Study of the Structure and Bioactivity of Polysaccharides from Different Parts of Stemona tuberosa Lour.

The polysaccharides from Stemona tuberosa Lour, a kind of plant used in Chinese herbal medicine, have various pharmacological activities, such as anti-inflammatory and antioxidant properties. However, the effects of the extraction methods and the activity of polysaccharides from different parts are still unknown. Therefore, this study aimed to evaluate the effects of different extraction methods on the yields, chemical compositions, and bioactivity of polysaccharides extracted from different parts of Stemona tuberosa Lour. Six polysaccharides were extracted from the leaves, roots, and stems of Stemona tuberosa Lour through the use of hot water (i.e., SPS-L1, SPS-R1, and SPS-S1) and an ultrasound-assisted method (i.e., SPS-L2, SPS-R2, and SPS-S2). The results showed that the physicochemical properties, structural properties, and biological activity of the polysaccharides varied with the extraction methods and parts. SPS-R1 and SPS-R2 had higher extraction yields and total sugar contents than those of the other SPSs (SPS-L1, SPS-L2, SPS-S1, and SPS-S2). SPS-L1 had favorable antioxidant activity and the ability to downregulate MUC5AC expression. An investigation of the anti-inflammatory properties showed that SPS-R1 and SPS-R2 had greater anti-inflammatory activities, while SPS-R2 demonstrated the strongest anti-inflammatory potential. The results of this study indicated that SPS-L1 and SPS-L2, which were extracted from non-medicinal parts, may serve as potent natural antioxidants, but further study is necessary to explore their potential applications in the treatment of diseases. The positive anti-inflammatory effects of SPS-R1 and SPS-R2 in the roots may be further exploited in drugs for the treatment of inflammation.

Reduction in Placental Metal and Metalloid in Preeclampsia: A Case-Control Study.

Preeclampsia is a primary placental disorder, with impaired placental vascularization leading to uteroplacental hypoperfusion. We aimed to investigate differences in metal and metalloid content between the placentas of women with preeclampsia and healthy controls. This was a case-control study in 63 women with preeclampsia and 113 healthy women. Clinical data were obtained from medical records. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the placental metals and metalloids content. Compared with healthy control subjects, preeclampsia was associated with a significantly lower concentration of essential elements (magnesium, calcium, iron, copper, zinc, and selenium) in the placental tissue. After multivariable adjustment, an interquartile range (IQR) increase in selenium concentration was associated with a reduced risk of preeclampsia with an OR of 0.50 (95% CI: 0.33-0.77). The joint effects of multiple selected metals and metalloids were associated with a reduced risk of preeclampsia. The lower placental magnesium, chromium, iron, zinc, and selenium concentrations of preeclampsia cases indicate a potential link to its pathogenesis. It also provides an intriguing avenue for future research in revealing the underlying mechanisms and potential intervention strategies for preeclampsia.

Effect of transvaginal Lactobacillus supplementation on reversing lower genital tract dysbiosis and improving perinatal outcomes in PCOS patients after IVF-FET: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Significant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization-frozen embryo transfer (IVF-FET) among polycystic ovary syndrome (PCOS) patients have been previously reported by our group. We aimed to assess whether transvaginal Lactobacillus supplementation can reverse LGT dysbiosis and further improve perinatal outcomes in PCOS patients after IVF-FET. METHODS/DESIGN: This is a protocol for a multicenter, open-label, randomized controlled trial in China. Women diagnosed with PCOS who are undergoing IVF-FET treatment will be recruited. Allocation to the intervention/control arms at a ratio of 1:1 will be executed by an electronic randomization system. Participants in the intervention arm will receive the live Lactobacillus capsule vaginally for 10 consecutive days before embryo transfer, while those in the control arm will receive standard individualized care. The primary outcomes will be the clinical pregnancy rate, implantation rate, and live birth rate. 16S rRNA sequencing and liquid chromatography-mass spectrometry will be conducted to evaluate the LGT microbiome and systemic metabonomics before and after the intervention. A sample of 260 participants will provide 95% power to detect a 20% increase in the rate of clinical pregnancy (α = 0.025, one-tailed test, 15% dropout rate). A total of 300 participants will be recruited. DISCUSSION: This is the first large and multicenter randomized controlled trial aimed at assessing the efficacy of transvaginal Lactobacillus supplementation on restoring the LGT microbiome and improving perinatal outcomes in PCOS patients after IVF-FET. This pragmatic trial is promising for increasing the rates of clinical pregnancy and live birth in PCOS patients after IVF-FET. ETHICS AND DISSEMINATION: Ethical review approval was obtained from the Medical Research Ethics Committees of the International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University (15 October 2020, GKLW 2020-29). To maximize dissemination, these findings will be reported in open access publications in journals with high impact, and oral and poster conference presentations will be performed. TRIAL REGISTRATION: ChiCTR ChiCTR2000036460. Registered on 13 September 2020, https://www.chictr.org.cn/showproj.html?proj=59549 .

