Single-Molecule Force Spectroscopy Studies of Missense Titin Mutations That Are Likely Causing Cardiomyopathy.

The giant muscle protein titin plays important roles in heart function. Mutations in titin have emerged as a major cause of familial cardiomyopathy. Missense mutations have been identified in cardiomyopathy patients; however, it is challenging to distinguish disease-causing mutations from benign ones. Given the importance of titin mechanics in heart function, it is critically important to elucidate the mechano-phenotypes of cardiomyopathy-causing mutations found in the elastic I-band part of cardiac titin. Using single-molecule atomic force microscopy (AFM) and equilibrium chemical denaturation, we investigated the mechanical and thermodynamic effects of two missense mutations, R57C-I94 and S22P-I84, found in the elastic I-band part of cardiac titin that were predicted to be likely causing cardiomyopathy by bioinformatics analysis. Our AFM results showed that mutation R57C had a significant destabilization effect on the I94 module. R57C reduced the mechanical unfolding force of I94 by ∼30-40 pN, accelerated the unfolding kinetics, and decelerated the folding. These effects collectively increased the unfolding propensity of I94, likely resulting in altered titin elasticity. In comparison, S22P led to only modest destabilization of I84, with a decrease in unfolding force by ∼10 pN. It is unlikely that such a modest destabilization would lead to a change in titin elasticity. These results will serve as the first step toward elucidating mechano-phenotypes of cardiomyopathy-causing mutations in the elastic I-band.

Association between cognitive vulnerability to depression - dysfunctional attitudes and glycaemic control among in-patients with type 2 diabetes in a hospital in Beijing: a multivariate regression analysis.

This cross-sectional study aimed to investigate the relationship between glycosylated haemoglobin (HbA1c) and cognitive vulnerability to depression (dysfunctional attitudes) in patients with type 2 diabetes mellitus. A total of 245 valid records from June 2016 to December 2016 were collected from a hospital in Beijing. Participants were asked to complete four questionnaires (Dysfunctional Attitudes Scale, Automatic Thoughts Questionnaire, Zung Self-rating Depression Scale, and World Health Organization Quality of Life Instrument-Short Form) to assess mental health and quality of life. Multivariate regression analysis was conducted to determine the correlations between HbA1c, mental health, quality of life and other clinical variables. The results showed that dysfunctional attitudes were associated with HbA1c, with a standardized regression coefficient (ß) of .13 (p = .01), although 1 h C-peptide (ß = -.75, p < .0001) was the most significant predictor of HbA1c in the regression model. The results indicated that dysfunctional attitudes, as a cognitive vulnerability to depression, were a relevant factor in HbA1c, although further studies are needed to establish the nature of the connection between dysfunctional attitudes and glycaemic control in diabetes patients.

Cinnamaldehyde Ameliorates Diet-Induced Obesity in Mice by Inducing Browning of White Adipose Tissue.

BACKGROUND/AIMS: Obesity has become a major health concern with few effective medications. Cinnamaldehyde (CA) has been reported to exhibit anti-diabetic and anti-inflammatory properties. However, whether CA shows anti-obesity activity remains unknown. Therefore, the present study aimed to investigate the potential anti-obesity effects of CA on mice fed a high-fat diet (HFD) and to explore the possible mechanisms involved. METHODS: Male C57BL/6J mice fed an HFD for 12 weeks were supplemented with CA (40 mg/kg/day) via gavage for an additional 8 weeks. Mice fed a standard diet were used as normal controls. RESULTS: The results revealed that CA treatment decreased body weight, fat mass, food intake, and serum lipid, free fatty acid and leptin levels. CA administration also improved insulin sensitivity in HFD-induced obese mice. Additionally, CA inhibited the hypertrophy of adipose tissue and induced browning of white adipose tissue. Uncoupling protein 1 (UCP1) was expressed in white adipose tissue after the oral administration of CA. Furthermore, CA enhanced the expression of the peroxisome proliferator-activated receptor γ (PPARγ), PR domain-containing 16 (PRDM16) and PPARγ coactivator 1α (PGC-1α) proteins in both brown and white adipose tissues. CONCLUSIONS: The results suggest that CA exhibits therapeutic potency against obesity by inducing the browning of white adipose tissue in HFD-fed mice.

