Tracking the hologenome dynamics in aquatic invertebrates by the holo-2bRAD approach.

The "hologenome" concept is an increasingly popular way of thinking about microbiome-host for marine organisms. However, it is challenging to track hologenome dynamics because of the large amount of material, with tracking itself usually resulting in damage or death of the research object. Here we show the simple and efficient holo-2bRAD approach for the tracking of hologenome dynamics in marine invertebrates (i.e., scallop and shrimp) from one holo-2bRAD library. The stable performance of our approach was shown with high genotyping accuracy of 99.91% and a high correlation of r > 0.99 for the species-level profiling of microorganisms. To explore the host-microbe association underlying mass mortality events of bivalve larvae, core microbial species changed with the stages were found, and two potentially associated host SNPs were identified. Overall, our research provides a powerful tool with various advantages (e.g., cost-effective, simple, and applicable for challenging samples) in genetic, ecological, and evolutionary studies.

The effects of thioredoxin peroxidase from Cysticercus cellulosae excretory-secretory antigens on TGF-ß signaling pathway and Th17 cells differentiation in Jurkat cells by transcriptomics.

Thioredoxin peroxidase (TPx) protein from the excretory-secretory antigens (ESAs) of Cysticercus cellulosae (C. cellulosae) has been shown to regulate the differentiation of host Treg and Th17 cells, resulting in an immunosuppressive response dominated by Treg cells. However, the molecular mechanism by which TPx protein from the ESAs of C. cellulosae regulates the imbalance of host Treg/Th17 cell differentiation has not been reported. TPx protein from porcine C. cellulosae ESAs was used to stimulate Jurkat cells activated with PMA and ionomycin at 0, 24, 48, and 72 h. Transcriptomic analysis was performed to investigate the signaling pathways associated with Jurkat cells differentiation regulated by TPx protein from C. cellulosae ESAs. Gene Set Enrichment Analysis (GSEA) revealed that TPx protein from porcine C. cellulosae ESAs could induce upregulation of the TGF-ß signaling pathway and downregulation of Th17 cell differentiation in Jurkat cells. TPx protein from porcine C. cellulosae ESAs can activate the TGF-ß signaling pathway in Jurkat cells, thereby regulating the differentiation of Treg/Th17 cells and leading to an immunosuppressive response dominated by Treg cells, enabling evasion of the host immune attack. This study provides a foundation for further validation of these pathways and further elucidates the molecular mechanisms underlying immune evasion caused by porcine C. cellulosae.

Adaptive neural network prescribed performance control for dual switching nonlinear time-delay system.

This paper investigates the adaptive neural network prescribed performance control problem for a class of dual switching nonlinear systems with time-delay. By using the approximation of neural networks (NNs), an adaptive controller is designed to achieve tracking performance. Another research point of this paper is tracking performance constraints which can solve the performance degradation in practical systems. Therefore, an adaptive NNs output feedback tracking scheme is studied by combining the prescribed performance control (PPC) and backstepping method. With the designed controller and the switching rule, all signals of the closed-loop system are bounded, and the tracking performance satisfies the prescribed performance.

Effects of Cysticercus cellulosae Excretory-Secretory Antigens on the TGF-ß Signaling Pathway and Th17 Cell Differentiation in Piglets, a Proteomic Analysis.

Excretory-secretory antigens (ESAs) of Cysticercus cellulosae can directly regulate the proliferation and differentiation of host T regulatory (Treg) cells, thus inhibiting host immune responses. However, previous studies have only focused on this phenomenon, and the molecular mechanisms behind the ways in which C. cellulosae ESAs regulate the differentiation of host Treg/Th17 cells have not been reported. We collected CD3+ T cells stimulated by C. cellulosae ESAs through magnetic bead sorting and used label-free quantification (LFQ) proteomics techniques to analyze the signaling pathways of C. cellulosae ESAs regulating Treg/Th17 cell differentiation. Through gene set enrichment analysis (GSEA), we found that C. cellulosae ESAs could upregulate the TGF-ß signaling pathway and downregulate Th17 cell differentiation in piglet T cells. Interestingly, we also found that the IL-2/STAT5 signaling pathway also affects the downregulation of Th17 cell differentiation. C. cellulosae ESAs activate the TGF-ß signaling pathway and the IL-2/STAT5 signaling pathway in host T cells to further regulate the differentiation of Treg/Th17 cells in order to evade host immune attack. This study lays the foundation for the subsequent verification of these pathways, and further clarifies the molecular mechanism of C. cellulosae-mediated immune evasion.

