Tetrahedral framework nucleic acids-based delivery of microRNA-155 alleviates intervertebral disc degeneration through targeting Bcl-2/Bax apoptosis pathway.

Intervertebral disc degeneration (IDD) is one of the most common causes of chronic low back pain, which does great harm to patients' life quality. At present, the existing treatment options are mostly aimed at relieving symptoms, but the long-term efficacy is not ideal. Tetrahedral framework nucleic acids (tFNAs) are regarded as a type of nanomaterial with excellent biosafety and prominent performance in anti-apoptosis and anti-inflammation. MicroRNA155 is a non-coding RNA involved in various biological processes such as cell proliferation and apoptosis. In this study, a complex named TR155 was designed and synthesised with microRNA155 attached to the vertex of tFNAs, and its effects on the nucleus pulposus cells of intervertebral discs were evaluated both in vitro and in vivo. The experimental results showed that TR155 was able to alleviate the degeneration of intervertebral disc tissue and inhibit nucleus pulposus cell apoptosis via Bcl-2/Bax pathway, indicating its potential to be a promising option for the treatment of IDD.

Sex-Specific Risk Factors Associated with Helicobacter pylori Infection Among Individuals Undergoing Health Examinations in China.

Purpose: Helicobacter pylori is one of the most common causes of peptic ulcers, gastritis, and gastric cancers. This study investigated sex-specific differences in the prevalence of H. pylori infection and its associated factors among individuals undergoing hospital-based health examinations in southern China. Methods: This study enrolled consecutive healthy individuals who underwent regular health examinations at a hospital physical examination center between September 2020 and September 2021. Anthropometric characteristics and biochemical profiles were measured. All individuals underwent carbon-13 urea breath tests. Univariate and multivariate analyses were used to evaluate the factors associated with H. pylori infection. Results: A total of 5035 individuals (men, 59.1%; women, 40.9%) were included in the analyses. The total rate of H. pylori infection was 35.0% (men, 35.5%; women, 34.3%). In the multivariate analysis, the risk factors identified for H. pylori infections were high fasting blood glucose levels and blood pressure ≥160 mmHg in men and older age, high body mass index, and low albumin levels in women. Conclusion: These findings suggest that physicians must be aware of the metabolic factors associated with H. pylori infections in the Chinese population. Early detection of these factors and timely intervention are expected to reduce H. pylori infections and provide a theoretical basis for the primary prevention of several gastrointestinal diseases.

Tetrahedral Framework Nucleic Acids Ameliorate Insulin Resistance in Type 2 Diabetes Mellitus via the PI3K/Akt Pathway.

Insulin resistance (IR) is one of the essential conditions in the development of type 2 diabetes mellitus (T2DM). IR occurs in hepatic cells when the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is downregulated; thus, activating this pathway can significantly improve insulin sensitivity and ameliorate T2DM. Tetrahedral framework nucleic acids (tFNAs), a DNA nanomaterial, are synthesized from four single-stranded DNA molecules. tFNAs possess excellent biocompatibility and good water solubility and stability. tFNAs can promote cell proliferation, cell autophagy, wound healing, and nerve regeneration by activating the PI3K/Akt pathway. Herein, we explore the effects and underlying mechanisms of tFNAs on IR. The results displayed that tFNAs could increase glucose uptake and ameliorate IR by activating the IRS-1/PI3K/Akt pathway in glucosamine (GlcN)-stimulated HepG2 cells. By employing a PI3K inhibitor, we confirmed that tFNAs reduce IR through the PI3K/Akt pathway. Moreover, tFNAs can promote hepatic cell proliferation and inhibit GlcN-induced cell apoptosis. In a T2DM mouse model, tFNAs reduce blood glucose levels and ameliorate hepatic IR via the PI3K/Akt pathway. Taken together, tFNAs can improve hepatic IR and alleviate T2DM through the PI3K/Akt pathway, making contribution to the potential application of tFNAs in T2DM.

Evaluation of early changes of macular function and morphology by multifocal electroretinograms in patients with nasopharyngeal carcinoma after radiotherapy.

