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BACKGROUND: High glucose levels are a primary cause of diabetes-associated cellular dysfunction and tissue damage. Muscles are the key insulin target organ and therefore, have a high level of sensitivity to hyperglycemia. Our previous study revealed that 20(S)-ginsenoside Rg3 (S-Rg3) is a monomer with a good myogenic differentiation effect in ginsenoside. Furthermore, it can alleviate dexamethasone-induced muscle atrophy by protecting mitochondrial function. However, whether S-Rg3 is effective for diabetic-induced muscle atrophy has not been reported. PURPOSE: This study aimed to investigate the protective effect of S-Rg3 on diabetic-induced muscle atrophy. METHODS: C2C12 myoblasts, Drosophila, and mice were used as model systems, and the protective effect of S-Rg3 on diabetes was evaluated by assessing the levels of glucose and lipids. Furthermore, H&E, toluidine blue, Giemsa, and immunofluorescence staining were performed to detect the effects of S-Rg3 on muscle atrophy and myogenic differentiation. Moreover, the effects of S-Rg3 on mitochondrial morphology and function were also evaluated by electron microscopy, flow cytometry, and Seahorse. In addition, the underlying pathways of S-Rg3 effects were detected by Western blot. The related inhibitors and gene mutations in Drosophila were used for validation. RESULTS: The analysis of diabetic mice model fed with a high-fat diet (HFD) and high glucose (HG) revealed that in the injured C2C12 myoblasts, S-Rg3 treatment significantly reduced the levels of triglycerides and glucose. Furthermore, it promoted the differentiation of myoblasts and inhibited mitochondrial dysfunction. In the Drosophila HG and HFD diabetic model, S-Rg3 reduced triglyceride and trehalose levels, increased climbing distance values, promoted myoblasts differentiation, preserved mitochondrial function, and inhibited muscle atrophy. Mechanistically, the beneficial effects of S-Rg3 were at least partially associated with the phosphorylation of AMPK and FoxO3 together with the inhibition of Smad3 phosphorylation, this pathway was validated by the UAS-AMPKα-RNAi Drosophila model. CONCLUSION: In summary, this study revealed mechanistic insights into how S-Rg3 protects against diabetes-associated muscle atrophy in cells, Drosophila, and mice.
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ETHNOPHARMACOLOGICAL RELEVANCE: Jiedu Tongluo Tiaogan Formula (JTTF), a traditional Chinese herbal decoction, exhibits the potential to treat type 2 diabetes mellitus (T2DM) by inhibiting endoplasmic reticulum stress (ERS) and excessive autophagy, which are the risk factors for the abnormal development and progression of ß cells. AIM OF THE STUDY: We aimed to assess the effect of JTTF on pancreatic glucotoxicity by inhibiting ERS and excessive autophagy, for which db/db mice and INS-1 insulinoma cells were used. MATERIALS AND METHODS: The chemical composition of the JTTF was analyzed by UPLC-Q/TOF-MS. Diabetic (db/db) mice were treated with distilled water or JTTF (2.4 and 7.2 g/kg/day) for 8 weeks. Furthermore, INS-1 cells induced by high glucose (HG) levels were treated with or without JTTF (50, 100, and 200 µg/mL) for 48 h to elucidate the protective mechanism of JTTF on glucose toxicity. The experimental methods included an oral glucose tolerance test, hematoxylin-eosin staining, immunohistochemistry, western blotting, RT-qPCR, and acridine orange staining. RESULT: 28 chemical components of JTTF were identified. Additionally, treatment with JTTF significantly decreased the severity of glycemic symptoms in the db/db mice. Moreover, the treatment partially restored glucose homeostasis in the db/db mice and protected the pancreatic ß-cell function. JTTF protected INS-1 cells from HG injury by upregulating GSIS and PDX1, MafA mRNA expression. Further, treatment with JTTF downregulated GRP78 and ATF6 expression, whereas it inhibited Beclin-1 and LC3 activation. The treatment protected the cells from HG-induced ERS and excessive autophagy by downregulating the CaMKKß/AMPK pathway. CONCLUSIONS: The present study findings show that JTTF may protects ß-cells by inhibiting the CaMKKß/AMPK pathway, which deepens our understanding of the effectiveness of JTTF as a treatment strategy against T2DM.