Asymmetric Dihydroxylation-Based Kinetic Resolution of Allylic Amides Enabled by Noncovalent π-Interactions.

While Sharpless asymmetric dihydroxylation is widely utilized to convert various alkenes into diols with excellent enantioselectivies, kinetic resolution by means of this fundamental catalysis has generally proven to be ineffective. Here we report that, by relying on noncovalent π-interactions that purposely include the substrate's stereocenter in the corresponding catalyst-substrate interaction framework, AD-based kinetic resolution of allylic amides is realized. This method enables such versatile chiral building blocks to be easily accessed with excellent enantiomeric excesses (ee's).

Adaptive neural network control for uncertain dual switching nonlinear systems.

Dual switching system is a special hybrid system that contains both deterministic and stochastic switching subsystems. Due to its complex switching mechanism, few studies have been conducted for dual switching systems, especially for systems with uncertainty. Usually, the stochastic subsystems are described as Markov jump systems. Based upon the upstanding identity of RBF neural network on approaching nonlinear data, the tracking models for uncertain subsystems are constructed and the neural network adaptive controller is designed. The global asymptotic stability almost surely (GAS a.s.) and almost surely exponential stability (ES a.s.) of dual switching nonlinear error systems are investigated by using the energy attenuation theory and Lyapunov function method. An uncertain dual switching system with two subsystems, each with two modes, is studied. The uncertain functions of the subsystems are approximated well, and the approximation error is controlled to be below 0.05. Under the control of the designed adaptive controller and switching rules, the error system can obtain a good convergence rate. The tracking error is quite small compared with the original uncertain dual switching system.

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.

Airborne Microplastic Concentrations in Five Megacities of Northern and Southeast China.

Airborne microplastics (MPs) are receiving increasing attention due to their ubiquitous nature and the potential human health consequences resulting from inhalation. The limited data for airborne MP concentrations vary widely among studies (∼4 orders of magnitude), but comparisons are tenuous due to the inconsistent collection and detection/enumeration methodologies among studies. Herein, we used uniform methodologies to obtain comparable airborne MP concentration data to assess MP exposure intensity in five Chinese megacities. Airborne MP concentrations in northern cities (358 ± 132 items/m3) were higher than those in southeast cities (230 ± 94 items/m3) but of a similar order of magnitude, unlike previous studies. The majority (94.7%) of MPs found in air samples were smaller than 100 µm, and the main shape of airborne MPs was fragments (88.2%). Polyethylene, polyester, and polystyrene were the dominant polymers comprising airborne MPs. No consistent relationships were detected between airborne MP concentration and typical socioeconomic indices, and the spatial and diurnal patterns for airborne MPs were different from various components of air quality indices (PM2.5, PM10, etc.). These findings reflect the contrasting source/generation dynamics between airborne MPs and other airborne pollutants. Maximum annual exposure of humans to airborne MPs was estimated in the range of 1-2 million/year in these megacities, highlighting the need for additional research examining the human health risks from the inhalation of airborne MPs.

Mental health consequences during alerting situations and recovering to a new normal of coronavirus epidemic in 2019: a cross-sectional study based on the affected population.

BACKGROUND: As a major virus outbreak in the twenty-first century, the coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented hazards to mental health globally. METHODS: We performed a cross-sectional study based on the results of an online survey. The survey was conducted 1 month after the outbreak (February 18-29, 2020) and repeated at the time of resuming activity (April 8-14, 2020). The 15-item Death Anxiety Scale (T-DAS) was used to assess the degree of death anxiety, and the Chinese version of PTSD checklist-civilian version (PCL-C), for PTSD symptom clusters. Through convenient sampling, a total of 7678 cases were collected. RESULTS: Our findings showed that even after the lockdown was lifted, the prevalence of the symptoms of post-traumatic stress disorder (PTSD) and death anxiety remained significantly high in the general population affected by the outbreak. Regression model analysis showed that PTSD was significantly associated with age > 50 years, contact history/living community, poor health status of participants, past traumatic experience (PTE), and medical occupation. Moreover, death anxiety mediated the relationship between life-threatening PTE and PTSD, indicating that reducing death anxiety could buffer the negative effects of PTE on PTSD. CONCLUSIONS: Despite the lifting of the lockdown, long-term adverse psychological effects remain in the affected general population. The management of mental health after major public health events is important, and high-risk groups such as the elderly and healthcare workers should receive targeted interventions. In addition, the study suggests that methods for alleviating death anxiety must be included in plans to manage the psychological impact of public health emergencies.