OBJECTIVE: To assess the role of multifocal electroretinograms (mfERGs) and optical coherence tomography (OCT) for detecting early changes in macular functions of patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: mfERGs and OCT were used to examine a NPC group (36 NPC patients after radiotherapy without clinically visible radiation retinopathy, 36 eyes) and a normal control group (25 healthy individuals, 25 eyes) with the same procedure and parameters. The two groups of mfERG were summarized by calculating ring averages, response density, N1 amplitude and P1 and N1 latencies were analysed. OCT scan thickness was summarized into ETDRS regions for comparison. RESULTS: Compared with controls, the NPC group had significantly decreased P1 response densities in 1-4 ring regions and N1 amplitudes in 1-3 rings (P < 0.01). P1 latencies were obviously prolonged in rings 1 (P < 0.01). In four quadrants (inferonasal, superonasal, inferotemporal and superotemporal) of the mfERG response waveforms, the NPC group had significantly decreased P1 response densities and N1 amplitudes mainly in the inferonasal and inferotemporal quadrants, showing statistically significant differences from the control group (P < 0.0125). But for the OCT results, there is no statistically significant difference between the NPC group and the control group. CONCLUSIONS: In NPC patients after radiotherapy, there may be changes in the mfERGs before any visible fundus lesions appeared as radiation macular oedema. Since the global OCT macular thickness analysis cannot reveal early changes, the mfERGs can objectively and quantitatively assess the earlier changes in macular function in NPC patients.

Assessing the Pharmacological and Therapeutic Efficacy of Traditional Chinese Medicine Liangxue Tongyu Prescription for Intracerebral Hemorrhagic Stroke in Neurological Disease Models.

Intracerebral hemorrhage is a fatal subtype of stroke, with crucial impact on public health. Surgical removal of the hematoma as an early-stage treatment for ICH can't improve long-term prognosis remarkably. Liangxue tongyu prescription (LP), a Traditional Chinese Medicine (TCM) formula, includes eight ingredients and has been used to treat ICH in the clinical. In the study, we elucidated the pharmacological efficacy and therapeutic efficacy of LP to dissect the mechanism of LP against ICH via network analysis and experimental validation. First, we discovered 34 potential compounds and 146 corresponding targets in LP based on network prediction. 24 signal pathway were obtained by the Clue Go assay based on potential compounds in LP against ICH. Second, we found that LP can not only decreased the level of high sensitive C reactive protein (HS-CRP), tumor necrosis factor-α (TNF-α), NF-kß, D-dimmer (D2D), estradiol (E2), S-100B, neuron specific enolase (NSE), and interleukin 1 (IL-1) in plasma on spontaneously hypertensive rats (SHRs), but also promoted cell proliferation and inhibited cell apoptosis on the glutamate-induced PC12 cell. The compounds including Taurine, Paeonol, and Ginsenoside Rb1 in LP can activate PI3K/AKT pathway. Third, from the three-factor two-level factorial design, compound combinations in LP, such as Taurine and Paeonol, Taurine and Geniposide, Ginsenoside Rg1, and Ginsenoside Rb1, had first-level interactions on cell proliferation. Compound combinations including Taurine and Paeonol, Ginsenoside Rg1 and Ginsenoside Rb1 had as significant increase in efficiency on inhibiting the apoptosis of PC12 cells at the low concentration and up-regulating of PI3K and AKT. Overall, our results suggested that LP had integrated therapeutic effect on ICH due to activities of anti-inflammatory, anti-coagulation, blood vessel protection, and protection neuron from excitotoxicity based on the way of "multi-component, multi-target, multi-pathway," and compound combination in LP can offer protection neuron from excitotoxicity at the low concentration by activation of the PI3K/Akt signal pathway.

Therapeutic Effects of Cyathula officinalis Kuan and Its Active Fraction on Acute Blood Stasis Rat Model and Identification Constituents by HPLC-QTOF/MS/MS.

