MTHFD2-mediated redox homeostasis promotes gastric cancer progression under hypoxic conditions.

OBJECTIVES: Cancer cells undergo metabolic reprogramming to adapt to high oxidative stress, but little is known about how metabolic remodeling enables gastric cancer cells to survive stress associated with aberrant reactive oxygen species (ROS) production. Here, we aimed to identify the key metabolic enzymes that protect gastric cancer (GC) cells from oxidative stress. METHODS: ROS level was detected by DCFH-DA probes. Multiple cell biological studies were performed to identify the underlying mechanisms. Furthermore, cell-based xenograft and patient-derived xenograft (PDX) model were performed to evaluate the role of MTHFD2 in vivo. RESULTS: We found that overexpression of MTHFD2, but not MTHFD1, is associated with reduced overall and disease-free survival in gastric cancer. In addition, MTHFD2 knockdown reduces the cellular NADPH/NADP+ ratio, colony formation and mitochondrial function, increases cellular ROS and cleaved PARP levels and induces in cell death under hypoxia, a hallmark of solid cancers and a common inducer of oxidative stress. Moreover, genetic or pharmacological inhibition of MTHFD2 reduces tumor burden in both tumor cell lines and patient-derived xenograft-based models. DISCUSSION: our study highlights the crucial role of MTHFD2 in redox regulation and tumor progression, demonstrating the therapeutic potential of targeting MTHFD2.

LncRNA UCA1 promotes vasculogenic mimicry by targeting miR-1-3p in gastric cancer.

Long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been implicated in several tumors. UCA1 promotes cell proliferation, migration and invasion of GC cells, but the molecular mechanism has not been fully elucidated. This study revealed the oncogenic effects of UCA1 on cell growth and invasion. Furthermore, UCA1 expression was significantly correlated with the overall survival of GC patients, and the clinicopathological indicators, including tumor size, depth of invasion, lymph node metastasis, and TNM stage. Additionally, miR-1-3p was identified as a downstream target of UCA1, which was negatively regulated by UCA1. MiR-1-3p inhibited cell proliferation and vasculogenic mimicry (VM), and induced cell apoptosis by upregulating BAX, BAD, and tumor suppressor TP53 expression levels. Moreover, miR-1-3p almost completely reversed the oncogenic effect caused by UCA1, including cell growth, migration and VM formation. This study also confirmed UCA1 promoted tumor growth in vivo. In this study, we also revealed the correlation between UCA1 and VM formation, which is potentially crucial for tumor metastasis. Meanwhile, its downstream target miR-1-3p inhibited VM formation in GC cells. In summary, these findings indicate that UCA1/miR-1-3p axis is potential target for GC treatment.

Promotion of apoplastic oxidative burst by artificially selected GhCBSX3A enhances Verticillium dahliae resistance in upland cotton.

Verticillium wilt (VW) is a devasting disease affecting various plants, including upland cotton, a crucial fiber crop. Despite its impact, the genetic basis underlying cotton's susceptibility or defense against VW remains unclear. Here, we conducted a genome-wide association study on VW phenotyping in upland cotton and identified a locus on A13 that is significantly associated with VW resistance. We then identified a cystathionine ß-synthase domain gene at A13 locus, GhCBSX3A, which was induced by Verticillium dahliae. Functional analysis, including expression silencing in cotton and overexpression in Arabidopsis thaliana, confirmed that GhCBSX3A is a causal gene at the A13 locus, enhancing SAR-RBOHs-mediated apoplastic oxidative burst. We found allelic variation on the TATA-box of GhCBSX3A promoter attenuated its expression in upland cotton, thereby weakening VW resistance. Interestingly, we discovered that altered artificial selection of GhCBSX3A_R (an elite allele for VW) under different VW pressures during domestication and other improved processes allows specific human needs to be met. Our findings underscore the importance of GhCBSX3A in response to VW, and we propose a model for defense-associated genes being selected depending on the pathogen's pressure. The identified locus and gene serve as promising targets for VW resistance enhancement in cotton through genetic engineering.

