Bergenin alleviates proliferative arterial diseases by modulating glucose metabolism in vascular smooth muscle cells.

BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation and phenotypic switching are key mechanisms in the development of proliferative arterial diseases. Notably, reprogramming of the glucose metabolism pattern in VSMCs plays an important role in this process. PURPOSE: The aim of this study is to investigate the therapeutic potential and the mechanism underlying the effect of bergenin, an active compound found in Bergenia, in proliferative arterial diseases. METHODS: The effect of bergenin on proliferative arterial disease was evaluated using platelet-derived growth factor (PDGF)-stimulated VSMCs and a mouse model of carotid artery ligation. VSMC proliferation and phenotypic switching were evaluated in vitro using cell counting kit-8, 5-ethynyl-2-deoxyuridine incorporation, scratch, and transwell assays. Carotid artery neointimal hyperplasia was evaluated in vivo using hematoxylin and eosin staining and immunofluorescence. The expression of proliferation and VSMC contractile phenotype markers was evaluated using PCR and western blotting. RESULTS: Bergenin treatment inhibited PDGF-induced VSMC proliferation and phenotypic switching and reduced neointimal hyperplasia in the carotid artery ligation model. Additionally, bergenin partially reversed the PDGF-induced Warburg-like glucose metabolism pattern in VSMCs. RNA-sequencing data revealed that bergenin treatment significantly upregulated Ndufs2, an essential subunit of mitochondrial complex I. Ndufs2 knockdown attenuated the inhibitory effect of bergenin on PDGF-induced VSMC proliferation and phenotypic switching, and suppressed neointimal hyperplasia in vivo. Conversely, Ndufs2 overexpression enhanced the protective effect of bergenin. Moreover, Ndufs2 knockdown abrogated the effects of bergenin on the regulation of glucose metabolism in VSMCs. CONCLUSION: These findings suggest that bergenin is effective in alleviating proliferative arterial diseases. The reversal of the Warburg-like glucose metabolism pattern in VSMCs during proliferation and phenotypic switching may underlie this therapeutic mechanism.

Efficacy of omega-3 fatty acids for hospitalized COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Emerging expert consensuses and guidelines recommend that omega-3 fatty acids may have anti-inflammatory effects in hospitalized patients with coronavirus disease (COVID-19). However, these recommendations are based on pathophysiological studies of inflammation rather than direct clinical evidence. We conducted this systematic review and meta-analysis to evaluate the efficacy of omega-3 fatty acid supplementation in hospitalized patients with COVID-19. METHODS AND STUDY DESIGN: We retrieved literature from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), WANFANG, Chinese Biomedical Literature Database, and Cochrane Library databases up to May 1, 2023. Data from studies comparing omega-3 fatty acids with a placebo or other pharmaceutical nutrients were analyzed. RESULTS: Of 3032 records, 42 full-text articles were reviewed, five eligible studies were identified, and one study was found in the references. In total of six studies involving 273 patients were included, pooled, and analyzed. Compared to the control group, omega-3 fatty acid intervention reduced the overall mortality of hospitalized patients with COVID-19 (RR=0.76; 95% CI, [0.61, 0.93]; p=0.010). No serious or unexpected drug-related adverse events were observed. No statistical significance was observed in inflammatory markers such as CRP (MD=-9.69; 95% CI, [-22.52, 3.15]; p=0.14; I2=97%) and IL-6; however, the neutrophil/lymphocyte ratio was significantly lower in the omega-3 FAs group on day 7 of intervention (p < 0.001). CONCLUSIONS: Omega-3 fatty acid administration may be associated with reduced mortality in hospitalized patients with COVID-19. Given the small sample size of enrolled studies, more rigorous and large-scale trials are urgently needed in the future to verify its efficacy.

m6A RNA Methylation Regulators Contribute to Predict and as a Therapy Target of Pulmonary Fibrosis.

