Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome

Stroke is the second leading cause of death and a major cause of disability worldwide,and biological sex is an important determining factor in stroke incidence and pathology.From childhood through adulthood,men have a higher incidence of stroke compared with women.Abundant research has confirmed the beneficial effects of estrogen in experimental ischemic stroke but genetic factors such as the X-chromosome complement can also play an important role in determining sex differences in stroke.Autophagy is a self-degrading cellular process orchestrated by multiple core proteins,which leads to the engulfment of cytoplasmic material and degradation of cargo after autophagy vesicles fuse with lysosomes or endosomes.The levels and the activity of components of these signaling pathways and of autophagy-related proteins can be altered during ischemic insults.Ischemic stroke activates autophagy,however,whether inhibiting autophagy after stroke is beneficial in the brain is still under a debate.Autophagy is a potential mechanism that may contribute to differences in stroke progression between the sexes.Furthermore,the effects of manipulating autophagy may also differ between the sexes.Mechanisms that regulate autophagy in a sex-dependent manner in ischemic stroke remain unexplored.In this review,we summarize clinical and pre-clinical evidence for sex differences in stroke.We briefly introduce the autophagy process and summarize the effects of gonadal hormones in autophagy in the brain and discuss X-linked genes that could potentially regulate brain autophagy.Finally,we review pre-clinical studies that address the mechanisms that could mediate sex differences in brain autophagy after stroke.

Mechanisms of Immune Tolerance and Inflammation via Gonadal Steroid Hormones in Preterm Birth

In 2019,preterm births(PTB)accounted for approximately 0.66 million deaths globally.PTB is also associated with a significantly higher risk of mortality and long-term complications for newborns.Long-term studies associated several factors,including disruption of immune tolerance and inflammation,with PTB.However,the pathogenesis of PTB remains unclear.Gonadal steroid hormones are critical for pregnancy maintenance and regulation of immune and inflammatory responses.However,it is not clear how unbalanced gonadal steroid hormones,such as imbalanced estrogen/androgen or estrogen/progesterone contribute to PTB.In this review,we discuss how gonadal steroid hormones mediate dysfunction in immune tolerance and inflammatory responses,which are known to promote the occurrence of PTB,and provide insight into PTB prediction.

Effects of Estrogen and/or Progesterone on Morphology of Pituitary Luteinizing Hormone Cells

Objective To identify the morphological characteristics of pituitary luteinizing hormone (LH) cells after exogenous gonadal hormone treatment Methods Effects of various doses of estrogen, progesterone and their combination on morphological parameters, including the size and shape of pituitary LH cells, the size of endocellular vacuoles, were observed and measured by immuno histochemistry and computer image analysis. Results Different kinds of gonadal hormones could recover the magnified LH cells to the normal level in ovariectomized rats. However, their final effects on the gonadotrophin levels and the cellular morphological characters of the LH cells were different. The low dose of estrogen elicited abundant hormone stored in the LH cells to an easy released status with a lot of different size of vacuoles. On the contrary, the high dose of estrogen inhibited the storage of LH, and the LH cells were filled with secretory granules and few vacuoles. The progesterone could promote the storage of LH in an uneasy released status. The administration of estrogen progesterone combination not only inhibited the storage of LH, but also the release of LH. In this group, the LH cells containing a large amount of secretory granules and a few vacuoles showed a better uniform shape compared with those administrated with high dose of estrogen. Conclusion: Different kinds of gonadal hormones could reverse the excessive secretion of LH and recover the morphological change of LH cells to the normally physiological condition.

Progesterone is neuroprotective by inhibiting cerebral edema after ischemia

Ischemic edema can alter the structure and permeability of the blood-brain barrier. Recent studies have reported that progesterone reduces cerebral edema after cerebral ischemia. However, the underlying mechanism of this effect has not yet been elucidated. In the present study, progesterone effectively reduced Evans blue extravasation in the ischemic penumbra, but not in the ischemic core, 48 hours after cerebral ischemia in rats. Progesterone also inhibited the down-regulation of gene and protein levels of occludin and zonula occludens-1 in the penumbra. These results indicate that progesterone may effectively inhibit the down-regulation of tight junctions, thereby maintaining the integrity of the blood-brain barrier and reducing cerebral edema.

Protective effect of thyroid and restores of ovarian function of Buzhong Yiqi granule(补中益气颗粒)on experimental autoimmune thyroiditis in female rats

OBJECTIVE:To observe the effects of Buzhong Yiqi granule(补中益气颗粒)on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis(EAT).METHODS:EAT model was replicate by using the method of mixing and injecting porcine thyroglobulin with Freund's adjuvant and high iodine.Rats were randomly divided into normal control(NC)group,EAT model(EAT)group,selenium yeast(PC)group,low dose Buzhong Yiqi(BZYQ-L)group,medium dose Buzhong Yiqi(BZYQ-M)group and high dose Buzhong Yiqi(BZYQ-H)group.After two months of drug intervention according to dosage,enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of free triiodothyronine(FT3),free thyroxine(FT4),thyroid-stimulating hormone(TSH),antithyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb)in peripheral blood of rats.The pathological changes of rat thyroid tissues were observed under light microscope with HE staining;ELISA was used to determine estradiol(E2),follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),antimüllerian hormone(AMH),and the pathological changes of rat ovarian tissues were observed under light microscope with hematoxylin and eosin staining.RESULTS:Compared with the NC group,BZYQ granule improved the thyroid and ovarian tissue morphology,and the levels of TPOAb,TGAb and TSH in the model group rats significantly increased(P<0.05),the thyroid tissue was severely destroyed,the levels of E2,FSH,LH,T,AMH significantly increased(P<0.05),and the ovary exhibited polycystic changes;Compared with the model group,TSH level in the BZYQ-L group rats decreased(P<0.05),FSH,T,AMH levels decreased(P<0.05),in the BZYQ-M group TPOAb,TSH levels decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),BZYQ-H group TPOAb,TGAb,TSH levels significantly decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),with the greatest improvement and significantly better than selenium yeast group(P<0.05).CONCLUSIONS:BZYQ granule could regulate the thyroid function of EAT rats,reduce thyroid antibody titers,then act on the ovarian function,regulate hormone disorders,and alleviate the pathological damage of rat's ovarian tissues.The effect of high dose Buzhong Yiqi granule is the best.

