Licochalcone Mediates the Pain Relief by Targeting the Voltage-Gated Sodium Channel.

Licorice is a traditional Chinese medicine and recorded to have pain relief effects in national pharmacopoeia, but the mechanisms behind these effects have not been fully explored. Among the hundreds of compounds in licorice, licochalcone A (LCA) and licochalcone B (LCB) are two important components belonging to the chalcone family. In this study, we compared the analgesic effects of these two licochalcones and the molecular mechanisms. LCA and LCB were applied in cultured dorsal root ganglion (DRG) neurons, and the voltage-gated sodium (NaV) currents and action potentials were recorded. The electrophysiological experiments showed that LCA can inhibit NaV currents and dampen excitabilities of DRG neurons, whereas LCB did not show inhibition effect on NaV currents. Because the NaV1.7 channel can modulate Subthreshold membrane potential oscillations in DRG neuron, which can palliate neuropathic pain, HEK293T cells were transfected with NaV1.7 channel and recorded with whole-cell patch clamp. LCA can also inhibit NaV1.7 channels exogenously expressed in HEK293T cells. We further explored the analgesic effects of LCA and LCB on formalin-induced pain animal models. The animal behavior tests revealed that LCA can inhibit the pain responses during phase 1 and phase 2 of formalin test, and LCB can inhibit the pain responses during phase 2. The differences of the effects on NaV currents between LCA and LCB provide us with the basis for developing NaV channel inhibitors, and the novel findings of analgesic effects indicate that licochalcones can be developed into effective analgesic medicines. SIGNIFICANCE STATEMENT: This study found that licochalcone A (LCA) can inhibit voltage-gated sodium (NaV) currents, dampen excitabilities of dorsal root ganglion neurons, and inhibit the NaV1.7 channels exogenously expressed in HEK293T cells. Animal behavior tests showed that LCA can inhibit the pain responses during phase 1 and phase 2 of formalin test, whereas licochalcone B can inhibit the pain responses during phase 2. These findings indicate that licochalcones could be the leading compounds for developing NaV channel inhibitors and effective analgesic medicines.

Novel xanthone antibacterials: Semi-synthesis, biological evaluation, and the action mechanisms.

α-Mangostin (α-MG) has demonstrated to display potent activities against Gram-positive bacterial. However, the contribution of phenolic hydroxyl groups of α-MG to the antibacterial activity remains obscure, severely hampering selection of structure modification to develop more potential α-MG-based anti-bacterial derivatives. Herein, twenty-one α-MG derivatives are designed, synthesized and evaluated for the antibacterial activities. The structure activity relationships (SARs) reveal that the contribution of the phenolic groups ranks as C3 > C6 > C1, and the phenolic hydroxyl group at C3 is essential to the antibacterial activity. Of note, compared to the parent compound α-MG, 10a with one acetyl at C1 exhibits the higher safety profiles due to its higher selectivity and no hemolysis, and the more potent antibacterial efficacy in an animal skin abscess model. Our evidences further present that, in comparison with α-MG, 10a has a stronger ability in depolarizing membrane potentials and leads to more leakage of bacterial proteins, consistent with the results observed by transmission electron microscopy (TEM). Transcriptomics analysis demonstrates those observations possibly relate to disturbed synthesis of proteins participating in the biological process of membrane permeability and integrity. Collectively, our findings provide a valuable insight for developing α-MG-based antibacterial agents with little hemolysis and new action mechanism via structural modifications at C1.

Patch-Transformer Network: A Wearable-Sensor-Based Fall Detection Method.

