Fixed Time-Point Analysis Reveals Repetitive Mild Traumatic Brain Injury Effects on Resting State Functional Magnetic Resonance Imaging Connectivity and Neuro-Spatial Protein Profiles.

Repetitive mild traumatic brain injuries (rmTBIs) are serious trauma events responsible for the development of numerous neurodegenerative disorders. A major challenge in developing diagnostics and treatments for the consequences of rmTBI is the fundamental knowledge gaps of the molecular mechanisms responsible for neurodegeneration. It is both critical and urgent to understand the neuropathological and functional consequences of rmTBI to develop effective therapeutic strategies. Using the Closed-Head Impact Model of Engineered Rotational Acceleration, or CHIMERA, we measured neural changes following injury, including brain volume, diffusion tensor imaging, and resting-state functional magnetic resonance imaging coupled with graph theory and functional connectivity analyses. We determined the effect of rmTBI on markers of gliosis and used NanoString-GeoMx to add a digital-spatial protein profiling analysis of neurodegenerative disease-associated proteins in gray and white matter regions. Our analyses revealed aberrant connectivity changes in the thalamus, independent of microstructural damage or neuroinflammation. We also identified distinct changes in the levels of proteins linked to various neurodegenerative processes including total and phospho-tau species and cell proliferation markers. Together, our data show that rmTBI significantly alters brain functional connectivity and causes distinct protein changes in morphologically intact brain areas.

Intracerebral but Not Peripheral Infection of Live Porphyromonas gingivalis Exacerbates Alzheimer's Disease Like Amyloid Pathology in APP-TgCRND8 Mice.

The impact of oral microbial dysbiosis on Alzheimer's disease (AD) remains controversial. Building off recent studies reporting that various microbes might directly seed or promote amyloid ß (Aß) deposition, we evaluated the effects of periodontal bacteria (Porphyromonas gingivalis, Treponema denticola) and supragingival commensal (Streptococcus gordonii) oral bacterial infection in the APP-transgenic CRND8 (Tg) mice model of AD. We tracked bacterial colonization and dissemination, and monitored effects on gliosis and amyloid deposition. Chronic oral infection did not accelerate Aß deposition in Tg mice but did induce alveolar bone resorption, IgG immune response, and an intracerebral astrogliosis (GFAP: glial fibrillary acidic protein). In contrast, intracerebral inoculation of live but not heat-killed P. gingivalis increased Aß deposition and Iba-1 (ionized calcium-binding adaptor-1) microgliosis after 8 weeks of bacterial infection but not at 4 days. These data show that there may be differential effects of infectious microbes on glial activation and amyloid deposition depending on the species and route of inoculation, and thereby provide an important framework for future studies. Indeed, these studies demonstrate marked effects on amyloid ß deposition only in a fairly non-physiologic setting where live bacteria is injected directly into the brain.

Ethnobotanical survey of medicinal plants used in the management of cancer and diabetes.

OBJECTIVE: To conduct an ethnobotanical survey and document the traditional anticancer and antidiabetic plants used by the local tribes of Mizoram, Northeast India. METHODS: A systematic survey was conducted in rural and urban areas of Mizoram by interviewing traditional practitioners, and cancer and diabetes patients. A detailed literature search was carried out using MEDLINE and SCOPUS and available literatures were selected and included in the study. The use value (UV) of the selected plants was calculated based on the number of citations per species given by informants. RESULTS: Data was obtained for 201 traditional medicinal plants from Mizoram, Northeast India. These plants were from 72 different families and belonged to 140 genera. Of these, 103 plants were reported for the first time as possessing either anticancer or antidiabetic potential, and 105 plants were identified that were used for the treatment of both diseases. Three plants (Phlogacanthus thysiformis, Solanum gilo and Lobelia angulata) with antidiabetic potential, and six plants (Dillenia scabrella, Circium sinesis, Eupatorium nodiflorum, Pratia begonifolia, Vernonia teres and Plantago erosa) with both as anticancer and antidiabetic potential were documented for the first time. CONCLUSION: In this study, we documented several explored and unexplored medicinal plants that may be useful for the management of cancer and diabetes. This study suggests that there is a broad scope fordeveloping potent anticancer and antidiabetic agent from the flora of Mizoram, Northeast India.

Phytol ameliorated benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice via inhibition of oxidative stress and apoptosis.

