A Senescence-Associated Secretory Phenotype of Bone Marrow Mesenchymal Stem Cells Inhibits the Viability of Breast Cancer Cells.

Breast cancer, the most prevalent malignancy in women, often progresses to bone metastases, especially in older individuals. Dormancy, a critical aspect of bone-metastasized breast cancer cells (BCCs), enables them to evade treatment and recur. This dormant state is regulated by bone marrow mesenchymal stem cells (BMMSCs) through the secretion of various factors, including those associated with senescence. However, the specific mechanisms by which BMMSCs induce dormancy in BCCs remain unclear. To address this gap, a bone-specific senescence-accelerated murine model, SAMP6, was utilized to minimize confounding systemic age-related factors. Confirming senescence-accelerated osteoporosis, distinct BMMSC phenotypes were observed in SAMP6 mice compared to SAMR1 counterparts. Notably, SAMP6-BMMSCs exhibited premature senescence primarily due to telomerase activity loss and activation of the p21 signaling pathway. Furthermore, the effects of conditioned medium (CM) derived from SAMP6-BMMSCs versus SAMR1-BMMSCs on BCC proliferation were examined. Intriguingly, only CM from SAMP6-BMMSCs inhibited BCC proliferation by upregulating p21 expression in both MCF-7 and MDA-MB-231 cells. These findings suggest that the senescence-associated secretory phenotype (SASP) of BMMSCs suppresses BCC viability by inducing p21, a pivotal cell cycle inhibitor and tumor suppressor. This highlights a heightened susceptibility of BCCs to dormancy in a senescent microenvironment, potentially contributing to the increased incidence of breast cancer bone metastasis and recurrence observed with aging.

Region-specific sympatho-adrenergic regulation of specialized vasculature in bone homeostasis and regeneration.

Type H vessels couple angiogenesis with osteogenesis, while sympathetic cues regulate vascular and skeletal function. The crosstalk between sympathetic nerves and type H vessels in bone remains unclear. Here, we first identify close spatial connections between sympathetic nerves and type H vessels in bone, particularly in metaphysis. Sympathoexcitation, mimicked by isoproterenol (ISO) injection, reduces type H vessels and bone mass. Conversely, beta-2-adrenergic receptor (ADRB2) deficiency maintains type H vessels and bone mass in the physiological condition. In vitro experiments reveal indirect sympathetic modulation of angiogenesis via paracrine effects of mesenchymal stem cells (MSCs), which alter the transcription of multiple angiogenic genes in endothelial cells (ECs). Furthermore, Notch signaling in ECs underlies sympathoexcitation-regulated type H vessel formation, impacting osteogenesis and bone mass. Finally, propranolol (PRO) inhibits beta-adrenergic activity and protects type H vessels and bone mass against estrogen deficiency. These findings unravel the specialized neurovascular coupling in bone homeostasis and regeneration.

[Analysis of hydroxylation and O-glycosylation on lysine sites in deer-hide gelatin].

Nano-LC MS/MS was used to analyze trypsin digested deer-hide gelatin(DHG) samples, hydroxylation and O-glycosylation on lysine sites of DHG were comprehensive identified by using PEAKS Studio software. The sites, sorts and amounts of hydroxylation and O-glycosylation on Type Ⅰ collagen α1 chain(COL1 A1) and α2 chain(COL1 A2) of DHG were revealed. As a result, 5 284 peptides were identified from DHG samples, which were mainly from COL1 A1 and COL1 A2. Among these peptides, there were 449 peptides with hydroxylysine, 442 with galactosyl-hydroxylysine, 449 with glucosyl-galactosyl-hydroxylysine. The major modified sites of hydroxylation and O-glycosylation in DHG were shown as follow: α1-9 N and α2-5 N in N-telopeptides, α1-87, α1-174, α1-930, α2-87, α2-174, α2-933 in triple helix domain, and α1-16 C in C-telopeptides. These hydroxylation and O-glycosylation were correlated with the formation and stability of collagen molecules and collagen fibrils. It is feasible for the collagens and peptides dissolving from deer skin collagen fibrils under high temperature and pressure decocting, high temperature and pressure also might destroy inter-molecular covalent cross-linking and help those glycol-peptides formations. The present study provided ideas and strategies for the in-depth investigation on DHG chemical constituents, and showed good theoretical significance and application value.

[Herbalogical study on Cervi Colla].

Cervi Colla, deer's gelatin, had two kinds of original sources historically, including the skin and antler of deer, known as Cervi Corii Colla(Lupijiao, LPJ) and Cervi Cornus Colla(Lujiaojiao, LJJ) respectively.LJJ is the mainstream of the market, while LPJ is only used by common people in Guizhou and Jilin etc. This article sorted out the ancient and modern literature(since Rites of the Zhou in Zhou Dynasty) on Cervi Colla and conducted the herbalogical study. The results of the study include:① In ancient China, there were six types of commonly-used Colla derived from six animals, including deer, horse, cow, rat, fish and rhinoceros. Cervi Colla was ranked the most top among them, and it was often used as adhesive to make bow and Chinese inksticks and more commonly used as a medicine.Cervi Cornus Colla was first described as a medicinal by the name "Bai Jiao"(white gelatin)in The Divine Husbandman's Classic of Material Medica(Shen Nong Ben Cao Jing).② Initially, both the skin and antler were used as raw materials to make Cervi Colla, but antler became the only raw material, and deer skin disappeared from the mainstream of raw materials for Cervi Colla. This can be attributed to other diverse and luxurious uses of the skin, such as making dress and hats, etc., and the easy accessibility of deer antlers. ③ The sources of Cervi Colla were not limited to Cervus elaphus(red deer) or C. nippon(sika deer), and it also included animal from the family Cervidae, such as Elaphurus davidianus(elk) and C. unicolor(sambar). ④ The processing method was passed down from ancient times to the present, and no significant changes had occurred. ⑤ LPJ and LJJ had many similar effects, and their nature was both warm. The effect of LJJ was to warm the liver and kidney, replenish vital essence and blood, and to reinforce Yang. While the effect of LPJ was to reinforce both Yin and Yang, replenish blood, and stop bleeding. It has a unique advantage for both reinforcing Yin and Yang. The findings of this paper can provide support for the promotion of LPJ and the development of its medicinal value.

[Comparative study on four major active compounds of Sanvitalia procumbens and Chrysanthemum morifolium cv 'Hangju' and 'Gongju'].

The contents of chlorogenic acid, 3,5-O-caffeoylquinic acid, galuteolin and quercitrin in Sanvitalia procumbens and Chrysanthemum morifolium cv. 'Hangju' and 'Gongju' were determined by RP-HPLC. The main active ingredient of S. procumbens was similar to C. morifolium cv. 'Hangju' and 'Gongju'. The content varied significantly. The contents of chlorogenic acid, quercitrin and galuteolin in S. procumbens were 7.46, 46.58, 26.01 mg x g(-1), respectively, and they were the highest among the samples. The content of 3,5-O-caffeoylquinic acid in C. morifolium cv. 'Hangju' was 14.70 mg x g(-1), it was the highest among the samples. The data of the study provide a basis for further research and development of S. procumbens.