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Proteínas Quinasas Activadas por AMP , Autofagia , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina , Medicamentos Herbarios Chinos , Estrés del Retículo Endoplásmico , Células Secretoras de Insulina , Transducción de Señal , Animales , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Autofagia/efectos de los fármacos , Ratones , Masculino , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Ratas , Chaperón BiP del Retículo Endoplásmico , Ratones Endogámicos C57BL , Línea Celular Tumoral , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológicoRESUMEN
The incidence of allergic reactions has risen steadily in recent years, prompting growing interest in the identification of efficacious and safe natural compounds that can prevent or treat allergic diseases. Phellodendron amurense Rupr. has long been applied as a treatment for allergic diseases, whose primary component is phellodendrine. However, the efficacy of phellodendrine as a treatment for allergic diseases remains to be assessed. Mast cells are the primary effectors of allergic reactions, which are not only activated by IgE-dependent pathway, but also by IgE-independent pathways via human MRGPRX2, rat counterpart MRGPRB3. As such, this study explored the effect and mechanism of phellodendrine through this family receptors in treating allergic diseases in vitro and in vivo. These analyses revealed that phellodendrine administration was sufficient to protect against C48/80-induced foot swelling and Evans blue exudation in mice, and suppressed C48/80-induced RBL-2H3 rat basophilic leukemia cells degranulation, and ß-HEX, HIS, IL-4, and TNF-α release. Moreover, phellodendrine could reduce the mRNA expression of MRGPRB3 and responsiveness of MRGPRX2 by altering its structure. It was able to decrease Ca2+ levels, phosphorylation levels of CaMK, PLCß1, PKC, ERK, JNK, p38, and p65, and inhibit the degradation of IκB-α. These analyses indicate that berberine inhibits the activation of PLC and downregulates the release of Ca2+ in the endoplasmic reticulum by altering the conformation of MRGPRB3/MRGPRX2 protein, thereby inhibiting the activation of PKC and subsequently inhibiting downstream MAPK and NF-κB signaling, ultimately suppressing allergic reactions. There may thus be further value in studies focused on developing phellodendrine as a novel anti-allergic drug.
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Degranulación de la Célula , Hipersensibilidad , Mastocitos , Receptores Acoplados a Proteínas G , Animales , Ratas , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Degranulación de la Célula/efectos de los fármacos , Ratones , Humanos , Hipersensibilidad/tratamiento farmacológico , Hipersensibilidad/inmunología , Receptores Acoplados a Proteínas G/metabolismo , Antialérgicos/farmacología , Antialérgicos/uso terapéutico , Citocinas/metabolismo , p-Metoxi-N-metilfenetilamina , Masculino , Phellodendron/química , Línea Celular Tumoral , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Receptores de NeuropéptidoRESUMEN
PURPOSE: The age-induced imbalance in ecological niches leads to the loss of GSCs, which is the main reason for ovarian germline senescence. Ginsenoside Rg1 can delay ovarian senescence. Here, we shed light on new insights of ginsenoside Rg1 in regulating the niche to maintain GSCs self-renewal and discussing related molecular mechanisms. METHODS: The differences among GSC number, reproductive capacity of naturally aging female Drosophila after ginsenoside Rg1 feeding were analyzed by immunofluorescence and behavior monitoring. The expressions of the active factors in the niche and the BMP signaling were analyzed through Western blot and RT-qPCR. The target effect was verified in the ECR mutant and combined with the molecular docking. RESULTS: Ginsenoside Rg1 inhibited the age-induced reduction of the GSCs number and restored offspring production and development. Ginsenoside Rg1 promoted the expression of anchor proteins E-cadherin, stemness maintenance factor Nos and differentiation promoting factor Bam, thereby GSCs niche homeostasis was regulated. In addition, ginsenoside Rg1 was bound to the LBD region of the hormone receptor ECR. Ginsenoside Rg1 promotes the regeneration of GSCs by targeting the ECR to increase pSmad1/5/8 expression and thereby activating the BMP signaling pathway. In addition, ginsenoside Rg1 maintenance of niche homeostasis to promote GSCs regeneration is dependent on ECR as demonstrated in ECR mutants. CONCLUSIONS: Ginsenoside Rg1 regulated the ecological niche homeostasis of GSCs and promoted the regeneration of GSCs by targeting the ECR/BMP signaling pathway in hormone-deficient states in aging ovaries. It is of great significance for prolonging fertility potential and delaying ovarian senescence.
