2.Effects of bisphenol A and bisphenol analogs on the nervous system.
Chunxia LI ; Chen SANG ; Shuo ZHANG ; Sai ZHANG ; Hui GAO
Chinese Medical Journal 2023;136(3):295-304
Estrogen impacts neural development; meanwhile, it has a protective effect on the brain. Bisphenols, primarily bisphenol A (BPA), can exert estrogen-like or estrogen-interfering effects by binding with estrogen receptors. Extensive studies have suggested that neurobehavioral problems, such as anxiety and depression, can be caused by exposure to BPA during neural development. Increasing attention has been paid to the effects on learning and memory of BPA exposure at different developmental stages and in adulthood. Further research is required to elucidate whether BPA increases the risk of neurodegenerative diseases and the underlying mechanisms, as well as to assess whether BPA analogs, such as bisphenol S and bisphenol F, influence the nervous system.
Receptors, Estrogen/metabolism*
;
Estrogens
;
Benzhydryl Compounds/pharmacology*
;
Nervous System/metabolism*
3.Management of menopausal syndrome in women with dyslipidemia.
Yang Mei LI ; Xun LEI ; Li Li YU
Chinese Journal of Preventive Medicine 2023;57(11):1908-1914
The prevalence of dyslipidemia is increased in postmenopausal women due to dysregulation of lipid metabolism and deficiency of estrogen levels. At the same time, some postmenopausal women also have menopausal syndromes such as vasomotor symptoms, physical physiology, mental psychology, and urogenital tract atrophy. Menopausal hormone therapy is the most effective measure to alleviate menopausal syndrome. And initiating MHT in early menopause can reduce cardiovascular damage. However, menopausal hormone therapy can also bring the risk of thromboembolic diseases such as venous embolism, myocardial infarction and stroke. Different drug regimens have different effects on lipid metabolism. Women with menopausal syndrome should take individualized treatment plans for different types of dyslipidemia. Therefore, this article reviews the management and treatment of menopausal syndrome in women with dyslipidemia, so as to provide a reference for personalized management of dyslipidemia in postmenopausal women.
Female
;
Humans
;
Menopause
;
Estrogen Replacement Therapy
;
Cardiovascular Diseases/epidemiology*
;
Estrogens/pharmacology*
;
Dyslipidemias/drug therapy*
4.Research Progress in the Role of Tamoxifen in Nervous System and Cognitive Function.
Jin-Nong WANG ; Yi TIAN ; Qing-Yi CAO
Acta Academiae Medicinae Sinicae 2023;45(2):334-340
Neurological diseases include a variety of neurodegenerative diseases and other brain damage diseases.The treatment schemes for neurological diseases are still in research.The existing clinical and basic studies have confirmed that traditional estrogen therapy has certain protective effect on the nervous system,while it increases the risk of breast or endometrial cancer.The emergence of the selective estrogen receptor modulators (SERMs) can avoid the above mentioned problems.The available studies have confirmed the protective effect of tamoxifen as a SERM on the nervous system.This paper reviews the role and functioning mechanisms of tamoxifen in the nervous system and cognitive function,aiming to provide guidance for the future application of tamoxifen in the treatment of neurological diseases and the improvement of cognitive function.
Tamoxifen/therapeutic use*
;
Selective Estrogen Receptor Modulators/therapeutic use*
;
Cognition
;
Nervous System
5.Management of menopausal syndrome in women with dyslipidemia.
Yang Mei LI ; Xun LEI ; Li Li YU
Chinese Journal of Preventive Medicine 2023;57(11):1908-1914
The prevalence of dyslipidemia is increased in postmenopausal women due to dysregulation of lipid metabolism and deficiency of estrogen levels. At the same time, some postmenopausal women also have menopausal syndromes such as vasomotor symptoms, physical physiology, mental psychology, and urogenital tract atrophy. Menopausal hormone therapy is the most effective measure to alleviate menopausal syndrome. And initiating MHT in early menopause can reduce cardiovascular damage. However, menopausal hormone therapy can also bring the risk of thromboembolic diseases such as venous embolism, myocardial infarction and stroke. Different drug regimens have different effects on lipid metabolism. Women with menopausal syndrome should take individualized treatment plans for different types of dyslipidemia. Therefore, this article reviews the management and treatment of menopausal syndrome in women with dyslipidemia, so as to provide a reference for personalized management of dyslipidemia in postmenopausal women.
Female
;
Humans
;
Menopause
;
Estrogen Replacement Therapy
;
Cardiovascular Diseases/epidemiology*
;
Estrogens/pharmacology*
;
Dyslipidemias/drug therapy*
6.Guidelines for pharmaceutical care of endocrine therapeutics for breast cancer(2023 edition).