An Isolable Diboron-Centered Diradical with a Triplet Ground State.

Two new diboranes, 2,6-bis(BMes2 )mesitylene (1) and 3,3'-bis(BMes2 )bimesitylene (3), were synthesized. Two-electron reduction of 1 with elemental potassium afforded the C-H activation product [(18-c-6)K(THF)2 ]2+ ⋅22- bearing a BC3 four-membered ring as colorless crystals, whereas the reduction of 3 with potassium led to the isolation of [(18-c-6)K(THF)2 ]2+ ⋅32-.. as dark blue crystals. Both reduction products were characterized by structural and spectroscopic methods. Electron paramagnetic resonance (EPR) spectroscopy and theoretical calculations revealed that the electron spin density of 32-.. mainly resides on the two boron nuclei and features a triplet ground state, which was confirmed by superconducting quantum interference device (SQUID) measurements as well as theoretical calculations. 32-.. represents the first structurally characterized boron-centered diradical with a triplet ground state. In addition, the reactivity of [(18-c-6)K(THF)2 ]2+ ⋅32-.. toward PhSeSePh and nBu3 SnH was investigated, which is consistent with its radical character.

Efficacy and safety of Yinchenwuling powder for hyperlipidemia: a systematic review and Meta-analysis.

OBJECTIVE: To assess the clinical effectiveness and adverse effects of Yinchenwuling powder (YCWLP) in the treatment of hyperlipidemia using Meta-analysis. METHODS: Seven electronic databases were searched for randomized controlled trials designed to evaluate the clinical effectiveness of YCWLP for hyperlipidemia published in any language prior to February 2015. Two reviewers independently identified articles, extracted data, assessed quality, and cross-checked the results. Revman 5.3 was used to analyze the data. RESULTS: Only five randomized controlled trials with poor methodology were included in the analysis. The five trials compared YCWLP with conventional lipid-lowering drugs. Meta-analysis indicated that YCWLP was more effective at the levels of total cholesterol and triglycerides, while increasing the level of high-density lipoprotein cholesterol without serious adverse effects. However, it was not more effective than lipid-lowering drugs in reducing low-density lipoprotein cholesterol and improving hemorheology. CONCLUSION: YCWLP appeared to improve lipid levels. However, given the high risk of bias among the trials, we could not conclude that YCWLP was beneficial to patients with hyperlipidemia. More rigorous trials are required to provide stronger evidence for the conclusion.

Two-Molecule Force Spectroscopy on Proteins.

Many elastomeric proteins, which play important roles in a wide range of biological processes, exist as parallel/antiparallelly arranged dimers or multimers to perform their mechanobiological functions. For example, in striated muscle sarcomeres, the giant muscle protein titin exists as hexameric bundles to mediate the passive elasticity of muscles. However, it has not been possible to directly probe the mechanical properties of such parallelly arranged elastomeric proteins. And it remains unknown if the knowledge obtained from single-molecule force spectroscopy studies can be directly extrapolated to such parallelly/antiparallelly arranged systems. Here, we report the development of atomic force microscopy (AFM)-based two-molecule force spectroscopy to directly probe the mechanical properties of two elastomeric proteins that are arranged in parallel. We developed a twin-molecule approach to allow two parallelly arranged elastomeric proteins to be picked up and stretched simultaneously in an AFM experiment. Our results clearly revealed the mechanical features of such parallelly arranged elastomeric proteins during force-extension measurements and allowed for the determination of mechanical unfolding forces of proteins in such an experimental setting. Our study provides a general and robust experimental strategy to closely mimic the physiological condition of such parallel elastomeric protein multimers.