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Proteínas de Drosophila , Drosophila , Ginsenósidos , Animales , Femenino , Drosophila/fisiología , Proteínas de Drosophila/metabolismo , Simulación del Acoplamiento Molecular , Células Madre/metabolismo , Transducción de Señal , Hormonas/metabolismo , Células GerminativasRESUMEN
Hemorrhoids are a proctological disease primarily characterized by bleeding, prolapse, edema, and pain, severely affecting the quality of life. Surgery is an effective treatment for hemorrhoids, but the cost is relatively high, and complications such as difficulty in defecation, persistent pain, and heavy bleeding may occur postoperatively. Traditional Chinese Medicine (TCM) has a distinctive advantage in alleviating the clinical symptoms of hemorrhoid patients, reducing pain, and improving the quality of life. However, there are few summary literature about the mechanism of TCM in the prevention and treatment of hemorrhoids. Based on the etiology of hemorrhoids in both traditional Chinese and Western medicine, this paper reviews the recent research on the mechanism of TCM in the treatment of hemorrhoids, hoping to provide a basis for the better application of TCM in clinical and experimental research.
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Borates provide an excellent platform for investigating the optical nonlinearity and linearity of crystals as photoelectric functional materials. In our work, borate derivatives with isolated [B3O3] six-membered rings as structural features are the preferred system due to their simple functional units and excellent properties. Herein, by utilizing the target-oriented synthesis, a series of borate derivatives, A2[B3O3F4(OH)] (A= NH4, Rb, Cs) (ABOFH), K2.3Cs0.7B3O3F6 (KCsBOF), and Cs3[B3O3(OH)3]Cl3 (CsBOHCl), with novel heteroanionic groups containing [BOxF4-x] (x = 0-3) and/or [BO2(OH)] units were obtained. ABOFH, KCsBOF, and CsBOHCl construct different two-dimensional pesudolayers featuring [B3O3F4(OH)], [B3O3F6], and [B3O3(OH)3] units, respectively. Also, the optical properties and the arrangement information of these anionic groups were studied. Among the total five compounds, (NH4)2[B3O3F4(OH)] and Cs3[B3O3(OH)3]Cl3 with enlarged birefringence and sufficient band gaps were screened out as promising birefringent crystals due to the optimally aligned configuration of birefringence-active heteroanionic units. The successful results of target-oriented synthesis indicate a more profound conclusion that the borate system now has more diversified structural chemistry, and an effective strategy was proposed to modify the arrangement and species of anionic units to optimize the performance of optical crystals.
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The design of new materials with special performances is still a great challenge, especially for the deep-ultraviolet nonlinear optical materials in which it is difficult to balance large bandgaps and strong second harmonic generation responses due to their inverse relationship. Cation variation not only influences the whole structure frameworks but also directly participates in the formation of electronic structures, both of which could lead to the uncontrollability of the properties of the designed materials. Here, a novel approach, aiming at purposeful and foreseeable material designs, is proposed to characterize the role of cations. By the verification of several series of borates, the influences of cation variation on property changes are explored systematically. Accordingly, a feasible strategy of designing deep-ultraviolet nonlinear optical materials by substituting barium for lead has been concluded, which could obviously blue-shift the ultraviolet cutoff edge and maintain the relatively strong second harmonic generation response (more than 2 times of KH2PO4), achieving the property optimization, and especially works efficiently in fluorooxoborates. The property optimization design strategy and the cation characterization method are not only helpful in exploring nonlinear optical materials but also enlightening in material design and selection.
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The electronic stopping power of palladium (Pd) for protons is investigated based on time-dependent density functional theory combined with Ehrenfest molecular dynamics simulations. The electronic stopping power of Pd with explicitly considering inner electrons for protons is calculated and the excitation mechanism for the inner electrons of Pd is revealed. The velocity proportionality of the low-energy stopping power of Pd is reproduced. Our study verified that the inner electron excitation contributes significantly to the electronic stopping power of Pd in the high energy range, which is strongly dependent on the impact parameter. The electronic stopping power obtained from the off-channeling geometry is in quantitative agreement with the experimental data in a wide velocity range, and the discrepancy around the stopping maximum is further reduced by considering the relativistic correction on the binding energy of inner electrons. The velocity dependence of the mean steady-state charge of protons is quantified, and the results showed that the participation of 4p-electrons reduces the mean steady-state charge of protons, and consequently decreases the electronic stopping power of Pd in the low energy range.
