Comorbid pathology of the mammary glands and endometriosis: risk factors and prognosis.

OBJECTIVE: Aim: based on a retrospective analysis, the relationship between external genital endometriosis and comorbid breast pathology was established and risk factors were identified, their comparison and the formation of a prognostic risk criterion were determined. PATIENTS AND METHODS: Materials and Methods: to address the objectives of the study, a retrospective analysis of 470 cases of patients treated for external genital endometriosis after surgical treatment and comorbid breast pathology was conducted. The control group included 30 healthy non-pregnant women. Statistical processing was performed on a personal computer using the statistical software package Statistica 10. RESULTS: Results: As a result of the analysis, the age of the patients ranged from 23 to 40 years. The average age of patients in the study group was (32.2}1.18) years, and in the control group (31.1}1.35) (p>0.05). The groups were homogeneous in terms of age (p>0.05), marital status (p>0.05) and level of education (p>0.05). Close relatives in 208 (44.25}2.18) % (OR=8.86; 95 % CI: (0.68-10.53); p<0.002) cases suffered from benign (hormone-dependent) tumours and tumour-like diseases of the uterus and appendages in isolation or in various combinations (fibroids, adenomyosis, endometrial hyperplasia). It was also found that 102 (21.70}1.67) % of patients had endometriosis, which may indicate a genetic predisposition to this disease. In the closest relatives of EM patients: in 118 (25.10}2.01) % of the examined parents, breast problems were noted, in 66 (14.04}1.12) % - diabetes mellitus, and in 98 (20.85}1.22) % thyroid diseases were detected, which in total amounted to (60.00}2.23) % (OR=9.12; 95 % CI: (0.58-11.54); p<0.002). Early menarche almost tripled the risk of EM (OR=2.72; 95% CI: (1.02-5.11); p<0.002), and menstrual irregularities doubled it (OR=2.04; 95% CI: (1.09-3.14); p<0.05), higher education, urban residents - 2.2 times higher (OR= 2.27; 95 % CI: (1.11-3.63); p<0.05), diseases of the gastrointestinal tract and hepatobiliary complex - 5.2 times higher (OR=5.27; 95 % CI: (1.89-12.03); p<0.05), frequently recurrent inflammatory diseases of the appendages - 3 times higher (OR=3.14; 95 % CI: (0.91-5.14); p<0.05), dysmetabolic manifestations (thyroid dysfunction) - 5 times higher (OR=5.11; 95 % CI: (1.61-9.503); p<0.002). CONCLUSION: Conclusions: Thus, in endometriosis and dyshormonal diseases of the mammary glands, menstrual and generative function disorders, along with clinical symptoms of pelvic pain, dysmenorrhoea, autonomic nervous system disorders and sexual dysfunction, are significant components of this problem, initiating comorbidity processes in target organs in the setting of hormonal maladaptation. Therefore, these comorbidities become a trigger for the activation of systemic hormonal imbalance and become an urgent interdisciplinary problem that requires further study.

Antioxidative Sirt1 and the Keap1-Nrf2 Signaling Pathway Impair Inflammation and Positively Regulate Autophagy in Murine Mammary Epithelial Cells or Mammary Glands Infected with Streptococcus uberis.

Streptococcus uberis mastitis in cattle infects mammary epithelial cells. Although oxidative responses often remove intracellular microbes, S. uberis survives, but the mechanisms are not well understood. Herein, we aimed to elucidate antioxidative mechanisms during pathogenesis of S. uberis after isolation from clinical bovine mastitis milk samples. S. uberis's in vitro pathomorphology, oxidative stress biological activities, transcription of antioxidative factors, inflammatory response cytokines, autophagosome and autophagy functions were evaluated, and in vivo S. uberis was injected into the fourth mammary gland nipple of each mouse to assess the infectiousness of S. uberis potential molecular mechanisms. The results showed that infection with S. uberis induced early oxidative stress and increased reactive oxygen species (ROS). However, over time, ROS concentrations decreased due to increased antioxidative activity, including total superoxide dismutase (T-SOD) and malondialdehyde (MDA) enzymes, plus transcription of antioxidative factors (Sirt1, Keap1, Nrf2, HO-1). Treatment with a ROS scavenger (N-acetyl cysteine, NAC) before infection with S. uberis reduced antioxidative responses and the inflammatory response, including the cytokines IL-6 and TNF-α, and the formation of the Atg5-LC3II/LC3I autophagosome. Synthesis of antioxidants determined autophagy functions, with Sirt1/Nrf2 activating autophagy in the presence of S. uberis. This study demonstrated the evasive mechanisms of S. uberis in mastitis, including suppressing inflammatory and ROS defenses by stimulating antioxidative pathways.