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.

Ginsenoside Rb1, salvianolic acid B and their combination modulate gut microbiota and improve glucolipid metabolism in high-fat diet induced obese mice.

BACKGROUND: To observe the effect of ginsenoside Rb1, salvianolic acid B and their combination on glucolipid metabolism and structural changes of gut microbiota. METHODS: Eight-week-old C57BL/6J mice were fed 45% high-fat diet to induce obesity. The obese mice were randomly divided into four groups, Con group as model control, ginsenoside Rb1 (Rb1) group, salvianolic acid B (SalB) group and ginsenoside Rb1+ salvianolic acid B (Rb1SalB) group. Mice in Rb1, SalB and Rb1SalB group were treated by gavage with ginsenoside Rb1, salvianolic acid B and the combination of the two ingredients, respectively. While mice in Con group were given the same amount of sterile water. The intervention lasted 8 weeks. Body weight and fasting blood glucose were measured every 2 weeks. Oral glucose tolerance test was conducted on the 4th and 8th week of drug intervention. At the end of the experiment, total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol and non-esterified fatty acid content as well as glycated hemoglobin were measured and feces were collected for 16S rDNA sequencing. RESULTS: Both ginsenoside Rb1 and Rb1SalB combination decreased body weight significantly (P < 0.05). Ginsenoside Rb1, salvianolic acid B and their combination alleviated fasting blood glucose, glycated hemoglobin and blood lipid profiles effectively (P < 0.05, compared with the corresponding indicators in Con group). Oral glucose tolerance test results at the 8th week showed that glucose tolerance was significantly improved in all three treatment groups. Ginsenoside Rb1, salvianolic acid B and their combination reduced the overall diversity of gut microbiota in feces and changed the microbial composition of the obese mice. LDA effect size (LefSe) analysis revealed the key indicator taxa corresponding to the treatment. CONCLUSION: Ginsenoside Rb1, salvianolic acid B and their combination could lower blood glucose and lipid level, and improve glucose tolerance of obese mice. The above effect may be at least partially through modulation of gut microbial composition.

A New Biscarbazole-Based Metal-Organic Framework for Efficient Host-Guest Energy Transfer.

A new metal-organic framework (MOF), [Zn6 L4 (Me2 NH2 + )4 ⋅3 H2 O] (1) was constructed based on [9, 9'-biscarbazole]-3, 3', 6, 6'-tetracarboxylic acid (H4 L) and Zn2+ ions. The porous framework and intense blue fluorescence of the MOF based on the biscarbazole moiety of the ligand could facilitate efficient host to guest energy transfer, which makes it an ideal platform for the tuning of luminescence.

Berberine Induces Cell Apoptosis through Cytochrome C/Apoptotic Protease-Activating Factor 1/Caspase-3 and Apoptosis Inducing Factor Pathway in Mouse Insulinoma Cells.

OBJECTIVE: To investigate apoptotic effects of berberine, a significant alkaloids component existing in Rhizoma coptidis, and its possible acting mechanism in insulinoma cells. METHODS: Different concentrations of berberine were used to treat mouse insulinoma (MIN6) cells for various period of time. The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay, flow cytometry and enzyme-linked immuno sorbent assay. Changes in the relating pro- and anti-apoptosis proteins were detected by western-blotting. RESULTS: The half-maximal inhibitory concentration (IC50) of berberine was 5.7 µmol/L on MIN6 cells viability for 16 h. Berberine caused a 20% reduction (P<0.05) in cell number after only 4-h incubation; which reached 50% after 24 h (P<0.01). Berberine treatment for 16 h significantly increased the level of DNA fragmentation. The flow cytometry showed the apoptotic rate increased 2.9- and 4.6-fold after treating with berberine (5 µmol/L) for 8 and 16 h, while 3- and 8.7-fold after 10 µmol/L treatment for 8 and 16 h (P<0.01). Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2. Meanwhile, berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm. Apoptotic protease-activating factor 1 (Apaf-1) was subsequently activated after cytochrome C release. Furthermore, caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade. CONCLUSION: High concentration (5 and 10 µmol/L) of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf-1/caspase-3 and apoptosis inducing factor (AIF) pathway.