Two molecule force spectroscopy on ligand-receptor interactions.

Many biological processes involve the rupture of multiple ligand-receptors or multivalent ligand-receptors. It is challenging to study the rupture of such parallelly arranged multiple ligand-receptors due to the difficulties in engineering such systems in a well-controlled fashion. Here we report the use of two-molecule force spectroscopy to investigate the rupture of two parallelly arranged monomeric streptavidin (mSA)-biotin complexes. By using SpyCatcher-SpyTag chemistry, we successfully engineered a molecular twin of biotin, in which two biotins are arranged in parallel. By reacting mSA with twin biotin, we constructed parallelly arranged two mSA-biotin complexes for force spectroscopy experiments. The incorporation of single molecule fingerprint domains into our mSA-biotin dimers allowed us to identify and assign the rupture events of the parallelly arranged mSA-biotin complexes without any ambiguity in the two-molecule force spectroscopy experiments. Our results revealed that the rupture force of the parallel dimer mSA-biotin is 172 pN at a pulling speed of 400 nm s-1, which is about 1.6 times of that of single mSA-biotin (105 pN). Furthermore, our findings indicate that the two mSA-biotin behave as non-interacting, independent ligand-receptors. The strategy we demonstrated here can be extended to other ligand-receptors and may open up an avenue toward rigorously testing the theoretic predictions proposed in various models regarding the rupture of multiple parallel ligand-receptors.

Molecular homogeneity of GB1 revealed by single molecule force spectroscopy.

In single molecule studies, the ergodic hypothesis is inherently assumed, which states that the time average of a physical quantity of a single member of an ensemble is the same as the average of the same quantity on the whole ensemble at a given time. This hypothesis implies the homogeneity of a molecular ensemble of a system of interest. However, it is difficult to test the validity of the ergodic hypothesis experimentally. Recent theoretical work suggested that heterogeneity may be widely present in single molecule force spectroscopy studies. Here we used atomic force microscope based single molecule force spectroscopy to examine the molecular homogeneity/heterogeneity of a small globular protein GB1 in its mechanical unfolding reaction. Using a polyprotein (GB1)4, we directly measured the ensemble average and time average for a single molecule of the mechanical unfolding force and kinetic parameters that characterize the mechanical unfolding free energy profile of GB1. Our results showed that the ensemble averages of these physical quantities are indeed the same as the time averages for single molecules, and individual molecules did not show any differences amongst them in these physical quantities. These results are consistent with the expectation of the ergodic hypothesis and indicate that GB1 is a homogeneous molecular ensemble in its mechanical unfolding reaction on the time scale of our force spectroscopy experiments.

Mapping combined with principal component analysis identifies excellent lines with increased rice quality.

Quality-related traits are some of the most important traits in rice, and screening and breeding rice lines with excellent quality are common ways for breeders to improve the quality of rice. In this study, we used 151 recombinant inbred lines (RILs) obtained by crossing the northern cultivated japonica rice variety ShenNong265 (SN265) with the southern indica rice variety LuHui99 (LH99) and simplified 18 common rice quality-related traits into 8 independent principal components (PCs) by principal component analysis (PCA). These PCs included peak and hot paste viscosity, chalky grain percentage and chalkiness degree, brown and milled rice recovery, width length rate, cooked taste score, head rice recovery, milled rice width, and cooked comprehensive score factors. Based on the weight ratio of each PC score, the RILs were classified into five types from excellent to poor, and five excellent lines were identified. Compared with SN265, these 5 lines showed better performance regarding the chalky grain percentage and chalkiness degree factor. Moreover, we performed QTL localization on the RIL population and identified 94 QTLs for quality-related traits that formed 6 QTL clusters. In future research, by combining these QTL mapping results, we will be using backcrossing to aggregate excellent traits and achieve quality improvement of SN265.