L-tryptophan anaerobic fermentation for indole acetic acid production: Bacterial enrichment and effects of zero valent iron.

Indole acetic acid (IAA) as a plant hormone, was one of the valuable products of anaerobic fermentation. However, the enriching method remained unknown. Moreover, whether zero valent iron (ZVI) could enhance IAA production was unexplored. In this work, IAA producing bacteria Klebsiella (63 %) was enriched successfully. IAA average production rate and concentration were up to 3 mg/L/h and 56 mg/L. With addition of 1 g/L ZVI, IAA average production rate and concentration was increased for 2 and 3 folds. Mechanisms indicated ZVI increased Na+K+-ATP activity and electron transport activity for 2 folds and 1 fold. Moreover, macro transcription determined indole pyruvate pathway activity like primary-amine oxidase, indole pyruvate decarboxylase and aldehyde dehydrogenase were increased for 146 %, 187 %, and 557 %, respectively. Therefore, ZVI was suitable for enhancement IAA production from mixed culture anaerobic fermentation.

[Correlation Analysis of the Number of Hemophagocytes and Peripheral Blood Cells in Bone Marrow].

OBJECTIVE: To study the correlation between the number of hemophagocytes and peripheral blood cells in bone marrow of patients with fever of unknown origin. METHODS: A total of 465 patients with fever of unknown origin in our hospital from January 2019 to December 2021 were selected as the research objects, which was to reviewed retrospectively the correlation between the number of hemophagocytes and peripheral blood cells in bone marrow. RESULTS: The positive rates of hemophagocytes detected in the three lines decreased group, the two lines decreased group, the one line decreased group, normal group of the three lines and at least one of the three lines increased group were 86.4%, 62.1%, 38.3%, 34.6% and 33.3%, respectively. The number of hemophagocytes per unit area in the three lines decreased group was significantly higher than that in the other four groups ( P < 0.001). The number of hemophagocytes per unit area in the two lines decreased group was higher than that in the one line decreased group, normal group of three lines and at least one of the three lines increased group ( P < 0.01). There was no significant difference in the number of hemophagocytes per unit area between the group with a decreased number of one line and the other two groups with a normal number of three lines and the group with at least one increased number of three lines (P >0.05). The missed rates of hemophagocytes in the five groups were 15.78%, 22.03%, 62.22%, 77.78% and 53.84%, respectively. CONCLUSION: For patients with fever of unknown origin, especially those with obvious decrease in the number of three lines and two lines in peripheral blood cells, which should pay attention to the detection of hemophagocytes in bone marrow. Meanwhile, if the number of three lines was normal even at least one of the three lines increased, the presence of hemophagocytes in the bone marrow slice should be also carefully observed.

Different regions and environments have critical roles on yield, main quality and industrialization of an industrial purple-fleshed sweetpotato (Ipomoea batatas L. (Lam.)) "Xuzishu8".

Purple-fleshed sweetpotato (PFSP) (Ipomoea batatas (L.) Lam), whose flesh is purple to dark purple, is a special variety type of sweetpotato, which has the characteristics of food crop, industrial crop and medicinal crop. The storage root (SR) of PFSP is rich in anthocyanins, starch, protein, soluble sugar, mineral elements, polyphenol, dietary fiber and so on, which has balanced and comprehensive nutritional value. And in recent years, its unique nutritional elements are increasingly known for their health functions. At present, there is no article on the characteristics and quality analysis of industrial xz8 variety. To explore the influence of different environments on the processing quality of xz8, we selected nine regions (Xuzhou, Jiawang, Pizhou, Xinyi, Peixian, Sihong, Yanchen, Xiangyang and Tianshui) to measure its yield and quality changes. The data demonstrated that xz8 has a very consistent high yield performance. In Tianshui, the anthocyanins, protein and minerals contents were significantly higher and yield also above average. Moreover, the variety with the lowest starch content exhibited the best taste. On the basis of the above results, it suggested that quite practicable to promote xz8 cultivation and suitable for processing in these areas. Thus, our present findings improve our understanding of xz8 variety and provide the basis for the industrial production of PFSP with strong prospects for success.