Background: Pulmonary fibrosis is difficult to treat. Early diagnosis and finding potential drug therapy targets of pulmonary fibrosis are particularly important. There were still various problems with existing pulmonary fibrosis markers, so it is particularly important to find new biomarkers and drug treatment targets. m6A (N6,2'-O-dimethyladenosine) RNA methylation was the cause of many diseases, and it is regulated by m6A methylation regulators. So, whether RNA methylation regulators can be a diagnostic marker and potential drug therapy target of early pulmonary fibrosis needs to be explored. Materials and Methods: Using GSE110147 and GSE33566 in the GEO database to predict the m6A methylation regulators that may be related to the development of pulmonary fibrosis, we used 10 mg/ml bleomycin to induce mouse pulmonary fibrosis models and human pulmonary fibrosis samples, to confirm whether this indicator can be an early diagnostic marker of pulmonary fibrosis. Results: According to the database prediction results, METTL3 can predict the occurrence and development of pulmonary fibrosis, and the results of MASSON and HE staining show that the fibrosis model of mice is successful, and the fibrosis of human samples is obvious. The results of immunohistochemistry showed that the expression of METTL3 was significantly reduced in pulmonary fibrosis. Conclusions: The m6A methylation regulator METTL3 can be considered as an important biomarker for diagnosing pulmonary fibrosis occurrence, furthermore it could be considered as a drug target because of its low expression in pulmonary fibrosis.

Schizophrenia patients and their healthy siblings share decreased prefronto-thalamic connectivity but not increased sensorimotor-thalamic connectivity.

The pattern of decreased prefronto-thalamic connectivity and increased sensorimotor-thalamic connectivity has been consistently documented in schizophrenia. However, whether this thalamo-cortical abnormality pattern is of genetic predisposition remains unknown. The present study for the first time aimed to investigate the common and distinct characteristics of this circuit in schizophrenia patients and their unaffected siblings who share half of the patient's genotype. Totally 293 participants were recruited into this study including 94 patients with schizophrenia, 96 their healthy siblings, and 103 healthy controls scanned using gradient-echo echo-planar imaging at rest. By using a fine-grained atlas of thalamus with 16 sub-regions, we mapped the thalamocortical network in three groups. Decreased thalamo-prefronto-cerebellar connectivity was shared between schizophrenia and their healthy siblings, but increased sensorimotor-thalamic connectivity was only found in schizophrenia. The shared thalamo-prefronto-cerebellar dysconnectivity showed an impressively gradient reduction pattern in patients and siblings comparing to controls: higher in the controls, lower in the patients and intermediate in the siblings. Anatomically, the decreased thalamic connectivity mostly centered on the pre-frontal thalamic subregions locating at the mediodorsal nucleus, while the increased functional connectivity with sensorimotor cortices was only observed in the caudal temporal thalamic subregion anchoring at the dorsal and ventral lateral nuclei. Moreover, both decreased thalamo-prefronto-cerebellar connectivity and increased sensorimotor-thalamic connectivity were related to clinical symptoms in patients. Our findings extend the evidence that the decreased thalamo-prefronto-cerebellar connectivity may be related to the high genetic risk in schizophrenia, while increased sensorimotor-thalamic connectivity potentially represents a neural biomarker for this severe mental disorder.

Hydrothermal synthesis of novel rhombic dodecahedral SnS nanocrystals for highly efficient photothermal therapy.

Novel rhombic dodecahedral SnS nanocrystals were prepared via a facile one-pot hydrothermal method for the first time, which exhibit a large extinction coefficient of 36.8 L g-1 cm-1 and a high photothermal conversion efficiency of 39.4% under irradiation with a 785 nm laser. Moreover, they show good performance for photothermal therapy of HeLa tumors.

Screening for cytotoxic chemical constituents from Justicia procumbens by HPLC-DAD-ESI-MS and NMR.

