Effects of Different Feed Additives on Intestinal Metabolite Composition of Weaned Piglets.

To study the effects of different feed additives on the weaning stress of Tibetan piglets, we selected 28 healthy, 30-day-old Tibetan weaned piglets and divided them into four groups, namely, the control group (basal feed without any antibiotic additions) (Nor), the group with the addition of the antibiotic lincomycin (Ant), the group with the addition of fifteen-flavor black pills of Tibetan medicine (Tib), and the group with the addition of fecal bacterial supernatant (Fec). We measured growth performance, blood physiological indexes, and metabolomics. The results showed that the Ant, Tib, and Fec groups significantly reduced the ratio of diarrhea to feed/weight (F/G) and increased the average daily gain (ADG) compared with the Nor group (p < 0.01). The Nor group had significantly lower leukocyte counts, hemoglobin levels, and erythrocyte counts compared with the other three groups at 21 d (p < 0.05). These physiological indexes tended to stabilize at 42 d. We found that there were beneficial metabolites and metabolic pathways for gastrointestinal function. Specifically, the porphyrin metabolic pathway was elevated in the Ant group, and the tryptophan metabolic pathway was significantly elevated in the Tib and Fec groups compared with the Nor group (p < 0.05). In conclusion, adding fecal bacterial supernatant and fifteen-flavor black pills of Tibetan medicine to the feed reduced the rate of diarrhea and improved the growth performance of the piglets. Moreover, it had an effect on the microorganisms and their metabolites and pathways in the gastrointestinal tract of the animals, which might be the main reason for influencing the diarrhea rate of weaned Tibetan piglets and the growth and development of the piglets. This study provides a new approach for anti-stress applications in weaned Tibetan piglets and the development of substitute anti-products.

Efficacy and safety of oral gonadotropin-releasing hormone antagonists in moderate-to-severe endometriosis-associated pain: a systematic review and network meta-analysis.

PURPOSE: The aim of this NMA is to comprehensively analyze evidence of oral GnRH antagonist in the treatment of moderate-to-severe endometriosis-associated pain. METHODS: Literature searching was performed to select eligible studies published prior to April 2022 in PubMed, Cochrane, Embase and Web of Science. Randomized controlled trials involving patients who suffered from moderate-to-severe endometriosis-associated pain and treated with oral nonpeptide GnRH antagonists or placebo were included. RESULTS: Elagolix 400 mg and ASP1707 15 mg were most efficient in reducing pelvic pain, dysmenorrhea and dyspareunia. Relugolix 40 mg was best in reducing the analgesics use. The rates of any TEAEs and TEAEs-related discontinuation were highest in relugolix 40 mg and elagolix 250 mg, respectively, while rates of hot flush and headache were highest in relugolix 40 mg and elagolix 150 mg. Significantly decreased spinal BMD was observed in elagolix 250 mg. CONCLUSION: Oral GnRH antagonists were effective in endometriosis-associated pain in 12w, and most of the efficiency and safety outcomes were expressed in a dose-dependent manner, but linzagolix 75 mg was an exception.

Dimethyl Sulfoxide is Less Effective in Immersing Cryopreserved Large Pieces of Tissue: A Rabbit Hind-Limb Model.

BACKGROUND Dimethyl sulfoxide (DMSO) cryoprotectant can effectively alleviate the damage to single tissue during cryopreservation and restore its physiological activity after rewarming. However, studies have not been successful for preserving large tissue. This study aimed to investigate the application conditions of DMSO in large composite-tissue by performing femoral artery perfusion and soaking in a rabbit hind-limb model. MATERIAL AND METHODS A microdialysis-freezing point osmometer was used to detect the minimum time required for effective perfusion of 10% v/v perfusion and 20% v/v perfusion group. Magnetic resonance spectroscopy (MRS) was used to detect the area under the spectrum peak of DMSO in perivascular, intramuscular, subcutaneous areas, and compare the area under the spectrum peak in the 20% vascular perfusion group and other whole immersion groups. RESULTS The minimum time required for effective perfusion of muscle in the 10% v/v group was 30 minutes, the DMSO concentration was stable at 5% v/v; In the 20% v/v group the minimum time was at 20 minutes, stable at 12% v/v. There was a statistically difference of the area under the spectrum peak in the 10% group and the 20% v/v group after vascular perfusion in different tissue locations (P<0.05). The 20% vascular perfusion group and the different concentration of DMSO in the large tissue soaking group were statistically different (P<0.05). There was a significant difference in the 20% v/v vascular perfusion group compared to the low concentration immersion group, but no difference compared to the 50% immersion group. CONCLUSIONS The effect of blood perfusion on cryopreservation in large tissue by using DMSO was slightly better than overall soaking, especially in preservation of skin and subcutaneous tissue.

Breast cancer cells promote osteoblastic differentiation via Sema 3A signaling pathway in vitro.

Breast cancer bone metastases are attributed to multiple cellular and molecular interactions between the cancer cells and the bone microenvironment. Some breast cancers (about 10%) manifest predominant osteoblastic bone metastases. However, the effects of cancer cell-produced factors on osteoblastic differentiation are not fully understood. Semaphorin 3A (Sema 3A) is a newly identified regulatory factor of bone rebuilding. In the present study, we demonstrated that human breast cancer MCF-7 cells, which preferentially form osteoblastic bone metastases, exhibited increased Sema 3A expression levels. We also found that MCF-7 cell-derived Sema 3A stimulated osteoblastic differentiation and nuclear ß-catenin accumulation, and these effects could be blocked by shRNA Sema 3A or a Sema 3A-neutralizing antibody. In conclusion, our data suggest that MCF-7 cell-derived Sema 3A plays a causative role in osteoblastic bone metastases progression by stimulating osteoblastic differentiation.

Prostate cancer cells induce osteoblastic differentiation via semaphorin 3A.

BACKGROUND: Prostate cancer metastasis to bone is the second most commonly diagnosed malignant disease among men worldwide. Such metastatic disease is characterized by the presence of osteoblastic bone lesions, and is associated with high rates of mortality. However, the various mechanisms involved in prostate cancer-induced osteoblastic differentiation have not been fully explored. Semaphorin 3A (Sema 3A) is a newly identified regulator of bone metabolism which stimulates differentiation of pre-osteoblastic cells under physiological conditions. We investigated in this study whether prostate cancer cells can mediate osteoblastic activity through Sema 3A. METHODS: We cultured osteoprogenitor MC3T3-E1 cells in prostate cancer-conditioned medium, and analyzed levels of Sema 3A protein in diverse prostate cancer cell lines to identify cell lines in which Sema 3A production showed a positive correlation with osteo-stimulation. C4-2 cells were stably transfected with Sema 3A short hairpin RNA to further determine whether Sema 3A contributes to the ability of C4-2 cells to induce osteoblastic differentiation. RESULTS: Down-regulation of Sema 3A expression decreased indicators of C4-2 CM-induced osteoblastic differentiation, including alkaline phosphatase production and mineralization. Additionally, silencing or neutralizing Sema 3A in C4-2 cells resulted in diminished ß-catenin expression in osteogenitor MC3T3-E1 cells. CONCLUSIONS: Our results suggest that prostate cancer-induced osteoblastic differentiation is at least partially mediated by Sema 3A, and may be regulated by the ß-catenin signalling pathway. Sema 3A may represent a novel target for treatment of prostate cancer-induced osteoblastic lesions.