The press-assisted fusion scheme significantly mitigates the quantity of HVJ-E required in mitochondrial replacement techniques.

In brief: The impact of HVJ-E employed in mitochondrial replacement techniques (MRTs) on embryonic development remains uncertain. This study has exhibited the influence of HVJ-E utilized in MRTs on embryonic development and has devised a novel HVJ-E-induced fusion approach to curtail the amount of HVJ-E employed in MRTs. Abstract: Mitochondrial replacement techniques (MRTs) provide a viable option for women carrying pathogenic mitochondrial DNA (mtDNA) variants to conceive disease-free offspring with a genetic connection. In comparison to electrofusion, HVJ-E-induced fusion has been identified as the most promising approach for clinical translation of MRTs due to its absence of electrical interference. However, despite confirmation of the absence of RNA activity in HVJ-E, a reduction in blastocyst quality has been observed in various MRTs studies utilizing the HVJ-E-induced fusion scheme. Recent investigations have revealed a dose-dependent elevation of reactive oxygen species (ROS) levels in various cancer cells incubated with HVJ-E. However, the impact of HVJ-E as a sole determinant on embryonic development in MRTs remains unverified. This investigation establishes that the augmented concentration of HVJ-E utilized in the conventional HVJ-E fusion protocol is an autonomous variable that influences embryonic development in MRTs. This effect may be attributed to amplified DNA damage resulting from heightened levels of ROS in reconstructed embryos. To mitigate the presence of HVJ-E in reconstructed zygotes while maintaining optimal fusion efficiency in MRTs, a novel HVJ-E-induced fusion approach was devised, namely, press-assisted fusion. This technique offers potential advantages in reducing detrimental factors that impede embryo development in MRTs.

The mechanisms of ferroptosis and its role in atherosclerosis.

Ferroptosis is a newly identified form of non-apoptotic programmed cell death, characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species (ROS) and peroxidation of membrane polyunsaturated fatty acid phospholipids (PUFA-PLs). Ferroptosis is unique among other cell death modalities in many aspects. It is initiated by excessive oxidative damage due to iron overload and lipid peroxidation and compromised antioxidant defense systems, including the system Xc-/ glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathway and the GPX4-independent pathways. In the past ten years, ferroptosis was reported to play a critical role in the pathogenesis of various cardiovascular diseases, e.g., atherosclerosis (AS), arrhythmia, heart failure, diabetic cardiomyopathy, and myocardial ischemia-reperfusion injury. Studies have identified dysfunctional iron metabolism and abnormal expression profiles of ferroptosis-related factors, including iron, GSH, GPX4, ferroportin (FPN), and SLC7A11 (xCT), as critical indicators for atherogenesis. Moreover, ferroptosis in plaque cells, i.e., vascular endothelial cell (VEC), macrophage, and vascular smooth muscle cell (VSMC), positively correlate with atherosclerotic plaque development. Many macromolecules, drugs, Chinese herbs, and food extracts can inhibit the atherogenic process by suppressing the ferroptosis of plaque cells. In contrast, some ferroptosis inducers have significant pro-atherogenic effects. However, the mechanisms through which ferroptosis affects the progression of AS still need to be well-known. This review summarizes the molecular mechanisms of ferroptosis and their emerging role in AS, aimed at providing novel, promising druggable targets for anti-AS therapy.

Simply and Cheaply Prepared Liposomal Membrane for Nanocarriers: High Encapsulation Efficiency Based on Broad Regulation of Surface Charges and pH-Switchable Performance.