Breast milk transmission and involvement of mammary glands in tick-borne flavivirus infected mice.

Tick-borne flaviviruses (TBFs) are transmitted to humans through milk and tick bites. Although a case of possible mother-to-child transmission of tick-borne encephalitis virus (TBEV) through breast milk has been reported, this route has not been confirmed in experimental models. Therefore, in this study, using type I interferon receptor-deficient A129 mice infected with Langat virus (LGTV), we aimed to demonstrate the presence of infectious virus in the milk and mammary glands of infected mice. Our results showed viral RNA of LGTV in the pup's stomach milk clots (SMCs) and blood, indicating that the virus can be transmitted from dam to pup through breast milk. In addition, we observed that LGTV infection causes tissue lesions in the mammary gland, and viral particles were present in mammary gland epithelial cells. Furthermore, we found that milk from infected mice could infect adult mice via the intragastric route, which has a milder infection process, longer infection time, and a lower rate of weight loss than other modes of infection. Specifically, we developed a nano-luciferase-LGTV reporter virus system to monitor the dynamics of different infection routes and observed dam-to-pup infection using in vivo bioluminescence imaging. This study provides comprehensive evidence to support breast milk transmission of TBF in mice and has helped provide useful data for studying TBF transmission routes.IMPORTANCETo date, no experimental models have confirmed mother-to-child transmission of tick-borne flavivirus (TBF) through breastfeeding. In this study, we used a mouse model to demonstrate the presence of infectious viruses in mouse breast milk and mammary gland epithelial cells. Our results showed that pups could become infected through the gastrointestinal route by suckling milk, and the infection dynamics could be monitored using a reporter virus system during breastfeeding in vivo. We believe our findings have provided substantial evidence to understand the underlying mechanism of breast milk transmission of TBF in mice, which has important implications for understanding and preventing TBF transmission in humans.

Borrelia burgdorferi colonizes the mammary glands of lactating C3H mice: does not cause congenital Lyme disease.

Transplacental transmission of syphilis causing spirochete, Treponema pallidum subspecies pallidum, from mother to child results in congenital syphilis, an ever-expanding devastating disease worldwide. Although adverse effects of untreated gestational Lyme disease, caused by a related spirochete, Borrelia burgdorferi on fetus viability and development have been observed, cases of congenital Lyme disease are not reported. In this study, we show that B. burgdorferi colonizes mammary glands of C3H mice only postpartum; however, neither transmission of these spirochetes from dams-to-pups occurs nor congenital Lyme disease is observed in pups.

Evaluation of breast skin and tissue stiffness using a non-invasive aspiration device and impact of clinical predictors.

A personalized 3D breast model could present a real benefit for preoperative discussion with patients, surgical planning, and guidance. Breast tissue biomechanical properties have been poorly studied in vivo, although they are important for breast deformation simulation. The main objective of our study was to determine breast skin thickness and breast skin and adipose/fibroglandular tissue stiffness. The secondary objective was to assess clinical predictors of elasticity and thickness: age, smoking status, body mass index, contraception, pregnancies, breastfeeding, menopausal status, history of radiotherapy or breast surgery. Participants were included at the Montpellier University Breast Surgery Department from March to May 2022. Breast skin thickness was measured by ultrasonography, breast skin and adipose/fibroglandular tissue stiffnesses were determined with a VLASTIC non-invasive aspiration device at three different sites (breast segments I-III). Multivariable linear models were used to assess clinical predictors of elasticity and thickness. In this cohort of 196 women, the mean breast skin and adipose/fibroglandular tissue stiffness values were 39 and 3 kPa, respectively. The mean breast skin thickness was 1.83 mm. Only menopausal status was significantly correlated with breast skin thickness and adipose/fibroglandular tissue stiffness. The next step will be to implement these stiffness and thickness values in a biomechanical breast model and to evaluate its capacity to predict breast tissue deformations.

