TRIM22 governs tumorigenesis and protects against endometrial cancer-associated cachexia by inhibiting inflammatory response and adipose thermogenic activity
Ling Zhang, Ping Zhang, Qin Li
Meiting Wu, Xiushan Feng, Weichao Dai, Pai-Lien Chen, Dan Chen, Zhiqun Zheng, Xiaoyan Lin, Gang Wei
Endometrial cancer (EC) is one of the most common cancers in women, with a short overall survival and poor prognosis. Besides the biologically aggressive EC properties, Cancer-associated cachexia is the main factor. However, the detailed mechanism underlying EC-related cachexia and its harmful effects on EC progression and patient prognosis remains unclear.
Methods
For clinical specimen and the vitro experiment, we detected TRIM22 expression level, EC patients' survival time, EC cell functional change, and adipose thermogenic changes to identify the function of TRIM22 in EC progression, EC-associated cachexia, and their molecular mechanisms. Then, for the vivo experiment, we exploited the xenografts in mice to identify the function of TRIM22 again, and to screen the drug therapeutic schedule.
Results
Herein, we demonstrated that TRIM22 inhibited EC cell growth, invasion, and migration. Interleukin (IL)-6 mediated brown adipose tissue activation and white adipose tissue browning which induced EC-related cachexia. TRIM22 suppressed the EC cells' secretion of IL-6, and IL-6 mediated EC-related cachexia. Mechanistically, TRIM22 inhibited EC progression by suppressing the nucleotide-binding oligomerization domain 2(NOD2)/nuclear factor-kappaB (NF-κB) signaling pathway, with the purpose of impeding the production of IL-6. Moreover, we revealed that TRIM22 inhibited EC-associated cachexia by suppressing the IL-6/IL-6 receptor (IL-6R) signaling pathway. Therapeutically, we demonstrated that combination treatment with a TRIM22 inducer (progesterone) and a thermogenic inhibitor (IL-6R antibody) synergistically augmented the antitumor efficacy of carbotaxol (carboplatin and paclitaxel), in vivo.
Conclusion
Our data reveals that TRIM22-EC-IL-6-cachexia cross-communication has important clinical relevance and that the use of combined therapy holds great promise for enhancing the efficacy of anti-ECs. (Fig. graphical abstract).
Attention-Deficit/Hyperactivity Disorder (ADHD) in girls and women is under-recognised and under-researched, despite increasing awareness of clinical challenges and unmet needs. This review by the Eunethydis Special Interest Group on Female ADHD, addresses current knowledge and identifies research gaps for future work. Issues in women with ADHD across the lifespan such as late diagnosis, pubertal development, sexual health, hormonal birth control, executive function difficulties, and gynaecological disorders associated with ADHD are highlighted. The review synthesises existing literature and self-reported experiences of women with ADHD to explore the impact of hormonal fluctuations [puberty, menstrual cycle, pregnancy, (peri)menopause] on ADHD symptoms and mood disturbances. It examines the interplay of oestrogen and progesterone with dopaminergic pathways, when periods of lower oestrogen may affect cognition, as well as the manifestation of executive function deficits, and the intersection of ADHD with reproductive health. Hormonal transitions exacerbate ADHD symptoms and mood disturbances, yet pharmacological research and tailored treatments are lacking. Executive function deficits manifest differently in girls and women with ADHD and are influenced by neuropsychological and neurobiological profiles. Diagnostic practices and sociocultural factors contribute to delayed diagnoses, increasing the risk of comorbidities, impaired functioning, and diminished quality of life. Undiagnosed women have increased vulnerability to premenstrual dysphoric disorder, postpartum depression, and cardiovascular disease during perimenopause. Longitudinal, sex-specific studies incorporating hormonal status and lived experience are needed. Individualised interventions should be developed to address the unique needs of girls and women with ADHD. Addressing these gaps will advance more equitable diagnosis, management, and support for girls and women with ADHD, improving outcomes across the female lifespan.
General OB/GYNReproductive Endocrinology
Open Access
Autoimmune disorders are characterized as a condition in which the host's immune system mistakenly attacks itself. These disorders cause the immune system to cause a systemic reaction by attacking multiple organs or may be localized to attacking one specific organ, such as the skin. The exact mechanism of such autoimmune conditions is not well understood; however, the presumed mechanism tends to vary amongst the disorders. Autoimmune diseases present with a clear gender bias with a greater prevalence amongst women, occurring at a rate of 2 to 1. Many autoimmune disorders tend to affect women during periods of extensive stress, such as pregnancy, or during a great hormonal change. A far greater number of women are affected every year with autoimmune diseases, leading to researchers attempting to identify the underlying factors, which could be responsible for this disparity. Autoimmune disorders occur as a result of multiple factors as some disorders may be genetic, while others are sporadic. Throughout this review, various hypotheses are explored that provide insight into the increased susceptibility of autoimmune disorders within women.
Reproductive EndocrinologyGeneral OB/GYN
Open Access
Three prior cases of hemoperitoneum associated with immune thrombocytopenia (ITP) have been reported in adolescents. This reports a case of hemoperitoneum after ovulation in an adult. A 34-year-old nulligravida presented with abdominal pain after a heavy period and rebound tenderness. Urine beta-hCG was negative, hemoglobin was 5.4, and platelet count was zero. CT revealed hemoperitoneum and contrast blush surrounding the left ovary. She was treated for newly diagnosed systemic lupus erythematosus and steroid-refractory ITP. Her platelet count and symptoms improved. Hemoperitoneum after ovulation in ITP is rare; this represents the first adult case in the literature and reviews differential diagnosis of thrombocytopenia. The obstetrician/gynecologist is part of a multidisciplinary team caring for patients with bleeding of gynecological origin and should withhold surgical intervention for hemoperitoneum when medical therapy is warranted.
Trying to kick drug addiction without medicines is said to be like relying on willpower to overcome diabetes or asthma. Enter naltrexone, which has been around since 1984 and reduces the cravings for drugs and alcohol by fine-tuning the brain's chemical reward system. Why has it recently increased in popularity? How does it compare to similar strategies? Has it made a difference? Our authors, who have long studied addiction and the brain, confront a drug and alcohol addiction problem that today kills more Americans each day than gun violence or car accidents.