Falls can easily cause major harm to the health of the elderly, and timely detection can avoid further injuries. To detect the occurrence of falls in time, we propose a new method called Patch-Transformer Network (PTN) wearable-sensor-based fall detection algorithm. The neural network includes a convolution layer, a Transformer encoding layer, and a linear classification layer. The convolution layer is used to extract local features and project them into feature matrices. After adding positional coding information, the global features of falls are learned through the multi-head self-attention mechanism in the Transformer encoding layer. Global average pooling (GAP) is used to strengthen the correlation between features and categories. The final classification results are provided by the linear layer. The accuracy of the model obtained on the public available datasets SisFall and UnMib SHAR is 99.86% and 99.14%, respectively. The network model has fewer parameters and lower complexity, with detection times of 0.004 s and 0.001 s on the two datasets. Therefore, our proposed method can timely and accurately detect the occurrence of falls, which is important for protecting the lives of the elderly.

α-naphthoflavone-derived cytochrome P450 (CYP)1B1 degraders specific for sensitizing CYP1B1-mediated drug resistance to prostate cancer DU145: Structure activity relationship.

We previously discovered extrahepatic cytochrome P450 1B1 (CYP1B1) degraders able to overcome drug resistance toward docetaxel using a PROTACs technology, however, the underexplored structure activity relationships and poor water solubility posed a major hurdle in the development of CYP1B1 degraders. Herein, continuous efforts are made to develop more promising α-naphthoflavone (ANF)-derived chimeras for degrading CYP1B1. Guided by the strongest ANF-derived CYP1B1 degrader 3a we ever reported, 17 ANF analogues are designed and synthesized to evaluate the CYP1B1 degradation and resultant resistance reversal. In degrading CYP1B1 and sensitizing drug resistance, 4d with a 1, 5-cis triazole coupling mode at (C3') of B ring of ANF exhibited the similar potency as 3a carrying a 1, 4-trans triazole fragment at (C4') of B ring, but more obvious selectivity of 4d toward CYP1B1 over CYP1A2 is observed. When an oxygen was inserted into the linker of 4d, 4f demonstrated better water solubility, a more potent ability in degrading CYP1B1 and reversing drug resistance, and a promising selectivity. Collectively, a substitution position, an alkyne-azide cyclization and a liker type significantly affect the ability of ANF-thalidomide conjugates in eliminating drug resistance of CYP1B1-expressing DU145 (DU145/CY) cells to docetaxel via targeted CYP1B1 degradation.

Modeling the crosstalk between the circadian clock and ROS in Neurospora crassa.

The circadian clock regulates the expression of clock-controlled genes and adapts to environmental changes. Reactive oxygen species (ROS) also undergo circadian rhythms and have a role in circadian timekeeping. To elucidate crosstalk between ROS and the circadian clock in Neurospora crassa, we build an integrative network model, characterizing the circadian oscillator, ROS system and their interactions. Notably, the (de)phosphorylation and nuclear-cytoplasmic shuttling of clock proteins are modeled in detail. Simulation results quantitatively reproduce the essential features of circadian rhythm (both in constant darkness and under light/dark cycles) and the changes in period length and phase when ROS levels are altered under diverse conditions. This work clarifies the effects of three interactions between ROS and the clock on the circadian rhythm, suggesting that the regulation of WCC activity by protein phosphatase 2A in an O2--dependent manner plays a predominant role. The functional significance of such modulations is also discussed.

Oncofetal long noncoding RNA PVT1 promotes proliferation and stem cell-like property of hepatocellular carcinoma cells by stabilizing NOP2.