In the present study, the modulatory effect of phytol against benzo(a)pyrene [B(a)P] induced lung carcinogenesis was investigated in Swiss albino mice. During the experimental period, phytol treatment showed no adverse toxic effect and mortality to the experimental animals. Lung tumor was observed in B(a)P treated group and also in animals post-treated with low concentration (50 mg/kg) of phytol. No neoplastic changes were observed in the lung tissue of the animals treated with the maximum dose of phytol (100 mg/kg). An elevated level of antioxidant enzymes combined with macromolecular damage (lipid peroxidation, protein carbonyl content) was observed upon B(a)P treatment whereas, phytol restored the level of antioxidant enzymes which were comparable to the vehicle control group. Moreover, administration of B(a)P induced apoptosis, as observed by the highest expression of Bax, caspase-3, and caspase-9 proteins in lung tissue of B(a)P alone treated animals. However, phytol treatment reduced the expression of Bax, caspase-3, and caspase-9 protein and maintained the constant expression of anti-apoptotic protein Bcl-2. These observations positively reveal that phytol regulates the antioxidant enzymes and thereby protects the cells against B(a)P induced carcinogenesis without showing any adverse toxic effect to the animals.

Phytol shows anti-angiogenic activity and induces apoptosis in A549 cells by depolarizing the mitochondrial membrane potential.

In the present study, the antiproliferative activity of phytol and its mechanism of action against human lung adenocarcinoma cell line A549 were studied in detail. Results showed that phytol exhibited potent antiproliferative activity against A549 cells in a dose and time-dependent manner with an IC50 value of 70.81 ±â€¯0.32 µM and 60.7 ±â€¯0.47 µM at 24 and 48 h, respectively. Phytol showed no adverse toxic effect in normal human lung cells (L-132), but mild toxic effect was observed when treated with maximum dose (67 and 84 µM). No membrane-damaging effect was evidenced by PI staining and SEM analysis. The results of mitochondrial membrane potential analysis, cell cycle analysis, FT-IR and Western blotting analysis clearly demonstrated the molecular mechanism of phytol as induction of apoptosis in A549 cells, as evidenced by formation of shrinked cell morphology with membrane blebbing, depolarization of mitochondrial membrane potential, increased cell population in the sub-G0 phase, band variation in the DNA and lipid region, downregulation of Bcl-2, upregulation of Bax and the activation of caspase-9 and -3. In addition, phytol inhibited the CAM vascular growth as evidenced by CAM assay, which positively suggests that phytol has anti-angiogenic potential. Taken together, these findings clearly demonstrate the mode of action by which phytol induces cell death in A549 lung adenocarcinoma cells.

Gracilaria edulis exhibit antiproliferative activity against human lung adenocarcinoma cell line A549 without causing adverse toxic effect in vitro and in vivo.

In the present study, the antiproliferative potential of various solvent extracts of Gracilaria edulis (GE) was tested against various cancer cell lines. In the A549 lung cancer cell line model, GE ethyl acetate extract (GEEA) (100 µg mL(-1)) treated group showed the maximum and significant (P < 0.05) growth inhibition at 48 h. The IC50 value was found to be 24.5 ± 19.1 µg mL(-1) at 48 h. Moreover, a low level of LDH release was observed at 48 h at various concentrations of (40, 60, 80 and 100 µg mL(-1)) GEEA extract-treated group compared to a control group. Changes in the cell morphology and echinoid spikes formation were observed at 48 h. Safety evaluation of GEEA in a non-cancerous liver cell line, PBMC and in Wistar rats positively revealed that the extract did not show any adverse toxic effects. The GEEA extract was partially purified by column chromatography and the active fraction was characterized through LC-MS analysis. Furthermore, HPLC and FT-IR analysis of the active fractions confirmed the presence of phytol, a diterpene compound with potent antiproliferative activity, which positively suggests that the red alga G. edulis contains a potent anticancer active principle.

Evaluation of physicochemical properties, proximate and nutritional composition of Gracilaria edulis collected from Palk Bay.

Gracilaria edulis, a red alga present in southeast coast of India was evaluated for its nutritional composition. FT-IR analysis of soluble polysaccharides revealed the presence of galactans, 3,6-anhydro-α-L-galactopyranose, sulphated galactose and the gelling agent agar, with the sulphate content estimated as 51.01 µg/mg of polysaccharide. Results of physicochemical properties and nutritional profile reveal the presence of dietary fibre (8.9 ± 0.62% DW), carbohydrate (101.61 ± 1.8 mg/g DW), crude protein (6.68 ± 0.94 mg/g DW) and lipid content (8.3 ± 1.03 mg/g DW). G. edulis contains biologically important fatty acids like palmitic acid (2.06%), linolenic acid (2.56%), and oleic acid (1.98%). The other nutritional components present in high amounts are proline, chlorophyll A and B, all the essential amino acids and vitamin A, E and C. These findings suggest that G. edulis has potent nutritional value which might be used as a source of nutrients for human and animals.