Blocking SIG1R Along with Low Cadmium Exposure Display Anti-cancer Qualities in Both MCF7 and MDA-MB-231 Cells.

Sigma-1 receptor (SIG1R) is a chaperone that modulates inositol 1,4,5-trisphosphate receptor type1 (IP3R1) calcium (Ca2+) channels on the endoplasmic reticulum. Therefore, SIG1R functions as an indirect regulator of Ca2+ and acts as an apoptosis modulator. Increased expression of SIG1R is associated with poor prognosis in breast cancers (BC), and SIG1R antagonists like BD1047 induce apoptosis. As a heavy metal, cadmium (Cd2+) is competitive with Ca2+ due to its physicochemical similarities and may trigger apoptosis at low concentrations. Our study investigated the SIG1R protein expression in 74 BC patients and found a significant increase in SIG1R expression in the triple-negative BC subtype. We also examined the apoptotic and anti-cancer effects of BD1047 in combination with CdCl2 in MCF7 and MDA-MB-213 cells. Cells were treated with CdCl2 at doses of 1 µM, 25 µM, and 50 µM, along with BD1047. Higher doses of CdCl2 were cytotoxic on both cancer cells and significantly increased DNA breaks. However, low-dose CdCl2 with BD1047 increased cell death and the apoptotic index in BC cells, although it did not exhibit cytotoxic effects on HUVEC cells. Co-administration of low-dose CdCl2 with BD1047 also reduced the migration and colony-forming ability of BC cells. Moreover, the expression of SIG1R protein in these groups decreased significantly compared to groups treated with BD1047 or low-dose CdCl2 alone. In conclusion, low-dose CdCl2 is thought to increase the apoptotic ability of BD1047 in BC cells by reducing SIG1R expression.

Clinical assessment of epidural analgesia induced by xylazine-lidocaine combination accompanied by xylazine sedation in calves.

: The aim of the present study was to investigate whether epidural administration of a xylazine-lidocaine combination accompanied by xylazine sedation would provide satisfactory analgesia for some surgical procedures on 10 calves admitted to the Department of Veterinary Surgery, University of Kafkas with perineal urolithiasis (n:2), rectovaginal fistula (n:1), atresia ani (n:2), omphalophlebitis (n:2), omphaloarteritis (n:1) and umbilical hernia (n:2).Following intramuscular injection of xylazine at a dose of 0.05 mg/kg for sedation, xylazine-lidocaine combination (0.2 mg/kg lidocaine + 0.02 mg/kg xylazine + 5 ml 0.9% NaCl) was administrated into the lumbosacral (L6-S1), sacrococcygeal (S5-Co1) or intercoccygeal (Co1-Co2) space. Heart rate, respiratory rate and rectal temperature were recorded prior to and during analgesia at 5, 10, 15, 30 and 60 minutes. Furthermore, depth and duration of analgesia were evaluated during surgical intervention.The study revealed that the combination of epidural xylazine-lidocaine with xylazine sedation was highly satisfactory for surgery of the lower urinary tract and the perineal region, but it was less so for surgery of the umbilical area.