview, we analyze the documented work on the acute brain damage and late consequences induced by radiotherapy, identify the biomarkers, in particular, the predictive biomarkers for the damage, and summarize the biological significance of the biomarkers. It is expected that translation of these research advance to radiotherapy would assist stratifying patients for optimized treatment and improving therapeutic efficacy and the quality of life.

Potential of a fly gut microbiota incorporated gel-based larval diet for rearing Bactrocera dorsalis (Hendel).

BACKGROUND: The Oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), is an important polyphagous pest of horticultural produce. The sterile insect technique (SIT) is a proven control method against many insect pests, including fruit flies, under area-wide pest management programs. High quality mass-rearing process and the cost-effective production of sterile target species are important for SIT. Irradiation is reported to cause severe damage to the symbiotic community structure in the mid gut of fruit fly species, impairing SIT success. However, studies have found that target-specific manipulation of insect gut bacteria can positively impact the overall fitness of SIT-specific insects. RESULTS: Twelve bacterial genera were isolated and identified from B. dorsalis eggs, third instars larval gut and adults gut. The bacterial genera were Acinetobacter, Alcaligenes, Citrobacter, Pseudomonas, Proteus, and Stenotrophomonas, belonging to the Enterobacteriaceae family. Larval diet enrichment with the selected bacterial isolate, Proteus sp. was found to improve adult emergence, percentage of male, and survival under stress. However, no significant changes were recorded in B. dorsalis egg hatching, pupal yield, pupal weight, duration of the larval stage, or flight ability. CONCLUSIONS: These findings support the hypothesis that gut bacterial isolates can be used in conjunction with SIT. The newly developed gel-based larval diet incorporated with Proteus sp. isolates can be used for large-scale mass rearing of B. dorsalis in the SIT program.

Antihyperglycemic and antinociceptive activity evaluation of 'khoyer' prepared from boiling the wood of Acacia catechu in water.

'Khoyer' is prepared by boiling the wood of Acacia catechu in water and then evaporating the resultant brew. The resultant hard material is powdered and chewed with betel leaves and lime with or without tobacco by a large number of the people of Bangladesh as an addictive psycho-stimulating and euphoria-inducing formulation. There are folk medicinal claims that khoyer helps in the relief of pain and is also useful to diabetic patients to maintain normal sugar levels. Thus far no scientific studies have evaluated the antihyperglycemic and antinociceptive effects of khoyer. The present study was carried out to evaluate the possible glucose tolerance efficacy of methanolic extracts of khoyer using glucose-induced hyperglycemic mice, and antinociceptive effects with acetic acid-induced gastric pain models in mice. In antihyperglycemic activity tests, the extract at different doses was administered one hour prior to glucose administration and blood glucose level was measured after two hours of glucose administration (p.o.) using glucose oxidase method. The statistical data indicated the significant oral hypoglycemic activity on glucose-loaded mice at all doses of the extracts tested. Maximum anti-hyperglycemic activity was shown at 400 mg extract per kg body weight, which was less than that of a standard drug, glibenclamide (10 mg/kg body weight). In antinociceptive activity tests, the extract also demonstrated a dose-dependent significant reduction in the number of writhing induced in mice through intraperitoneal administration of acetic acid. Maximum antinociceptive activity was observed at a dose of 400 mg extract per kg body weight, which was greater than that of a standard antinociceptive drug, aspirin, when administered at a dose of 400 mg per kg body weight. The results validate the folk medicinal use of the plant for reduction of blood sugar in diabetic patients, as well as the folk medicinal use for alleviation of pain.