The zeta potential of nanoparticles impacts their distribution and metabolism in the body as well as their interaction with medications of varying charges, hence altering therapeutic efficacy and safety. In this paper, the external charges of liposomes were regulated by utilizing a simple and economical method based on competition for protons of cationic chitosan (CS) and anion hyaluronic acid (HA). The charge regulation of a liposomal membrane is generally accomplished by adjusting the ratio of charged lipids within a liposome (e.g., cationic DOTAP or anionic DOPS), the stability of which was maintained by the coating materials of cationic chitosan (CS) or anion hyaluronic acid (HA). A series of nanoparticles could respond to pH-stimulation with adjustable surface charge. Moreover, the sizes of liposomes coated with CS and HA remain within a narrow range. In vitro cytotoxicity tests revealed that the nanocarriers were safe, and the nanoparticles containing antitumor medicines were efficient in tumor therapy. Considering liposomes with different external surface charges could be aimed at diverse therapy purposes. The strategies for regulating liposomal surface charges with high encapsulation rates and certain release cycles reported here could provide a versatile platform as carriers for the delivery of drugs and other macromolecules into human bodies.

Plasmodium immunotherapy combined with gemcitabine has a synergistic inhibitory effect on tumor growth and metastasis in murine Lewis lung cancer models.

Objective: Our previous studies have demonstrated that Plasmodium immunotherapy (infection) has antitumor effects in mice. However, as a new form of immunotherapy, this therapy has a weakness: its specific killing effect on tumor cells is relatively weak. Therefore, we tested whether Plasmodium immunotherapy combined with gemcitabine (Gem), a representative chemotherapy drug, has synergistic antitumor effects. Methods: We designed subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) models to test the antitumor effect of Plasmodium chabaudi ASS (Pc) infection in combination with Gem treatment and explored its underlying mechanisms. Results: We found that both Pc infection alone and Gem treatment alone significantly inhibited tumor growth in the subcutaneous model, and combination therapy was more effective than either monotherapy. Monotherapy only tended to prolong the survival of tumor-bearing mice, while the combination therapy significantly extended the survival of mice, indicating a significant synergistic effect of the combination. In the mechanistic experiments, we found that the combination therapy significantly upregulated E-cadherin and downregulated Snail protein expression levels, thus inhibiting epithelial-mesenchymal transition (EMT) of tumor cells, which may be due to the blockade of CXCR2/TGF-ß-mediated PI3K/Akt/GSK-3ß signaling pathway. Conclusion: The combination of Pc and Gem plays a synergistic role in inhibiting tumor growth and metastasis, and prolonging mice survival in murine lung cancer models. These effects are partially attributed to the inhibition of EMT of tumor cells, which is potentially due to the blockade of CXCR2/TGF-ß-mediated PI3K/Akt/GSK-3ß/Snail signaling pathway. The clinical transformation of Plasmodium immunotherapy combined with Gem for lung cancer is worthy of expectation.

A novel CT-responsive hydrogel for the construction of an organ simulation phantom for the repeatability and stability study of radiomic features.

Radiomic features have demonstrated reliable outcomes in tumor grading and detecting precancerous lesions in medical imaging analysis. However, the repeatability and stability of these features have faced criticism. In this study, we aim to enhance the repeatability and stability of radiomic features by introducing a novel CT-responsive hydrogel material. The newly developed CT-responsive hydrogel, mineralized by in situ metal ions, exhibits exceptional repeatability, stability, and uniformity. Moreover, by adjusting the concentration of metal ions, it achieves remarkable CT similarity comparable to that of human organs on CT scans. To create a phantom, the hydrogel was molded into a universal model, displaying controllable CT values ranging from 53 HU to 58 HU, akin to human liver tissue. Subsequently, 1218 radiomic features were extracted from the CT-responsive hydrogel organ simulation phantom. Impressively, 85-97.2% of the extracted features exhibited good repeatability and stability during coefficient of variability analysis. This finding emphasizes the potential of CT-responsive hydrogel in consistently extracting the same features, providing a novel approach to address the issue of repeatability in radiomic features.

In vitro and in vivo anticancer activity of novel Rh(III) and Pd(II) complexes with pyrazolopyrimidine derivatives.

