The potential role of short chain fatty acids improving T and CAR-T cell fitness and expansion for cancer immunotherapies.

Adoptive cell therapies, like tumor-infiltrating lymphocytes or chimeric antigen receptor T cells, have become an important immunotherapeutic approach against cancer. One of the main struggles of T cell immunotherapies is how to obtain the most effective T cell phenotype, persistence, and differentiation potential to infuse into patients. Adjusting the T cell cell culture conditions is a key factor to increase and improve the efficacy of cellular immunotherapies.

Prolonged exposure to melatonin leads to time-dependent sensitization of adenylate cyclase and down-regulates melatonin receptors in pars tuberalis cells from ovine pituitary.

In photoperiodic mammals, seasonal cycles of growth and reproduction are cued by changes in the duration of the nocturnal profile of secretion of the pineal hormone melatonin. To investigate the likely mode of action of this hormone on target tissues, the effect of prolonged treatment with melatonin on the sensitivity of the adenylate cyclase (AC) system was examined in primary cultures of ovine pars tuberalis (PT) cells. When cells were exposed to melatonin (100 pM or 1 microM) for 16 h, and the hormone was then removed by a series of washes, basal production of cAMP was elevated over that observed in cells not treated with melatonin.

mRNA transcription determines the lag period for the induction of pineal melatonin synthesis in the Syrian hamster pineal gland.

The nocturnal pattern of Syrian hamster pineal melatonin synthesis is characterized by a 6-8 h lag period, followed by a late-night, short-duration peak in both N-acetyltransferase (NAT) activity and melatonin content. Administration of cycloheximide (20 mg/kg body weight) given either at the time of lights out or 4 h into the dark phase to Syrian hamsters blocked the nocturnal increase in both pineal NAT activity and melatonin content. Actinomycin D (5 mg/kg body weight) prevented the nocturnal increase in both constituents only when it was administered at darkness onset, being significantly less effective when injected after 4 h of dark exposure.

Androgenic control of N-acetyltransferase activity in the harderian glands of the Syrian hamster is mediated by 5 alpha-dihydrotestosterone.

N-acetyltransferase (NAT) activity in the Harderian glands of intact and gonadectomized male and female Syrian hamsters was evaluated. The exogenous administration of 5 alpha-dihydrotestosterone (DHT) to castrated males and intact females produced an increase in NAT values, which reached the values present in the glands of intact males. The administration of a 5 alpha-reductase inhibitor to intact males led to a decrease in NAT activity, suggesting that testosterone is converted in DHT within the glands.

5 alpha-dihydrotestosterone administration converts indolamine metabolism and porphyrin content of the female Syrian hamster Harderian gland to the male type.

The effects of ovariectomy and exogenous androgen administration on the indole and porphyrin metabolism of Syrian hamster Harderian glands were studied. Ovariectomy alone had no effect on any of the parameters analyzed. The administration of either testosterone or 5 alpha-dihydrotestosterone increased the activity of N-acetyltransferase in the Harderian glands.