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.

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.

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.

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.

Differential Expression of Long Noncoding RNAs between Sperm Samples from Diabetic and Non-Diabetic Mice.

To investigate the potential core reproduction-related genes associated with the development of diabetes, the expression profiles of long noncoding RNA (lncRNA) and messenger RNA (mRNA) in the sperm of diabetic mice were studied. We used microarray analysis to detect the expression of lncRNAs and coding transcripts in six diabetic and six normal sperm samples, and differentially expressed lncRNAs and mRNAs were identified through Volcano Plot filtering. The function of differentially expressed mRNA was determined by pathway and gene ontology (GO) analysis, and the function of lncRNAs was studied by subgroup analysis and their physical or functional relationships with corresponding mRNAs. A total of 7721 lncRNAs and 6097 mRNAs were found to be differentially expressed between the diabetic and normal sperm groups. The diabetic sperm exhibited aberrant expression profiles for lncRNAs and mRNAs, and GO and pathway analyses showed that the functions of differentially expressed mRNAs were closely related with many processes involved in the development of diabetes. Furthermore, potential core genes that might play important roles in the pathogenesis of diabetes-related low fertility were revealed by lncRNA- and mRNA-interaction studies, as well as coding-noncoding gene co-expression analysis based on the microarray expression profiles.

JiangTang XiaoKe granule attenuates cathepsin K expression and improves IGF-1 expression in the bone of high fat diet induced KK-Ay diabetic mice.

AIM: To assess the beneficial effects of JiangTang XiaoKe (JTXK) granule on the bone metabolism in high fat diet (HFD) fed KK-Ay diabetic mice. MATERIALS AND METHODS: The KK-Ay mice were used as a diabetic model, while C57BL/6 mice were utilized as the non-diabetic control. The left tibia was used for determining bone mineral density (BMD) and bone ash coefficient. The HE and alizarin red S staining of femur were employed to evaluate bone pathology and calcium deposition. The expressions of alkaline phosphatase (ALP), insulin growth factor 1 (IGF-1) and cathepsin K were assessed by western blotting and immunohistochemical staining. KEY FINDINGS: JTXK granule significantly improved the bone ash coefficient, the distribution of trabecular bone and the calcification nodules deposition in KK-Ay mice with diabetes. IGF-1 and ALP expressions were significantly decreased, and cathepsin K expression was dramatically increased in the HFD fed KK-Ay diabetic model mice, which can be reversed by JTXK granule treatment. JTXK granule at medium or high dosage was more efficient in improving diabetic bone quality when compared with that in mice with a low dosage. However, the BMD values in each group of KK-Ay diabetic mice were not significantly different. SIGNIFICANCE: We demonstrate that cathepsin K expression is increased in KK-Ay diabetic mouse model. JTXK granule treatment inhibits osteoclastic bone resorption and promotes the new bone formation by decreasing cathepsin K activity and increasing IGF-1 and ALP levels. These changes may contribute to the increase of bone strength and thus reducing the risk of bone fractures.

Ginsenoside Rb1 promotes browning through regulation of PPARγ in 3T3-L1 adipocytes.

Browning of white adipocyte tissue (WAT) has received considerable attention due to its potential implication in preventing obesity and related comorbidities. Ginsenoside Rb1 is reported to improve glycolipid metabolism and reduce body weight in obese animals. However whether the body reducing effect mediates by browning effect remains unclear. For this purpose, 3T3-L1 adipocytes were used to study the effect of ginsenoside Rb1 on browning adipocytes specific genes and oxygen consumptions. The results demonstrate that 10 µM of ginsenoside Rb1 increases basal glucose uptake and promoted browning evidenced by significant increases in mRNA expressions of UCP-1, PGC-1α and PRDM16 in 3T3-L1 mature adipocytes. Further, ginsenoside Rb1 also increases PPARγ activity. And the browning effect is abrogated by GW9692, a PPARγ antagonist. In addition, ginsenoside Rb1 increases basal respiration rate, ATP production and uncoupling capacity in 3T3-L1 adipocytes. Those effects are also blunted by GW9692. The results suggest that ginsenoside Rb1 promote browning of 3T3-L1 adipocytes through induction of PPARγ. Our finding offer a new source to discover browning agonists and also useful to understand and extend the applications of ginseng and its constituents.