UNLABELLED: Many protein-coding oncofetal genes are highly expressed in murine and human fetal liver and silenced in adult liver. The protein products of these hepatic oncofetal genes have been used as clinical markers for the recurrence of hepatocellular carcinoma (HCC) and as therapeutic targets for HCC. Herein we examined the expression profiles of long noncoding RNAs (lncRNAs) found in fetal and adult liver in mice. Many fetal hepatic lncRNAs were identified; one of these, lncRNA-mPvt1, is an oncofetal RNA that was found to promote cell proliferation, cell cycling, and the expression of stem cell-like properties of murine cells. Interestingly, we found that human lncRNA-hPVT1 was up-regulated in HCC tissues and that patients with higher lncRNA-hPVT1 expression had a poor clinical prognosis. The protumorigenic effects of lncRNA-hPVT1 on cell proliferation, cell cycling, and stem cell-like properties of HCC cells were confirmed both in vitro and in vivo by gain-of-function and loss-of-function experiments. Moreover, mRNA expression profile data showed that lncRNA-hPVT1 up-regulated a series of cell cycle genes in SMMC-7721 cells. By RNA pulldown and mass spectrum experiments, we identified NOP2 as an RNA-binding protein that binds to lncRNA-hPVT1. We confirmed that lncRNA-hPVT1 up-regulated NOP2 by enhancing the stability of NOP2 proteins and that lncRNA-hPVT1 function depends on the presence of NOP2. CONCLUSION: Our study demonstrates that the expression of many lncRNAs is up-regulated in early liver development and that the fetal liver can be used to search for new diagnostic markers for HCC. LncRNA-hPVT1 promotes cell proliferation, cell cycling, and the acquisition of stem cell-like properties in HCC cells by stabilizing NOP2 protein. Regulation of the lncRNA-hPVT1/NOP2 pathway may have beneficial effects on the treatment of HCC.

Melatonin synergistically enhances docetaxel induced endoplasmic reticulum stress to promote apoptosis by suppressing NF-κB activation in cervical cancer.

Cervical cancer is the fourth most common malignancy in women globally. Although chemotherapy significantly improves the survival of cervical cancer patients, the development of drug resistance is inevitable. In the present study, our study showed that melatonin suppressed the proliferation, cell survival, colony formation, and the ability of adhering to fibronectin in cervical cancer cells. Our data suggested that docetaxel insensitivity was caused by NF-κB pathway activation, and followed by reducing endoplasmic reticulum stress and apoptosis. We showed that melatonin functioned as an oncostatic agent via inhibition of NF-κB signaling in cervical cancer cells. Interestingly, melatonin not only reduced the basal and inducible NF-κB pathway activation, but also prevented docetaxel induced NF-κB pathway activation by stabilizing IκBα protein. Importantly, inhibition of NF-κB pathway activation by melatonin abrogated the protective effect of NF-κB activation on docetaxel provoked endoplasmic reticulum stress, and further enhanced endoplasmic reticulum stress and apoptosis to produce synergistic oncostatic effects in cervical cancer cells. In summary, we revealed that melatonin was a novel agent to enhance docetaxel sensitivity by abolishing NF-κB activation and aggravating endoplasmic reticulum stress. Our results might provide a rationale for the clinical application of melatonin to overcome docetaxel resistance in cervical cancer patients.

Disability risk prediction model based on machine learning among Chinese healthy older adults: results from the China Health and Retirement Longitudinal Study.

Background: Predicting disability risk in healthy older adults in China is essential for timely preventive interventions, improving their quality of life, and providing scientific evidence for disability prevention. Therefore, developing a machine learning model capable of evaluating disability risk based on longitudinal research data is crucial. Methods: We conducted a prospective cohort study of 2,175 older adults enrolled in the China Health and Retirement Longitudinal Study (CHARLS) between 2015 and 2018 to develop and validate this prediction model. Several machine learning algorithms (logistic regression, k-nearest neighbors, naive Bayes, multilayer perceptron, random forest, and XGBoost) were used to assess the 3-year risk of developing disability. The optimal cutoff points and adjustment parameters are explored in the training set, the prediction accuracy of the models is compared in the testing set, and the best-performing models are further interpreted. Results: During a 3-year follow-up period, a total of 505 (23.22%) healthy older adult individuals developed disabilities. Among the 43 features examined, the LASSO regression identified 11 features as significant for model establishment. When comparing six different machine learning models on the testing set, the XGBoost model demonstrated the best performance across various evaluation metrics, including the highest area under the ROC curve (0.803), accuracy (0.757), sensitivity (0.790), and F1 score (0.789), while its specificity was 0.712. The decision curve analysis (DCA) indicated showed that XGBoost had the highest net benefit in most of the threshold ranges. Based on the importance of features determined by SHAP (model interpretation method), the top five important features were identified as right-hand grip strength, depressive symptoms, marital status, respiratory function, and age. Moreover, the SHAP summary plot was used to illustrate the positive or negative effects attributed to the features influenced by XGBoost. The SHAP dependence plot explained how individual features affected the output of the predictive model. Conclusion: Machine learning-based prediction models can accurately evaluate the likelihood of disability in healthy older adults over a period of 3 years. A combination of XGBoost and SHAP can provide clear explanations for personalized risk prediction and offer a more intuitive understanding of the effect of key features in the model.