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The design of new birefringent materials is very significant owing to their indispensable role in modulating the polarization of light and is vital in laser technology. Herein, by applying a large optical anisotropy-oriented construction induced by a synergy effect of multiple anionic groups, a promising carbonate-nitrate chloride, Na3Rb6(CO3)3(NO3)2Cl·(H2O)6, has been designed and synthesized successfully by the solvent evaporation method and single crystals of centimeter size were obtained by the recrystallization method in aqueous solution. It crystallizes in the hexagonal P63/mcm space group, the RbO9Cl polyhedra and the NaO7 polyhedra construct a three-dimensional (3D) framework by sharing O or Cl atoms and trigonal plane units (CO3 and NO3). The transmittance spectrum based on a 1 mm thick single-crystal plate shows that its short UV cut-off edge is about 231 nm. And the refractive index differences (0.14 @ 546 nm) measured by using a polarizing microscope on the (101) crystal plane, proves that Na3Rb6(CO3)3(NO3)2Cl·(H2O)6 has a large birefringence, which has potential application in the solar blind ultraviolet region. The theoretical calculations reveal that the π-conjugated CO3 and NO3 groups are the main cause of the birefringence. It demonstrates that combining π-conjugated CO3 and NO3 groups in one structure is an extremely effective strategy to explore new UV birefringent crystals.
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Exploration of nonlinear optical (NLO) crystals that are competent in generating short-wavelength ultraviolet (UV, λ ≤ 266 nm, and even deep-UV, λ ≤ 200 nm) coherent light output by direct second harmonic generation (SHG) remains a formidable challenge. Herein, four UV/deep-UV NLO crystals, M2B4SO10 (M = K, Rb, and Cs) and Rb3B11PO19F3, were successfully synthesized by evolving the KBe2BO3F2 (KBBF) structure into mixed-anionic borosulfate and fluoroborophosphate systems. They display functional [B4SO10]∞ or [B11PO19F3]∞ KBBF-type layers that are composed of [BO3], [BO4], and [SO4] groups or [BO3], [BO4], [BO3F], and [PO4] groups, respectively. Experimental characterization and numerical computation results indicate that these crystals possess exceptional NLO performance, including large SHG responses (0.9-1.7 × KDP at 1064 nm and 0.1-0.3 × ß-BBO at 532 nm) and adequate birefringence to fulfill the SHG phase-matching (PM) condition at 266 nm. In particular, the shortest type-I PM wavelength (λPM) of Rb3B11PO19F3 reaches 180 nm, which implies that Rb3B11PO19F3 can become a prospective deep-UV NLO crystal. In addition, single crystals of K2B4SO10, Rb2B4SO10, and Cs2B4SO10 are easily obtained by the high-temperature solution approach. This work will facilitate the discovery of short-wavelength PM NLO crystals by using the KBBF structure as the template.
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Background: Aerobic cellular respiration provides chemical energy, adenosine triphosphate (ATP), to maintain multiple cellular functions. Sirtuin 1 (SIRT1) can deacetylate peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) to promote mitochondrial biosynthesis. Targeting energy metabolism is a potential strategy for the prevention and treatment of various diseases, such as cardiac and neurological disorders. Ginsenosides, one of the major bioactive constituents of Panax ginseng, have been extensively used due to their diverse beneficial effects on healthy subjects and patients with different diseases. However, the underlying molecular mechanisms of total ginsenosides (GS) on energy metabolism remain unclear. Methods: In this study, oxygen consumption rate, ATP production, mitochondrial biosynthesis, glucose metabolism, and SIRT1-PGC-1α pathways in untreated and GS-treated different cells, fly, and mouse models were investigated. Results: GS pretreatment enhanced mitochondrial respiration capacity and ATP production in aerobic respiration-dominated cardiomyocytes and neurons, and promoted tricarboxylic acid metabolism in cardiomyocytes. Moreover, GS clearly enhanced NAD+-dependent SIRT1 activation to increase mitochondrial biosynthesis in cardiomyocytes and neurons, which was completely abrogated by nicotinamide. Importantly, ginsenoside monomers, such as Rg1, Re, Rf, Rb1, Rc, Rh1, Rb2, and Rb3, were found to activate SIRT1 and promote energy metabolism. Conclusion: This study may provide new insights into the extensive application of ginseng for cardiac and neurological protection in healthy subjects and patients.