Chinese Journal of Oncology 2023;45(10):834-862
Endocrine therapy is one of the primary treatment methods for hormone receptor-positive breast cancer patients. As of June 1 2023, the National Medical Product Administration has approved 56 drugs related to endocrine therapy in patients with HR+ /HER-2- breast cancer (including generic drugs that have passed the consistency evaluation), including 44 endocrine drugs which can be categorized according to their mechanisms of action into selective estrogen receptor modulators, selective estrogen receptor down-regulators, aromatase inhibitors, luteinizing hormone-releasing hormone analogs, and progestogens and 12 targeted drugs for combined with endocrine therapy, including CDK4/6 inhibitors, mTOR inhibitors, and HDAC inhibitors. The different pharmacological characteristics, mechanisms of action, and long-term medication factors of breast cancer endocrine therapy-related drugs can directly affect patients' medication adherence and medication safety. To standardize the pharmaceutical care of endocrine therapy drugs for breast cancer and promote rational use in clinical settings, the Oncology Specialty Pharmacist Subcommittee, in conjunction with multidisciplinary experts nationwide, has developed the "Guidelines for pharmaceutical care of endocrine therapy drugs for breast cancer (2023 edition)". The guidelines is based on clinical evidence-based evidence, relevant regulations of pharmaceutical management, and pharmaceutical care practices. The Delphi method and expert interviews were used to formulate the guidelines. The GRADE approach was used for assessing the certainty of evidence. This guideline mainly focuses on endocrine therapy for HR+ /HER-2- breast cancer patients. Due to space constraints, HER-2 positive targeted drugs were not included in the guideline. It covers 6 dimensions and 22 key problems of pharmaceutical care in the whole process of drug therapy, providing a scientific basis for pharmacists to carry out pharmaceutical care of such drugs.
Humans
;
Female
;
Breast Neoplasms/drug therapy*
;
Aromatase Inhibitors/therapeutic use*
;
Receptors, Estrogen
7.Therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea in rats and its metabolomic analysis.
Liu-Jun WU ; Yan CHEN ; Zi-Wei LIN ; Chen SUN ; Liang XIONG ; Xiao-Fang XIE ; Cheng PENG
China Journal of Chinese Materia Medica 2023;48(22):6093-6106
This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E_2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E_2(PGE_2), prostaglandin F_(2α)(PGF_(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E_2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE_2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF_(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P<0.05 or P<0.01), significantly reduce the uterine and ovarian coefficients(P<0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE_2 content was significantly increased(P<0.05), COX-2, PGF_(2α) and Ca~(2+) content, and PGF_(2α)/PGE_2 was significantly decreased(P<0.05 or P<0.01), and OT content was decreased, while E_2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P<0.05 or P<0.01) and ERα protein expression was upregulated(P<0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P<0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.
Humans
;
Rats
;
Female
;
Animals
;
Estrogen Receptor alpha
;
Oxytocin
;
Dysmenorrhea/metabolism*
;
Cyclooxygenase 2
;
Dinoprostone
;
RNA, Messenger/metabolism*
;
Dinoprost
8.Searching for the emotional roots of breast cancer: A cross-disciplinary analysis integrating psychology, Chinese medicine, and oncology biomarkers.
Ofer BARANOVITCH ; Meirav WOLFF-BAR ; Meora FEINMESSER ; Chen SADE-ZALTZ ; Ilan TSARFATY ; Victoria NEIMAN
Journal of Integrative Medicine 2022;20(1):57-64
OBJECTIVE:
We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience, psychology, physiology, traditional Chinese medicine (CM), modern practice of CM, and oncology to explore the effect of patients' repression of negative emotions and traumatic events on breast cancer (BC) pathogenesis.
METHODS:
BC female patients, older than 18 years of age, with available pathology reports who were treated at Rabin Medical Center were recruited. All participants completed questionnaires regarding medical history, behavioral tendencies, negative emotions, trauma, symptoms, and pathology (from a CM perspective). Data on tumor characteristics were collected from the pathology reports. The associations were examined using hierarchical binary logistic regressions.