BACKGROUND: The Acanthaceae family is an important source of therapeutic drugs and ethno medicines. There are many famous medicinal plants from this family, such as Andrographis paniculata, Baphicacanthus cusia, and Dicliptera chinensis. Justicia procumbens (J. procumbens) is widely distributed in tropical and sub-tropical of the world. It has long been used in traditional Chinese medicine for cancer. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed the ethyl acetate extract of J. procumbens had a cytotoxic activity. Therefore, qualitative and quantitative analysis of the chemical constituents in the ethyl acetate extract was important for understanding its pharmacological mechanism. RESULTS: A high-performance liquid chromatography with diode array detection coupled to electrospray ionisation quadrupole time-of-flight tandem mass spectrometry procedure was established. Eleven dibenzylbutanes and four arylnaphthalenes were confirmed by HPLC-DAD-ESI-QTOF-MS analysis. A novel dibenzylbutane (5-methoxy-4,4'-di-O-methylsecolariciresinol-9'-monoacetate) and seven isomers of arylnaphthalene were isolated and characterized by NMR and QTOF-MS. Compounds 1, 2, and 13 were detected for the first time. The content of six lignans were determinated in the ethyl acetate extract. CONCLUSIONS: This study showed that the cytotoxic activity assay of J. procumbens could be mainly attributed to the constituents of lignans. The bioactivity of the ethyl acetate extract and determined compounds support the traditional use of this plant in cancer. These chemical constituents may be developed as novel therapeutics.

Comparative Morphology, Transcription, and Proteomics Study Revealing the Key Molecular Mechanism of Camphor on the Potato Tuber Sprouting Effect.

Sprouting regulation in potato tubers is important for improving commercial value and producing new plants. Camphor shows flexible inhibition of tuber sprouting and prolongs the storage period of potato, but its underlying mechanism remains unknown. The results of the present study suggest that camphor inhibition caused bud growth deformities and necrosis, but after moving to more ventilated conditions, new sprouts grew from the bud eye of the tuber. Subsequently, the sucrose and fructose contents as well as polyphenol oxidase (PPO) activity were assessed after camphor inhibition. Transcription and proteomics data from dormancy (D), sprouting (S), camphor inhibition (C), and recovery sprouting (R) samples showed changes in the expression levels of approximately 4000 transcripts, and 700 proteins showed different abundances. KEGG (Kyoto encyclopaedia of genes and genomes) pathway analysis of the transcription levels indicated that phytohormone synthesis and signal transduction play important roles in tuber sprouting. Camphor inhibited these processes, particularly for gibberellic acid, brassinosteroids, and ethylene, leading to dysregulation of physiological processes such as cutin, suberine and wax biosynthesis, fatty acid elongation, phenylpropanoid biosynthesis, and starch and sucrose metabolism, resulting in bud necrosis and prolonged storage periods. The KEGG pathway correlation between transcripts and proteins revealed that terpenoid backbone biosynthesis and plant-pathogen interaction pathways showed significant differences in D vs. S samples, but 13 pathways were remarkably different in the D vs. C groups, as camphor inhibition significantly increased both the transcription levels and protein abundance of pathogenesis-related protein PR-10a (or STH-2), the pathogenesis-related P2-like precursor protein, and the kirola-like protein as compared to sprouting. In recovery sprouting, these genes and proteins were decreased at both the transcriptional level and in protein abundance. It was important to find that the inhibitory effect of camphor on potato tuber sprout was reversible, revealing the action mechanism was similar to resistance to pathogen infection. The present study provides a theoretical basis for the application of camphor in prolonging seed potato storage.

[Cloning, subcellular lacalization and expression analysis of chloroplast-targeted Obg gene in Cyathula officinalis].

According to ObgC gene sequences from Cyathula officinalis genomic data, the specific primers were designed, and a full-length CoObgC cDNA (2 226 bp) was obtained by polymerase chain reaction (PCR) and rapid amplification of cDNA ends (RACE) methord. Sequence alignment showed that CoObgC gene contained a 1 818 bp open reading frame (ORF) encoding 605 amino acids. Sequence analysis predicted that molecular weight of CoObgC protein was about 66.39 kDa, the academic isoelectric point was 5.35, and the protein was stable protein. Then multiple sequence alignment was applied to construct phylogenetic tree. The real-time fluorescence quantification PCR (RT-qPCR) demonstrated that a high expression level in leaf, followed by root and flower, the low transcription was in stem. The recombinant vector pCABIA2300-CoObgC was constructed and introduced into tobacco epidermal cells by agrobacterium-mediated transformation, green fluorescence was tested and targeted to chloroplast under a laser scanning confocal microscope. These findings will be helpful to lay a foundation for studying the structure and function of CoObgC gene, and elucidating C. officinalis molecular biology experiment.