Targeting NLRP3 Inflammasome in the Treatment Of Diabetes and Diabetic Complications: Role of Natural Compounds from Herbal Medicine.

Diabetes, a common metabolic disease with various complications, is becoming a serious global health pandemic. So far there are many approaches in the management of diabetes; however, it still remains irreversible due to its complicated pathogenesis. Recent studies have revealed that nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays a vital role in the progression of diabetes and many of its complications, making it a promising therapeutic target in pharmaceutical design. Natural derived herbal medicine, known for its utilization of natural products such as herbs or its bioactive ingredients, is shown to be able to ameliorate hyperglycemia-associated symptoms and to postpone the progression of diabetic complications due to its anti-inflammatory and anti-oxidative properties. In this review, we summarized the role of NLRP3 inflammasome in diabetes and several diabetic complications, as well as 31 active compounds that exert therapeutic effect on diabetic complications via inhibiting NLRP3 inflammasome. Improving our understanding of these promising candidates from natural compounds in herbal medicine targeting NLRP3 inflammasome inspires us the relationship between inflammation and metabolic disorders, and also sheds light on searching potential agents or therapies in the treatment of diabetes and diabetic complications.

Curcumin improves adipocytes browning and mitochondrial function in 3T3-L1 cells and obese rodent model.

Accumulating evidence suggests that mitochondrial dysfunction and adipocyte differentiation promote lipid accumulation in the development of obesity and diabetes. Curcumin is an active ingredient extracted from Curcuma longa that has been shown to exhibit antioxidant and anti-inflammatory potency in metabolic disorders. However, the underlying mechanisms of curcumin in adipocytes remain largely unexplored. We studied the effects of curcumin on adipogenic differentiation and mitochondrial oxygen consumption and analysed the possible mechanisms. 3T3-L1 preadipocytes were used to assess the effect of curcumin on differentiation of adipocytes. The Mito Stress Test measured by Seahorse XF Analyzer was applied to investigate the effect of curcumin on mitochondrial oxygen consumption in 3T3-L1 adipocytes. The effect of curcumin on the morphology of both white and brown adipose tissue (WAT and BAT) was evaluated in a high-fat diet-induced obese mice model. We found that curcumin dose-dependently (10, 20 and 35 µM) induced adipogenic differentiation and the intracellular fat droplet accumulation. Additionally, 10 µM curcumin remarkably enhanced mature adipocyte mitochondrial respiratory function, specifically, accelerating basic mitochondrial respiration, ATP production and uncoupling capacity via the regulation of peroxisome proliferator-activated receptor γ (PPARγ) (p < 0.01). Curcumin administration also attenuated the morphological changes in adipose tissues in high-fat diet-induced obese mice. Moreover, curcumin markedly increased the mRNA and protein expressions of mitochondrial uncoupling protein 1 (UCP1), PPARγ, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PR domain protein 16 (PRDM16) in vivo and in vitro. Collectively, the results demonstrate that curcumin promotes the adipogenic differentiation of preadipocytes and mitochondrial oxygen consumption in 3T3-L1 mature adipocytes by regulating UCP1, PRDM16, PPARγ and PGC-1α expression.

Protective Effect of Jiang Tang Xiao Ke Granules against Skeletal Muscle IR via Activation of the AMPK/SIRT1/PGC-1α Signaling Pathway.

