Search Results (588)

In dairy cows, teat keratinization occurs where keratinized tissue rings form around teat tips (opening). Manifesting as skin damage in mechanically milked dairy cows, keratinization presents as dry, rough, pale, or milky-white keratinous protrusions around teat orifices and progresses via the combined effects of mechanical stress, management practices, host genetics, environmental influences, and nutritional metabolism. The teat hole is the first physiological barrier protecting the mammary glands from external pathogen invasion. Most mastitis cases are caused by pathogens invading the mammary tissues from the teat end, thereby significantly impacting mammary gland health. Thus, there are no safe, effective, economical, and standardized treatment protocols for terminal teat hyperkeratosis in dairy cows. To address this, we treated keratinization lesions using pharmacological interventions and evaluated their efficacy in 91 cows at a large commercial dairy farm in Heilongjiang Province. Urea ointment, salicylic acid ointment, and 5% azelaic acid acne cream exerted therapeutic or alleviating effects toward teat keratosis, whereas retinoic acid ointment demonstrated poor therapeutic efficacy. In a three-daily application regimen, the optimal treating dose was 0.3 g. These findings provide a scientific basis for the clinical management of hyperkeratosis in large-scale dairy farms and the development of related veterinary therapeutics. Full article

The incidence of cancer in young adults has risen worldwide. Women comprise a disproportionate share of young-onset cases, among whom breast cancer predominates. This shift parallels globalization and urbanization, including the wider adoption of Western-pattern diets. Although hereditary syndromes explain a minority of cases, the secular rise underscores the impact of modifiable exposures, particularly diet. Prenatal life, neonatal life, childhood, adolescence, and early adulthood are critical periods during which dietary exposures may shape long-term mammary development. Mammary tissue undergoes rapid proliferation and differentiation during development, creating windows of heightened susceptibility to carcinogenic insults. However, most existing studies emphasize dietary exposures during a single developmental period; the entire span of critical developmental windows plays a formative role in shaping young-onset breast cancer (YoBC) risk, and the mechanisms underlying this life-course shaping remain insufficiently characterized. This review comprehensively synthesizes evidence on how nutrition across sensitive developmental windows shapes the risk of YoBC. We evaluate protective and adverse dietary factors within these stages and examine mechanistic pathways linking early-life nutrition to carcinogenesis, focusing on hormonal regulation, epigenetic programming, chronic inflammation, and the gut microbiome. A structured literature search was conducted in PubMed, Embase, and Web of Science for English-language articles published from 1990 through May 2026, supplemented by hand-searching of relevant reviews and key primary studies. By framing nutrition and breast cancer through a life-course lens, this review provides an integrated foundation for stage-specific prevention strategies and identifies priority directions for future research on early-life dietary determinants of YoBC. Full article

Heat stress (HS) is at the top of the challenges facing modern dairy production, with annual losses according to global projections, under high-emission scenarios, reaching US$14.7–40.0 billion by the end of the century. This review emphasizes three interconnected topics that account for most of the proportion of the productive and reproductive losses during HS. First, the physiological consequences of HS are reviewed, with emphasis on the pair-fed thermal neutral (PFTN) paradigm, which established that reduced dry matter intake (DMI) accounts for only 35–50% of the observed milk yield decline, with the remainder arising from tissue-level effects of hyperthermia on mammary function, metabolism, and reproductive performance. Second, HS-induced microbiome disruption is examined as an active pathophysiological amplifier, whereby rumen dysbiosis compromises intestinal barrier integrity and drives systemic endotoxaemia, chronically amplifying the immune suppression already imposed by the thermal insult. Third, we focus on the integration of multi-omics platforms as a management approach, since single-omics analyses capture only a fraction of the biological complexity underlying the HS response. As the available datasets expand in coverage and scale, their integration through AI-driven analytical frameworks has the potential to substantially advance beyond the current fragmented picture, progressively building toward a systems-level model of thermal stress. Evidence-based mitigation strategies spanning environmental cooling, targeted nutritional supplementation, and genomic selection are critically evaluated within this framework, with emphasis on equity of access to evidence-based solutions across global dairy production systems. Full article