Effect of an individualised nutritional intervention on gestational diabetes mellitus prevention in a high-risk population screened by a prediction model: study protocol for a multicentre randomised controlled trial.

BACKGROUND: The ability of a preventive nutritional intervention to reduce the morbidity of gestational diabetes mellitus (GDM) remains controversial. We aim to assess whether GDM can be prevented by an individualised nutritional intervention in pregnant women who are at high risk for the disease based on a prediction model. METHODS/DESIGN: A multicentre randomised controlled trial was designed to assess the efficacy of an individualised nutritional intervention for the prevention of GDM in a high-risk population screened by a novel prediction model in the first trimester. Pregnant women evaluated to be at high risk for GDM by the prediction model at less than 14 gestational weeks will be included. Women with pre-existing chronic diseases, including pregestational diabetes, or who are currently prescribed medicines that affect glucose values will be excluded. Allocation to intervention/control at a ratio of 1:1 will be conducted by a computerized randomisation system. The intervention group will complete 3-day food records and receive 3 individualised nutritional consultations with professional dieticians before the oral glucose tolerance test. The primary intention of the intervention is to promote a long-term healthy dietary pattern and prevent excessive gestational weight gain throughout pregnancy. The control group will complete 3-day food records at designated gestational weeks and receive standard antenatal care according to local health care provisions. The primary outcome is the incidence of GDM according to the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG). A sample of 464 participants will provide 80% power to detect a 30% reduction in GDM incidence (α = 0.05 two tailed, 10% dropout). A total of 500 participants will be recruited. DISCUSSION: To date, this is the first randomised controlled trial aimed to evaluate the protective effect of an individualised nutritional intervention against GDM based on a logistic regression prediction model. Eligibility is not limited to obese women or singleton pregnancies, as in previous studies. This pragmatic trial is expected to provide valuable information on early screening and effective GDM prevention methods. TRIAL REGISTRATION NUMBER: ChiCTR, ChiCTR1900026963 . Registered 27 October 2019.

Curcumin-Microsphere/IR820 Hybrid Bifunctional Hydrogels for In Situ Osteosarcoma Chemo-co-Thermal Therapy and Bone Reconstruction.

Conventional biomaterial-mediated osteosarcoma therapy mainly focuses on its antitumor effect yet often fails to overcome the problem of post-treatment bone tissue defect repair. Simultaneously, minimally invasive drug delivery methods are becoming spotlights for normal tissue preservation. Herein, an injectable curcumin-microsphere/IR820 coloaded hybrid methylcellulose hydrogel (Cur-MP/IR820 gel) platform was designed for osteosarcoma therapy and bone regeneration. In vitro, the K7M2wt osteosarcoma cells were eradicated by hyperthermia and curcumin. Later, the sustained release of curcumin promoted alkaline phosphatase expression and calcium deposition of bone mesenchymal stem cells. In vivo, this hybrid hydrogel could reach tumor site via injection and turned into hydrogel due to heat sensitivity. Under the irradiation of an 808 nm laser, localized hyperthermia (∼51 °C) generated in 5 min to ablate the tumor. Meanwhile, the thermal-accelerated curcumin release and thermal-increased cell membrane permeability led to tumor cell apoptosis. Tumors in photothermal-co-chemotherapy group were successfully restrained from day 2 after treatment. After that, bone reconstruction was promoted because of sustained released curcumin. The chemo-co-thermal efficacy and osteogenic capacity of Cur-MP/IR820 hydrogel suggest a promising approach to the treatment of osteosarcoma and provide provoking inspiration for treating bone tumors and repairing bone tissue.

Amylin receptor insensitivity impairs hypothalamic POMC neuron differentiation in the male offspring of maternal high-fat diet-fed mice.