Exploring the mechanism of Xihuang Pill's anti-hyperplasia of mammary glands effect based on UPLC-Q-orbitrap-MS technology / 药学学报

Based on UPLC-Q-orbitrap-MS and biological network analysis tools, the mechanism of Xihuang Pill in improving hyperplasia of mammary glands was systematically analyzed. The rat model of hyperplasia of mammary glands was established by intramuscular injection of estradiol benzoate and progesterone. LC-MS tissue metabolomics was used to explore the key metabolites and metabolic pathways of Xihuang Pill in improving hyperplasia of mammary glands in rat. The network analysis of the key metabolites regulated by Xihuang Pill was carried out by integrating biological network analysis tools, focusing on the key metabolic pathways, and exploring the potential targets of Xihuang Pill to improve hyperplasia of mammary glands. Compared with the control group, there were significant differences in the content of 49 differential metabolites in the tissues of the model group (P < 0.05). Xihuang Pills could significantly call back 17 metabolites such as L-alanine, threonine, indole-3-carboxylic aldehyde, lysine, arginine, alanylleucine, glycyltyrosine, γ-glutamyl leucine, vitamin B3, serine leucine, threonine leucine, isoleucine glutamic acid, γ-glutamyl tyrosine, decanoyl-L-carnitine, uric acid, leucylleucine, S-adenosyl-methionine. Further network analysis and literature research on the key metabolites regulated by Xihuang Pills showed that the AGE-RAGE signaling pathway may be one of the important pathways for Xihuang Pills to improve hyperplasia of mammary glands. STAT3, MAPK1, EGFR, CASP3, CASP8, PRKCA and JUN in the AGE-RAGE signaling pathway may be potential targets for Xihuang Pills to improve hyperplasia of mammary glands. The animal experiment operations involved in this paper follow the provisions of the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine and pass the ethical review of animal experiments (approval number: 2022-705).

Quantitative Study on the Breast Density and the Volume of the Mammary Gland According to the Patient's Age and Breast Quadrant.

OBJECTIVES: Breast density is considered an independent risk factor for the development of breast cancer. This study aimed to quantitatively assess the percent breast density (PBD) and the mammary glands volume (MGV) according to the patient's age and breast quadrant. We propose a regression model to estimate PBD and MGV as a function of the patient's age. METHODS: The breast composition in 1027 spiral breast CT (BCT) datasets without soft tissue masses, calcifications, or implants from 517 women (57 ± 8 years) were segmented. The breast tissue volume (BTV), MGV, and PBD of the breasts were measured in the entire breast and each of the four quadrants. The three breast composition features were analyzed in the seven age groups, from 40 to 74 years in 5-year intervals. A logarithmic model was fitted to the BTV, and a multiplicative inverse model to the MGV and PBD as a function of age was established using a least-squares method. RESULTS: The BTV increased from 545 ± 345 to 676 ± 412 cm3, and the MGV and PBD decreased from 111 ± 164 to 57 ± 43 cm3 and from 21 ± 21 to 11 ± 9%, respectively, from the youngest to the oldest group (p < 0.05). The average PBD over all ages were 14 ± 13%. The regression models could predict the BTV, MGV, and PBD based on the patient's age with residual standard errors of 386 cm3, 67 cm3, and 13%, respectively. The reduction in MGV and PBD in each quadrant followed the ones in the entire breast. CONCLUSIONS: The PBD and MGV computed from BCT examinations provide important information for breast cancer risk assessment in women. The study quantified the breast mammary gland reduction and density decrease over the entire breast. It established mathematical models to estimate the breast composition features-BTV, MGV, and PBD, as a function of the patient's age.

Xiaozheng pill exerts an anti-mammary hyperplasia effect through Raf/ERK/ELK and HIF-1α/bFGF pathways.

Background and aim: The purpose of this study is to explore whether the Xiaozheng pill (XZP) has the effect of anti-hyperplasia of mammary glands (HMG) and to identify the related signaling pathways. Experimental procedure: We analyzed the effective chemical components of the XZP, as well as the key chemical components, key proteins, main biological processes, and pathways in the treatment of HMG; Secondly, the levels of Estradiol (E2), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Progesterone (P), Raf/ERK/ELK and HIF-1α/bFGF pathways related proteins were detected; Finally, the effect of XZP on metabolites was analyzed by metabolomics. Results and conclusion: In this study, we identified key targets and pathways for XZP therapy of HMG, including EGFR, VEGFA, ER, and Ras signaling pathways. Animal experiments show that XZP can reduce the levels of E2, LH, and FSH and increase the expression of P in HMG mice. XZP can restore the normal structure of breast tissue and reduce ERα, ERß, and PR expression in breast tissue. In addition, metabolomics results show that XZP also regulates HMG metabolites, including HIF-1α and metabolic pathways. The Western blot results showed that XZP intervention can reduce the protein expression of p-Raf1, Raf1, p-ERK1/2, ERK1/2, ELK, HIF-1α, and bFGF in the breast tissue of HMG mice. XZP may eliminate abnormal breast hyperplasia through inhibition of apoptosis and angiogenesis, which may be linked with the regulation of the Raf/ERK/ELK and HIF-1α/bFGF signaling pathways in HMG mice. These results suggest that XZP treatment may be beneficial for the management of HMG.

miR-30a-3p Regulates Autophagy in the Involution of Mice Mammary Glands.

The mammary gland undergoes intensive remodeling during the lactation cycle, and the involution process of mammary gland contains extensive epithelial cells involved in the process of autophagy. Our studies of mice mammary glands suggest that miR-30a-3p expression was low during involution compared with its high expression in the mammary glands of lactating mice. Then, we revealed that miR-30a-3p negatively regulated autophagy by autophagy related 12 (Atg12) in mouse mammary gland epithelial cells (MMECs). Restoring ATG12, knocking down autophagy related 5 (Atg5), starvation, and Rapamycin were used to further confirm this conclusion. Overexpression of miR-30a-3p inhibited autophagy and altered mammary structure in the involution of the mammary glands of mice, which was indicative of alteration in mammary remodeling. Taken together, these results elucidated the molecular mechanisms of miR-30a-3p as a key induction mediator of autophagy by targeting Atg12 within the transition period between lactation and involution in mammary glands.

[Research progress on traditional Chinese medicine compounds combined with external therapy in treatment of hyperplasia of mammary glands].

Hyperplasia of mammary glands is a benign breast disease with disordered breast structure. Nowadays, the incidence rate of breast hyperplasia in women is increasing year by year, and the etiology is related to the imbalance of estrogen and progesterone in the body. The symptoms include breast pain, breast nodules, or nipple discharge, which can develop into breast cancer in the context of psychological pressure. Therefore, it is timely and effectively necessary for people to treat the symptoms. At present, traditional Chinese medicine(TCM) often treats breast hyperplasia by oral drug, external application, acupuncture, moxibustion, and massage, while western medicine often uses hormone therapy or surgery. TCM can regulate hormone levels to treat breast hyperplasia. Acupuncture, moxibustion, and other methods can stimulate acupoints to reduce breast lumps. However, since TCM is easy to produce hepatorenal toxicity after long-term use and simple external treatment is slow to take effect, rapid and effective treatment is difficult to be achieved. Although western medicine can inhibit the disease, it is easy to produce toxic and side effects if taken for a long time. In addition, surgery can only remove the focus and the recurrence rate is high. Some studies have found that the combination of oral and external use of TCM compounds has a significant effect, with mild toxic and side effects, few adverse reactions, and a low recurrence rate. Based on the relevant literature in recent years, this article reviewed the combination of oral and external treatment of TCM in the treatment of hyperplasia of mammary glands, discussed the effectiveness, clinical evaluation indexes, and mechanism, and pointed out the existing shortcomings to explore a comprehensive therapy worthy of clinical application.

Tebuconazole Induces ER-Stress-Mediated Cell Death in Bovine Mammary Epithelial Cell Lines.

Tebuconazole (TEB) is a triazole fungicide used to increase crop production by controlling fungi, insects, and weeds. Despite their extensive use, people are concerned about the health risks associated with pesticides and fungicides. Numerous studies have defined the cellular toxicity of triazole groups in pesticides, but the mechanisms of TEB toxicity in bovine mammary gland epithelial cells (MAC-T cells) have not yet been studied. Damage to the mammary glands of dairy cows directly affects milk production. This study investigated the toxicological effects of TEB on MAC-T cells. We found that TEB decreases both cell viability and proliferation and activates apoptotic cell death via the upregulation of pro-apoptotic proteins, such as cleaved caspases 3 and 8 and BAX. TEB also induced endoplasmic reticulum (ER) stress via the upregulation of Bip/GRP78; PDI; ATF4; CHOP; and ERO1-Lα. We found that TEB induced mitochondria-mediated apoptotic MAC-T cell death by activating ER stress. This cell damage eventually led to a dramatic reduction in the expression levels of the milk-protein-synthesis-related genes LGB; LALA; CSN1S1; CSN1S2; and CSNK in MAC-T cells. Our data suggest that the exposure of dairy cows to TEB may negatively affect milk production by damaging the mammary glands.

Effects of silver nanoparticles on maternal mammary glands and offspring development under lactation exposure.

The widespread applications of silver nanoparticles (AgNPs) throughout our daily lives have raised concerns regarding their environmental health and safety (EHS). Despite an increasing number of studies focused on the EHS impacts of AgNPs, there remain significant knowledge gaps with respect to their potential health impacts on susceptible populations, such as lactating mothers and infants. Herein, we aimed to investigate the deleterious effects of AgNPs with different sizes (20 and 40 nm) and surface coatings (PVP and BPEI) on maternal mice and their offspring following lactation exposure at doses of 20, 100 and 400 µg/kg body weight. We discovered that AgNPs could accumulate in the maternal mammary glands and disrupt the epithelial barrier in a dose-dependent manner. Notably, BPEI-coated AgNPs caused more damage to the mammary glands than PVP-coated particles. Importantly, we observed that, while AgNPs were distributed throughout the blood and main tissues, they were particularly enriched in the brains of breastfed offspring after maternal exposure during lactation, exhibiting exposure dosage- and particle coating-dependent patterns. Compared to PVP-coated nanoparticles, BPEI-coated AgNPs were more readily transferred to the offspring, possibly due to their enhanced deposition in maternal mammary glands. Moreover, we observed reduced body weight, blood cell toxicity, and tissue injuries in breastfed offspring whose dams received AgNPs. As a whole, these results reveal that maternal exposure to AgNPs results in the translocation of AgNPs into offspring via breastfeeding, inducing developmental impairments in these breastfed offspring. This study provides important new insights into the EHS impacts of AgNP consumption during lactation.

Metabolomic Alterations in Mammary Glands from Pubertal Mice Fed a High-Fat Diet.

Dietary malpractice is a risk factor for obesity. This study tested the hypothesis that consumption of a high-fat diet alters mammary metabolome in pubertal mice. We performed untargeted metabolomic analysis of primary metabolism on mammary glands from pubertal mice fed the AIN93G standard diet or a high-fat diet (HFD) for 3 weeks. We identified 97 metabolites for statistical comparisons. The HFD altered the amino acid metabolism considerably. This included elevated expression of branched-chain amino acids, non-essential amino acids (aspartic acid and glutamic acid), and methionine sulfoxide (oxidized methionine) and an alteration in the aminoacyl-tRNA biosynthesis pathway. Furthermore, elevations of fumaric acid and malic acid (both are citrate cycle intermediates) and glyceric acid (its phosphate derivatives are intermediates of glycolysis) in HFD-fed mice suggest an acceleration of both citrate cycle and glycolysis. Lower expression of glycerol, oleic acid, and palmitoleic acid, as well as decreased mammary expression of genes encoding lipid metabolism (Acaca, Fads1, Fasn, Scd1, and Srebf1) in HFD-fed mice indicate an attenuated lipid metabolism in the presence of adequate dietary fat. In conclusion, consumption of the HFD for 3 weeks alters metabolic profile of pubertal mammary glands. This alteration may affect mammary development and growth in pubertal mice.

[Mechanism of blood-activating and mass-dissipating Chinese patent medicine against hyperplasia of mammary glands and use with other medicine: a review].

Caused by endocrine disorder, hyperplasia of mammary glands(HMG) tends to occur in the young with increasing incidence, putting patients at the risk of cancer and threatening the health of women. Therefore, the prevention and treatment of HMG is attracting more and more attention. Amid the modernization of traditional Chinese medicine(TCM), many scholars have found that Chinese patent medicine has unique advantages and huge potential in treatment of endocrine disorder. Particularly, Chinese patent medicine with the function of blood-activating and mass-dissipating, such as Xiaojin Pills and Xiaozheng Pills, has been commonly used in clinical treatment of HMG, which features multiple targets, obvious efficacy, small side effect, and ease of taking and carrying around. Clinical studies have found that the combination of Chinese patent medicine with other medicine can not only improve the efficacy and relieve symptoms such as hyperplasia and pain but also reduce the toxic and side effects of western medicine. Therefore, based on precious pharmacological research and clinical research, this study reviewed the mechanisms of blood-activating mass-dissipating Chinese patent medicine alone and in combination with other medicine, such as regulating levels of in vivo hormones and receptors, promoting apoptosis, inhibiting angiogenesis, improving hemorheology indexes, enhancing immunity, and boosting antioxidant ability. In addition, limitations and problems were summarized. Thereby, this study is expected to lay a theoretical basis for the further study and clinical application of blood-activating mass-dissipating Chinese patent medicine alone or in combination with other medicine against HMG.

Polymorphism of glutathione S-transferase P1 of dogs with mammary tumours.

Mammary tumours constitute more than half of neoplasms in female dogs from different countries. Genome sequences are associated with cancer susceptibility but there is little information available about genetic polymorphisms of glutathione S-transferase P1 (GSTP1) in canine cancers. The aim of this study was to find single nucleotide polymorphisms (SNPs) in GSTP1 of dogs (Canis lupus familiaris) with mammary tumours compared to healthy dogs and to determine the association between GSTP1 polymorphisms and the occurrence of these tumours. The study population included 36 client-owned female dogs with mammary tumours and 12 healthy female dogs, with no previous diagnosis of cancer. DNA was extracted from blood and amplified by PCR assay. PCR-products were sequenced by Sanger method and analysed manually. The 33 polymorphisms were found in GSTP1: 1 coding SNP (exon 4), 24 non-coding SNPs (9 in exon 1), 7 deletions and 1 insertion. The 17 polymorphisms have been found in introns 1, 4, 5 and 6. The dogs with mammary tumours have significant difference from healthy in SNPs I4 c.1018 + 123 T > C (OR 13.412, 95%CI 1.574-114.267, P = .001), I5 c.1487 + 27 T > C (OR 10.737, 95%CI 1.260-91.477, P = .004), I5 c.1487 + 842 G > C (OR 4.714, 95% CI 1.086-20.472, P = .046) and I6 c.2481 + 50 A > G (OR 12.000, 95% CI 1.409-102.207, P = .002). SNP E5 c.1487 T > C and I5 c.1487 + 829 delG also differed significantly (P = .03) but not to the confidence interval. The study, for the first time, showed a positive association of SNPs in GSTP1 with mammary tumours of dogs, that can possibly be used to predict the occurrence of this pathology.

Feeding Corn Silage or Grass Hay as Sole Dietary Forage Sources: Overall Mechanism of Forages Regulating Health-Promoting Fatty Acid Status in Milk of Dairy Cows.

Different dietary forage sources regulate health-promoting fatty acids (HPFAs), such as conjugated linoleic acids (CLAs) and omega-3 polyunsaturated fatty acids (n-3 PUFAs), in the milk of lactating cows. However, the overall mechanism of forages regulating lipid metabolism from the gastrointestinal tract to the mammary glands (MGs) is not clear. Three isocaloric diets that contained (1) 46% corn silage (CS), (2) a mixture of 23% corn silage and 14% grass hays (MIX), and (3) 28% grass hays (GH) as the forage sources and six cannulated (rumen, proximal duodenum, and terminal ileum) lactating cows were assigned to a double 3 × 3 Latin square design. Our results show that a higher proportion of grass hay in the diets increased the relative contents of short-chain fatty acids (SCFAs), CLAs, and n-3 PUFAs. The lower relative content of SCFA in the milk of CS was predominantly due to the reduction in acetate production in the rumen and arteriovenous differences in the MG, indicating that the de novo synthesis pathways were inhibited. The elevated relative contents of total CLA and n-3 PUFA in the milk of GH were attributed to the increases in apparent intestinal digestion and arteriovenous differences in total CLA and n-3 PUFA, together with the higher Δ9-desaturase activity in the MG. In conclusion, this study provides an overall mechanism of dietary forages regulating HPFA status in the milk of dairy cows.

[Mechanism of anti-hyperplasia of mammary glands of Xihuang Pills blood-entering component based on UPLC-Q-TOF-MS and network pharmacology].

In this study, based on network pharmacology and molecular docking method, the mechanism of anti-hyperplasia of mammary glands of Xihuang Pills blood-entering components was explored, and the efficacy and key targets of Xihuang Pills blood-entering components were experimentally verified by MCF-10A proliferation model of human mammary epithelial cells. In order to clarify the material basis and mechanism of Xihuang Pills in realizing anti-hyperplasia of mammary glands, the blood-entering components of Xihuang Pills were qualitatively analyzed by UPLC-Q-TOF-MS, and 22 blood-entering components were identified. By taking the blood-entering components as the research object, the network pharmacology prediction and molecular docking verification were carried out, and finally, three key targets were screened out, namely JAK1, SRC, and CDK1. In vitro experiments show that Xihuang Pills can inhibit the proliferation of MCF-10A cells, promote the apoptosis of MCF-10A cells, and reduce the expression of JAK1, SRC, and CDK1 targets in cells. To sum up, Xihuang Pills can promote the apoptosis of mammary epithelial cells by regulating the expression of JAK1, SRC, and CDK1 and then play an anti-hyperplasia role, which provides an experimental basis for clarifying the material basis of Xihuang Pills for anti-hyperplasia effect.

Caracterización morfométrica nuclear de glándulas mamarias sanas en mujeres adultas mayores

Introducción: Las glándulas mamarias son órganos que durante las diferentes etapas de la vida en la mujer sufren modificaciones, donde se involucran los procesos de proliferación, diferenciación y apoptosis, bajo el control hormonal. Sin embargo, una vez que cesan dichas influencias hormonales ocurren cambios que llevan a la involución de dicho órgano. Objetivo: Caracterizar el factor de forma, perímetro, área y volumen de los núcleos de las células epiteliales glandulares mamarias. Métodos: Para caracterizar las glándulas mamarias sanas en mujeres de 60 años y más, se realizó un estudio de serie de casos en 14 mujeres fallecidas que no tenían lesiones benignas o malignas del órgano. Todas examinadas por el departamento de Anatomía Patológica del Hospital Provincial Vladimir Ilich Lenin en Holguín, en el período comprendido de septiembre 2018 a septiembre 2019. Para mejor valoración, la muestra de estudio se dividió en dos grupos de edades: de 60-75 años de edad y mayores de 75 años. Resultados: Tanto el factor de forma como el perímetro, área y volumen de los núcleos de las células epiteliales de los conductos mamarios son menores en las mujeres mayores de 75 años. Conclusiones: Existen diferencias notables en los indicadores morfométricos estudiados en ambos grupos de edades. Específicamente el tamaño y la forma de los núcleos de células epiteliales se ven afectados con la edad, lo cual se corresponde con la baja actividad metabólica de las células epiteliales mamarias en esta etapa de la vida.

Introduction: The mammary glands are organs that during the different stages of life in women undergo modifications, where the processes of proliferation, differentiation and apoptosis are involved, under hormonal control. However, once these hormonal influences cease, changes occur that lead to the involution of said organ. Objective: To determine the shape factor, perimeter, area and volume of the nuclei of glandular epithelial cells. Methods: To characterize healthy mammary glands in women aged 60 years and older, a case series study was conducted on 14 deceased women who had no benign or malignant lesions of the organ. All examined by the Department of Pathological Anatomy of the Provincial Hospital V.I. Lenin in Holguín, in the period between September, 2018 - September, 2019. For a better assessment, the study sample was divided into two age groups: from 60 to 75 years of age; age and older than 75 years. Results: Both the shape factor and the perimeter, area and volume of the nuclei of the epithelial cells of the mammary ducts are lower in women older than 75 years. Conclusions: There are notable differences in the morphometric indicators studied. Epithelial cell nuclei are affected with age, which corresponds to the low metabolic activity of mammary epithelial cells at this stage of life.

Age dependence of chemical element contents in normal human breast investigated using inductively coupled plasma atomic emission spectrometry / Estudio mediante espectrometría de emisión atómica de plasma acoplado inductivamente de la dependencia de la edad en el contenido de elementos químicos en las mamas humanas normales

Introduction: Breast cancer in women is an actual global medical and social problem. The etiology of this disease remains largely unclear. However, it is well known that the incidence of breast cancer increases with age. In the presented work, for the first time, the age dependence of Al, Ca, Cu, Fe, K, Mg, Na, P, S, Si, Sr, and Zn content in the mammary gland of women aged 16-60 years was investigated.Material and methods: For this purpose, a method of inductively coupled plasma atomic emission spectrometry (ICP-AES) was developed, which makes it possible to determine the content of these elements in microsamples (mass from 10 mg) of breast tissue. With the help of the developed technique, the material obtained during the autopsy of 38 practically healthy women aged 16-60 years who died suddenly was studied.Results: Using the parametric Student's t-test and the non-parametric Wilcoxon-Mann-Whitney U-test to compare two age groups (16-40 years and 41-60 years), as well as Pearson's correlation coefficients between age and chemical element content, it was found that the level of K, Mg, Na and S in normal breast tissue decrease with age.Conclusions: The phenomenon of the age-related decrease in the chemical element contents in the normal mammary gland, discovered for the first time, requires further detailed study. (AU)

Introducción: El cáncer de mama en la mujer es un problema médico y social actual a nivel mundial. La etiología de esta enfermedad sigue sin estar clara. Sin embargo, es bien sabido que la incidencia del cáncer de mama aumenta con la edad. En el trabajo presentado se analiza por primera vez la dependencia de la edad del contenido de Al, Ca, Cu, Fe, K, Mg, Na, P, S, Si, Sr y Zn en la glándula mamaria de mujeres de 16 a 60 años. fue investigado.Material y métodos: Para ello se desarrolló un método de espectrometría de emisión atómica con plasma acoplado inductivamente (ICP-AES), que permite determinar el contenido de estos elementos en micromuestras (masa a partir de 10 mg) de tejido mamario. Con la ayuda de la técnica desarrollada se estudió el material obtenido durante la autopsia de 38 mujeres prácticamente sanas de entre 16 y 60 años que murieron repentinamente.Resultados: Utilizando la prueba t de Student paramétrica y la prueba U no paramétrica de Wilcoxon-Mann-Whitney para comparar dos grupos de edad (16-40 años y 41-60 años), así como los coeficientes de correlación de Pearson entre edad y elemento químico. contenido, se encontró que el nivel de K, Mg, Na y S en el tejido mamario normal disminuye con la edad.Conclusiones: El fenómeno de la disminución del contenido de elementos químicos en la glándula mamaria normal relacionado con la edad, descubierto por primera vez, requiere un estudio más detallado. (AU)

Mechanism of anti-hyperplasia of mammary glands of Xihuang Pills blood-entering component based on UPLC-Q-TOF-MS and network pharmacology / 中国中药杂志

In this study, based on network pharmacology and molecular docking method, the mechanism of anti-hyperplasia of mammary glands of Xihuang Pills blood-entering components was explored, and the efficacy and key targets of Xihuang Pills blood-entering components were experimentally verified by MCF-10A proliferation model of human mammary epithelial cells. In order to clarify the material basis and mechanism of Xihuang Pills in realizing anti-hyperplasia of mammary glands, the blood-entering components of Xihuang Pills were qualitatively analyzed by UPLC-Q-TOF-MS, and 22 blood-entering components were identified. By taking the blood-entering components as the research object, the network pharmacology prediction and molecular docking verification were carried out, and finally, three key targets were screened out, namely JAK1, SRC, and CDK1. In vitro experiments show that Xihuang Pills can inhibit the proliferation of MCF-10A cells, promote the apoptosis of MCF-10A cells, and reduce the expression of JAK1, SRC, and CDK1 targets in cells. To sum up, Xihuang Pills can promote the apoptosis of mammary epithelial cells by regulating the expression of JAK1, SRC, and CDK1 and then play an anti-hyperplasia role, which provides an experimental basis for clarifying the material basis of Xihuang Pills for anti-hyperplasia effect.