The mammary gland is a heterogeneous organ that modulates ductal morphogenesis and alveolar differentiation. Obesity is a significant risk factor for several cancers, including postmenopausal breast cancer. We and others have described an association between obesity and increased breast cancer growth. However, the effects of obesity on the mammary fat pad microenvironment (MFPME) remain understudied. Here, we investigated the effect of the Western Diet (WD) on immunocompetent female mice and on their MFPME. Our data suggest that the WD increased body, liver, and perigonadal white adipose tissue (pWAT) weight, as well as myeloid cell infiltration into these tissues. Interestingly, we did not find any significant change in CD4⁺ and CD8⁺ T cells in the liver, blood, and pWAT. NanoString data demonstrates that various cellular processes, including the complement system, innate immune system, phagocytic activity, immune metabolism, and NOD-like receptor (NLR) signaling, were upregulated in the MFPME of obese mice. RNA-Seq data suggest that WD significantly modulated MFPME physiology through regulation of gene expression, cellular processes, and signaling pathways. Further investigation is necessary to determine how WD-mediated changes in MFPME modulate breast cancer biology. Full article

Background and Clinical Significance: Hidradenitis suppurativa (HS) is a chronic, debilitating skin disorder that often affects the inframammary fold (IMF). While surgical management, particularly wide local excision (WLE), is the gold standard for severe cases, less is known about the role of breast surgery techniques in treating HS in this area; Case Presentation: This report presents two cases of female patients with bilateral inframammary HS and mammary hypertrophy, both treated with reduction mammaplasty to excise diseased tissue while addressing breast volume and contour. Both patients had experienced inadequate response to medical therapies, including biologic treatments, and presented with distinct clinical features—one with significant asymmetry and active disease, and the other with more scarring and hypertrophic lesions. During follow-up, no recurrence of disease was observed and both patients reported improved breast appearance and satisfaction; Conclusions: These cases underscore the importance of a multidisciplinary approach, with dermatologists and surgeons both playing a key role in the management of this complex condition. Full article

Mastitis is one of the most prevalent diseases in dairy cows, leading to significant economic losses and increased antibiotic usage. The development of safe and effective alternatives is therefore urgently needed. In this study, we investigated the protective effects of Forsythiaside A (FTA), a natural compound, against LPS-induced mastitis in bovine mammary epithelial (MAC-T) cells and a murine model. FTA significantly reduced intracellular reactive oxygen species (ROS), decreased lipid peroxidation, and restored antioxidant capacity. Furthermore, FTA increased the expression of GPX4 and SLC7A11, indicating inhibition of ferroptosis. The ferroptosis inducer RSL3 partially reversed these protective effects, supporting the involvement of GPX4-associated ferroptosis regulation in the protective effects of FTA. In vivo, FTA alleviated mammary tissue injury, reduced inflammatory cell infiltration, and improved redox balance. These findings suggest that FTA may serve as a potential natural therapeutic agent for mastitis, providing a promising alternative to antibiotic-based treatments in dairy production. Full article

Bovine mastitis is a persistent and challenging illness in dairy industry, bringing about devastating economic losses to the sector. The longstanding over-reliance on antibiotic therapy has raised severe public health concerns, highlighting the critical need to develop safe and effective alternative regimens. Pulsatilla saponin B4 (PSB4), a plant-derived triterpenoid saponin, has been shown to regulate inflammation. However, the effect of PSB4 on mastitis in lactating cows has not been elucidated. The aim of this study was to explore the anti-inflammatory property and the molecular mechanisms of PSB4 in bovine mammary epithelial cells (BMECs) and mouse mastitis model. In cultured cells, PSB4 alleviated LPS-induced inflammatory reaction by suppressing the expression of pro-inflammatory mediators in BMECs. Notably, RNA-seq analysis indicated that the anti-inflammatory effect of PSB4 was correlated with IL-17RA and NF-κB signaling, with subsequent Western blot validation. Moreover, BMECs were stimulated with recombinant interleukin-17A (rIL-17A) to induce inflammation and challenged with Taltz to specifically inhibit IL-17RA signaling. The results showed that PSB4 reversed the rIL-17A-induced upregulation of elements within the IL-17RA pathway and its downstream MAPK/NF-κB cascade, including their downstream effectors. Furthermore, Taltz blocked the efficacy of PSB4 in protecting against LPS-induced inflammation. In vivo, PSB4 alleviated the inflammatory damage of mammary gland, pro-inflammatory mediator levels in mammary gland tissue and se-rum, while blocking the activation of IL-17RA signal along with downstream MAPK/NF-κB signal in LPS-induced mouse mastitis model. Taken together, studies in both BMECs and mice demonstrated that PSB4 alleviates mastitis by inhibiting IL-17RA signaling and downstream MAPK/NF-κB pathway, which may be a new strategy and a target for the management of mastitis. Full article