The Jiang Tang Xiao Ke (JTXK) granule is a classic Chinese herbal formula that has been put into clinical use in the treatment of type 2 diabetes mellitus for decades. However, whether its ability to ameliorate skeletal muscle insulin resistance (IR) is through modulation of the AMPK/SIRT1/PGC-1α signaling pathway remains unknown. Therefore, we aimed to investigate the effects of JTXK granules on IR in skeletal muscle of high-fat diet-induced diabetic mice and C2C12 cells and analyze the underlying mechanisms. In the present study, we showed that JTXK granules attenuated body weight gain, reduced body fat mass, improved body lean mass, and enhanced muscle performance of diabetic mice. JTXK granules also improved glucose metabolism and skeletal muscle insulin sensitivity and partially reversed abnormal serum lipid levels, which might be related to the regulation of the AMPK/SIRT1/PGC-1α pathway, both in skeletal muscle tissue of diabetic mice and in C2C12 cells. Furthermore, drug-containing serum of JTXK granules was capable of enhancing glucose uptake and mitochondrial respiration in C2C12 cells, and AMPKα was proven to be closely involved in this process. Taken together, these results suggest that the JTXK granule ameliorates skeletal muscle IR through activation of the AMPK/SIRT1/PGC-1α signaling pathway, which offers a novel perspective of this formula to combat IR-related metabolic diseases.

Risk Factors in Patients with Diabetes Hospitalized for COVID-19: Findings from a Multicenter Retrospective Study.

METHODS: In this multicenter retrospective study, patients with COVID-19 in China were included and classified into two groups according to whether they were complicated with diabetes or not. Demographic symptoms and laboratory data were extracted from medical records. Univariable and multivariable logistic regression methods were used to explore the risk factors. RESULTS: 538 COVID-19 patients were finally included in this study, of whom 492 were nondiabetes and 46 were diabetes. The median age was 47 years (IQR 35.0-56.0). And the elderly patients with diabetes were more likely to have dry cough, and the alanine aminotransferase, lactate dehydrogenase, Ca, and mean hemoglobin recovery rate were higher than the other groups. Furthermore, we also found the liver and kidney function of male patients was worse than that of female patients, while female cases should be paid more attention to the occurrence of bleeding and electrolyte disorders. Moreover, advance age, blood glucose, gender, prothrombin time, and total cholesterol could be considered as risk factors for COVID-19 patients with diabetes through the multivariable logistic regression model in our study. CONCLUSION: The potential risk factors found in our study showed a major piece of the complex puzzle linking diabetes and COVID-19 infection. Meanwhile, focusing on gender and age factors in COVID-19 patients with or without diabetes, specific clinical characteristics, and risk factors should be paid more attention by clinicians to figure out a targeted intervention to improve clinical efficacy worldwide.

Clinical features and risk factors for severe inpatients with COVID-19: A retrospective study in China.

BACKGROUND: A worldwide outbreak of coronavirus disease (COVID-19), since 2019, has brought a disaster to people all over the world. Many researchers carried out clinical epidemiological studies on patients with COVID-19 previously, but risk factors for patients with different levels of severity are still unclear. METHODS: 562 patients with laboratory-confirmed COVID-19 from 12 hospitals in China were included in this retrospective study. Related clinical information, therapies, and imaging data were extracted from electronic medical records and compared between patients with severe and non-severe status. We explored the risk factors associated with different severity of COVID-19 patients by logistic regression methods. RESULTS: Based on the guideline we cited, 509 patients were classified as non-severe and 53 were severe. The age range of whom was 5-87 years, with a median age of 47 (IQR 35.0-57.0). And the elderly patients (older than 60 years old) in non-severe group were more likely to suffer from fever and asthma, accompanied by higher level of D-dimer, red blood cell distribution width and low-density lipoprotein. Furthermore, we found that the liver and kidney function of male patients was worse than that of female patients in both severe and non-severe groups with different age levels, while the severe females had faster ESR and lower inflammatory markers. Of major laboratory markers in non-severe cases, baseline albumin and the lymphocyte percentage were higher, while the white blood cell and the neutrophil count were lower. In addition, severe patients were more likely to be accompanied by an increase in cystatin C, mean hemoglobin level and a decrease in oxygen saturation. Besides that, advanced age and indicators such as count of white blood cell, glucose were proved to be the most common risk factors preventing COVID-19 patients from aggravating. CONCLUSION: The potential risk factors found in our study have shown great significance to prevent COVID-19 patients from aggravating and turning to critical cases during treatment. Meanwhile, focusing on gender and age factors in groups with different severity of COVID-19, and paying more attention to specific clinical symptoms and characteristics, could improve efficacy of personalized intervention to treat COVID-19 effectively.