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It is unclear whether ginseng-derived nanoparticles (GDNPs) can prevent tumor cell epithelial-mesenchymal transition (EMT). Here, we describe typical characteristics of GDNPs and possible underlying mechanisms for GDNP antitumor activities. First, GDNPs particle sizes and morphology were determined using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM), respectively, while cellular uptake of PKH67-labeled GDNPs was also assessed. Next, we evaluated GDNPs antitumor effects by determining whether GDNPs inhibited proliferation and migration of five tumor cell lines derived from different cell types. The results indicated that GDNPs most significantly inhibited proliferation and migration of lung cancer-derived tumor cells (A549, NCI-H1299). Moreover, GDNPs treatment also inhibited cell migration, invasion, clonal formation, and adhesion tube formation ability and reduced expression of EMT-related markers in A549 and NCI-H1299 cells in a dose-dependent manner. Meanwhile, Kaplan-Meier analysis of microarray data revealed that high-level thymidine phosphorylase (TP) production, which is associated with poor lung cancer prognosis, was inhibited by GDNPs treatment, as reflected by decreased secretion of overexpressed TP and downregulation of TP mRNA-level expression. In addition, proteomic analysis results indicated that GDNPs affected pentose phosphate pathway (PPP) activity, with ELISA results confirming that GDNPs significantly reduced levels of PPP metabolic intermediates. Results of this study also demonstrated that GDNPs-induced downregulation of TP expression led to PPP pathway inhibition and repression of lung cancer cell metastasis, warranting further studies of nano-drugs as a new and promising class of anti-cancer drugs.
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BACKGROUND: Chronically elevated free fatty acid levels can adversely affect pancreatic ß-cells, leading to insulin resistance and eventually type 2 diabetes mellitus (T2DM). Polydatin (PD) from Polygonum cuspidatum has been shown to regulate blood lipid content and lower cholesterol levels. However, there have been no reports on the potential therapeutic effects and actions of PD on lipotoxicity in ß-cells. PURPOSE: This study aimed to investigate the protective effects of PD on palmitate (PA)-treated INS-1 insulinoma cells and diabetic mice. METHODS: Cells were incubated with PA and varying concentrations of PD for 24 h. Viability assays, morphological observations, flow cytometric analysis, western blotting, and reverse transcription-quantitative polymerase chain reaction were used to assess the effects of PD on PA-induced lipotoxicity. Western blotting was used to measure the endoplasmic reticulum stress (ERS) and the levels of autophagy-related factors after incubation with inducers and inhibitors of ERS and autophagy. Diabetic mice were treated with intragastric PD for 6 weeks followed by the measurement of their physiological and blood lipid indices and assessment of the results of histological and immunofluorescence analyses. RESULTS: Treatment with PD after PA exposure enhanced insulin secretion and the expression of diabetes-associated genes. PD promoted ß-cell function by reducing the levels of proteins associated with ERS and autophagy while also attenuating ERS triggered by tunicamycin. PD also reduced tunicamycin-induced autophagy, indicating that it regulated ERS-mediated autophagy and reduced PA-induced cellular dysfunction. In addition, treatment of db/db mice with PD substantially reduced body weight gain, alleviated dyslipidemia, improved ß-cell function, and reduced insulin resistance. CONCLUSION: These results suggest that PD protects ß-cells from lipotoxicity-induced dysfunction and apoptosis by inhibiting ERS and preventing excessive autophagy. Our study provides a new basis for exploring the potential of PD against ß-cell lipotoxicity and T2DM.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Células Secretoras de Insulina , Animales , Apoptosis , Autofagia , Colesterol/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Estrés del Retículo Endoplásmico , Ácidos Grasos no Esterificados/metabolismo , Glucósidos , Ratones , Palmitatos/metabolismo , Palmitatos/toxicidad , Estilbenos , TunicamicinaRESUMEN
Birefringent materials play indispensable roles in modulating the polarization of light and are vital in the laser science and technology. Currently, the design of birefringent materials operating in the deep-ultraviolet region (DUV, λ ≤200 nm) is still a great challenge. In this work, we developed a new DUV birefringent crystal LiBO2 based on [BO2]∞ infinite chains in the Li-B-O system, which simultaneously achieves the shortest UV cutoff edge (164 nm) and the largest birefringence (≥0.168 at 266 nm) among all the reported borate-based DUV birefringent materials. Single crystals of LiBO2 with dimensions up to Ø55 × 34 mm3 were grown by the Czochralski method, providing access to large-sized single crystal with low cost. Moreover, it has a high laser damage threshold and stable physicochemical properties. These outstanding characters unambiguously support that LiBO2 can be an excellent birefringent material for DUV application.