Background: The insulin-like growth factor 1 receptor (IGF1R) is a receptor tyrosine kinase whose both overexpression and underexpression have been implicated in the initiation and progression of breast tumorigenesis. The mechanism through which underexpression of the receptor contributes to a more aggressive phenotype is currently less understood. Methods: Through the expression of a dominant-negative IGF1R, we studied the phenotypic effects of receptor inhibition on early MMTV-Wnt1 mouse mammary tumors. Utilizing histopathological techniques and single-cell RNA-sequencing, we explored cellular heterogeneity and transcriptional alterations that occur as a result of IGF1R inhibition. Results: Examination of primary tumors failed to reveal obvious differences in tissue architecture or expression of differentiation markers with IGF1R inhibition. Both cohorts of tumors produced metastatic lesions in the lung. Single-cell RNA-sequencing identified previously unknown epithelial subpopulations that were present in both tumor types. In tumors with inhibited IGF1R, a previously undescribed epithelial population marked by expression of both Krt14 and Krt6a was identified, transcriptionally distinct from its MMTV-Wnt1 counterpart, and present in the smallest lung metastases. In human breast cancer patients, expression levels of KRT14 and KRT6A negatively correlated with expression of IGF1R. Conclusions: Inhibition of the IGF1R in a mouse model of basal-like breast cancer produces transcriptionally distinct Krt6a⁺/Krt14⁺ epithelial cells, which are present in the smallest metastatic lesions identified in the lung. Expression of genes associated with this population may potentially be effective biomarkers of metastatic capacity in basal-like breast tumors with low levels of IGF1R expression. Full article

Zearalenone (ZEA) is a common contaminant in crops and animal feed. However, research on the effects of ZEA on animal mammary tissue is relatively limited. Sulforaphane (SFN) is a naturally active compound mainly derived from cruciferous vegetables (such as broccoli), with significant antioxidant and cytoprotective effects. The purpose of this study is the effect of SFN on ZEA-induced toxicity in bovine mammary epithelial cells (MAC-T). By treating MAC-T cells with different concentrations of ZEA and SFN for 24 h, the results showed that different concentrations of ZEA (10, 20, 40, 60, 80, or 100 μM) could inhibit MAC-T cell viability. Treatment with SFN at concentrations of 1, 2.5, and 5 μM had no significant effect on cell viability. The results of combined treatment with 10 μM ZEA and 1, 2.5, or 5 μM SFN showed that SFN could significantly reverse the decrease in cell viability caused by ZEA; reduce the increase in lactate dehydrogenase (LDH) release, reactive oxygen species (ROS), and malondialdehyde (MDA) content induced by ZEA; and increase the levels of glutathione (GSH), superoxide dismutase (SOD), and mitochondrial membrane potential that were decreased by ZEA. SFN can significantly inhibit the upregulation of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) induced by ZEA exposure and markedly reverse the increase in cell apoptosis rate caused by ZEA. Compared with the control group, the expression of genes nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase 1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (GCLM), and glutathione peroxidase 1 (GPX1) was significantly reduced in the ZEA group, while the addition of SFN effectively increased the expression levels of these genes. Corresponding protein detection results were consistent with the trends in gene expression. This study demonstrated that SFN alleviates ZEA-induced damage to MAC-T cells by activating the Nrf2 pathway, providing a theoretical basis for the subsequent application of SFN in dairy farming to prevent and control breast health risks related to mycotoxins. Full article