Efficient, biosafe and tissue adhesive hemostatic cotton gauze with controlled balance of hydrophilicity and hydrophobicity.

Cotton gauze is a widely used topical hemostatic material for bleeding control, but its high blood absorption capacity tends to cause extra blood loss. Therefore, development of rapid hemostatic cotton gauze with less blood loss is of great significance. Here, we develop an efficient hemostatic cotton gauze whose surface is slightly modified with a catechol compound which features a flexible long hydrophobic alkyl chain terminated with a catechol group. Its hemostatic performance in animal injuries is superior to standard cotton gauze and Combat GauzeTM. Its biosafety is similar to cotton gauze and rebleeding hardly occurs when the gauze is removed. Here, we show its hemostatic capability is attributable to the rapid formation of big and thick primary erythrocyte clots, due to its effective controlling of blood movement through blocking effect from tissue adhesion by catechol, blood wicking in cotton, and the hydrophobic effect from long alkyl chains.

Tough polyacrylamide-tannic acid-kaolin adhesive hydrogels for quick hemostatic application.

Adhesive hydrogels for wet and dynamic tissues are important for biomedical applications in order to withstand cyclic loading such as in the case of hemorrhaging control on the curved skins and heart tissues. However, the fabrication of hydrogels with strong mechanical properties, high adhesion strength, and hemostatic efficiency remains a big challenge. Inspired by the great adhesive behavior of mussels and Arion subfuscus, novel adhesive and hemostatic polyacrylamide-tannic acid-kaolin (PAAm-TA-KA) hydrogels were reported in this work. The hydrogels displayed high strength and toughness due to their physical and chemical crosslinking structures. The abundant catechol groups on tannic acid endow the hydrogels with strong and durable adhesion strength of up to 500 kPa on porcine skin. When applied onto human skin, the hydrogels could be easily peeled off without leaving any remains and causing any damages. The kaolin nanoparticles incorporated in the PAAm-TA-KA hydrogels not only served as a physical crosslinking agent, but an activator of the blood clotting factor FXII for accelerating the formation of thrombus. The strong tissue adhesion and blood coagulant potential of the PAAm-TA-KA hydrogels imparted them high hemostatic efficiency. The free-standing, adhesive, tough, cytocompatible, and hemostatic hydrogels are highly promising for traumatic bleeding control materials.

[Signal transduction of BMP/Smad and its relationship with mammalian folliculogenesis].

BMPs belong to the transforming growth factor-b superfamily. BMPs have been proved to have extensive biological functions in mammals, including growth regulation, cell proliferation and differentiation. More and more evidence has shown that BMPs play a key role in fertility, especially in folliculogenesis in female mammals. Smad proteins are intra-cellular signaling transduction molecules of BMP family, which can transduce the BMP signal from the cell membrane to the nucleus. In this review, BMPs, BMP/Smad-related signal transduction and the regulation of BMP activity were summarized, and the regulatory roles of BMP/Smad signal transduction pathway in folliculogenesis were discussed.

Roles of cellular heterogeneity, intrinsic and extrinsic noise in variability of p53 oscillation.