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CONTEXT: Jiedutongluotiaogan formula (JTTF), a traditional Chinese medicine (TCM), could promote islet function. However, the potential effect of JTTF on endoplasmic reticulum stress (ERS) and autophagy have not been reported. OBJECTIVE: This study explores the potential effect of JTTF on ERS and autophagy in the pancreas. MATERIALS AND METHODS: The Zucker diabetic fatty (ZDF) rats were randomised into five groups, control, model, JTTF (1, 3, 5 g/kg/day for 12 weeks). LPS induced pancreatic ß-cells were treated with JTTF (50, 100, 200 µg/mL). LPS was used to induce pancreatic ß-cell injury, with cell viability and insulin secretion evaluated using MTT, glucose-stimulated insulin secretion (GSIS) assays, and PCR. Intracellular Ca2+ concentration was measured using flow cytometry, while ERS and autophagy levels were monitored via Western blotting and/or immunostaining. RESULTS: Compared with the model group, body weight, FGB, HbA1c, IPGTT, FINs, and HOMA-IR in JTTF treatment groups were significantly reduced. In islets cells treated with JTTF, the pancreatic islet cells in the JTTF group were increased, lipid droplets were reduced, and there was a decrease in Ca2+ (16.67%). After JTTF intervention, PERK, p-PERK, IRE1α, p- IRE1α, ATF6, eIF2α, GRP78, p-ULK1, LC3 and p62 expression decreased, whereas Beclin1and p-mTOR expression increased. In addition, the expression of proteins related to apoptosis in the JTTF groups were lower than those in the control group. DISCUSSION AND CONCLUSIONS: JTTF may alleviate pancreatic ß-cell injury by inhibiting ER stress and excessive autophagy in diabetic rats. This provides a new direction for treating diabetes and restoring pancreatic dysfunction by TCM.
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Diabetes Mellitus Experimental , Estrés del Retículo Endoplásmico , Animales , Apoptosis , Autofagia , Endorribonucleasas , Lipopolisacáridos/farmacología , Proteínas Serina-Treonina Quinasas , Ratas , Ratas ZuckerRESUMEN
A number of studies demonstrated that some tea extracts exert inhibitory effects on osteoclastogenesis induced by receptor activator of nuclear factor κB ligand (RANKL). However, the effect of purple tea, a famous tea in China, on osteoclastogenesis remains unclear. In this study, a water-based purple tea extract (PTE) was found to suppress osteoclast formation, osteoclastic resorption pit area formation, and F-actin ring formation within RANKL-stimulated bone marrow macrophages (BMMs). Furthermore, our results demonstrated that PTE could inhibit expression of master transcription factors NFATc1 and c-Fos and their target genes DC-STAMP, Ctsk, and Atp6v0d2. Western blot analysis revealed that PTE treatment led to reduced RANKL-induced phosphorylation of Akt and GSK3ß without altering transient activation of NF-κB and MAPKs (p38, JNK, ERK1/2) signaling. In addition, the results demonstrated that PTE treatment of RANKL-stimulated BMMs could down-regulate Blimp1 expression and up-regulate Irf8 expression. In summary, these results suggest that PTE treatment of RANKL-stimulated BMMs inhibited osteoclast differentiation via modulation of Blimp1-Irf8 and Akt/GSK3ß signaling pathways. Aligning with our in vitro results, in vivo PTE administration ameliorated bone loss in LPS-treated mice. Taken together, the results presented in this work suggest that PTE treatment possesses anti-osteolytic activity.