BACKGROUND: Cyathula officinalis Kuan is widely used in the clinics for the treatment of blood stasis in China. OBJECTIVE: To evaluate the improving blood rheology and anti-inflammatory properties of C. officinalis Kuan extract (CO) and its active fraction (ACO) on acute blood stasis model Wistar rats and characterize the correlative constituents. MATERIALS AND METHODS: CO at 0.26, 0.53, and 1.04 g/kg and ACO at 0.38, 0.75, and 1.5 g/kg were administered to acute blood stasis model Wistar rats for 3 days. Whole blood viscosity, plasma viscosity, and the levels of interleukin-6 (IL-6), nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and cyclooxygenase-2 (COX-2) in the plasma were measured. HPLC-QTOF/MS/MS method was used to identify the major constituents of ACO; the properties of two representative components (cyasterone and chikusetsusaponin IV) from ACO on thrombin-induced human umbilical vein endothelial cells damage model were also assessed by the levels of thromboxane A2 (TXA2), endothelin (ET), malondialdehyde (MDA), COX-2, endothelial nitric oxide synthase (eNOS), and superoxide dismutase (SOD). RESULTS: CO and ACO significantly reduced whole blood viscosity, plasma viscosity, and levels of IL-6, NO, TNF-α, and COX-2 in vivo. Forty compounds were identified from ACO, mainly as phytoecdysteroids and saponins. Cyasterone and chikusetsusaponin IV could significantly inhibit levels of TXA2, ET, MDA, and COX-2 and promote the activities of eNOS and SOD in vitro. CONCLUSION: CO and ACO possessed significant improving blood rheology and anti-inflammatory effects on acute blood stasis model rats and the representative components Cyasterone and chikusetsusaponin IV showed significant anti-inflammatory, antioxidant, and anticoagulant effects in vitro. SUMMARY: Cyathula officinalis Kuan is widely used in the clinic for the treatment of blood stasis in ChinaThe C. officinalis Kuan extract and the active fraction of C. officinalis Kuan (ACO) possessed significant improving blood rheology and anti-inflammatory effects on acute blood stasis model ratsForty compounds were identified from ACO, mainly as phytoecdysteroids and saponins Abbreviations used: TCM: Traditional Chinese Medicine, CO: Cyathula officinalis Kuan extract, ACO: Active fraction of Cyathula officinalis Kuan, ROS: Reactive oxygen species, IL-6: Interleukin-6, TNF-α: Tumor necrosis factor alpha, NO: Nitric oxide, COX-2: Cyclooxygenase-2, TXA2: Thromboxane A2, ET: Endothelin, MDA: Malondialdehyde, eNOS: Endothelial nitric oxide synthase, SOD: Superoxide dismutase, ESI: Electronic spray ionization, ELISA: Enzyme-linked immunosorbent assay, HUVECs: Human umbilical vein endothelial cells, DMEM: Dulbecco's modified Eagle medium, MMP: Matrix metalloproteinase.

Study on anti-inflammatory efficacy and correlative ingredients with pharmacodynamics detected in acute inflammation rat model serum from Caulis Lonicerae japonicae.

BACKGROUND: Caulis Lonicerae japonicae (CLJ) is often used for the treatment of inflammation such as acute fever, headache, respiratory infection and epidemic diseases. Nevertheless, domestic and foreign researches simply fail to focus on reports of CLJ, especially its anti-inflammatory effects and correlative components. PURPOSE: In this study, we investigated anti-inflammatory effects and serum components of Caulis Lonicerae japonicae (CLJ) in models of acute inflammation and correlative analysis between anti-inflammatory effects and serum components of CLJ in rat serum to analyze the changes in the relative contents of components in serum with time and in the corresponding values to characterize active fractions of CLJ and identify the major active components of CLJ in rats. STUDY DESIGN: Active fractions of CLJ were screened using xylene-induced ear oedema mice model. Anti-inflammatory effects were evaluated using carrageenan-induced paw oedema rat model, and then correlative components in rat serum were demonstrated with HPLC-QTOF/MS/MS method explored. METHODS: HPLC-QTOF/MS/MS was developed to analyze the components absorbed in rat serum after oral administration of CLJ. RESULTS: Ethyl acetate extracts (ECLJ) and n-butanol extracts (BCLJ) of CLJ were preliminarily screened as active fractions of CLJ (EBCLJ) using xylene-induced ear oedema mice model, and effectively inhibited edema and values of interleukin-1 (IL-l), nuclear factor-kappaB (NF-kB), tumor necrosis factor-α (TNF-α) activities and prostaglandinE2 (PGE2) productions using carrageenan-induced paw oedema rat model. 33 peaks were found in total ion current chromatograms of EBCLJ, and 27 components were observed in EBCLJ-treated rat serum, only 11 of which were correlated with anti-inflammatory effects. CONCLUSIONS: The present study contributes to the study on the pharmacodynamic basis of CLJ and provides potent evidence for developing CLJ as a safe and promising natural drug in inflammation treatment.