Six pyrazolopyrimidine rhodium(III) or palladium(II) complexes, [Rh(L1)(H2O)Cl3] (1), [Rh(L2)(CH3OH)Cl3] (2), [Rh(L3)(H2O)Cl3] (3), [Rh2(L4)Cl6]·CH3OH (4), [Rh(L5)(CH3CN)Cl3]·0.5CH3CN (5), and [Pd(L5)Cl2] (6), were synthesized and characterized. These complexes showed high cytotoxicity against six tested cancer cell lines. Most of the complexes showed higher cytotoxicity to T-24 cells in vitro than cisplatin. Mechanism studies indicated that complexes 5 and 6 induced G2/M phase cell cycle arrest through DNA damage, and induced apoptosis via endoplasmic reticulum stress response. In addition, complex 5 also induced cell apoptosis via mitochondrial dysfunction. Complexes 5 and 6 showed low in vivo toxicity and high tumor growth inhibitory activity in mouse tumor models. The inhibitory effect of rhodium complex 5 on tumor growth in vivo was more pronounced than that of palladium complex 6.

Toward flame-retardant and toughened poly(lactic acid)/cross-linked polyurethane blends via the interfacial reaction with the modified bio-based flame retardants.

Incorporating bio-based flame retardants into polylactic acid (PLLA) to improve flame retardancy has always been the focus of research, but the improvement of flame retardancy is usually at the expense of mechanical properties. How to successfully balanced the material's mechanical and combustion properties has puzzled many scholars. Herein, ammonium polyphosphate (APP) and chitosan (CS) were used as acid source and carbon source respectively. Biological flame retardant APP@CS was designed and synthesized by electrostatic self-assembly method. In addition, toughened PLLA composites were prepared by reactive blending with the in-situ formed polyurethane (PU) as toughening phase. The results show that the CS shell not only reduces the hydrophilicity of the flame retardant, but also has good flame retardant property because of its excellent char forming property. The addition of 10 phr APP@CS can endow PLLA/crosslinked PU (CPU) with UL-94 V-2 rating and a LOI value of 24.9 %. Interestingly, CS shell participates in the in-situ reaction, which improves the mechanical properties of the composite with elongation at break of 74 %, which is higher than that of sample doped with the same amount of APP. This work provides guidance for the high performance modification of PLLA and is expected to expand the practical application range.

Rhodium(III)-Picolinamide Complexes Act as Anticancer and Antimetastasis Agents via Inducing Apoptosis and Autophagy.

As a continuation of our endeavors in discovering metal-based drugs with cytotoxic and antimetastatic activities, herein, we reported the syntheses of 11 new rhodium(III)-picolinamide complexes and the exploration of their potential anticancer activities. These Rh(III) complexes showed high antiproliferative activity against the tested cancer cell lines in vitro. The mechanism study indicated that Rh1 ([Rh(3a)(CH3CN)Cl2]) and Rh2 ([Rh(3b)(CH3CN)Cl2]) inhibited cell proliferation by multiple modes of action via cell cycle arrest, apoptosis, and autophagy and inhibited cell metastasis via FAK-regulated integrin ß1-mediated suppression of EGFR expression. Furthermore, Rh1 and Rh2 significantly inhibited bladder cancer growth and breast cancer metastasis in a xenograft model. These rhodium(III) complexes could be developed as potential anticancer agents with antitumor growth and antimetastasis activity.

Prognostic model for the prediction of cancer-specific survival in elderly patients with stage I-III gastric cancer.

Elderly patients with gastric cancer (GC) exhibit unique physiological conditions and population characteristics. However, no efficient predictive tools have been developed for this patient subgroup. We extracted data on elderly patients diagnosed with stage I-III GC between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database, and applied Cox regression analysis to examine factors associated with cancer-specific survival (CSS). A prognostic model was developed and validated to predict CSS. We assessed the performance of the prognostic model and stratified patients based on their prognostic scores. Notably, 11 independent prognostic factors, including age, race, grade, the tumor-node-metastasis (TNM) stage, T-stage, N-stage, operation, tumor size, regional nodes, radiation, and chemotherapy, associated with CSS were identified using multivariate Cox regression. A nomogram was constructed based on these predictors. The C-index score of the nomogram was 0.802 (95% (confidence interval) [CI]: 0.7939-0.8114), which is superior to the American Joint Commission on Cancer (AJCC) TNM staging prediction ability in the training cohort (C-index: 0.589; 95% CI: 0.5780-0.6017). Based on the receiver operating characteristic (ROC) and calibration curve, the predicted value of the nomogram demonstrated a satisfactory accuracy with the actual observation value. Additionally, decision curve analysis (DCA) showed that the nomogram had a more ideal clinical net benefit than TNM staging. Survival analysis of the different risk groups confirmed the noteworthy clinical and statistical utility of the nomogram in prognosis stratification. This retrospective study reports the successful creation and validation of a nomogram for predicting CSS at 1-, 3- and 5-years in elderly patients with stage I-III GC. This nomogram critically guides personalized prognostic assessments and may contribute to clinical decision-making and consultation for postoperative survival.