Although human mammary glands were traditionally considered sterile, accumulating evidence has established the presence of distinct microbial communities that may have colonized breast tissue primarily via retrograde nipple flow or via hematogenous or lymphatic translocation from other body sites. Comparative studies reveal differences in the microbiota of healthy and diseased breast tissues, with variations in microbial signatures across breast cancer subtypes and in comparison with adjacent normal tissues. This review synthesizes current evidence on the composition of the breast microbiome, the factors shaping its development, and alterations it undergoes in inflammatory and malignant breast diseases. Furthermore, the article discusses mechanistic insights, methodological challenges, and future therapeutic perspectives based on published studies employing culture-independent approaches, such as 16S rRNA gene sequencing and metagenomic analyses. Key host-related factors influencing breast-associated microbial communities, including hormonal regulation, environmental exposure, diet, and therapeutic interventions, are explored. The existing literature is assessed to identify key associations between the breast microbiome and host signaling pathways, as well as the significant challenges that remain unresolved, including low biomass contamination, inter-study variability, limited longitudinal data, and an incomplete understanding of causality. Addressing these limitations is critical for advancing microbiome-based diagnostic and therapeutic strategies for breast disease. Full article

Cadmium (Cd) is a ubiquitous heavy metal environmental toxicant, and exposure poses a persistent public health concern due to its bioaccumulative properties. However, the impact of maternal Cd exposure on mammary gland function during lactation remains insufficiently understood. In this study, we investigated the effects of Cd exposure during pregnancy and lactation on mammary gland development, hormonal homeostasis, and lactational performance using a drinking water exposure model. Pregnant 7-week-old ICR mice were randomly assigned into Control and Cd groups. The Control group received standard drinking water, while the Cd group was administered water supplemented with Cd (12 mg/L). Results demonstrated that maternal Cd exposure markedly reduced maternal and offspring weight, respectively. Histological analysis revealed that Cd exposure resulted in decreased numbers of mammary alveoli and widened interstitial spaces, indicating impaired mammary development. In addition, Cd exposure markedly compromised lactational performance, as reflected by reduced milk yield and decreased levels of milk protein, fat, and lactose across multiple lactation stages. Integrated metabolomic and transcriptomic analyses further revealed substantial alterations in hormonal profiles and metabolic pathways associated with mammary gland function. Notably, Cd accumulation was detected in mammary tissue and milk, accompanied by transcriptional changes in genes involved in milk synthesis and lipid metabolism. In conclusion, these findings indicated that maternal Cd exposure during pregnancy and lactation is associated with structural and functional alterations of the mammary gland, leading to reduced lactational performance and impaired offspring growth. The findings contribute to a better understanding of the risks posed by environmental Cd exposure, emphasizing the need for effective public health strategies to mitigate its impact on maternal and infant health. Full article

Bovine mastitis causes significant economic losses in the dairy industry. Emerging evidence highlights the critical role of long non-coding RNAs (lncRNAs) in inflammation-associated epigenetic regulation through competing endogenous RNA (ceRNA) networks. In this study, we established a bovine mastitis model in three healthy primiparous Holstein cows by intramammary infection with S. aureus. Infected and control mammary tissue samples were then collected for transcriptomic profiling, which identified 2005 differentially expressed lncRNAs. Among them, BMNCR was significantly upregulated in S. aureus-infected mammary tissues and S. aureus-stimulated BMECs. We evaluated the coding potential of BMNCR and confirmed its non-coding nature. Functional studies in BMECs demonstrated that knockdown of BMNCR suppressed proliferation, promoted apoptosis, and altered the expression of inflammatory factors, including IL-2, IL-6, IL-8, and IL-12. Mechanistically, BMNCR acted as a sponge for bta-miR-145, thereby leading to the derepression of ANO6. Silencing ANO6 partly recapitulated the effects of BMNCR knockdown, impairing proliferation and increasing IL-8 expression. Collectively, these findings suggest that the BMNCR/miR-145/ANO6 axis is involved in the regulation of inflammatory responses and epithelial homeostasis during bovine mastitis, with BMNCR functioning as a protective regulator in this process. Full article

