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Background: This study investigates the relative expression of the Na+, HCO3- cotransport gene NBCn1, and caspase-3 within the tumor microenvironment of human breast cancer, considering the in vivo microenvironment. Method: In this experimental study, breast cancer MDA-MB-231 cells were cultured under normoxia/hypoxia conditions for 24, 48, and 72 hours with varying glucose concentrations (5.5, 11, and 25 mM). The mRNA expression of NBCn1 and caspase-3 was evaluated using real-time polymerase chain reaction. The stability and binding pocket of NBCn1 were assessed using DispHred and the Computed Atlas of Surface Topography of proteins (CASTp) servers, respectively. The location prediction of the protein was determined using the Transmembrane Helices; Hidden Markov Model (TMHMM) server. Results: Normoxia led to an increase in NBCn1 expression during all three time periods, displaying heterogeneity. The expression was particularly elevated at glucose concentrations of 25 and 5.5 mM. In hypoxic conditions, gene expression was reduced; however, an increase in glucose concentration enhanced SLC4A7 expression. Specifically, a glucose concentration of 25 mM led to decreased caspase-3 expression under hypoxic conditions. In silico studies revealed that SLC4A7 becomes disordered when the pH falls below 7, with most amino acids in the binding pocket being nonpolar. Conclusion: The heightened risk of breast cancer metastasis may be linked to the upregulation of SLC4A7 and downregulation of caspase-3 expression, underscoring their fundamental roles in cancer treatment and prevention. SLC4A7 is a transmembrane protein, and its folding is pH-dependent. [ABSTRACT FROM AUTHOR]

Brucellosis is a momentous zoonotic disease. Unpasteurized milk and milk products are the leading sources of Brucella transmission to humans. The present research was conducted to investigate the contamination of local crumbled Kope cheeses distributed in Urmia city with Brucella species and evaluate the antibiotic -resistance pattern of the isolates. Fifty samples of local cow’s Kope cheese were randomly collected from traditional dairy retailers in different regions of Urmia by sterile conditions in 2022. The samples were cultured in Brucella enrichment broth and then in Brucella selective agar with a supplement. Molecular identification of Brucella spp. was done using specific primers by polymerase chain reaction (PCR). Antimicrobial susceptibility testing on the isolates was performed by the Kirby -Bauer disc diffusion method. Among the tested samples, two samples were contaminated with Brucella (4%). One was contaminated with B. abortus bv. 1, 2, and 4 (2%), and the other with B. melitensis (2%). The isolates were sensitive to azithromycin, imipenem, doxycycline, rifampin, and co -trimoxazole antibiotics and were resistant to ampicillin, amoxicillin -clavulanic acid, tetracycline, gentamicin, and ceftriaxone antibiotics. Also, the B. abortus strain was sensitive to ciprofloxacin, but the B. melitensis strain was resistant. The isolates showed multi -drug resistance (MDR) characteristics. From the findings, it can be concluded that Brucella contamination in local Kope cheeses distributed in Urmia city is low; However, due to the high pathogenicity of B. melitensis for humans, it is recommended to screen infected cows, vaccinate sheep and goat herds, and prevent the supply of unpasteurized milk and milk products. It is also recommended to evaluate azithromycin and imipenem antibiotics along with other common antibiotics in brucellosis. [ABSTRACT FROM AUTHOR]