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Resorción Ósea , Ligando RANK , Animales , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/genética , Resorción Ósea/metabolismo , Diferenciación Celular , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Ratones , FN-kappa B/genética , FN-kappa B/metabolismo , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Osteoclastos , Osteogénesis , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ligando RANK/metabolismo , Té/metabolismo , Agua/metabolismoRESUMEN
Borates with tunable structure and property currently provide a new rich source for solid-state chemistry and materials science. Realization of property improvement via simple structural regulation is a rising hot spot of borate-based research. Herein, a new aluminoborate fluoride, Li3Cs6Al2B14O28F, with [B7O14] clusters was discovered, and it was found to melt congruently. The optimally aligned [B2O5] dimers within [B7O14] clusters make Li3Cs6Al2B14O28F an enhanced birefringence, which is about 4.3× higher than its congener compound Li4Cs3B7O14 with same [B7O14] clusters. Structural analysis and additional theoretical calculations have revealed the origin of enhanced optical anisotropy.
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Androgen exposure may be an important factor in promoting the development of polycystic ovary syndrome (PCOS) and disease progression. Bushen Huoxue Formula (BHF), a traditional Chinese medicine, is prescribed in clinical settings as a PCOS remedy, albeit with unclear pharmacological effects on granulosa cells. The present research explores potentially advantageous BHF impacts and whereby BHF alleviates dehydroepiandrosterone (DHEA)-induced inflammation and endocrine disruption. Six chemical components in BHF were identified and fingerprint analysis showed good reproducibility. Using a human granulosa cell line (KGN), BHF effects on cell viability, secretion of steroidogenic and inflammatory factors were evaluated and TLR4/NF-κB pathway expression was examined. Our results demonstrate that BHF treatment of KGN cells in a DHEA-induced inflammatory state led to increased cell viability, decreased testosterone and estradiol production, and decreased CYP19A1 and HSD3B2 mRNA expression. Further experiments revealed that BHF inhibited the expression of pro-inflammatory cytokines and considerably hindered up-regulation in protein levels of TLR4, MyD88, and TRAF6, while inhibiting the activation of NF-κB and phosphorylation of IκBα. Collectively, BHF administration protected granulosa cells from DHEA-induced injuries through down-regulating pro-inflammatory cytokines and blocking the pathway of TLR4/NF-κB. Therefore, BHF hold promise as a therapeutic formulation for preventing androgen induced PCOS.
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FN-kappa B , Síndrome del Ovario Poliquístico , Andrógenos/metabolismo , Andrógenos/farmacología , Andrógenos/uso terapéutico , Citocinas/metabolismo , Deshidroepiandrosterona/metabolismo , Deshidroepiandrosterona/farmacología , Deshidroepiandrosterona/uso terapéutico , Medicamentos Herbarios Chinos , Femenino , Células de la Granulosa/metabolismo , Humanos , Inflamación/metabolismo , FN-kappa B/metabolismo , Síndrome del Ovario Poliquístico/inducido químicamente , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/metabolismo , Reproducibilidad de los Resultados , Transducción de Señal , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismoRESUMEN
(1) Background: pancreatic cancer is one of the most serious cancers due to its rapid and inevitable fatality, which has been proved very difficult to treat, compared with many other common cancers. Thus, developing an effective therapeutic strategy, especially searching for potential drugs, is the focus of current research. The exact mechanism of rutin in pancreatic cancer remains unknown. (2) Method: three pancreatic cancer cell lines were used to study the anti-pancreatic cancer effect of rutin. The potent anti-proliferative, anti-migration and pro-apoptotic properties of rutin were uncovered by cell viability, a wound-healing migration assay, and a cell apoptosis assay. High-throughput sequencing technology was used to detect the change of miRNAs expression. Immunoblotting analysis was used to detect the expression of apoptotic proteins. (3) Results: CCK-8 and EDU assays revealed that rutin significantly inhibited pancreatic cancer cells' proliferation (p < 0.05). A wound-healing assay showed that rutin significantly suppressed pancreatic cancer cells' migration (p < 0.05). A flow cytometric assay showed that rutin could promote pancreatic cancer cells' apoptosis. Intriguingly, rutin significantly upregulated miR-877-3p expression to repress the transcription of Bcl-2 and to induce pancreatic cancer cell apoptosis. Accordingly, rutin and miR-877-3p mimics could promote apoptotic protein expression. (4) Conclusions: our findings indicate that rutin plays an important role in anti-pancreatic cancer effects through a rutin-miR-877-3p-Bcl-2 axis and suggests a potential therapeutic strategy for pancreatic cancer.