The p53 protein is a key mediator of the cellular response to various stress signals. In response to DNA damage, the concentration of p53 can temporally oscillate with fluctuations in both the amplitude and period. The underlying mechanism for p53 variability is not fully understood. Here, we construct a core regulatory network of p53 dynamics comprising the ATM-p53-Wip1 and p53-Mdm2 negative feedback loops. We dissect the contributions of cellular heterogeneity, intrinsic noise, and multiple forms of extrinsic noise to p53 variability in terms of the coefficients of variation of four quantities. Cellular heterogeneity greatly determines the fraction of oscillating cells among a population of isogenic cells. Intrinsic noise-fluctuation in biochemical reactions-has little impact on p53 variability given large amounts of molecules, whereas extrinsic colored noise with proper strength and correlation time contributes much to oscillatory variability in individual cells. With the three sources of noise combined, our results reproduce the experimental observations, suggesting that the long correlation time of colored noise is essential to p53 variability. Compared with previous studies, the current work reveals both the individual and integrated effects of distinct noise sources on p53 variability. This study provides a framework for exploring the variability in oscillations in cellular signaling pathways.

Inequality of female health and its relation with urbanization level in China: geographic variation perspective.

Urbanization development plays a vital role in the health of modern residents; however, there have been very limited researches to specifically and comprehensively explore the relationship between urbanization level evaluating indicators (ULEIs) and female health outcomes. The mortality rate of breast cancer (BC), cervical cancer (CC), and ovarian cancer (OC) and classified urbanization factor are collected at provincial level. Stepwise regression model (SRM) and geographically weighted regression model (GWRM) are conducted to obtain spatial relationship between the mortality rate of those cancer and ULEI. Our results show that there is remarkable difference of mortality rate of BC, CC, and OC in different provinces as well as higher BC, CC, and OC distributed in northern regions. The increase of value added of primary industry (VAPI), taxi, and coal consumption has detrimental effect on BC and CC. Fuel oil consumption (FOC) ultimately results in increase of mortality rate of BC and OC, and urban fixed asset investment (UFAI) poses a risk to increase the mortality rate of OC. Contrarily, natural gas consumption (NGC) appear to mitigate mortality rate of BC. In particular, our findings demonstrate that there exist spatial differences for VAPI, FOC, NGC, taxi, and coal consumption influencing BC, CC, and OC. It is suggested that policy makers should take account of regional discrepancy and implement a sustainable urbanization development considering female health.

Effects of aerobic exercise on the expressions and activities of nitric oxide synthases in the blood vessel endothelium in prediabetes mellitus.

Previous studies by our group have indicated that exercise intervention can ameliorate endothelial dysfunction, which is an early pathophysiological change of prediabetes mellitus. The present study aimed to test the hypothesis that nitric oxide synthases (NOSs), which are expressed in blood vessel endothelium, contribute to the mitigation of vascular endothelium-dependent dysfunction by aerobic exercise in prediabetes mellitus. A prediabetic rat model was established by feeding the rats an additional high-energy diet, and was confirmed by testing blood glucose levels, the area-under-the-curve for the blood glucose tests (P<0.05) and the changes to the histological morphology of the thoracic aorta. Further examination identified that NOS expression changed significantly between the control and prediabetes groups, indicating endothelial dysfunction in the prediabetic rats. Following aerobic exercise, a significant increase in NOS, endothelial (eNOS) mRNA and protein expression (P<0.05), and a significant decrease in NOS, inducible (iNOS) mRNA and protein expression (P<0.05) was identified in the prediabetic rats compared with the control group. No significant change in nitric oxide synthase, brain expression was observed in the prediabetic rat group compared with the control group. Notably, there was also a significant increase and decrease in eNOS and iNOS activity, respectively, in the prediabetes group compared with the control group (P<0.05). Furthermore, nitric oxide (NO) concentration in the vascular endothelium was detected, which revealed a significant increase in NO concentration in the prediabetic rats following aerobic exercise compared with the control (P<0.05). The present study provided results that demonstrated that aerobic exercise ameliorated the vascular endothelium-dependent dysfunction through the NOS/NO signaling pathway, which is primarily regulated by NOS expression and activity, in prediabetes mellitus. The current study provided the theoretical basis for the use of exercise intervention to prevent diabetes mellitus during the early stage.