OBJECTIVE: Amylin was found to regulate glucose and lipid metabolism by acting on the arcuate nucleus of the hypothalamus (ARC). Maternal high-fat diet (HFD) induces sex-specific metabolic diseases mediated by the ARC in offspring. This study was performed to explore 1) the effect of maternal HFD-induced alterations in amylin on the differentiation of hypothalamic neurons and metabolic disorders in male offspring and 2) the specific molecular mechanism underlying the regulation of amylin and its receptor in response to maternal HFD. METHODS: Maternal HFD and gestational hyper-amylin mice models were established to explore the role of hypothalamic amylin and receptor activity-modifying protein 3 (Ramp3) in regulating offspring metabolism. RNA pull-down, mass spectrometry, RNA immunoprecipitation, and RNA decay assays were performed to investigate the mechanism underlying the influence of maternal HFD on Ramp3 deficiency in the fetal hypothalamus. RESULTS: Male offspring with maternal HFD grew heavier and developed metabolic disorders, whereas female offspring with maternal HFD showed a slight increase in body weight and did not develop metabolic disorders compared to those exposed to maternal normal chow diet (NCD). Male offspring exposed to a maternal HFD had hyperamylinemia from birth until adulthood, which was inconsistent with offspring exposed to maternal NCD. Hyperamylinemia in the maternal HFD-exposed male offspring might be attributed to amylin accumulation following Ramp3 deficiency in the fetal hypothalamus. After Ramp3 knockdown in hypothalamic neural stem cells (htNSCs), amylin was found to fail to promote the differentiation of anorexigenic alpha-melanocyte-stimulating hormone-proopiomelanocortin (α-MSH-POMC) neurons but not orexigenic agouti-related protein-neuropeptide Y (AgRP-Npy) neurons. An investigation of the mechanism involved showed that IGF2BP1 could specifically bind to Ramp3 in htNSCs and maintain its mRNA stability. Downregulation of IGF2BP1 in htNSCs in the HFD group could decrease Ramp3 expression and lead to an impairment of α-MSH-POMC neuron differentiation. CONCLUSIONS: These findings suggest that gestational exposure to HFD decreases the expression of IGF2BP1 in the hypothalami of male offspring and destabilizes Ramp3 mRNA, which leads to amylin resistance. The subsequent impairment of POMC neuron differentiation induces sex-specific metabolic disorders in adulthood.

[Study on physicochemical properties of paeonol-Helix aspersa muller nanogel and its inhibitory effects on hypertrophic scar tissue in rabbit ear].

To prepare Helix aspersa muller-paeonol nanogel( PAE-HAM-Gels) with anti-proliferative scar effect,evaluate its skin penetration,retention and irritation,and to investigate its prevention and treatment effect for hypertrophic scar in rabbit ears. The dermal retention,transdermal rate and cumulative permeability of paeonol were investigated in vitro by using the modified Franz diffusion cell and the abdominal skin of suckling pigs,SD rats and KM mice,respectively,and the in vitro permeation curves were drawn. The normal skin of the back of New Zealand rabbits was continuously treated with PAE-HAM-Gels for 7 days,and the physiological state of the skin was observed under light microscope after HE staining by using homologous left and right contrast method. The hypertrophic scar model in rabbit ears was established,and the New Zealand rabbits were randomly divided into blank group,model group,positive drug group,PAE-Gels group and PAE-HAM-Gels group. After 28 days of administration,the scar hyperplasia rate and scar elevation index( SEI) of each group were calculated; the scar tissues were taken and stained with Masson for observation of collagen fibers and muscle fibers hyperplasia under light microscope,and the expression level of TGF-ß1 in each group was detected. The Qnof PAE-HAM-Gels in aqueous solution was in line with the Higuchi equation,and its transdermal rate,cumulative permeation and dermal retention in different animal skins were all higher than those of PAE-Gels. The skin of the drug-administered group was intact,without erythema,edema or other phenomena; under light microscope,the subcutaneous tissue and the epidermal cells were neatly arranged with uniform thickness,which showed no difference from the blank group. The scar hyperplasia rate of the PAE-HAM-Gels group was 62. 50%; SEI was 2. 17±0. 33 and TGF-ß1 was( 815. 4±34. 69) ng·L~(-1),significantly different from those in model group( P<0. 01). Masson staining showed that as compared with the model group,the number of collagen fibers and muscle fibers was small and the arrangement was loose and tidy in the PAE-HAM-Gels group,with regular arrangement of chondrocytes and a small number of inflammatory cells and microvessels.PAE-HAM-Gels have good transdermal properties and dermal retention without skin irritation,offering a promising therapeutic strategy for transdermal delivery during the prevention and treatment of hypertrophic scar in rabbit ears.