RESULTS:
A total of 155 BC patients were enrolled. The median age was 52 years, with a range of 26-79; 95% were mothers; 28% had estrogen receptor (ER)-negative BC, 52% had progesterone receptor (PR)-negative BC, 48% had human epidermal growth factor receptor 2-negative BC, and antigen Ki-67 ≥ 20% was reported for 52% of tumors. Statistically significant associations were found between the emotional markers (sense of motherhood failure, and lack of self-fulfillment), avoidance behavior, and physical symptoms that are related to emotional repression based on CM. Significant associations were also found between variables associated with physical symptoms of emotional repression, which involves the production and accumulation of non-substantial phlegm (i.e., "high-lipid Qi-like microscopic phlegm"), avoidance behavior which unconsciously uses "high-lipid Qi-like microscopic phlegm" in order to achieve emotional repression, and tumor parameters including tumor grade, PR status, and Ki-67. Patients with higher levels of "high-lipid Qi-like microscopic phlegm" were more likely to have tumors with worse prognosis (PR-negative, higher grade, and higher Ki-67).
CONCLUSION
We demonstrated a relationship between emotional parameters, behavioral tendencies, CM parameters, and oncologic parameters in BC. Additional research is warranted to explore these associations and their relevance to clinical practice.
Adult
;
Aged
;
Breast Neoplasms
;
Emotions
;
Female
;
Humans
;
Medicine, Chinese Traditional
;
Middle Aged
;
Receptor, ErbB-2
;
Receptors, Estrogen
;
Receptors, Progesterone
9.Preparation and characterization of Ad-ERα-36-Fc-GFP.
Yuqiong XIE ; Chunchun LI ; Xiaoye LI ; Lihong CHEN ; Maoxiao YAN ; Jiang CAO
Chinese Journal of Biotechnology 2022;38(3):1086-1095
ERα-36 is a novel subtype of estrogen receptor α which promotes tumor cell proliferation, invasion and drug resistance, and it serves as a therapeutic target. However, only small-molecule compounds targeting ERα-36 are under development as anticancer drugs at present. Gene therapy approach targeting ERα-36 can be explored using recombinant adenovirus armed with decoy receptor. The recombinant shuttle plasmid pDC316-Ig κ-ERα-36-Fc-GFP was constructed via genetic engineering to express an Ig κ-signaling peptide-leading secretory recombinant fusion protein ERα-36-Fc. The recombinant adenovirus Ad-ERα-36-Fc-GFP was subsequently packaged, characterized and amplified using AdMaxTM adenovirus packaging system. The expression of fusion protein and functional outcome of Ad-ERα-36-Fc-GFP transduction were further analyzed with triple-negative breast cancer MDA-MB-231 cells. Results showed that the recombinant adenovirus Ad-ERα-36-Fc-GFP was successfully generated. The virus effectively infected MDA-MB-231 cells which resulted in expression and secretion of the recombinant fusion protein ERα-36-Fc, leading to significant inhibition of EGFR/ERK signaling pathway. Preparation of the recombinant adenovirus Ad-ERα-36-Fc-GFP provides a basis for further investigation on cancer gene therapy targeting ERα-36.
Adenoviridae/genetics*
;
Cell Proliferation
;
Estrogen Receptor alpha/metabolism*
;
Recombinant Proteins
;
Transfection
10.Intervention of ERRα Expression on Apoptosis Induction of Multiple Myeloma MM.1S Cells Cultured in Vitro.
Rui-Xi ZHANG ; Yu-Qing GAO ; Lei LEI ; De-Pei WU ; Ting-Ting ZHU ; Jian-Hong CHU
Journal of Experimental Hematology 2022;30(2):476-480
OBJECTIVE:
To investigate the effect of two different approaches ERRα strategy on the apoptosis in multiple myeloma cell line MM.1S.
METHODS:
For the one strategy, shRNA was mediated by lentivirus. Stable cell clones were established by transfecting the lentivirus into MM.1S cells and screened by puromycin. For the other strategy, XCT790, a specific reverse agonist of ERRα, was used to treat MM.1S cells. The apoptosis of the cells was analyzed by flow cytometry after ERRα was down-regulated. Western blot assay was used to detect the apoptosis of related proteins.
RESULTS:
The knocked down ERRα was achieved, lentivirus with shERRα were successfully infected into MM.1S and ERRα was reduced significantly. Knockdown of ERRα could induce MM.1S cell apoptosis dramatically. Meanwhile, the expression of cleaved PARP (a kind of apoptosis related markers) was significantly increased following depletion of ERRα in MM.1S cells. XCT790 could significantly down-regulate the expression of ERRα protein in MM.1S cells, which was consistent with the effect caused by shRNA.
CONCLUSION
Interference the expression of ERRα by shRNA or XCT790 can induce apparent apoptosis in MM.1S cells, which indicating that ERRα is crucial for the survival of myeloma cells.
Apoptosis
;
Cell Line, Tumor
;
Cell Proliferation
;
Humans
;
Lentivirus
;
Multiple Myeloma
;
RNA, Small Interfering/pharmacology*
;
Receptors, Estrogen

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