Background/Objectives: Body Protection Compound-157 (BPC 157) is a stable gastric pentadecapeptide with cytoprotective, pro-angiogenic, and nitric oxide (NO)-modulating properties that has gained increasing attention for its therapeutic potential. Although vasodilatory effects have been demonstrated in animal models, functional evidence in human arterial tissue remains limited. This study investigated the effects of BPC 157 on vascular tone in human internal mammary artery (IMA) rings and evaluated the contribution of endothelial NO signaling. Methods: Residual IMA segments obtained from elective coronary artery bypass graft surgeries (n = 12) were dissected into endothelium-intact and endothelium-denuded rings. Following equilibration, the rings were challenged by phenylephrine (PheE; 3 × 10⁻⁶ M) to induce contraction. Cumulative concentration–response curves of BPC 157 (0.01–1 mg/mL) for five consecutive doses were constructed. The involvement of NO was assessed by BPC 157 dose–response curves in the nitric oxide synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; 10⁻⁶ M) pre-incubated rings. Maximum force of contraction, area under the curve, maximum response (Emax), and negative logarithm of the half-maximal effective concentration (pEC50) values were analyzed. Results: BPC 157 produced a concentration-dependent reduction in PheE-induced contraction in both groups, with significantly greater relaxation in endothelium-intact rings (p < 0.05). L-NAME increased contractile responsiveness in intact rings and attenuated BPC 157-induced relaxation. Under NOS inhibition, differences between groups progressively diminished and concentration–response curves converged at higher concentrations. Emax analysis demonstrated that endothelial integrity markedly enhanced maximal vasorelaxation, whereas this advantage was largely abolished after NOS inhibition. Conclusions: BPC 157 induces concentration-dependent vasorelaxation in human arterial tissue, predominantly mediated via an endothelium-dependent NO pathway. Endothelial integrity primarily enhances maximal efficacy, while residual effects indicate additional mechanisms. These findings provide early mechanistic evidence for the vascular activity of BPC 157, although further molecular and in vivo studies are required to clarify its clinical relevance. Full article

The river buffalo is an economically important livestock species supplying milk and meat. However, a multi-tissue transcriptomic atlas for the key dairy river buffalo breeds, Murrah and Nili-Ravi, has not yet been established, and the lack of stable reference genes has hindered in-depth studies of their biological functions and the molecular mechanisms underlying key economic traits such as lactation. We established a multi-tissue gene expression atlas across 20 tissues and identified 717 housekeeping genes (HKGs), and RPL37A and EEF2 were further shown to be stable candidate reference genes under the conditions tested. We found 8368 tissue-specific genes (TSGs), predominantly enriched in the reproductive system. Exploratory analysis of mammary tissue (dry-period vs. public lactating samples, confounded by batch effects) revealed mammary-enriched hub genes including LALBA; these findings are preliminary and require validation. Dynamic analysis across lactation stages (early, peak, mid-, late) identified candidate genes including SEC14L2 and ACSM3. Phenotypic data showed strong negative correlations between milk yield and protein/fat content, and a positive correlation with lactose content. However, causal or regulatory roles were not inferred due to lack of paired individual-level data. Cross-dataset comparisons are descriptive only, and are not key conclusions. In summary, this study lays the foundation for advancing research in lactation trait genetics and functional genomics in river buffalo, with novel reference genes and lactation stage-specific transcriptional dynamics as its main contributions. Full article

Mastitis is a common disease in dairy cows, mainly caused by Staphylococcus aureus and Escherichia coli. Berberine (BBR) has antibacterial and anti-inflammatory potential, but its application is limited due to poor oral absorption and difficulty in reaching mammary tissue. To address this, this study developed a BBR-loaded composite ethosome hydrogel (BBR-CEH) to achieve targeted mammary delivery through local transdermal administration. The experimental results showed that BBR-CEH has good chemical stability and biosafety. Subsequently, a mouse mastitis model was established by intraductal injection of 50 µL of bacterial mixture (E. coli:S. aureus = 1:1, each at 1 × 10⁷ CFU/mL). The results showed that after BBR-CEH treatment, the mRNA expression of TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin-6), and IL-1β (interleukin-1 beta) was significantly decreased, the mRNA expression of ZO-1 (zonula occludens-1), Occludin, and Claudin-4 was significantly increased, and Bax/Bcl-2 (Bcl-2-associated X protein/B-cell lymphoma 2) was significantly reduced (p < 0.01), indicating alleviation of mastitis by reducing inflammation, improving tight junctions, and inhibiting apoptosis. Finally, network pharmacology and in vivo experiments confirmed that its mechanism involves the NF-κB (nuclear factor kappa-B) and PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathways. Thus, topical BBR-CEH may represent a promising new strategy for mastitis treatment. Full article