[Effect of Acupuncture on Prognosis and Immune Function of Sepsis Patients].

OBJECTIVE: To study the effect of acupuncture on the immune function of sepsis patients. METHODS: Ninety sepsis patients were assigned to the control group, the thymosin a1 group, and the acupuncture treatment group according to random digit table, 30 patients in each group. Patients in the control group were treated according to the guideline of Surviving Sepsis Campaign (SSC). Patients in the control group received routine treatment. Those in the thymosin alpha1 group additionally received subdermal injection of thymosin alpha1 (1.6 mg), once per day for 6 successive days. Needling at related points such as Zusanli (ST36), Yanglingquan (GB34), Neiguan (PC6), Guanyuan (RN4), and so on, was performed in patients of the acupuncture treatment group, once per day for 6 successive days. T cell subgroups (CD3+, CD4+, CD8+, CD4+ /CD8+) and immunoglobulin levels (IgG, IgA, IgM) were detected. The length of ICU hospital stay, hospital readmission rate, and 28-day mortality were compared among the three groups. RESULTS: After six days of treatment, CD3+, CD4+, CD8+, IgG, IgA, IgM, and CD4+ /CD8+ ratio of three groups were all significantly increased (P < 0.01). Of them, CD3+, CD4+, CD8+, IgG, IgA, and IgM increased more significantly in the thymosin alpha1 group and the acupuncture treatment group (P < 0.01). Compared with the control group, the ICU hospitalization length was significantly shortened, the hospital readmission rate and the 28-day mortality were lower in the thymosin alpha1 group and the acupuncture treatment group (P < 0.05, P < 0.01). There was no statistical difference in each index between the thymosin alpha1 group and the acupuncture treatment group (P > 0.05). CONCLUSION: Acupuncture could adjust the immune function of sepsis patients, improve their immunological indicators and prognoses.

[Physiological and biochemical change of Paris seed in after-ripening during variable temperature stratification].

In order to explore the dormancy physiological and biochemical mechanism of Paris seeds, the seed embryo growth courses, and the dynamic change of 5 enzymes, include SOD, POD, CAT, MDH, G-6-PDH were measured during variable temperature stratification. The results indicated that Paris seeds embryo grew quickly after 40 d in warm-stratification (18 ± 1) °C, at the meantime the metabolic activity was significantly strengthened. These facts showed that Paris seeds turned into physiological after-ripening process. After 60-80 d, the morphological embryo after-ripping process basically completed, and the following cold-stratification (4 ± 1) °C furthered Paris seed to finish physiological after-ripening. After 40 d, the activity of MDH decreased while G-6-PDH increased significantly. This showed that the main respiratory pathway of seed changed from TCA to PPP, which benifited breaking seed dormancy. In the whole period of stratification process, the activity variation of SOD and CAT was insignificantly and the activity of POD was enhanced significantly after shifting the seed in cold stratification process. This showed that SOD, CAT had no direct effects on breaking Paris seed dormancy but keeping the seed vigor, while the POD might involve in the process of Paris seed dormancy breaking.

Changes in composition and enamel demineralization inhibition activities of gallic acid at different pH values.