[Effect of cell penetrating peptide TAT-modified liposomes loaded with salvianolic acid B on proliferation,migration and cell cycle of human skin fibroblasts].

Hypertrophic scar( HS) is a very common skin fibrosis disorder after human skin injury and wound healing. The objective of this study was to investigate the efficacy of cell penetrating peptide TAT-modified liposomes loaded with salvianolic acid B( SAB-TAT-LIP) on proliferation,migration and cell cycle of human skin fibroblasts( HSF),and preliminarily evaluate its effect on prevention and treatment of HS. HSF were cultured in vitro,and MTT assay was used to detect the inhibitory effect of SAB-TAT-LIP on cell proliferation. Cell migration was assessed by Transwell chamber method and scratch method; and cell cycle change was detected by flow cytometry. In vitro cell studies showed that blank liposome basically had no toxic effect on HSF. Different concentrations of SABTAT-LIP inhibited proliferation on HSF in varying degrees after intervention for different periods in a dose and time dependent manner;meanwhile,SAB-TAT-LIP significantly inhibited the migration and invasion of HSF. At the same time,SAB-TAT-LIP could block the cell cycle at G0/G1 phase after intervention for 48 h,P<0.01 as compared with the blank control group. Conclusively,our experimental data quantitatively demonstrate that SAB-TAT-LIP has significant inhibitory effect on cells proliferation,invasion and migration,with blocking effect on G0/G1 phase. This may offer a promising therapeutic strategy for transdermal delivery in prevention and treatment of HS.

Prenatal High Estradiol Exposure Induces Sex-Specific and Dietarily Reversible Insulin Resistance Through Decreased Hypothalamic INSR.

An adverse intrauterine environment may induce adult disease in offspring, but the mechanisms are not well understood. It is reported that fresh embryo transfer (ET) in assisted reproductive technology leads to high maternal estradiol (E2), and prenatal high E2 exposure increases the risk of organ disorders in later life. We found that male newborns and children of fresh ET showed elevated fasting insulin and homeostasis model of assessment for insulin resistance index (HOMA-IR) scores. Male mice with high prenatal estradiol exposure (HE) grew heavier than control mice and developed insulin resistance; they also showed increased food intake, with increased orexigenic hypothalamic neuropeptide Y (NPY) expression. The hypothalamic insulin receptor (INSR) was decreased in male HE mice, associated with elevated promoter methylation. Chronic food restriction (FR) in HE mice reversed insulin resistance and rescued hypothalamic INSR expression by correcting the elevated Insr promoter methylation. Our findings suggest that prenatal exposure to high E2 may induce sex-specific metabolic disorders in later life through epigenetic programming of hypothalamic Insr promoter, and dietary intervention may reverse insulin resistance by remodeling its methylation pattern.

Acupuncture may improve the absorption of baicalin from the extracts of Scutellaria baicalensis Georgi in rats with pelvic inflammation.

The aim of the present study was to explore whether acupuncture may improve the absorption of baicalin from the extracts of Scutellaria baicalensis Georgi in rats with pelvic inflammation. 24 female Sprague-Dawley (SD) rats were randomly divided into groups A (a combination of oral administration of Scutellaria baicalensis Georgi extracts and acupuncture), B (oral administration of Scutellaria baicalensis Georgi extracts), C (model group) and D (normal control group), with 6 rats in each group. After treatment, the plasma concentration of baicalin was determined using high performance liquid chromatography (HPLC), the serum levels of tumor necrosis factor-alpha (TNF-alpha) and Interleukin 6 (IL-6) were detected with enzyme-linked immunosorbent assay (ELISA). The results showed that the plasma concentration of baicalin in group A was significantly higher than in group B, and the serum levels of TNF-alpha and IL-6 in group A were significantly lower than in group B. This indicates that acupuncture at certain acupoints may significantly improve the curative effects of Scutellaria baicalensis Georgi in rats with pelvic inflammation by enhancing the absorption of baicalin from the Scutellaria baicalensis Georgi extracts.