Formation mechanism and release behavior of poly(epsilon-caprolactone) microspheres containing disodium norcantharidate.

Disodium norcantharidate (DSNC) loaded poly(epsilon-caprolactone) (PCL) microspheres were prepared by s/o/w solvent evaporation technique, and the formation mechanism and release behavior of the microspheres were investigated. The particle formation of the microspheres was influenced by the osmotic effect of DSNC. During the microsphere preparation, water diffused into the emulsion droplets and dissolved the particles of DSNC. Thereafter, DSNC generated osmotic effect and drove the water to flow in the emulsion droplets more quickly, thus forming an inner water phase. As the water influx proceeded, the state of the emulsion was transferred from s/o/w to w/o/w, thus resulting in the porosity of the microspheres. The release tests were carried out in the release media of different osmotic pressures achieved by adding different amounts of dextrose. The results indicated that the initial release of DSNC from the microspheres was controlled by a combination of osmotic effect and diffusion, but the release after the initial was mainly controlled by diffusion. This study demonstrated that the osmotic effect of DSNC not only was responsible for the particle formation but also contributed to the release from the microspheres.

Disodium norcantharidate-loaded poly(epsilon-caprolactone) microspheres II. Modification of morphology and release behavior.

Disodium norcantharidate (DSNC)-loaded poly(epsilon-caprolactone) (PCL) microspheres were prepared by s/o/w solvent evaporation technique, and their morphology and drug release behavior were modified by adding NaCl (3, 6 and 9%) in the continuous phase during the preparation. The addition of NaCl decreased the water influx into the emulsion droplets and the porosity of the resultant microspheres. Higher NaCl concentration resulted in smaller particle size, lower density and higher drug loading of the microspheres. Despite higher drug loading and smaller particle size, the microspheres prepared with NaCl in the continuous phase exhibited slower drug release. The modification of the release profiles was correlated with the changes in the surface and internal morphology of the microspheres. Therefore, by adding NaCl in the continuous phase during the preparation, both morphology and release behavior of the microspheres can be modified to a certain extent.

Disodium norcantharidate loaded poly(epsilon-caprolactone) microspheres I. Preparation and evaluation.

Poly(epsilon-caprolactone) (PCL) microspheres encapsulating disodium norcantharidate (DSNC), a drug in salt form and with high water solubility, were prepared by s/o/w solvent evaporation technique and characterized in terms of size, morphology, encapsulation efficiency and drug release. The viscosity of s/o dispersion was crucial to the successful encapsulation of DSNC. Scanning electron microscopy (SEM) studies showed that the drug-loaded microspheres had coarse surface and porous internal structure. The analysis of X-ray diffraction (XRD) indicated that there was no interaction between DSNC and PCL, but the degree of crystallinity of PCL decreased with the introduction of the drug. The drug release profiles indicated an initial burst release followed by a slow release, and a further investigation into the release mechanism implied that the release of DSNC from PCL microspheres was caused by a combination of diffusion and osmotic pressure.

Overdrainage Secondary to Ventriculosinus Shunt.

BACKGROUND: Shunting to the cranial venous sinus represents a novel treatment strategy for hydrocephalus. To our knowledge, overdrainage as a complication after shunting to the cranial venous sinus has not previously been reported in the clinical literature. Here we report the case of a 50-year-old man who suffered from overdrainage after a ventriculosinus shunt insertion. CASE DESCRIPTION: A 50-year-old man was admitted to our hospital with recurring fever and gait difficulty 4 months after a ventriculoperitoneal shunt (VPS) insertion for primary communicating hydrocephalus. Cerebrospinal fluid cultures were positive. The previous VPS was removed, and after successful antibiotic treatment evidenced by repeated negative cerebrospinal fluid (CSF) cultures, we performed a ventriculosinus shunt operation. A postoperative computed tomography scan of the head showed an excessively contracted ventricular system, subdural hemorrhage, and effusion, indicating the occurrence of overdrainage. CONCLUSIONS: Ventriculosinus shunt surgery is a feasible and reliable option for the treatment of hydrocephalus, especially for cases of failed VPS. However, there remains a risk of overdrainage occurring postsurgery, and this should be taken into consideration in clinical practice.

Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome.

It is established that the physiological effects of insulin are primarily mediated by the insulin signaling pathway. However, a defective insulin signaling is closely associated with the clinical manifestations of polycystic ovary syndrome (PCOS), which include excess androgen levels, insulin resistance and anovulation, and is involved in the pathophysiology of PCOS at the molecular level. Dimethyldiguanide (DMBG) has been widely employed to alleviate reproduction dysfunction in women with PCOS, however, the exact mechanism of this effect remains unclear. The objective of the present study was to investigate the effects of DMBG on the expression of the insulin signaling pathway in the ovaries of rats with PCOS, and to identify the potential underlying molecular mechanisms of these effects in PCOS. In the present study, a PCOS rat model was induced by letrozole, and successful establishment of the model was confirmed by examining ovarian histology and determining serum testosterone levels, by hematoxylin and eosin staining and ELISA, respectively. Subsequently, the expression of two key elements of insulin signaling, insulin receptor substrate (IRS)­2 and phosphatidylinositol 3­kinase (PI3K), was determined by immunohistochemistry and western blot analysis. The results demonstrated that IRS­2 and PI3K expression was markedly decreased in PCOS ovaries, which was rescued by DMBG treatment. These results indicate that IRS­2/PI3K signaling may be involved in the development of PCOS and the therapeutic effects of DMBG on PCOS. To further confirm the effects of DMBG on insulin signaling expression during this process, the expression of an additional two downstream proteins, phosphoinositide­dependent kinase­1 (PDK­1) and the mammalian target of rapamycin (mTOR), was also investigated in the present study, and the results demonstrated that the expression of PDK­1 and mTOR was significantly reduced in PCOS ovaries and increased following DMBG treatment, further indicating that altered insulin signaling may have an important role in the development and treatment of PCOS. In conclusion, the results of the present study indicate that the reduced expression of proteins involved in insulin signaling may contribute to the development of the clinical features of PCOS, and DMBG reverses reduced expression of insulin signaling components, by a mechanism that is yet to be determined, to attenuate certain symptoms of PCOS, such as obesity. To the best of our knowledge, the present study is the first to provide data regarding the detailed changes of insulin signaling during the development and treatment of PCOS, and may provide an important reference for clinical PCOS treatment.

The IL6R gene polymorphisms are associated with sIL-6R, IgE and lung function in Chinese patients with asthma.

BACKGROUND: sIL-6R is involved in a variety of inflammatory diseases. The present study analyzed the potential associations between two IL6R gene polymorphisms (rs2228145 and rs12083537) and asthma in a Han Chinese population. METHODS: A cohort of 394 patients and 395 healthy controls were genotyped to detect the two polymorphisms using SNaPshot. In 66 asthma patients and 49 controls, peripheral eosinophil and serum immunoglobulin E (IgE) levels were determined using a routine blood test, and sIL-6R levels were measured by ELISA. RESULTS: No statistically significant differences were detected between the patients and controls in the distribution of the two independent IL6R polymorphisms (p>0.05). However, rs2228145 C and rs12083537 G were significantly associated with decreased lung function in patients with asthma; the rs2228145 A-C variant was also associated with increased sIL-6R and IgE levels. In addition, sIL-6R levels were positively associated with IgE and inversely associated with lung function in patients with asthma. CONCLUSIONS: Our results provide evidence that rs2228145 C and rs12083537 G are associated with poor lung function in patients with asthma. Furthermore, the rs2228145 A-C variant is associated with levels of sIL-6R and IgE.