Single molecule force spectroscopy reveals that the oxidation state of cobalt ions plays an important role in enhancing the mechanical stability of proteins.

Engineered bi-histidine (biHis)-based metal chelation is a general and robust method to enhance the mechanical stability of proteins. Here we used single molecule force spectroscopy techniques to investigate the effect of binding of Co2+/Co3+ on the mechanical stability of an engineered biHis mutant of protein GB1, G6-53. We found that the binding of Co2+/Co3+ can lead to an enhancement of the mechanical stability of G6-53, but the degree of enhancement is drastically different. The binding of Co2+ can only lead to marginal enhancement of G6-53's mechanical stability, while Co3+ has a much stronger effect. This large difference is likely due to the large difference in thermodynamic stability and kinetic lability of Co2+ and Co3+ complexes. These results opened up new avenues towards fine tuning the mechanical properties of proteins.

Correction: Long non-coding RNAs could act as vectors for paternal heredity of high fat diet-induced obesity.

[This corrects the article DOI: 10.18632/oncotarget.18138.].

Jiangtang Xiaoke granule attenuates glucose metabolism disorder via regulating endoplasmic reticulum stress in the liver of type 2 diabetes mellitus mice.

OBJECTIVE: To observe the effect of Jiangtang Xiaoke (JTXK) granule on endoplasmic reticulum (ER) stress in high fat diet (HFD)-induced type 2 diabetes mellitus (T2DM) KK-Ay mice. METHODS: KK-Ay mice were fed with HFD to induce the T2DM model, while normal control C57BL/6J mice were given standard feed. Fasting blood glucose (FBG) in all mice was measured weekly and oral glucose tolerance tests (OGTTs) were performed at 4 and 10 weeks after start of treatment to determine glucose metabolism. Serum fasting insulin (FINS) and insulin sensitivity index (ISI) were measured to determine insulin sensitivity. mRNA expressions of eukaryotic initiation factor-2 alpha (eIF2¦Á), glucose regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), and C/EBP homology protein (CHOP) were assessed by reverse transcription polymerase chain reaction and the protein expressions of p-eIF2¦Á, GRP78, and CHOP were assessed by Western blotting. RESULTS: JTXK granule significantly reduced FBG and free fatty acid levels and improved OGTT at the 120 min of the 10-week treatment in T2DM KK-Ay mice. FINS and HbAlc levels were reduced and insulin sensitivities were increased in KK-Ay diabetic mice, which were improved with the treatment of JTXK granule, especially at the 7 and 3.5 g/kg doses. JTXK granule at the 3.5 g/kg dose was most effective in reducing both gene and protein expressions of eIF2¦Á, GRP78, and CHOP. CONCLUSION: ER stress response is increased in T2DM KK-Ay mice. Treatment with JTXK granule attenuates glucose disorders, improves insulin sensitivity, and reduces serum FFA in T2DM KK-Ay mice. The mechanisms may be attributed to regulation of the signaling ER stress pathway via decreasing eIF2¦Á phosphorylation and suppressing eIF2¦Á- ATF4-CHOP activation.

Anti-Diabetic Effects of Jiang Tang Xiao Ke Granule via PI3K/Akt Signalling Pathway in Type 2 Diabetes KKAy Mice.