Therapeutic efficacy of moxibustion plus medicine in the treatment of infertility due to polycystic ovary syndrome and its effect on serum immune inflammatory factors

Objective:To explore the effects and related mechanism of heat-sensitive moxibustion plus clomifene citrate capsules for infertility due to polycystic ovary syndrome(PCOS).Methods:A total of 70 patients were randomized into a control group and an observation group by the random number table method,with 35 cases in each group.The control group was treated with clomifene citrate capsules,while the observation group was treated with heat-sensitive moxibustion on the basis of the medications in the control group.The treatment course lasted for 6 menstrual cycles.The endometrial thickness and ovarian volume of the patients were measured before and after treatment.The levels of serum sex hormones,tumor necrosis factor-α(TNF-α)and nuclear factor-κB(NF-κB)were detected.Follow-up was performed for 1 year after treatment,and the pregnancy rate was recorded.Results:After treatment,the endometrium of the patients in both groups was significantly thickened,the ovarian volume was significantly reduced,and the intra-group differences were statistically significant(all P<0.05).The endometrium thickness and ovarian volume in the observation group were significantly different from those in the control group(both P<0.05).After treatment,the levels of serum testostrn(T)and luteinizing hormone(LH)in both groups decreased significantly,the level of estradiol(E2)increased obviously,and the intra-group differences were statistically significant(all P<0.05).The levels of serum T and LH in the observation group were lower than those in the control group,and the E2 level in the observation group was higher than that in the control group,and the between-group differences were statistically significant(all P<0.05).After treatment,the levels of serum TNF-αand NF-κB of the patients in both groups decreased,and the intra-group differences were statistically significant(all P<0.05).The levels of serum TNF-αand NF-κB in the observation group were significantly lower than those in the control group(both P<0.05).After 1-year follow-up,the pregnancy rate was 20.0%in the control group,versus 51.5%in the observation group.The pregnancy rate in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Conclusion:The treatment of heat-sensitive moxibustion plus clomifene citrate capsules can increase the endometrium thickness,reduce the ovarian volume,improve the status of serum sex hormone disorders,and increase the conception rate in patients with infertility due to PCOS,which may be related to the adjustment of the levels of immune inflammatory factors such as serum TNF-αand NF-κB.

Clinical observation on herb-partitioned spreading moxibustion at Baliao points plus climen for diminished ovarian reserve

Objective:To observe the clinical efficacy of herb-partitioned spreading moxibustion at Baliao points plus climen for diminished ovarian reserve(DOR).Methods:A total of 60 patients with DOR were randomized into a spreading moxibustion group and a Western medicine group by the random number table method,with 30 cases in each group.The Western medicine group was treated with climen,starting from the 5th day of the menstrual cycle for 21 d.The spreading moxibustion group was treated with herb-partitioned spreading moxibustion at Baliao points on the basis of the medication in the Western medicine group,1 h per time,once a week.The treatment was performed for 1 month as one treatment course in both groups,for 3 courses in total.The serum follicle-stimulating hormone(FSH),luteinizing hormone(LH)and estradiol(E2)in the patients were measured before and after treatment.The peak systolic velocity(PSV)and resistance index(RI)were also detected.The traditional Chinese medicine(TCM)symptom score was evaluated.The clinical efficacy was evaluated after treatment.Results:The total effective rate in the spreading moxibustion group was 93.3%,which was significantly higher than 80.0%in the Western medicine group,and the difference between the groups was statistically significant(P<0.05).After treatment,the TCM symptom scores,the serum FSH levels,FSH/LH ratios and RI in both groups decreased,and the intra-group differences were all statistically significant(all P<0.05).The serum E2 level and PSV increased compared with those in the same group before treatment,and the intra-group differences were statistically significant(all P<0.05).After treatment,the TCM symptom score,the serum FSH level,FSH/LH ratio and RI in the spreading moxibustion group were lower than those in the Western medicine group,while the serum E2 level and PSV were higher than those in the Western medicine group,and the differences between the groups were statistically significant(all P<0.05).Conclusion:Herb-partitioned spreading moxibustion at Baliao points plus climen can produce valid therapeutic efficacy for DOR.It can improve the clinical symptoms,regulate serum hormone levels and increase ovarian blood perfusion,thus improving ovarian reserve function,producing more significant efficacy than climen alone.

Medical expulsion therapy for urinary calculi

C urrently, the predominant therapy for urinary calculi is minimally invasive treatment, which could reduce injury to patients while enhancing the success rate, compared to traditional open surgery. Minimally invasive treatments in urinary system include extracorporeal shock wave lithotripsy （ESWL）, percutaneous nephro- stolithotomy （PCNL）, ureteroscopic lithotripsy （URSL）, laparoscopy, and so on. Despite the relative small injury,