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The presented work summarizes the results of studies underlining the crucial role of estrogen receptor (ER) signaling in both innate and adaptive immune responses as well as in tissue repairing processes during respiratory virus infection. Experimental studies justify that among respiratory virus infected mice, a weaker ER signaling leads to increased morbidity and mortality in both males and females. In animal experiments, estrogen treatment silences the inflammatory reactions and decreases virus titers leading to improved survival rate; it seems to be an ideal prevention and therapy against COVID-19. We should overcome the widespread reluctance to estrogen therapy as we have a unique estrogen formula; conjugated estrogens, or conjugated equine estrogens available under the brand name of Premarin deriving from natural sources. Premarin can exert similar ER upregulative and gene repairing power like endogenous estrogen without any risk for adverse reactions. Premarin is capable of stopping the COVID-19 pandemic.

Six months after insertion of the grafts, the bone of the augmented sinus floor was strong and suitable for anchorage of dental implants, irrespective of whether autogenous bone or Cerasorb particles had been applied.

Currently available scientific evidence erroneously suggests that mutagenic weakness or loss of the BRCA1/2 genes may liberate the proliferative effects of estrogen signaling, which provokes DNA damage and genomic instability. Conversely, BRCA mutation seems to be an imbalanced defect, crudely inhibiting the upregulation of estrogen receptor expression and liganded transcriptional activity, whereas estrogen receptor-repressor functions become predominant. In BRCA-proficient cases, estrogen signaling orchestrates the activity of cell proliferation and differentiation with high safety, while upregulating the expression and DNA-stabilizing impact of BRCA genes. In turn, BRCA proteins promote estrogen signaling by proper estrogen synthesis via CYP19 gene regulation and by induction of the appropriate expression and transcriptional activity of estrogen receptors. In this exquisitely organized regulatory system, the dysfunction of each player may jeopardize genome stability and lead to severe chronic diseases, such as cancer development. Female organs, such as breast, endometrium, and ovary, exhibiting regular cyclic proliferative activity are particularly vulnerable in case of disturbances in either estrogen signaling or BRCA-mediated DNA repair. BRCA mutation carrier women may apparently be healthy or exhibit clinical signs of deficient estrogen signaling in spite of hyperestrogenism. Even women who enjoy sufficient compensatory DNA-defending activities are at risk of tumor development because many endogenous and environmental factors may jeopardize the mechanisms of extreme compensatory processes. Natural estrogens have numerous benefits in tumor prevention and therapy even in BRCA mutation carriers. There are no toxic effects even in sky-high doses and all physiologic cellular functions are strongly upregulated, while malignant tumor cells are recognized and killed in a Janus-faced manner.

Oral cancer (OC) is a neoplasm with fairly high male to female ratio in most populations. The conspicuously lower incidence of this tumor among women than man is suggestive of certain endocrine involvement in its development. The aim of the present case-control study was to clarify the origin of this gender-specific risk of OC incidence. 2660 inpatients (530 females and 2130 males) with squamous cell OC at the Department of Oral and Maxillofacial Surgery were included in a case-control study. Smoking, alcohol consumption, elevated fasting serum glucose level and menopausal histories of female cases were registered. Smoking and excessive alcohol intake proved to be strong risk factors for OC both in the male and female group. However, moderate alcohol consumption was a weaker risk factor for male patients, and it presented no risk for female cases. Elevated fasting glucose level was not a demonstrable OC risk factor among males, however, it proved to be strong risk factor for OC among female patients, especially in gingival cancer cases. The almost exclusively postmenopausal state of female OC patients and the long mean interval (17 years) between their menopause and OC diagnosis suggested an important role of estrogen deficiency in OC epidemiology. The significantly younger mean age at menopause and the significantly higher rate of hysterectomy among female OC cases in comparison with their controls also support the estrogen deficiency hypothesis. This novel hypothesis of estrogen deficiency and elevated fasting glucose as risk factors for OC in postmenopausal women may provide new insights into the etiology of oral malignancies.