Jiang Tang Xiao Ke (JTXK) granule, a Chinese herbal formula, has been used clinically to treat type 2 diabetes (T2DM) for decades. Our previous studies showed that JTXK granule exhibited anti-diabetic and anti-oxidative functions in experimental diabetic rats induced by a high fat diet and streptozotocin. However, the underlying mechanisms remain poorly understood. Herein, we aimed to investigate the therapeutic effect of JTXK granule on T2DM KKAy mice and the possible associations with skeletal muscle in the current study. Our results showed that JTXK granule significantly reduced food intake and body weight in T2DM KKAy mice. JTXK granule treatment also decreased the blood glucose and HbA1c levels and increased the insulin sensitivity in a time-dependent manner. Additionally, it ameliorated hyperlipidaemia and induced a lower free fatty acid level, displaying an effect on disorders of lipid metabolism. JTXK granule significantly increased the expression of insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K), protein kinase B (PKB/Akt) and glucose transporter 4 (Glut4) and decreased the expression of glycogen synthase kinase 3ß (GSK3ß). We concluded that JTXK granule is an effective drug for T2DM through regulating the PI3K/Akt signalling pathway in skeletal muscle.

Long non-coding RNAs could act as vectors for paternal heredity of high fat diet-induced obesity.

Long non-coding RNAs (lncRNAs) play an important role in epigenetic regulation, and abnormalities may lead to male infertility. To investigate whether lncRNAs are involved in intergenerational inheritance of obesity and obesity-induced decline in fertility, we divided mice into obesity (F0 mice fed a high-fat diet, F0-HFD) and non-obese (F0 mice fed normal chow, F0-NC) model groups and their male offspring (F1-HFD and F1-NC, respectively). We examined the differences in the expression levels of lncRNAs and mRNAs in the F0-HFD/F0-NC and F1-HFD/F1-NC groups. The results revealed similar expression patterns in the F1-HFD/F0-HFD groups at both the lncRNA and mRNA levels. The maximum difference in the lncRNA expression was observed between the F0-HFD and F0-NC groups. The differentially expressed lncRNA targets and mRNAs identified in our study are mainly involved in GnRH signalling pathway, metabolic process, and Hippo signalling pathway; similarly expressed lncRNAs and mRNAs in F1-HFD/F0-HFD are closely linked with G-protein coupled receptor signalling pathway, pancreatic polypeptide receptor activity, and lysine biosynthesis, which may play an important role in the molecular mechanism of intergenerational inheritance of obesity. Furthermore, potential genes that might play important roles in the pathogenesis of obesity-related low fertility were revealed by lncRNA-and mRNA-interaction studies based on the microarray expression profiles. In conclusion, we found that lncRNA could be involved in obesity-induced infertility by expressing abnormalities, which could act as genetic vectors of paternal inheritance of obesity.

Jiang Tang Xiao Ke Granule, a Classic Chinese Herbal Formula, Improves the Effect of Metformin on Lipid and Glucose Metabolism in Diabetic Mice.

In the present study, the hypoglycemic, hypolipidemic, and antioxidative effects of metformin (MET) combined with Jiang Tang Xiao Ke (JTXK) granule derived from the "Di Huang Tang" were evaluated in mice with type 2 diabetes mellitus (DM) induced by high-fat diet/streptozotocin. DM mice were orally treated with MET (0.19 g/kg) either alone or combined with different doses (1.75, 3.5, or 7 g/kg) of JTXK for 4 weeks. Results showed that the serum and hepatic glucose, lipids, and oxidative stress levels were elevated in DM mice, when compared with the normal mice. MET treatment decreased FBG and serum glucagon levels of DM mice. Combination treatment with MET and JTXK 3.5 g/kg increased the hypoglycemia and insulin sensitivity at 4 weeks when compared with the DM mice treated with MET alone. However, neither MET nor MET/JTXK treatment could completely reverse the hyperglycemia in DM mice. JTXK enhanced the serum triglyceride (TG) and hepatic lipid-lowering effect of MET in a dose-dependent manner in DM mice. JTXK 1.75 and 3.5 g/kg improved the hepatoprotective effect of MET in DM mice. Synergistic effect of combination treatment with MET and JTXK on antioxidant stress was also found in DM mice compared with MET alone.