The effect of tocotrienol-rich fraction supplementation on the ovarian metabolome and the quality of oocyte in aging mice

Ovarian aging has been associated with oxidative stress and loss of ovarian function. Tocotrienol has been proven to exert beneficial effects on the female reproductive system. However, the role of tocotrienol in affecting metabolism in the ovary and subsequently improving the quality of oocytes in aging mice remains unknown. Therefore, the relationship between metabolic changes in the ovary and the quality of oocytes in aging mice following tocotrienol-rich fraction (TRF) supplementation was investigated. Six-week-old female mice were used as the Young group. Six-month-old aged female mice were divided into four groups; the first group was given tocopherol-stripped corn oil (vehicle control) while the other three groups were supplemented with TRF at the dose of 90, 120, and 150 mg/kg, respectively. The treatment was given orally for two months. At the end of the treatment, mice from all groups were superovulated and then euthanised. Oocyte quality was assessed and non-targeted metabolomic analysis of the ovarian tissues was performed using liquid chromatography-tandem mass spectrometry of quadrupole time-of-flight (LC-MS Q-TOF). Percentages of normal oocytes were higher (p<0.001) while abnormal oocytes were lower (p<0.001) in TRF 150 mg/kg group compared to that of the control. Seventeen metabolites were identified to be significantly different in the ovarian tissue of the aging group when compared to the young group. 14 metabolites were identified to be significantly different in the ovarian tissue between the control and TRF supplemented groups. Pathway analysis revealed significantly altered metabolic pathways for fatty acid and amino acid metabolism that might influence the quality of oocytes. In conclusion, TRF supplementation causes metabolic changes in the ovary that delay the consequences of aging, thus improving the quality of oocytes in aging mice

Bauhinia purpurea leaves’ extracts exhibited in vitro antiproliferative and antioxidant activities

The antiproliferative and antioxidant activities of various extracts of the leaves of Bauhinia purpurea were studied using in vitro standard assays. The aqueous and chloroform extracts successfully inhibited the proliferation of all cancer cells while the methanol extract inhibited the proliferation of all cells except the CEMss cells when assessed using the 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. The aqueous extract was effective against MCF-7 (IC50 ≈ 9 μg/ml), MDA-MB 231 (IC50 ≈ 17 μg/ml) and Caov-3 (IC50 ≈ 16 μg/ml); the chloroform extract was highly effective against the CEMss (IC50 ≈ 18 μg/ml) and HeLa (IC50 ≈ 21 μg/ml); and the methanol extract was highly effective only against the HL-60 (≈ 12 μg/ml) cell lines. Interestingly, all extracts did not inhibit the proliferation of 3T3 cells suggesting their non-cytotoxic properties. The aqueous and methanol, but not chloroform, extracts of B. purpurea (20, 100 and 500 μg/ml) exhibited concentration-dependent antioxidant activity only in the superoxide scavenging assay, but low to moderate activity in the 2,2- diphenyl-1 picrylhydrazyl (DPPH) radical scavenging assay, which could be associated with their total phenolic contents. In conclusion, the B. purpurea leaf possesses potential antiproliferative and concentration-dependent antioxidant activities. Purification and determination of active compounds are required for further study.Keywords: Bauhinia purpurea, in vitro, antiproliferative activity, antioxidant activity, phenolic compound

Identification of Benzoxazolinone Derivatives Based Inhibitors for Depression and Pain Related Disorders Using Human Serotonin and Norepinephrine Transporter as Dual Therapeutic Target: A Computational Approach

Pain is commonly associated with depression. Both pain and depression share common biological pathways and neurotransmitters, which has implications for the treatment of both disorders. A drug that could ameliorate both pain and depression could be beneficial in the development of new therapeutics in the management of disorders associated with pain/depression dyad. Alterations in the neurotransmitters namely, serotonin and norepinephrine in the central nervous system (CNS) have been implicated in the pathophysiology of pain and depression. Serotonin and norepinephrine reuptake inhibitors (SNRIs) have been implicated as a novel therapeutic target for a wide range of biological functions, including pain, anxiety and depression. 2-benzoxazolinone (2-BOA) from the mangrove Acanthus ilicifolius and its derivatives have been reported for its analgesic and antidepressant activities. In the present work, docking studies were done on the crystal structure of human transporters of serotonin (hSERT) and on homology modeled human transporters of norepinephrine (hNET) as therapeutic targets of depression and pain related disorders using 2-BOA and its derivatives as potential candidates. A homology model for hNET was constructed using MODELLER and validated. Further docking studies were done on hSERT and hNET using 2-BOA and its structural analogs. The result of the study proposes the possible potential candidate among 2-BOA derivatives that may be further developed as a therapeutic lead compound for use in disorders associated with depression and pain

Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer

Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes

H. pylori-infection and antibody immune response in a rural Tanzanian population

BACKGROUND: Helicobacter pylori (H. pylori) infection is ubiquitous in sub-Saharan Africa, but paradoxically gastric cancer is rare. METHODS: Sera collected during a household-based survey in rural Tanzania in 1985 were tested for anti-H. pylori IgG and IgG subclass antibodies by enzyme immunoassay. Odds ratios (OR) and confidence intervals (CI) of association of seropositivity with demographic variables were computed by logistic regression models. RESULTS: Of 788 participants, 513 were aged ≤17 years. H. pylori seropositivity increased from 76% at 0–4 years to 99% by ≥18 years of age. Seropositivity was associated with age (OR 11.5, 95% CI 4.2–31.4 for 10–17 vs. 0–4 years), higher birth-order (11.1; 3.6–34.1 for ≥3(rd )vs. 1(st )born), and having a seropositive next-older sibling (2.7; 0.9–8.3). Median values of IgG subclass were 7.2 for IgG1 and 2.0 for IgG2. The median IgG1/IgG2 ratio was 3.1 (IQR: 1.7–5.6), consistent with a Th2-dominant immune profile. Th2-dominant response was more frequent in children than adults (OR 2.4, 95% CI 1.3–4.4). CONCLUSION: H. pylori seropositivity was highly prevalent in Tanzania and the immunological response was Th2-dominant. Th2-dominant immune response, possibly caused by concurrent bacterial or parasitic infections, could explain, in part, the lower risk of H. pylori-associated gastric cancer in Africa

Dynamic light diffusion, Anderson localization and lasing in disordered inverted opals: 3D ab-initio Maxwell-Bloch computation

We report on 3D time-domain parallel simulations of Anderson localization of light in inverted disordered opals displaying a complete photonic band-gap. We investigate dynamic diffusion processes induced by femtosecond laser excitations, calculate the diffusion constant and the decay-time distribution versus the strength of the disorder. We report evidence of the transition from delocalized Bloch oscillations to strongly localized resonances in self-starting laser processes.Comment: 4 pages, 5 figure

Should women under 50 be screened for breast cancer?

Should women under 50 be screened for breast cancer? Despite some controversy in recent years, the majority of experts agree on the evidence for effectiveness of breast screening by mammography for women aged 50 years and above, but for those under 50 years, the picture is much less clear. However, the issue remains of importance both to policy makers and to individual women; although the incidence of breast cancer is lower at younger ages, the life years lost due to cancers diagnosed below 50 years amount to a third of all those lost due to the disease