Effect of ligation on the vascular permeability in the gingiva and alveolar mucosa encircling the mandibular left 1st molar was studied in rats with and without capsaicin pretreatment. Vascular permeability was assessed by the Evans blue extravasation. Ligation caused a significant augmentation in vascular permeability of the gingivomucosal tissue at day 8 (right: 18.14 +/- 1.68 micrograms g-1; left (ligature): 38.21 +/- 2.43 micrograms g-1, n = 8, p < 0.001) and at day 14 (right: 20.31 +/- 1.71 micrograms g-1: left (ligature): 36.98 +/- 2.73 micrograms g-1, n = 8, p < 0.001). 4 days after ligation, no difference could be observed in vascular permeability in the oral mucosa of the ligated side (left: 23.14 +/- 1.21 micrograms g-1) as compared to the side without ligature (right: 23.5 +/- 1.45 micrograms g-1, n = 8, NS). There was no elevation of vascular permeability of gingivomuscosal tissue around the ligation in rats pretreated with capsaicin either in newborn age (right: 23.92 +/- 1.76 micrograms g-1; left (ligature): 23.51 +/- 2.16 micrograms g-1, n = 8, NS) or in adult age (right: 20.61 +/- 1.62 micrograms g-1; left (ligature): 20.85 +/- 1.07 micrograms g-1, n = 8, NS). Light microscopical studies of oral mucosa revealed, that 8 and 14 days after the ligature placed around the mandibular left 1st molar of the rat, there resulted an accumulation of inflammatory cells in the connective tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE -Numerous publications have already demonstrated that diabetes is a risk factor for the development of periodontal diseases and various inflammatory lesions in the oral mucosa. A possible correlation between diabetes and oral premalignancies and tumors was examined in this study, as no literature data are available concerning this problem.RESEARCH DESIGN AND METHODS -Stomato-oncological screening was carried out on 200 diabetic patients in the medical departments; the control group included 280 adult dentistry outpatients. The lesions found were classified into three groups: inflammatory lesions, benign tumors, and precancerous lesions. A retrospective diabetes screening of 610 inpatients with histologically confirmed oral malignancies was also performed. The control group comprised 574 complaint-and tumor-free adults. Fasting blood glucose levels were determined in both groups, and the tumor location was registered in the cancer patients.RESULTS -Benign tumors were found in 14.5% and precancerous lesions in 8% of diabetic patients. In the control group these values were significantly lower, at 6.4 and 3.2%, respectively (P Ͼ 0.01). Earlier Hungarian screening studies indicated similar frequency of these lesions in the general population. The proportion of oral cavity lesions was higher among diabetic patients compared with that of the control patients. In the oral cancer patient group, diabetes was present in 14.6% and an elevated blood glucose level in 9.7%. These values are significantly higher than those for the tumor-free control group (P Ͻ 0.01). The gingival and labial tumor location was significantly more frequent among diabetic cancer patients than in the nondiabetic group (P Ͻ 0.01). The combination of diabetes and smoking means a higher risk for oral precancerous lesions and malignancies.CONCLUSIONS -Diabetes may be a risk factor for oral premalignancies and tumors. Diabetes Care 27:770 -774, 2004C orrelations between diabetes and inflammatory oral lesions were first published in the 19th century (1). Gingivitis and destructive periodontitis with a rapid loss of the teeth were described as cardinal, pathognomic symptoms of diabetes (2,3).The discovery of insulin treatment justified a close correlation between the disorder of the carbohydrate metabolism and oral inflammatory complications (4). The adequate treatment of diabetes results in marked improvement of the gingival and periodontal lesions.Diabetes patients have further inflammatory complications of the oral mucosa. The decreased rate of saliva secretion and the low pH value result in chronic cheilitis and glossitis with progressive atrophy of the covering epithelial layer (5).The inflammation-mediated carcinogenesis is a well-known empirical fact, but the exact pathway of this transition has not been perfectly clarified until now (6 -9). Is there any correlation between diabetes and tumor genesis of the oral cavity? Surprisingly, there are no literature data concerning this problem. Accordingly, in the present study, we have attempted...

Epidemiologic studies strongly support that triple-negative breast cancers (TNBCs) may be distinct entities as compared with estrogen receptor (ER)+ tumors, suggesting that the etiologic factors, clinical characteristics, and therapeutic possibilities may vary by molecular subtypes. Many investigations propose that reproductive factors and exogenous hormone use differently or even quite inversely affect the risk of TNBCs and ER+ cancers. Controversies concerning the exact role of even the same risk factor in TNBC development justify that the biological mechanisms behind the initiation of both TNBCs and non-TNBCs are completely obscure. To arrive at a comprehensive understanding of the etiology of different breast cancer subtypes, we should also reconsider our traditional concepts and beliefs regarding cancer risk factors. Malignancies are multicausal, but the disturbance of proper estrogen signaling seems to be a crucial risk factor for the development of mammary cancers. The grade of defect in metabolic and hormonal equilibrium is directly associated with TNBC risk for women during their whole life. Inverse impact of menopausal status or parity on the development of ER+ and ER− breast cancers may not be possible; these controversial results derive from the misinterpretation of percentage-based statistical evaluations. Exogenous or parity-associated excessive estrogen supply is suppressive against breast cancer, though the lower the ER expression of tumors, the weaker the anticancer capacity. In women, the most important preventive strategy against breast cancers – included TNBCs – is the strict control and maintenance of hormonal equilibrium from early adolescence through the whole lifetime, particularly during the periods of great hormonal changes.