Biodegradation of trace sulfonamide antibiotics accelerated by substrates across oxic to anoxic conditions during column infiltration experiments.

Frequent occurrence of trace organic contaminants in aquatic environments, such as sulfonamide antibiotics in rivers receiving reclaimed water, is concerning. Natural attenuation by soil and sediment is increasingly relied upon. In the case of riverbank filtration for water purification, the reliability of antibiotic attenuation has been called into question due to incomplete understanding of their degradation processes. This study investigated influence of substrates and redox evolution along infiltration path on biotransformation of sulfonamides. Eight sand columns (length: 28 cm) with a riverbed sediment layer at 3-8 cm were fed by groundwater-sourced tap water spiked with 1 µg/L of sulfadiazine (SDZ), sulfamethazine (SMZ), and sulfamethoxazole (SMX) each, with or without amendments of dissolved organic carbon (5 mg-C/L of 1:1 yeast and humics) or ammonium (5 mg-N/L). Two flow rates were tested over 120 days (0.5 mL/min and 0.1 mL/min). Iron-reducing conditions persisted in all columns for 27 days during the initial high flow period due to respiration of sediment organics, evolving to less reducing conditions until the subsequent low flow period to resume more reducing conditions. With surplus substrates, the spatial and temporal patterns of redox conditions differentiated among columns. The removal of SDZ and SMZ in effluents was usually low (15 ± 11%) even with carbon addition (14 ± 9%), increasing to 33 ± 23% with ammonium addition. By contrast, SMX removal was higher and more consistent among columns (46 ± 21%), with the maximum of 64 ± 9% under iron-reducing conditions. When sulfonamide removal was compared between columns for the same redox zones during infiltration, their enhancements were always associated with the availability of dissolved or particulate substrates, suggesting co-metabolism. Manipulation of the exposure time to optimal redox conditions with substrate amendments, rather than to simply prolong the overall residence time, is recommended for nature-based solutions to tackle target antibiotics.

[Effect of "Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion on the expression of Fas/FADD/Caspase-8 of death receptor pathway in rats with primary ovarian insufficiency].

OBJECTIVE: To explore the effect of "Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion on the ovarian function in the rats with primary ovarian insufficiency (POI) and the potential effect mechanism based on the Fas/FADD/Caspase-8 of death receptor pathway. METHODS: Forty-eight female SD rats were randomly divided into a blank group, a model group, a medication group and an acupuncture group, with 12 rats in each group. Except in the blank group, the rats in the other groups were intraperitoneally injected with cyclophosphamide to establish the POI model. In the acupuncture group, after successful modeling, the intervention was given with "Zhibian" (BL 54)-to- "Shuidao" (ST 28) needle insertion, once daily, 30 min in each intervention; and the duration of intervention was 4 weeks. In the medication group, estradiol valerate tablets were administered intragastrically, 0.09 mg•kg-1•d-1, for 4 weeks. The general situation and the estrous cycle of the rats were compared among groups. Using ELISA, the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) in the serum were detected. HE staining was adopted to observe the morphological changes of ovarian tissue of rats. The protein expression of Fas, FADD and Caspase-8 in ovarian tissue was detected with immunohistochemistry and Western blot. RESULTS: After modeling, except the rats of the blank group, the rats of the other groups had dry fur, lost hair, low spirits, reduced food intake, increased urination and loose stool. After intervention, the stool became regular gradually in the acupuncture group and the medication group. The percentage of estrous cycle disturbance was increased in the rats of the model group when compared with the blank group (P<0.01); in comparison with the model group, the percentages of estrous cycle disturbance were reduced in the acupuncture group and the medication group after intervention (P<0.01). When compared with the blank group, the body mass and E2 content in the serum were lower (P<0.01), the levels of FSH and LH in the serum and the protein expression levels of Fas, FADD and Caspase-8 were increased (P<0.01) in the model group. Compared with the model group, the body mass and E2 contents in the serum were higher (P<0.01), the levels of FSH and LH in the serum and the protein expression levels of Fas, FADD and Caspase-8 were reduced (P<0.01) in the acupuncture group and the medication group. CONCLUSION: "Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion can effectively improve the ovarian function of POI rats, and its effect mechanism may be related to regulating the serum sex hormone levels, reducing the expression of Fas, FADD and Caspase-8 in ovarian tissue and retarding apoptosis of ovarian cells.

