Protease-activated receptor 2 expression in the mammary gland tissues in correlation with mastitis severity in goats

Mastitis is a common disease in small ruminant industry. The present study aimed to determine the presence of protease activated receptor-2 (PAR2) mRNA expression in the mammary gland of mastitis challenged goats. 30 clinically healthy mix breed lactating goats were divided into three groups, consisting of Staphylococcus aureus (Group 1), methicillin-resistant S. aureus (Group 2) and sterile phosphate-buffered saline (Control) groups. The data regarding physical condition of udder and clinical parameters of goats were recorded while milk samples and mammary gland tissues were collected at 24 and 48 hours post infection. Somatic cell count (SCC) was measured by direct microscopic method. The presence of PAR2 mRNA in the mammary gland tissue samples was detected by real-time PCR. Goats from group 1 developed mild to moderate clinical signs while Group 2 exhibited moderate to severe clinical signs. SCC was higher in both challenged groups than control group. PAR2 mRNA expression was detected in all mammary gland samples from Group 1 and Group 2. The gene expression was significantly highly in mammary gland tissue with severe clinical signs. The finding of PAR2 expression in caprine mammary gland is novel and important, suggesting serine proteases involved the development of mastitis in goat.

Malaria in the postpartum period causes damage to the mammary gland

Mastitis is an inflammation of the mammary gland in the breast and is typically due to bacterial infection. In malaria-endemic areas, mastitis with accompanying fever can be challenging to differentiate from malaria. At the same time, it is unclear whether malaria infection is directly involved in the development of mastitis. In the present study, whether mastitis develops during infection with malaria parasites was investigated using a rodent malaria model with Plasmodium berghei (P. berghei; Pb) ANKA. The course of parasitemia in postpartum mice infected with Pb ANKA was similar to the course in infected virgin mice. However, infected postpartum mice died earlier than did infected virgin mice. In addition, the weight of pups from mice infected with Pb ANKA was significantly reduced compared with pups from uninfected mice. The macroscopic and histological analyses showed apparent changes, such as destruction of the alveolus wall and extensive presence of leukocytes, in mammary gland tissue in mice infected during the postpartum period. The findings suggest that women during the postpartum period are more vulnerable to complications when infected with malaria parasites, particularly women who do not acquire protective immunity against malaria parasites. Based on the proteomic analysis, IFN-γ signaling pathway-related proteins in mammary gland tissue of the infected postpartum mice were increased. Our results indicate that inflammation induced by IFN-γ, a proinflammatory cytokine, may contribute to negative histological changes in mammary gland tissue of postpartum mice infected with Pb ANKA. In IFN-γ receptor 1-deficient (IFNGR1-KO) mice, the histological changes in mammary gland tissue of the infected postpartum wild-type mice were improved to almost normal mammary gland structure. Furthermore, weight loss in pups delivered by infected IFNGR1-KO postpartum mice was not observed. Taken together, these findings indicate that inflammation induced by IFN-γ is associated with development of mastitis in postpartum mice infected with Pb ANKA. The present study results may increase our understanding of how disease aggravation occurs during postpartum malaria.

Directed Expression of Tracheal Antimicrobial Peptide as a Treatment for Bovine-Associated Staphylococcus Aureus-Induced Mastitis in Mice

Bovine mastitis is perplexing the dairy industry since the initiation of intensive dairy farming, which has caused a reduction in the productivity of cows and an escalation in costs. The use of antibiotics causes a series of problems, especially the formation of bacterial antimicrobial resistance. However, there are limited antibiotic-free therapeutic strategies that can effectively relieve bacterial infection of bovine mammary glands. Hence, in this study, we constructed a mammary gland tissue-specific expression vector carrying the antimicrobial peptide of bovine-derived tracheal antimicrobial peptide (TAP) and evaluated it in both primary bovine mammary epithelial cells (pBMECs) and mice. The results showed that the vector driven by the β-lactoglobulin gene (BLG) promoter could efficiently direct the expression of TAP in pBMECs and the mammary gland tissue of mice. In addition, significant antibacterial effects were observed in both in vitro and in vivo experiments when introducing this vector to bovine-associated Staphylococcus aureus-treated pBMECs and mice, respectively. This study demonstrated that the mammary gland tissue-specific expression vector could be used to introduce antimicrobial peptide both in in vitro and in vivo and will provide a new therapeutic strategy in the treatment of bovine mastitis.