BACKGROUND: Gallic acid (GA) has been shown to inhibit demineralization and enhance remineralization of enamel; however, GA solution is highly acidic. This study was to investigate the stability of GA solutions at various pH and to examine the resultant effects on enamel demineralization. METHODS: The stability of GA in H2O or in phosphate buffer at pH 5.5, pH 7.0 and pH 10.0 was evaluated qualitatively by ultraviolet absorption spectra and quantified by high performance liquid chromatography with diode array detection (HPLC-DAD). Then, bovine enamel blocks were subjected to a pH-cycling regime of 12 cycles. Each cycle included 5 min applications with one of the following treatments: 1 g/L NaF (positive control), 4 g/L GA in H2O or buffered at pH 5.5, pH 7.0 and pH 10.0 and buffers without GA at the same pH (negative control), followed by a 60 min application with pH 5.0 acidic buffers and a 5 min application with neutral buffers. The acidic buffers were analysed for dissolved calcium. RESULTS: GA was stable in pure water and acidic condition, but was unstable in neutral and alkaline conditions, in which ultraviolet spectra changed and HPLC-DAD analysis revealed that most of the GA was degraded. All the GA groups significantly inhibited demineralization (p < 0.05) and there was no significant difference of the inhibition efficacy among different GA groups (p > 0.05). CONCLUSIONS: GA could inhibit enamel demineralization and the inhibition effect is not influenced by pH. GA could be a useful source as an anti-cariogenic agent for broad practical application.

[Effect of acupuncture on acute left heart failure by PiCCO technique].

OBJECTIVE: To observe the clinical effect of acupuncture on acute heart failure (AHF) patients. METHODS: Totally 60 patients who were diagnosed as AHF were assigned to the acupuncture group and the control group, 30 in each group. Those in the control group received inotropic agents, preload and afterload reducing therapy, anti-infection and so on. Besides, those in the acupuncture group received needling at relative points, once daily for 5 consecutive days. The mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), stroke volume index (SI), left ventricle working index (LCWI) were monitored by thermodilution pulse-indicated continuous cardiac output (PiCCO) technique. Changes of the aforesaid data were compared between before and after treatment. The ICU length of stay, readmission rate,and the 28-day mortality were also compared between the two groups. RESULTS: After 5 days of the treatment, CI, SI, and LCWI increased more obviously (P < 0.01), HR and MAP decreased significantly (P < 0.05). Of them, CI, SI, and LCWI increased more obviously in the acupuncture group (P < 0.05).There was no obvious difference in HR or MAP between the two groups (P > 0.05). Compared with the first day of admission in the same group, CI, SI, and LCWI obviously increased in the acupuncture group from the second day (P < 0.05). HR started to decrease since the fourth day (P < 0.05), and MAP began to decrease until the fifth day (P < 0.05). CI, SI, and LCWI started to increase in the control group from the third day (P < 0.05); HR and MAP both began to decrease since the fifth day (P < 0.05). Compared with the control group, the ICU length of stay was obviously shortened in the acupuncture group (P < 0.05). The readmission rate and the 28-day mortality rate were lower than those of the control group (P < 0.05). CONCLUSION: The combination of acupuncture and Western medical therapy might strengthen acute heart failure patients' heart functions, elevate the therapeutic effect, and improve the prognosis.

Biofeedback treatment for sleep bruxism: a systematic review.

PURPOSE: The aim of this systematic review was to evaluate the efficacy of any biofeedback treatment on sleep bruxism. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ISI Web of Science, System for Information on Grey Literature in Europe, Chinese Biomedical Literature Database, and PsycINFO up to October 2012 for randomized controlled trials and controlled clinical trials involving biofeedback treatment for sleep bruxism. Reference lists of relevant studies were hand searched. Quality assessment and data extraction were performed by two reviewers independently. RESULTS: Seven eligible studies involving 240 participants were finally included. Three of them had moderate risk of bias, and four had high risk of bias. In an electromyographic-measured sleep bruxism episode, meta-analysis showed no significant difference between contingent electrical stimulation and blank control (95% confidence interval = -12.33, 3.38, P = 0.26). Moreover, five studies reported electromyographic activity index. Due to the diversity of biofeedback modalities (auditory, electrical, and visual stimulus) and controls (splint, occlusal adjustment, etc.), these data were unable to be pooled, so only qualitative description was provided. CONCLUSIONS: In the current stage, there is no powerful evidence to support the use of biofeedback technology on sleep bruxism treatment. Contingent electrical stimulation which is defined as a kind of biofeedback modality shows no effect on reducing sleep bruxism episode compared with the no-treatment group. Although many studies support the efficacy of biofeedback treatment, more large sample-sized randomized controlled trials which adopt uniform outcome index are necessitated to verify its application.