[Effect of penetrative needling of "Zhibian" (BL54) through "Shuidao" (ST28) on expression of TRAIL and its receptors in rats with premature ovarian insufficiency].

OBJECTIVE: To observe the effect of penetrative needling of "Zhibian" (BL54) through "Shuidao" (ST28) on the expressions of death receptor pathway-related protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, as death receptor 4 (DR4), death receptor 5 (DR5), decoy receptor 1 (DcR1) and decoy receptor 2 (DcR2) in premature ovarian insufficiency (POI) rats, so as to explore its mechanisms underlying improvement of POI. METHODS: Forty female SD rats were randomly divided into blank control, model, penetrative needling and medication (estradiol valerate) groups, with 10 rats in each group. The POI model was established by intraperitoneal injection of cyclophosphamide (D1: 50 mg·kg-1·d-1, D2 to D15: 8 mg·kg-1·d-1, for a total of 15 d). After successful modeling, the rats in the penetrative needling group received penetrative needling of BL54 through ST28, with the needle retained for 30 min, once a day for a total of 4 weeks. Rats of the medication group received gavage of estradiol valerate (0.09 mg·kg-1·d-1) once daily for 4 weeks. After the intervention, the content of serum follicles of stimulation hormone (FSH),lateinizing hormone (LH),estradiol (E2) and vascular endothelial growth factor (VEGF) were assayed using enzyme-linked immunosorbent assay, and histopathological changes of ovarian tissue and the number of follicles were observed under light microscope after H.E. staining. The expression levels of TRAIL, DR4, DR5, DcR1, DcR2, and Fas-associated death domain (FADD) in ovarian tissues were detected using quantitative real-time PCR, and the immunoactivity of ovarian TRAIL, DR4 and DR5 detected using immunohistochemistry. The body weight and the damp weight of ovary were measured for calculating the ovarian coefficient. RESULTS: Compared with the blank control group, the E2 and VEGF contents, ovarian coefficient, and the number of the primary, secondary and sinus follicles were significantly decreased (P<0.01) in the model group, whereas FSH and LH contents, the atretic follicle number, TRAIL, DR4 and DR5 immunoactivity, and the expression levels of TRAIL, DR4, DR5 and FADD mRNAs considerably increased in the model group (P<0.01). In comparison with the model group, the decrease of the VEGF content, ovarian coefficient, and the number of the primary, secondary and sinus follicles, and the increase of the atretic follicle number, TRAIL, DR4 and DR5 immunoactivity, and expression levels of TRAIL, DR4, DR5 and FADD mRNAs were reversed in both penetrative needling and medication groups (P<0.01, P<0.05). The number of primary follicles was significantly more in the medication group than in the penetrative needling group (P<0.01). CONCLUSION: Penetrative needling of BL54 and ST28 can improve ovarian weight and promote follicular development in POI rats, which may be associated with its function in down-regulating the expression of pro-apoptotic proteins TRAIL, DR4, DR5 and FADD of the death receptor pathway to inhibit apoptosis of ovarian granulosa cells.