[Construction and identification of mouse wildtype-syndecan-1 and unshedding-syndecan-1 expressing vector].

AIM: To construct the expressing vector pcDNA3.0- wildtype-syndecan-1(WT-sdc1) and pcDNA3.0-unshedding-syndecan-1(uS-sdc1), and to explore the expression in vitro. METHODS: (1)The mouse WT-sdc1 DNA was successfully amplified by PCR and then cloned into pcDNA3.0. uS-sdc1 was construct by Gene splicing by overlap extension- PCR on the basis of WT-sdc1. The two vectors confirmed by DNA sequencing. (2)there are 4 groups in our research: control group, pcDNA3.0 transfected group, WT-sdc1 transfected group and uS-sdc1 transfected group. each vecter was transfected into IEC-6 cells by Lipofectamine(TM);2000. RT-PCR, Western blot and Dot blot were performed to detect the expression of syndecan-1 before and after stimulation of phorbol 12-myristate 13-acetate (PMA) for 15 min. RESULTS: The vector WT-sdc1 and uS-sdc1 were successfully constructed although an non-sense mutation was in uS-sdc1. Compared to control and pcDNA3.0 transfected groups, WT-sdc1 and uS-sdc1 groups showed a significant increase in the expression of syndecan-1 in both mRNA and protein levels. In response to the stimulation of PMA, the expression of syndecan-1 was down-regulated at the protein levels but not mRNA levels. CONCLUSION: The WT-sdc1 and uS-sdc1 are successfully constructed, which lays the foundation for further studying of syndecan-1 in gastrointestinal inflammation.

Composition and antioxidant activity of water-soluble polysaccharides from Tuber indicum.

Crude water-soluble Chinese truffle Tuber indicum polysaccharide (TIP) was extracted from the fruiting bodies with water and then successively purified by DEAE-cellulose 52 and Sephadex G-100 column chromatography, yielding two major polysaccharide fractions: TIP1-1 and TIP2-1. High-performance gel permeation chromatography analysis showed that the average molecular sizes of TIP1-1 and TIP2-1 were approximately 1.75×10(4) Da and 5.73×10(3) Da, respectively. Monosaccharide component analysis by gas chromatography indicated that TIP1-1 was composed of mannose, glucose, galactose, and rhamannose in the respective molar ratio of 3.93:1.24:0.75:1.26 and that TIP2-1 contained mannose, glucose, and arabinose in the respective molar ratio of 5.27:1.44:0.43. The antioxidant activity analyses revealed that TIP1-1 and TIP2-1 possessed considerable antioxidant activity. Compared with TIP1-1, which has a higher molecular weight and contains no uronic acid, TIP2-1 exhibited a protective effect on PC12 cells injured by H(2)O(2) and a higher scavenging activity against free radicals. The relative effects of the lower molecular size, the presence of uronic acid, and the antioxidant activity of TIP2-1 appear to be significant. Accordingly, the Chinese truffle T. indicum might serve as an effective antioxidative healthcare food and source of natural antioxidants.

[Antitumor activity of polysaccharides extracted from two wild amanitas].

OBJECTIVE: To investigate the anti-tumor activity of two wild Amanita strains, and to determine the inhibition ratio of their effective chemical components on tumor cells in vitro. METHODS: Two wild Amanita strains collected in Sichuan province were identified through morphology and molecular methods. The chemical components from the fruit body of the two strains were extracted with petroleum ether, chloroform, methanol and water. The anti-tumor activity of the extracts were tested on the cancer cells of MGC and Lovo strains. The polysaccharides were isolated with hot water and tested for its anti-tumor activity in vitro. RESULTS: The two wild Amanitas were identified as Amanita subjunquillea and Amanita pantherina. The water-soluble extracts from the Amanitas had anti-tumor effect, with polysaccharide as one of the main effective components. The IC50 value of the polysaccharide isolated from M1 was 3.790 mg/mL for the MGC cells. CONCLUSION: Polysaccharides isolated from the two wild Amanitas have considerable anti-tumor activity against MGC cells in vitro.