Low temperature and mTOR inhibition favor stem cell maintenance in human keratinocyte cultures.

Adult autologous human epidermal stem cells can be extensively expanded ex vivo for cell and gene therapy. Identifying the mechanisms involved in stem cell maintenance and defining culture conditions to maintain stemness is critical, because an inadequate environment can result in the rapid conversion of stem cells into progenitors/transient amplifying cells (clonal conversion), with deleterious consequences on the quality of the transplants and their ability to engraft. Here, we demonstrate that cultured human epidermal stem cells respond to a small drop in temperature through thermoTRP channels via mTOR signaling. Exposure of cells to rapamycin or a small drop in temperature induces the nuclear translocation of mTOR with an impact on gene expression. We also demonstrate by single-cell analysis that long-term inhibition of mTORC1 reduces clonal conversion and favors the maintenance of stemness. Taken together, our results demonstrate that human keratinocyte stem cells can adapt to environmental changes (e.g., small variations in temperature) through mTOR signaling and constant inhibition of mTORC1 favors stem cell maintenance, a finding of high importance for regenerative medicine applications.

Effect of Thermal Processing on Physicochemical and Antioxidant Properties of Raw and Cooked Moringa oleifera Lam. Pods.

Moringa is regarded as a miracle tree because all components of the plant, including the roots, leaves, pod, and flowers, have significant nutritional and therapeutic value. Moringa oleifera Lam. pods have excellent antioxidant characteristics and are a good source of protein, carbohydrate, fat, vitamins, beta-carotene, amino acids, and phenolic compounds. The pods of Moringa oleifera Lam. were collected from the local market of Sunamganj, and their nutritional value was assessed in raw condition and after thermal processing. The goal of this research was to observe how the thermal temperature affected the antioxidant and physicochemical qualities of thermally-processed Moringa oleifera Lam. pods. Thermal treatment diminished the amount of crude protein, fat, carbohydrate, ash, ascorbic acid, and beta-carotene in the pods, as well as DPPH, total phenol content, and total flavonoid content. The moisture percentage of raw and thermally-processed Moringa oleifera Lam. pods was determined to be 83.12%, 86.03% with a total ash level of 2.01%, and 1.8%, respectively. The crude protein, fat content, and carbohydrate were 3.0%, 0.1%, and 3.2%, respectively, in thermally-processed pods. The values for total phenol content, total flavonoid content, vitamin C, DPPH free radical scavenging activity, and ß-carotene were 28.13 mg, 2.98 mg, 38.23%, 3.98 mg, and 0.12 mg, respectively, in raw samples whereas 24.56 mg, 2.72 mg, 3.50 mg, 34.32%, and 0.0904 mg, respectively, in thermally-processed samples. According to the findings, Moringa oleifera Lam. pods have high nutritional content and thus can be used as an excellent source of diet, and even after thermal processing, a significant nutritive value remains in the Moringa oleifera Lam. pods.

Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation.

Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition.