The Microbiota-Bone-Allergy Interplay

Emerging knowledge suggests an increasing importance of gut microbiota in health and disease. Allergy and bone metabolism are closely interconnected, and the possible negative effects of common therapies are not the only aspects of this relationship. The immune system is influenced by the microbiota-host interactions, and several pieces of evidence suggest the existence of an interplay between microbiota, bone metabolism, and allergies. Understanding these inter-relationships is essential for the development of new potential strategies of treatment and prevention targeting microbiota. A wide range of substances and germs, prebiotics and probiotics, are capable of influencing and modifying the microbiota. Prebiotics and probiotics have been shown in several studies to have different actions based on various factors such as sex, hormonal status, and age. In this review, we summarize the latest knowledge on the topic, and we discuss practical implications and the need for further studies.

Associations of Sex Hormones and Hormonal Status With Arterial Stiffness in a Female Sample From Reproductive Years to Menopause

ObjectiveLoss of sex hormones has been suggested to underlie menopause-associated increment in cardiovascular risk. We investigated associations of sex hormones with arterial stiffness in 19–58-years-old women. We also studied associations of specific hormonal stages, including natural menstrual cycle, cycle with combined oral contraceptives (COC) and menopausal status with or without hormone therapy (HT), with arterial stiffness.MethodsThis study includes repeated measurements of 65 healthy women representing reproductive (n=16 natural, n=10 COC-users) and menopause (n=5 perimenopausal, n=26 postmenopausal, n=8 HT-users) stages. Arterial stiffness outcomes were aortic pulse wave velocity (PWVao) and augmentation index (AIx%) assessed using Arteriograph-device. Generalized estimating equation models were constructed to investigate associations of each hormone (wide age-range models) or hormonal stage (age-group focused models) with arterial stiffness. PWVao models with cross-sectional approach, were adjusted for age, relative fitness, fat mass and mean arterial pressure, while models with longitudinal approach were adjusted for mean arterial pressure. AIx% models used the same approach for adjustments and were also adjusted for heart rate.ResultsNegative and positive associations with arterial stiffness variables were observed for estradiol and follicle-stimulating hormone, respectively, until adjustment for confounding effect of age. In naturally menstruating women, AIx% was higher at ovulation (B=3.63, p<0.001) compared to the early follicular phase. In COC-users, PWVao was lower during active (B=-0.33 - -0.57, p<0.05) than inactive pills. In menopausal women, HT-users had higher PWVao (B=1.43, p=0.03) than postmenopausal non-HT-users.ConclusionsWhen using wide age-range assessments covering reproductive to menopausal lifespan it is difficult to differentiate age- and hormone-mediated associations, because age-mediated influence on arterial stiffness seemed to overrule potential hormone-mediated influences. However, hormonal status associated differentially with arterial stiffness in age-group focused analyses. Thus, the role of sex hormones cannot be excluded. Further research is warranted to resolve potential hormone-mediated mechanisms affecting arterial elasticity.

THERAPEUTIC PROFILING OF NANO ENCAPSULATED DIOSGENIN VIA ATTENUATING HORMONAL STATUS, CELL PROLIFERATION, INFLAMMATORY RESPONSES, AND APOPTOSIS IN AN ANIMAL MODEL OF MAMMARY ONCOGENESIS

Objective: The central motive of this study is to explore the therapeutic impact of Diosgenin encapsulated Chitosan nanoparticles (DG@CS-NP) on mammary carcinogenesis in female Sprague Dawley rats via modulating hormonal status, cell proliferation, inflammatory responses, and Apoptosis. Methods: 7,12-dimethylbenz(a)anthracene (DMBA) was administered subcutaneously near the mammary gland (25 mg/kg b. wt) to provoke mammary tumor in female Sprague Dawley rats. Following the progress of a tumor, DMBA-induced tumor-bearing rats were medicated orally with 5 mg/kg b. wt of DG@CS-NP. Consequently, the expression of ER, PR, PCNA, Cyclin D1, NF-κB, TNF-α, Bcl-2, Caspases-3, and p53 in experimental rats were revealed via architectural immunohistochemistry. Further, Diosgenin interactions with these proteins were evidently confirmed by molecular docking analysis. Results: As a result, we noticed diminished levels of ER, PR, PCNA, Cyclin D1, NF-κB, TNF-α, and Bcl-2 expressions in DG@CS-NP medicated rats as well as with elevated levels of Caspases-3 and p53 expressions. In DMBA rats, the expressions were vice versa. Additionally, molecular docking analyses support these outcomes by highlighting the strong interaction between Diosgenin and breast cancer targets. Conclusion: These reports prove that DG@CS-NP imposes its therapeutic impact by hormonal adjustments, downregulating proteins involved in inflammation and cellular proliferation, and thereby promotes apoptosis by impeding apoptotic inhibitors.

Primary hypothyroidism as a predictor of the hypogonadism development

Background. Human lifestyle significantly affects human health and reproductive functions. The presence of hypothyroidism negatively impacts the health, activity, and reproductive status. This study was aimed to assess hormonal status, metabolic and anthropometric parameters in men of active reproductive age with primary hypothyroidism. Materials and methods. Totally 60 males with primary hypothyroidism were included in the study. A comparative analysis of hormonal, anthropometric, and metabolic para­meters in 60 men with hypothyroidism (basic group) and 25 men wi­thout hypothyroidism and other chronic somatic diseases (control group) was performed. The mean age of the subjects was 42.4 ± 2.7 years. Results. It has been established that hypothyroidism was accompanied by an increase in serum concentrations of cholesterol and low-density lipoprotein cholesterol in comparison with control group (25 men without hypothyroidism) indicating metabolic disturbance. The data shows the significant effect of hypothyroidism on testosterone and follicle-stimulating hormone (FSH) serum concentration but not on luteinizing hormone, estradiol levels. Patients with hypothyroidism had lower circulating testosterone and higher FSH level in comparison with the controls. The reproductive hormone changes in men with hypothyroidism can result in deleterious effects on sexual functions including erectile dysfunction, reduced libido, and alteration in spermatogenesis. Conclusions. In men with hypothyroidism, changes in hormonal status have been found, which manifested in a decrease in testosterone and an increase in the blood level of follicle-stimulating hormone. The effect of hypothyroidism on the blood level of other hormones (luteini­zing, estradiol, cortisol) has not been established. Hypothyroidism in men is accompanied by changes in lipid metabolism (increased levels of total cholesterol and low-density lipoprotein cholesterol).

Clinical Value of Size, quadrant, and Hormonal Status in Predicting Axillary Node Metastasis in Early Clinico-Radiologically Negative Indian Breast Cancer- A Hospital Based Prospective Observational Study

Background: Sentinel lymph node biopsy (SLNB) is standard of care in clinico- radiologically negative axilla in early breast cancer case. It’s an oncologically safe alternative to Axillary lymph node dissection (ALND), however factors predicting sentinel node metastasis in Indian population is lacking. Methods: A prospective observational study which recruited 80 patients with breast cancer who underwent SLNB with or without ALND, with evaluation of predictive factors including size, type and quadrant , hormonal status of breast this characteristics were prospectively analyzed to predict the axillary metastasis and need of SLNB . Result: Mean age of the patients included in our study was 52.4 years. On univariate analysis, size (p<0.013), upper outer quadrant (UOQ) (p<0.038), central quadrant (CQ) (0.07) were significantly associated with axillary node metastasis in T2 tumors. While on multivariate analysis, UOQ (P<0.009), CQ (p<0.02) metastasis were associated with axillary node metastasis in T2 tumors. Overall sensitivity, specificity, positive predictive valve (PPV) and negative predictive valve (NPV) of SLNB in predicting axillary node status was 77.59%, 100%, 100% and 62.86% respectively. The overall accuracy was 83.7%. Conclusion: Upper outer quadrant, central quadrant and size of the tumors are important prognostic factors to predict axillary node metastasis without the need of sentinel node biopsy in early breast cancers.

High Pregnane X Receptor (PXR) Expression Is Correlated with Poor Prognosis in Invasive Breast Carcinoma

Pregnane X Receptor (PXR) is involved in human cancer, either by directly affecting carcinogenesis or by inducing drug-drug interactions and chemotherapy resistance. The clinical significance of PXR expression in invasive breast carcinoma was evaluated in the present study. PXR protein expression was assessed immunohistochemically on formalin fixed paraffin-embedded breast invasive carcinoma tissue sections, obtained from 148 patients, and was correlated with clinicopathological parameters, molecular phenotypes, tumor cells’ proliferative capacity, and overall disease-free patients’ survival. Additionally, the expression of PXR was examined on human breast carcinoma cell lines of different histological grade, hormonal status, and metastatic potential. PXR positivity was noted in 79 (53.4%) and high PXR expression in 48 (32.4%), out of 148 breast carcinoma cases. High PXR expression was positively associated with nuclear grade (p = 0.0112) and histological grade of differentiation (p = 0.0305), as well as with tumor cells’ proliferative capacity (p = 0.0051), and negatively with luminal A subtype (p = 0.0295). Associations between high PXR expression, estrogen, and progesterone receptor negative status were also recorded (p = 0.0314 and p = 0.0208, respectively). High PXR expression was associated with shorter overall patients’ survival times (log-rank test, p = 0.0009). In multivariate analysis, high PXR expression was identified as an independent prognostic factor of overall patients’ survival (Cox-regression analysis, p = 0.0082). PXR expression alterations were also noted in breast cancer cell lines of different hormonal status. The present data supported evidence that PXR was related to a more aggressive invasive breast carcinoma phenotype, being a strong and independent poor prognosticator.

Gene-Specific Sex Effects on Susceptibility to Infectious Diseases

Inflammation is an integral part of defense against most infectious diseases. These pathogen-induced immune responses are in very many instances strongly influenced by host’s sex. As a consequence, sexual dimorphisms were observed in susceptibility to many infectious diseases. They are pathogen dose-dependent, and their outcomes depend on pathogen and even on its species or subspecies. Sex may differentially affect pathology of various organs and its influence is modified by interaction of host’s hormonal status and genotype: sex chromosomes X and Y, as well as autosomal genes. In this Mini Review we summarize the major influences of sex in human infections and subsequently focus on 22 autosomal genes/loci that modify in a sex-dependent way the response to infectious diseases in mouse models. These genes have been observed to influence susceptibility to viruses, bacteria, parasites, fungi and worms. Some sex-dependent genes/loci affect susceptibility only in females or only in males, affect both sexes, but have stronger effect in one sex; still other genes were shown to affect the disease in both sexes, but with opposite direction of effect in females and males. The understanding of mechanisms of sex-dependent differences in the course of infectious diseases may be relevant for their personalized management.

Rathke cleft cyst apoplexy: Hormonal and clinical presentation

Background: Rathke cleft cyst (RCC) apoplexy is an uncommon type of lesion that is challenging to diagnose without histopathological samples. Very few articles have been published describing the details of RCC apoplexy. We studied a good number of published articles to analyze its demographics, clinical and hormonal presentations, and outcomes. Methods: A literature review of English language publications about RCC apoplexy or pituitary apoplexy was conducted using Medline and EMBASE search engines. Thirty articles with histological diagnosis of RCC apoplexy were identified, the earliest of which was published in 1990 and the latest in 2019. We combined the findings of these articles with our own case report and then compared the demographics, clinical and hormonal presentations, and outcomes between RCC apoplexy and pituitary adenoma apoplexy. Results: Our data included 29 patients with RCC, with a mean age of 36.87 years (8–72) and a predominance of female patients (68%). The hemorrhagic type was most common, reported in 86%. Headache was the most common presenting symptom, being reported in 93% followed by hypogonadism (73%) and hormonal deficits (52%). All but three patients improved neurologically (90%); however, 45% of patients required long-term hormonal replacement, mostly thyroid hormone. No cases of worsening neurological or hormonal status were reported. Conclusion: RCC apoplexy presents with less severe neurological and hormonal abnormalities than pituitary adenoma apoplexy; it also has a better prognosis in endocrine functional recovery. We recommend applying current management guidelines of pituitary adenoma apoplexy to RCC apoplexy.

Insights into the Pathogenesis of HS and Therapeutical Approaches

Hidradenitis suppurativa (HS) is a debilitating, chronic, (auto)inflammatory disease primarily affecting apocrine gland-rich areas of the body. Although pathogenic mechanisms responsible for HS have not yet been fully elucidated, it is a multifactorial process whose main target is the terminal follicle. The role of the inflammatory process (and consequently of cytokine milieu) and of several other factors (genetics, lifestyle, hormonal status, microbiome, innate and adaptive immune systems) involved in HS pathogenesis has been investigated (and often defined) over the years with a view to transferring research results from bench to bedside and describing a unique and universally accepted pathogenetic model. This review will update readers on recent advances in our understanding of HS pathogenesis and novel (potential) medical therapies for patients with moderate-to-severe HS.