Effects of 45S5 bioglass on surface properties of dental enamel subjected to 35% hydrogen peroxide.

Tooth bleaching agents may weaken the tooth structure. Therefore, it is important to minimize any risks of tooth hard tissue damage caused by bleaching agents. The aim of this study was to evaluate the effects of applying 45S5 bioglass (BG) before, after, and during 35% hydrogen peroxide (HP) bleaching on whitening efficacy, physicochemical properties and microstructures of bovine enamel. Seventy-two bovine enamel blocks were prepared and randomly divided into six groups: distilled deionized water (DDW), BG, HP, BG before HP, BG after HP and BG during HP. Colorimetric and microhardness tests were performed before and after the treatment procedure. Representative specimens from each group were selected for morphology investigation after the final tests. A significant color change was observed in group HP, BG before HP, BG after HP and BG during HP. The microhardness loss was in the following order: group HP>BG before HP, BG after HP>BG during HP>DDW, BG. The most obvious morphological alteration of was observed on enamel surfaces in group HP, and a slight morphological alteration was also detected in group BG before HP and BG after HP. Our findings suggest that the combination use of BG and HP could not impede the tooth whitening efficacy. Using BG during HP brought better protective effect than pre/post-bleaching use of BG, as it could more effectively reduce the mineral loss as well as retain the surface integrity of enamel. BG may serve as a promising biomimetic adjunct for bleaching therapy to prevent/restore the enamel damage induced by bleaching agents.

[Effect of Galla chinensis on the surface strengthening of bovine dentine in vitro].

PURPOSE: To evaluate the effect of Galla chinensis extract (GCE) on strengthening the surface properties of bovine dentine in vitro. METHODS: Forty-five bovine dentine blocks were prepared and randomly divided into three groups to undergo a modified anti-acid pH-cycling regimen. Treatments were 4 g/L aqueous solution of Galla chinensis, 1 g/L NaF(positive control) and distilled deionized water (DDW, negative control). Surface dentine microhardness was assessed before and after the pH-cycling regimen and the percentage of microhardness loss (PML) was calculated. Then specimens were analyzed with scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDXS). Statistical analysis was performed by SPSS17.0 software package. RESULTS: Compared with DDW, GCE significantly reduced dentinal microhardness loss (P<0.05). No significant difference of the PML was found between GCE and NaF groups (P>0.05). Both SEM images and elemental contents were similar between the GCE and NaF group. CONCLUSIONS: Galla chinensis can enhance the surface properties of bovine dentine and may inhibit dentine caries progression and protect tooth dentine from erosion in this laboratory study.

Characterization of dentin matrix biomodified by Galla chinensis extract.

INTRODUCTION: The aim of this study was to systemically investigate the potential of Galla chinensis extract (GCE) to interact with the dentin matrix to improve its biochemical and biomechanical properties and structural stability. METHODS: The fully demineralized dentin matrices were prepared and biomodified by 0.4% and 4% GCE solutions, with 5% glutaraldehyde and distilled deionized water as positive and negative controls, respectively. The GCE-dentin matrix interaction was assessed by Fourier transform infrared spectroscopy. The biomodification effects of GCE on the biochemical, biomechanical, and structural properties were assessed by a series of assays including denaturation temperature, swelling ratio and enzymatic biodegradation rate, elastic modulus, ultimate tensile strength, and transmission electron microscopy. RESULTS: GCE could interact with dentin matrix through formation of hydrogen bonds. Compared with negative control, the GCE and glutaraldehyde-treated dentin matrix showed significantly higher denaturation temperature, lowered swelling ratio, and reduced biodegradability against enzymatic digestion. GCE treatment significantly increased elastic modulus values of dentin matrix in a concentration- and time-dependent manner. Biomodification by GCE maintained the ultimate tensile strength and structural integrity of dentin matrix after storage in proteolytic conditions. CONCLUSIONS: GCE can stabilize the dentin matrix against thermal and proteolytic challenges, improve its biomechanical properties, and maintain its structural integrity with long duration. The mechanism is probably due to the formation of GCE-dentin matrix complex.