VCD induces premature ovarian insufficiency (POI) in rats by triggering the autophagy of granulosa cells through regulating the AKT/mTOR signal pathway

Purpose Investigating the pathological mechanism underlying POI modeling in animals with VCD. Methods QRT-PCR was used to detect the expression of miR-144 in the peripheral blood of POI patients, granulosa cells and the ovary tissues. MTT assay was used to evaluate the proliferation and the concentration of E2, FSH, LH, and AMH was determined by ELISA assay. The numbers of autophagosomes were detected by transmission electron microscope and autophagic flux assay. The expression of key proteins in AKT pathway and autophagy proteins was determined by Western blot. HE staining was used to check the state of follicles in the ovary tissues. Immunohistochemistry assay was used to evaluate the expression level of p-AKT, P62, and caspase-3 in the ovary tissues. Finally, the pregnancy rate and embryo resorption rate were calculated. Results MiR-144 was down-regulated in the peripheral blood of POI patients. Deceased cell viability, down-regulated miR-144, and increased autophagosomes were observed in VCD treated granulosa cells, which were reversed by the introduction of SC79 or miR-144. The increased concentration of FSH, and LH, decreased concentration of E2 and AMH, increased number of autophagosomes, up-regulated PTEN, and inactivated AKT/m-TOR signal pathway induced by VCD in both granulosa cells and ovary tissues were significantly reversed by SC79 or miR-144. Finally, the decreased follicles and pregnancy rate, as well as the increased embryo resorption rate induced by VCD were greatly reversed by SC79 or miR-144. Conclusion VCD induced POI in rats by triggering the autophagy of granulosa cells through regulating the AKT/mTOR signal pathway.

Inhibition of MTOR signaling impairs rat embryo organogenesis by affecting folate availability

Mechanistic target of rapamycin (MTOR) is essential for embryo development by acting as a nutrient sensor to regulate cell growth, proliferation and metabolism. Folate is required for normal embryonic development and it was recently reported that MTOR functions as a folate sensor. In this work, we tested the hypothesis that MTOR functions as a folate sensor in the embryo and its inhibition result in embryonic developmental delay affecting neural tube closure and that these effects can be rescued by folate supplementation. Administration of rapamycin (0.5 mg/kg) to rats during early organogenesis inhibited embryonic ribosomal protein S6, a downstream target of MTOR Complex1, markedly reduced embryonic folate incorporation (−84%, P < 0.01) and induced embryo developmental impairments, as shown by an increased resorption rate, reduced embryo somite number and delayed neural tube closure. These alterations were prevented by folic acid administered to the dams. Differently, although an increased rate of embryonic rotation defects was observed in the rapamycin-treated dams, this alteration was not prevented by maternal folic acid supplementation. In conclusion, MTOR inhibition during organogenesis in the rat resulted in decreased folate levels in the embryo, increased embryo resorption rate and impaired embryo development. These data suggest that MTOR signaling influences embryo folate availability, possibly by regulating the transfer of folate across the maternal–embryonic interface.

A dual regulatory effect of naringenin on bone homeostasis in two diabetic mice models

Objective: Naringenin (NAR), a flavanone in citrus fruits, has been reported to have both anti-diabetic and anti-osteoporotic effects. This study aimed to explore the effect of NAR on bone homeostasis under diabetic condition. Methods: High fat diet and streptozotocin (STZ) induced type 1 diabetic (T1DM) and leptin receptor knockout (db/db) type 2 diabetic (T2DM) mice were used to evaluate NAR effects. Melbine (DMBG) was administrated as positive control. Body weight and fasting blood glucose were monitored weekly and monthly. After 8 weeks and 74 days treatment, bone mass was evaluated by microcomputed tomography ([Formula: see text]CT) including BV/TV, Tb.N, and Tb.Th, as well as histological and histomorphometric detection. Bone resorption rate indicated by C-terminal telopeptide of type I collagen (CTIX) and N-terminal propeptide of type I procollagen (PINP) was examined by ELISA assays. Results: NAR treatment reduced body weight and blood glucose in both diabetic models, and had better hypoglycemic effect than DMBG at early stage. High fat diet and STZ-treated mice lost while db/db mice gained bone mass. NAR improved bone microarchitecture by regulating the related parameters to the similar levels as the control. Osteoblast activity was little affected, but osteoclast function was decreased in NAR-treated STZ mice. Consistently, NAR reduced bone resorption rate which was increased in both diabetic models. Conclusion: NAR exerts an anti-diabetic effect by lowering elevated level of blood glucose, regulating impaired bone mass, and reducing overactivated bone resorption rate in T1DM and T2DM conditions. Naringenin has a potential to prevent diabetes induced impairment in bone.

A study of the role of calcium and oxidative stress in pathophysiology of osteoporosis in postmenopausal women-a review

The aim of this review was to identify the role of calcium and oxidative stress as factors associated with osteoporosis in postmenopausal women. There are many diseases related to post-menstruation in women, the most important of which is osteoporosis. Calcium levels remains stable until menopause, when the bone resorption rate increases in association with the decrease in ovarian estrogen production that effect the intestinal calcium absorption. On the other hand, studies support that oxidative stress is directly involved in the genesis and development of osteoporosis. However, Oxidative stress blocks the activation of osteoblasts and activates the differentiation of osteoclasts which led to increased resorption rate without adequate and proper bone formation. In conclusion, Physiological changes in postmenopausal women lead to fluctuations in calcium metabolism and oxidative stress, which may lead to the occurrence or development of osteoporosis.

Effect of Injectable Platelet-Rich Fibrin on Diced Cartilage's Viability in Rhinoplasty

Diced cartilage is one of the most widely used camouflage technique in rhinoplasty. Its variable resorption rate creates issues in postoperative time period. Platelet-rich fibrin is an autologous concentrated blood derivative containing growth factors that accelerate tissue healing. The authors evaluate the effect of injectable platelet-rich fibrin (I-PRF) on the viability of diced cartilage, which has been used for dorsum camouflage in rhinoplasty. Forty patients were randomly divided into two groups based on dorsal camouflage grafts: diced cartilage with I-PRF (study group) and diced cartilage without I-PRF (control group). Cartilage graft thickness was measured by linear superficial tissue ultrasound at the postoperative first week and the third month in both groups. The mean cartilage graft thickness loss between the first-week and third-month ultrasound measurements was 0.58 ± 0.21 mm in the study group and 0.82 ± 0.35 mm in the control group. There was significant volume loss in the control group. I-PRF was successful in reducing the resorption rate of diced cartilage on nasal dorsum by either increasing the viability or keeping its form. Sticky cartilage is an easily applicable and reliable technique that may be used to camouflage dorsal irregularities in rhinoplasty.