IMPACT OF HYPOXIA AND INFECTION ON THE MORPHOLOGY OF THETHYROID GLAND

The investigation aimed to study the microscopic features of the thyroid gland under the influence of barochamber hypoxia and staphylococcal infection in the experiment. Materials and methods of the study. During the study 30 healthy adult male white rats weighing 180–200 g were used. Morphological features of the gland were studied by histological methods. Results of the study. Analysis of the study results shows that morphological changes occurring in the thyroid gland cells are more pronounced in animals of the infectious group than in animals of the hypoxia group. Thus, under the influence of infection, atrophic changes prevail in the gland tissue, and under the influence of hypoxia, hyperplasia, and hypertrophy, proliferation and differentiation of gland cells are observed. This can be considered a structural reconstruction of the gland tissue and its adaptation to new conditions.

Dietary nitrate supplementation prevents radiotherapy-induced xerostomia

Management of salivary gland hypofunction caused by irradiation (IR) therapy for head and neck cancer remains lack of effective treatments. Salivary glands, especially the parotid gland, actively uptake dietary nitrate and secrete it into saliva. Here, we investigated the effect of dietary nitrate on the prevention and treatment of IR-induced parotid gland hypofunction in miniature pigs, and elucidated the underlying mechanism in human parotid gland cells (hPGCs). We found that nitrate administration prevented IR-induced parotid gland damage in a dose-dependent manner, by maintaining the function of irradiated parotid gland tissue. Nitrate could increase sialin expression, a nitrate transporter expressed in the parotid gland, making the nitrate-sialin feedback loop that facilitates nitrate influx into cells for maintaining cell proliferation and inhibiting apoptosis. Furthermore, nitrate enhanced cell proliferation via the epidermal growth factor receptor (EGFR)-protein kinase B (AKT)-mitogen-activated protein kinase (MAPK) signaling pathway in irradiated parotid gland tissue. Collectively, nitrate effectively prevented IR-induced xerostomia via the EGFR–AKT-MAPK signaling pathway. Dietary nitrate supplementation may provide a novel, safe, and effective way to resolve IR-induce xerostomia.

High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing.

The mammary gland undergoes hormonally stimulated cycles of proliferation, lactation and involution. We hypothesized that these factors increase the mutational burden in glandular tissue and may explain high cancer incidence rate in the general population and recurrent disease. Hence, we investigated the DNA sequence variants in the normal mammary gland, tumor and peripheral blood from 52 reportedly sporadic breast cancer patients, including breast-conserving surgery cases. Targeted resequencing of 542 cancer associated genes revealed mosaic somatic pathogenic variants of: PIK3CA, TP53, AKT1, MAP3K1, CDH1, RB1, NCOR1, MED12, CBFB, TBX3 and TSHR in the normal mammary gland, at considerable allelic frequencies (9x10-2 to 5.2x10-1) indicating clonal expansion. Further evaluation of the frequently damaged PIK3CA and TP53 genes by ultra-sensitive duplex sequencing demonstrated a diversified picture of multiple low level-mosaic (in 10-2 to 10-4 alleles) hotspot pathogenic variants. Our results raise a question about the oncogenic potential in non-tumor mammary gland tissue of breast-conserving surgery patients.

Organoid Models for Salivary Gland Biology and Regenerative Medicine

The salivary gland is composed of an elegant epithelial network that secrets saliva and maintains oral homeostasis. While cell lines and animal models furthered our understanding of salivary gland biology, they cannot replicate key aspects of the human salivary gland tissue, particularly the complex architecture and microenvironmental features that dictate salivary gland function. Organoid cultures provide an alternative system to recapitulate salivary gland tissue in vitro, and salivary gland organoids have been generated from pluripotent stem cells and adult stem/progenitor cells. In this review, we describe salivary gland organoids, the advances and limitations, and the promising potential for regenerative medicine.